Author: "David Goltzman" - Searchworks@Jio Institute Digital Library Search Results

486 results on '"David Goltzman"'

1. The senolytic agent ABT263 ameliorates osteoporosis caused by active vitamin D insufficiency through selective clearance of senescent skeletal cells

Author: Cuicui Yang, Wanxin Qiao, Qi Xue, David Goltzman, Dengshun Miao, and Zhan Dong
Subjects: Cellular senescence, Osteoporosis, SASP, Senolytics, Vitamin D insufficiency, Diseases of the musculoskeletal system, RC925-935
Abstract: Background/Objective: Active vitamin D insufficiency accelerates the development of osteoporosis, with senescent bone cells and the senescence-associated secretory phenotype (SASP) playing crucial roles. This study aimed to investigate whether the senolytic agent ABT263 could correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent cells. Methods: Bone marrow mesenchymal stem cells (BM-MSCs) from young and aged mice were treated with ABT263 in vitro, and 1,25(OH)2D-insufficient (Cyp27b1+/−) mice were administered ABT263 in vivo. Cellular, molecular, imaging, and histopathological analyses were performed to compare treated cells and mice with control groups. Results: ABT263 induced apoptosis in senescent BM-MSCs by downregulating Bcl2 and upregulating Bax expression. It also induced apoptosis in senescent BM-MSCs from 1,25(OH)2D-insufficient mice. ABT263 administration corrected bone loss caused by 1,25(OH)2D insufficiency by increasing bone density, bone volume, trabecular number, trabecular thickness, and collagen synthesis. It also enhanced osteoblastic bone formation and reduced osteoclastic bone resorption in vivo. ABT263 treatment corrected the impaired osteogenic action of BM-MSCs by promoting their proliferation and osteogenic differentiation. Furthermore, it corrected oxidative stress and DNA damage caused by 1,25(OH)2D insufficiency by increasing SOD-2 and decreasing γ-H2A.X expression. Finally, ABT263 corrected bone cell senescence and SASP caused by 1,25(OH)2D insufficiency by reducing the expression of senescence and SASP-related genes and proteins. Conclusion: ABT263 can correct osteoporosis caused by active vitamin D insufficiency by selectively clearing senescent skeletal cells, reducing oxidative stress, DNA damage, and SASP, and promoting bone formation while inhibiting bone resorption. These findings provide new insights into the potential therapeutic application of senolytic agents in the treatment of osteoporosis associated with active vitamin D insufficiency. The translational potential of this article: This study highlights the therapeutic potential of ABT263, a senolytic compound, in treating osteoporosis caused by active vitamin D insufficiency. By selectively eliminating senescent bone cells and their associated SASP, ABT263 intervention demonstrates the ability to restore bone homeostasis, prevent further bone loss, and promote bone formation. These findings contribute to the growing body of research supporting the use of senolytic therapies for the prevention and treatment of age-related bone disorders. The translational potential of this study lies in the development of novel therapeutic strategies targeting cellular senescence to combat osteoporosis, particularly in cases where vitamin D insufficiency is a contributing factor. Further clinical studies are warranted to validate the efficacy and safety of ABT263 and other senolytic agents in the treatment of osteoporosis in humans.
Published: 2024
Full Text: View/download PDF

2. Corrigendum to 'Sirt1 protects against intervertebral disc degeneration induced by 1,25-Dihydroxyvitamin D insufficiency in mice by inhibiting the NF-κB inflammatory pathway'[Journal of Orthopaedic Translation 40 (2023) 13–26]

Author: Peng Wang, Cuicui Yang, Jinhong Lu, Yongxin Ren, David Goltzman, and Dengshun Miao
Subjects: Diseases of the musculoskeletal system, RC925-935
Published: 2024
Full Text: View/download PDF

3. Multiple Endocrine Neoplasia Type 1 Regulates TGFβ-Mediated Suppression of Tumor Formation and Metastasis in Melanoma

Author: Julien Boudreault, Lucie Canaff, Mostafa Ghozlan, Ni Wang, Vito Guarnieri, Antonio Stefano Salcuni, Alfredo Scillitani, David Goltzman, Suhad Ali, and Jean-Jacques Lebrun
Subjects: melanoma, TGFβ signaling, MEN1, tumor suppression, metastasis, MEN1 missense and frameshift mutations, Cytology, QH573-671
Abstract: Over the past few decades, the worldwide incidence of cutaneous melanoma, a malignant neoplasm arising from melanocytes, has been increasing markedly, leading to the highest rate of skin cancer-related deaths. While localized tumors are easily removed by excision surgery, late-stage metastatic melanomas are refractory to treatment and exhibit a poor prognosis. Consequently, unraveling the molecular mechanisms underlying melanoma tumorigenesis and metastasis is crucial for developing novel targeted therapies. We found that the multiple endocrine neoplasia type 1 (MEN1) gene product Menin is required for the transforming growth factor beta (TGFβ) signaling pathway to induce cell growth arrest and apoptosis in vitro and prevent tumorigenesis in vivo in preclinical xenograft models of melanoma. We further identified point mutations in two MEN1 family members affected by melanoma that led to proteasomal degradation of the MEN1 gene product and to a loss of TGFβ signaling. Interestingly, blocking the proteasome degradation pathway using an FDA-approved drug and RNAi targeting could efficiently restore MEN1 expression and TGFβ transcriptional responses. Together, these results provide new potential therapeutic strategies and patient stratification for the treatment of cutaneous melanoma.
Published: 2024
Full Text: View/download PDF

4. Sirt1 protects against intervertebral disc degeneration induced by 1,25-dihydroxyvitamin D insufficiency in mice by inhibiting the NF-κB inflammatory pathway

Author: Peng Wang, Cuicui Yang, Jinhong Lu, Yongxin Ren, David Goltzman, and Dengshun Miao
Subjects: Vitamin D, Vitamin D receptor, Sirt1, Intervertebral disc degeneration, NF-κB, Diseases of the musculoskeletal system, RC925-935
Abstract: Background: It has been demonstrated that vitamin D deficiency is associated with an increased risk of patients developing lumbar disc herniation. However, intervertebral disc degeneration caused by active vitamin D deficiency has not been reported. Thus, the purpose of this study was to e investigate the role and mechanism of 1,25-dihydroxyvitamin D (1,25(OH)2D) insufficiency in promoting intervertebral disc degeneration. Methods: The phenotypes of intervertebral discs were compared in wild-type mice and mice with heterozygous deletion of 1α-hydroxylase [1α(OH)ase+/−] at 8 mouths of age using iconography, histology and molecular biology. A mouse model that overexpressed Sirt1 in mesenchymal stem cells on a 1α(OH)ase+/− background (Sirt1Tg/1α(OH)ase+/−) was generated by crossing Prx1-Sirt1 transgenic mice with 1α(OH)ase+/− mice and comparing their intervertebral disc phenotypes with those of Sirt1Tg, 1α(OH)ase+/− and wild-type littermates at 8 months of age. A vitamin D receptor (VDR)-deficient cellular model was generated by knock-down of endogenous VDR using Ad-siVDR transfection into nucleus pulposus cells; VDR-deficient nucleus pulposus cells were then treated with or without resveratrol. The interactions between Sirt1 and acetylated p65, and p65 nuclear localization, were examined using co-immunoprecipitation, Western blots and immunofluorescence staining. VDR-deficient nucleus pulposus cells were also treated with 1,25(OH)2D3, or resveratrol or 1,25(OH)2D3 plus Ex527 (an inhibitor of Sirt1). Effects on Sirt1 expression, cell proliferation, cell senescence, extracellular matrix protein synthesis and degradation, nuclear factor-κB (NF-κB), and expression of inflammatory molecules, were examined, using immunofluorescence staining, Western blots and real-time RT-PCR. Results: 1,25(OH)2D insufficiency accelerated intervertebral disc degeneration by reducing extracellular matrix protein synthesis and enhancing extracellular matrix protein degradation with reduced Sirt1 expression in nucleus pulposus tissues. Overexpression of Sirt1 in MSCs protected against 1,25(OH)2D deficiency-induced intervertebral disc degeneration by decreasing acetylation and phosphorylation of p65 and inhibiting the NF-κB inflammatory pathway. VDR or resveratrol activated Sirt1 to deacetylate p65 and inhibit its nuclear translocation into nucleus pulposus cells. Knockdown of VDR decreased VDR expression and significantly reduced the proliferation and extracellular matrix protein synthesis of nucleus pulposus cells, significantly increased the senescence of nucleus pulposus cells and significantly downregulated Sirt1 expression, and upregulated matrix metallopeptidase 13 (MMP13), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) expression; the ratios of acetylated and phosphorylated p65/p65 in nucleus pulposus cells were also increased. Treatment of nucleus pulposus cells with VDR reduction using 1,25(OH)2D3 or resveratrol partially rescued the degeneration phenotypes, by up-regulating Sirt1 expression and inhibiting NF-κB inflammatory pathway; these effects in nucleus pulposus cells were blocked by inhibition of Sirt1. Conclusion: Results from this study indicate that the 1,25(OH)2D/VDR pathway can prevent the degeneration of nucleus pulposus cells by inhibiting the NF-κB inflammatory pathway mediated by Sirt1.The Translational Potential of This Article: This study provides new insights into the use of 1,25(OH)2D3 to prevent and treat intervertebral disc degeneration caused by vitamin D deficiency.
Published: 2023
Full Text: View/download PDF

5. Genetic Deletion of Menin in Mouse Mesenchymal Stem Cells: An Experimental and Computational Analysis

Author: Jad Abi‐Rafeh, Meisam Asgari, Ildi Troka, Lucie Canaff, Ahmed Moussa, Damiano Pasini, and David Goltzman
Subjects: BIOMECHANICS, BONE REMODELING, GENETIC MOUSE MODEL, MENIN AND BONE, MESENCHYMAL STROMAL/STEM CELLS, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935
Abstract: ABSTRACT Loss‐of‐function mutations in the MEN1 tumor‐suppressor gene cause the multiple endocrine neoplasia type 1 syndrome. Menin, the MEN1 gene product, is expressed in many tissues, including bone, where its function remains elusive. We conditionally inactivated menin in mesenchymal stem cells (MSCs) using paired‐related homeobox 1 (Prx1)‐Cre and compared resultant skeletal phenotypes of Prx1‐Cre;Men1f/f menin‐knockout mice (KO) and wild‐type controls using in vivo and in vitro experimental approaches and mechanics simulation. Dual‐energy X‐ray absorptiometry demonstrated significantly reduced bone mineral density, and 3‐dimensional micro‐CT imaging revealed a decrease in trabecular bone volume, altered trabecular structure, and an increase in trabecular separation in KO mice at 6 and 9 months of age. Numbers of osteoblasts were unaltered, and dynamic histomorphometry demonstrated unaltered bone formation; however, osteoclast number and activity and receptor activator of NF‐κB ligand/osteoprotegerin (RANKL/OPG) mRNA profiles were increased, supporting increased osteoclastogenesis and bone resorption. In vitro, proliferative capabilities of bone marrow stem cells and differentiation of osteoblasts and mineralization were unaltered; however, osteoclast generation was increased. Gross femur geometrical alterations observed included significant reductions in length and in mid‐metaphyseal cross‐sectional area. Atomic force microscopy demonstrated significant decreases in elasticity of both cortical and trabecular bone at the nanoscale, whereas three‐point bending tests demonstrated a 30% reduction in bone stiffness; finite element analysis showed morphological changes of the femur microgeometry and a significantly diminished femur flexural rigidity. The biomechanical results demonstrated the detrimental outcome of the accelerated osteoclastic bone resorption. Our studies have a twofold implication; first, MEN1 deletion from MSCs can negatively regulate bone mass and bone biomechanics, and second, the experimental and computational biomechanical analyses employed in the present study should be applicable for improved phenotypic characterization of murine bone. Furthermore, our findings of critical menin function in bone may underpin the more severe skeletal phenotype found in hyperparathyroidism associated with loss‐of‐function of the MEN1 gene. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Published: 2022
Full Text: View/download PDF

6. Effect of Menin Deletion in Early Osteoblast Lineage on the Mineralization of an In Vitro 3D Osteoid-like Dense Collagen Gel Matrix

Author: Ildi Troka, Gabriele Griffanti, Lucie Canaff, Geoffrey N. Hendy, David Goltzman, and Showan N. Nazhat
Subjects: menin, plastic compression, dense collagen, mineralization, osteoblastic differentiation, Technology
Abstract: Bone has a complex microenvironment formed by an extracellular matrix (ECM) composed mainly of mineralized type I collagen fibres. Bone ECM regulates signaling pathways important in the differentiation of osteoblast-lineage cells, necessary for bone mineralization and in preserving tissue architecture. Compared to conventional 2D cell cultures, 3D in vitro models may better mimic bone ECM and provide an environment to support osteoblastic differentiation. In this study, a biomimetic 3D osteoid-like dense collagen gel model was used to investigate the role of the nuclear protein menin plays in osteoblastic differentiation and matrix mineralization. Previous in vitro and in vivo studies have shown that when expressed at later stages of osteoblastic differentiation, menin modulates osteoblastogenesis and regulates bone mass in adult mice. To investigate the role of menin when expressed at earlier stages of the osteoblastic lineage, conditional knockout mice in which the Men1 gene is specifically deleted early (i.e., at the level of the pluripotent mesenchymal stem cell lineage), where generated and primary calvarial osteoblasts were cultured in plastically compressed dense collagen gels for 21 days. The proliferation, morphology and differentiation of isolated seeded primary calvarial osteoblasts from knockout (Prx1-Cre; Men1f/f) mice were compared to those isolated from wild-type (Men1f/f) mice. Primary calvarial osteoblasts from knockout and wild-type mice did not show differences in terms of proliferation. However, in comparison to wild-type cells, primary osteoblast cells derived from knockout mice demonstrated deficient mineralization capabilities and an altered gene expression profile when cultured in 3D dense collagen gels. In summary, these findings indicate that when expressed at earlier stages of osteoblast differentiation, menin is important in maintaining matrix mineralization in 3D dense collagen gel matrices, in vitro.
Published: 2022
Full Text: View/download PDF

7. Probing the Scope and Mechanisms of Calcitriol Actions Using Genetically Modified Mouse Models

Author: Dengshun Miao and David Goltzman
Subjects: DENTAL BIOLOGY, GENETIC ANIMAL MODELS, OSTEOMALACIA AND RICKETS, OSTEOPOROSIS, PTH/VIT D/FGF23, Orthopedic surgery, RD701-811, Diseases of the musculoskeletal system, RC925-935
Abstract: ABSTRACT Genetically modified mice have provided novel insights into the mechanisms of activation and inactivation of vitamin D, and in the process have provided phenocopies of acquired human disease such as rickets and osteomalacia and inherited diseases such as pseudovitamin D deficiency rickets, hereditary vitamin D resistant rickets, and idiopathic infantile hypercalcemia. Both global and tissue‐specific deletion studies leading to decreases of the active form of vitamin D, calcitriol [1,25(OH)2D], and/or of the vitamin D receptor (VDR), have demonstrated the primary role of calcitriol and VDR in bone, cartilage and tooth development and in the regulation of mineral metabolism and of parathyroid hormone (PTH) and FGF23, which modulate calcium and phosphate fluxes. They have also, however, extended the spectrum of actions of calcitriol and the VDR to include, among others: modulation, jointly and independently, of skin metabolism; joint regulation of adipose tissue metabolism; cardiovascular function; and immune function. Genetic studies in older mice have also shed light on the molecular mechanisms underlying the important role of the calcitriol/VDR pathway in diseases of aging such as osteoporosis and cancer. In the course of these studies in diverse tissues, important upstream and downstream, often tissue‐selective, pathways have been illuminated, and intracrine, as well as endocrine actions have been described. Human studies to date have focused on acquired or genetic deficiencies of the prohormone vitamin D or the (generally inactive) precursor metabolite 25‐hyrodxyvitamin D, but have yet to probe the pleiotropic aspects of deficiency of the active form of vitamin D, calcitriol, in human disease. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Published: 2021
Full Text: View/download PDF

8. Abstract 29: An Experimental And Computational Analysis Of Mouse Femur Biomechanics Following The Deletion Of Menin In The Osteoblast Lineage

Author: Jad Abi-Rafeh, MSc, MD, CM (c), Meisam Asgari, PhD, Ahmed Moussa, PhD, Geoffrey Hendy, PhD, Damiano Pasini, PhD, and David Goltzman, MD, FACS, FRCSC
Subjects: Surgery, RD1-811
Published: 2020
Full Text: View/download PDF

9. Abstract 36: Menin Functions Critically In Mesenchymal Stem Cells And Osteoblast Progenitors To Promote Bone Development And Maintenance In Vivo

Author: Jad Abi-Rafeh, MSc, Ildi Troka, MSc, Lucie Canaff, PhD, Geoffrey Hendy, PhD, and David Goltzman, MD, FACS, FRCSC
Subjects: Surgery, RD1-811
Published: 2020
Full Text: View/download PDF

10. Effects of the Administration of 25(OH) Vitamin D3 in an Experimental Model of Chronic Kidney Disease in Animals Null for 1-Alpha-Hydroxylase.

Author: Noelia Torremadé, Milica Bozic, David Goltzman, Elvira Fernandez, and José M Valdivielso
Subjects: Medicine, Science
Abstract: The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals. The dose needed to decrease PTH levels in CYP27B1-/- mice with CKD was 50 ng/g. That dose restored blood calcium levels without modifying phosphate levels, and increased the expression of genes responsible for calcium absorption (TRPV5 and calbindinD- 28K in the kidney, TRPV6 and calbindinD-9k in the intestine). The same dose of 25(OH)D3 did not modify PTH in CYP27B1+/+ animals with CKD. Blood calcium remained normal, while phosphate increased significantly. Blood levels of 25(OH)D3 in CYP27B1-/- mice were extremely high compared to those in CYP27B1+/+ animals. CYP27B1+/+ animals with CKD showed increases in TRPV5, TRPV6, calbindinD-28K and calbindinD-9K, which were not further elevated with the treatment. Furthermore, CYP27B1+/+ animals displayed an increase in vascular calcification. We conclude that the dose of 25(OH)D3 effective in decreasing PTH levels in CYP27B1-/- mice with CKD, has a potentially toxic effect in CYP27B1+/+ animals with CKD.
Published: 2017
Full Text: View/download PDF

11. PO-32 DIETARY CALCIUM INTAKE AND CARDIOVASCULAR HEALTH: IS THERE ANY RELATIONSHIP?

Author: Shubhabrata Das, Yessica-Haydee Gomez, David Goltzman, Angel M. Ong, Yessica H. Gomez, Jessica Gorgui, Michelle Wall, Suzanne N. Morin, and Stella S. Daskalopoulou
Subjects: Specialties of internal medicine, RC581-951, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Introduction: Calcium intake, recommended for osteoporosis prevention, has been associated with cardiovascular (CV) outcomes. We examined the association of dietary calcium intake (dCa) with surrogate CV markers, including carotid intima-media thickness (cIMT), arterial stiffness and hemodynamics in healthy postmenopausal women. Methods: Healthy postmenopausal women without any CV risk factors, from a randomized controlled trial studying the effect of calcium supplementation vs. dietary calcium on vascular heath, were recruited. Cross-sectional analyses of baseline data of the participants are presented. Peripheral systolic and diastolic blood pressures (pSBP, pDBP) were measured by BpTRU. cIMT of both common-carotid arteries was measured by B-mode ultrasonography (Philips-iU22). Arterial stiffness (carotid-to-femoral pulse wave velocity [cfPWV] and carotid-to-radial PWV), central SBP and DBP (cSBP, cDBP), mean arterial pressure (MAP), and hemodynamic parameters (pulse pressure, augmentation pressure, augmentation index corrected for 75 bpm) were obtained non-invasively (SphygmoCor). Usual dCa intake was estimated using a validated food frequency questionnaire. Measurements were compared across groups (1000 mg/day of dCa) by one-way analysis of variance and covariance. Results: We evaluated 83 postmenopausal women (mean age 60.4±6.3 years; BMI 25.6±3.8 kg/m2). Mean dCa was 857±333 mg/day. Although within normal range, vascular parameters had a non-significant, U-shaped relationship with dCa. In unadjusted analyses, women with dCa >1000 mg/day had significantly higher cfPWV, pSBP, cSBP, and MAP compared to those with 600–1000 mg/day; however, significance was lost for all other parameters except for MAP after adjustment for pertinent covariates (Table). Conclusion: In healthy postmenopausal women, a non-significant, U-shaped relationship of vascular parameters across the 3 dCa groups was noted; dietary calcium may have favourable effect on MAP for those consuming 600–1000 mg/day compared to >1000 mg/day intake. Of note, our population had optimal/normal BP. Our ongoing study including a larger sample-size will determine the relationship between dCa and surrogate CV markers.
Published: 2016
Full Text: View/download PDF

12. Correction: Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study.

Author: Lauren E Mokry, Stephanie Ross, Omar S Ahmad, Vincenzo Forgetta, George Davey Smith, David Goltzman, Aaron Leong, Celia M T Greenwood, George Thanassoulis, and J Brent Richards
Subjects: Medicine
Published: 2016
Full Text: View/download PDF

13. The Role of Parathyroid Hormone-Related Protein (PTHrP) in Osteoblast Response to Microgravity: Mechanistic Implications for Osteoporosis Development.

Author: Anne Camirand, David Goltzman, Ajay Gupta, Mohammadi Kaouass, Dibyendu Panda, and Andrew Karaplis
Subjects: Medicine, Science
Abstract: Prolonged skeletal unloading through bedrest results in bone loss similar to that observed in elderly osteoporotic patients, but with an accelerated timeframe. This rapid effect on weight-bearing bones is also observed in astronauts who can lose up to 2% of their bone mass per month spent in Space. Despite the important implications for Spaceflight travelers and bedridden patients, the exact mechanisms involved in disuse osteoporosis have not been elucidated. Parathyroid hormone-related protein (PTHrP) regulates many physiological processes including skeletal development, and has been proposed as a mechanosensor. To investigate the role of PTHrP in microgravity-induced bone loss, trabecular and calvarial osteoblasts (TOs and COs) from Pthrp +/+ and -/- mice were subjected to actual Spaceflight for 6 days (Foton M3 satellite). Pthrp +/+, +/- and -/- osteoblasts were also exposed to simulated microgravity for periods varying from 6 days to 6 weeks. While COs displayed little change in viability in 0g, viability of all TOs rapidly decreased in inverse proportion to PTHrP expression levels. Furthermore, Pthrp+/+ TOs displayed a sharp viability decline after 2 weeks at 0g. Microarray analysis of Pthrp+/+ TOs after 6 days in simulated 0g revealed expression changes in genes encoding prolactins, apoptosis/survival molecules, bone metabolism and extra-cellular matrix composition proteins, chemokines, insulin-like growth factor family members and Wnt-related signalling molecules. 88% of 0g-induced expression changes in Pthrp+/+ cells overlapped those caused by Pthrp ablation in normal gravity, and pulsatile treatment with PTHrP1-36 not only reversed a large proportion of 0g-induced effects in Pthrp+/+ TOs but maintained viability over 6-week exposure to microgravity. Our results confirm PTHrP efficacy as an anabolic agent to prevent microgravity-induced cell death in TOs.
Published: 2016
Full Text: View/download PDF

14. Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study.

Author: Lauren E Mokry, Stephanie Ross, Omar S Ahmad, Vincenzo Forgetta, George Davey Smith, David Goltzman, Aaron Leong, Celia M T Greenwood, George Thanassoulis, and J Brent Richards
Subjects: Medicine
Abstract: BackgroundObservational studies have demonstrated an association between decreased vitamin D level and risk of multiple sclerosis (MS); however, it remains unclear whether this relationship is causal. We undertook a Mendelian randomization (MR) study to evaluate whether genetically lowered vitamin D level influences the risk of MS.Methods and findingsWe identified single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D (25OHD) level from SUNLIGHT, the largest (n = 33,996) genome-wide association study to date for vitamin D. Four SNPs were genome-wide significant for 25OHD level (p-values ranging from 6 × 10-10 to 2 × 10-109), and all four SNPs lay in, or near, genes strongly implicated in separate mechanisms influencing 25OHD. We then ascertained their effect on 25OHD level in 2,347 participants from a population-based cohort, the Canadian Multicentre Osteoporosis Study, and tested the extent to which the 25OHD-decreasing alleles explained variation in 25OHD level. We found that the count of 25OHD-decreasing alleles across these four SNPs was strongly associated with lower 25OHD level (n = 2,347, F-test statistic = 49.7, p = 2.4 × 10-12). Next, we conducted an MR study to describe the effect of genetically lowered 25OHD on the odds of MS in the International Multiple Sclerosis Genetics Consortium study, the largest genetic association study to date for MS (including up to 14,498 cases and 24,091 healthy controls). Alleles were weighted by their relative effect on 25OHD level, and sensitivity analyses were performed to test MR assumptions. MR analyses found that each genetically determined one-standard-deviation decrease in log-transformed 25OHD level conferred a 2.0-fold increase in the odds of MS (95% CI: 1.7-2.5; p = 7.7 × 10-12; I2 = 63%, 95% CI: 0%-88%). This result persisted in sensitivity analyses excluding SNPs possibly influenced by population stratification or pleiotropy (odds ratio [OR] = 1.7, 95% CI: 1.3-2.2; p = 2.3 × 10-5; I2 = 47%, 95% CI: 0%-85%) and including only SNPs involved in 25OHD synthesis or metabolism (ORsynthesis = 2.1, 95% CI: 1.6-2.6, p = 1 × 10-9; ORmetabolism = 1.9, 95% CI: 1.3-2.7, p = 0.002). While these sensitivity analyses decreased the possibility that pleiotropy may have biased the results, residual pleiotropy is difficult to exclude entirely.ConclusionsA genetically lowered 25OHD level is strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials.
Published: 2015
Full Text: View/download PDF

15. The causal effect of vitamin D binding protein (DBP) levels on calcemic and cardiometabolic diseases: a Mendelian randomization study.

Author: Aaron Leong, Waheed Rehman, Zari Dastani, Celia Greenwood, Nicholas Timpson, Lisa Langsetmo, Claudie Berger, METASTROKE, Lei Fu, Betty Y L Wong, Suneil Malik, Rainer Malik, David A Hanley, David E C Cole, David Goltzman, and J Brent Richards
Subjects: Medicine
Abstract: BackgroundObservational studies have shown that vitamin D binding protein (DBP) levels, a key determinant of 25-hydroxy-vitamin D (25OHD) levels, and 25OHD levels themselves both associate with risk of disease. If 25OHD levels have a causal influence on disease, and DBP lies in this causal pathway, then DBP levels should likewise be causally associated with disease. We undertook a Mendelian randomization study to determine whether DBP levels have causal effects on common calcemic and cardiometabolic disease.Methods and findingsWe measured DBP and 25OHD levels in 2,254 individuals, followed for up to 10 y, in the Canadian Multicentre Osteoporosis Study (CaMos). Using the single nucleotide polymorphism rs2282679 as an instrumental variable, we applied Mendelian randomization methods to determine the causal effect of DBP on calcemic (osteoporosis and hyperparathyroidism) and cardiometabolic diseases (hypertension, type 2 diabetes, coronary artery disease, and stroke) and related traits, first in CaMos and then in large-scale genome-wide association study consortia. The effect allele was associated with an age- and sex-adjusted decrease in DBP level of 27.4 mg/l (95% CI 24.7, 30.0; n = 2,254). DBP had a strong observational and causal association with 25OHD levels (p = 3.2 × 10(-19)). While DBP levels were observationally associated with calcium and body mass index (BMI), these associations were not supported by causal analyses. Despite well-powered sample sizes from consortia, there were no associations of rs2282679 with any other traits and diseases: fasting glucose (0.00 mmol/l [95% CI -0.01, 0.01]; p = 1.00; n = 46,186); fasting insulin (0.01 pmol/l [95% CI -0.00, 0.01,]; p = 0.22; n = 46,186); BMI (0.00 kg/m(2) [95% CI -0.01, 0.01]; p = 0.80; n = 127,587); bone mineral density (0.01 g/cm(2) [95% CI -0.01, 0.03]; p = 0.36; n = 32,961); mean arterial pressure (-0.06 mm Hg [95% CI -0.19, 0.07]); p = 0.36; n = 28,775); ischemic stroke (odds ratio [OR] = 1.00 [95% CI 0.97, 1.04]; p = 0.92; n = 12,389/62,004 cases/controls); coronary artery disease (OR = 1.02 [95% CI 0.99, 1.05]; p = 0.31; n = 22,233/64,762); or type 2 diabetes (OR = 1.01 [95% CI 0.97, 1.05]; p = 0.76; n = 9,580/53,810).ConclusionsDBP has no demonstrable causal effect on any of the diseases or traits investigated here, except 25OHD levels. It remains to be determined whether 25OHD has a causal effect on these outcomes independent of DBP. Please see later in the article for the Editors' Summary.
Published: 2014
Full Text: View/download PDF

16. A high-calcium, high-phosphorus, high-lactose diet rescues the intervertebral disc degeneration phenotype induced by the deficiency of 1,25(OH)2D3

Author: Hao Xu, Daofang Ding, Dengshun Miao, David Goltzman, Qi Shi, Qianqian Liang, and Yongjun Wang
Subjects: Diseases of the musculoskeletal system, RC925-935
Published: 2016
Full Text: View/download PDF

17. WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk.

Author: Hou-Feng Zheng, Jon H Tobias, Emma Duncan, David M Evans, Joel Eriksson, Lavinia Paternoster, Laura M Yerges-Armstrong, Terho Lehtimäki, Ulrica Bergström, Mika Kähönen, Paul J Leo, Olli Raitakari, Marika Laaksonen, Geoffrey C Nicholson, Jorma Viikari, Martin Ladouceur, Leo-Pekka Lyytikäinen, Carolina Medina-Gomez, Fernando Rivadeneira, Richard L Prince, Harri Sievanen, William D Leslie, Dan Mellström, John A Eisman, Sofia Movérare-Skrtic, David Goltzman, David A Hanley, Graeme Jones, Beate St Pourcain, Yongjun Xiao, Nicholas J Timpson, George Davey Smith, Ian R Reid, Susan M Ring, Philip N Sambrook, Magnus Karlsson, Elaine M Dennison, John P Kemp, Patrick Danoy, Adrian Sayers, Scott G Wilson, Maria Nethander, Eugene McCloskey, Liesbeth Vandenput, Richard Eastell, Jeff Liu, Tim Spector, Braxton D Mitchell, Elizabeth A Streeten, Robert Brommage, Ulrika Pettersson-Kymmer, Matthew A Brown, Claes Ohlsson, J Brent Richards, and Mattias Lorentzon
Subjects: Genetics, QH426-470
Abstract: We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ∼2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2 × 10(-9)). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3 × 10(-12), and -0.16 SD per G allele, P = 1.2 × 10(-15), respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3 × 10(-9)), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9 × 10(-6) and rs2707466: OR = 1.22, P = 7.2 × 10(-6)). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16(-/-) mice had 27% (P
Published: 2012
Full Text: View/download PDF

18. Absence of PTHrP nuclear localization and carboxyl terminus sequences leads to abnormal brain development and function.

Author: Zhen Gu, Yahong Liu, Yongjie Zhang, Shulei Jin, Qi Chen, David Goltzman, Andrew Karaplis, and Dengshun Miao
Subjects: Medicine, Science
Abstract: We assessed whether the nuclear localization sequences (NLS) and C terminus of parathyroid hormone-related protein (PTHrP) play critical roles in brain development and function. We used histology, immunohistochemistry, histomorphometry, Western blots and electrophysiological recordings to compare the proliferation and differentiation of neural stem cells, neuronal hippocampal synaptic transmission, and brain phenotypes including shape and structures, in Pthrp knock-in mice, which express PTHrP (1-84), a truncated form of the protein that is missing the NLS and the C-terminal region of the protein, and their wild-type littermates. Results showed that Pthrp knock-in mice display abnormal brain shape and structures; decreased neural cell proliferative capacity and increased apoptosis associated with up-regulation of cyclin dependent kinase inhibitors p16, p21, p27 and p53 and down-regulation of the Bmi-1 oncogene; delayed neural cell differentiation; and impaired hippocampal synaptic transmission and plasticity. These findings provide in vivo experimental evidence that the NLS and C-terminus of PTHrP are essential not only for the regulation of neural cell proliferation and differentiation, but also for the maintenance of normal neuronal synaptic transmission and plasticity.
Published: 2012
Full Text: View/download PDF

19. The abnormal phenotypes of cartilage and bone in calcium-sensing receptor deficient mice are dependent on the actions of calcium, phosphorus, and PTH.

Author: Jingning Liu, Fangqiao Lv, Wen Sun, Chunxiang Tao, Guoxian Ding, Andrew Karaplis, Edward Brown, David Goltzman, and Dengshun Miao
Subjects: Genetics, QH426-470
Abstract: Patients with neonatal severe hyperparathyroidism (NSHPT) are homozygous for the calcium-sensing receptor (CaR) mutation and have very high circulating PTH, abundant parathyroid hyperplasia, and severe life-threatening hypercalcemia. Mice with homozygous deletion of CaR mimic the syndrome of NSHPT. To determine effects of CaR deficiency on skeletal development and interactions between CaR and 1,25(OH)(2)D(3) or PTH on calcium and skeletal homeostasis, we compared the skeletal phenotypes of homozygous CaR-deficient (CaR(-/-)) mice to those of double homozygous CaR- and 1α(OH)ase-deficient [CaR(-/-)1α(OH)ase(-/-)] mice or those of double homozygous CaR- and PTH-deficient [CaR(-/-)PTH(-/-)] mice at 2 weeks of age. Compared to wild-type littermates, CaR(-/-) mice had hypercalcemia, hypophosphatemia, hyperparathyroidism, and severe skeletal growth retardation. Chondrocyte proliferation and PTHrP expression in growth plates were reduced significantly, whereas trabecular volume, osteoblast number, osteocalcin-positive areas, expression of the ALP, type I collagen, osteocalcin genes, and serum ALP levels were increased significantly. Deletion of 1α(OH)ase in CaR(-/-) mice resulted in a longer lifespan, normocalcemia, lower serum phosphorus, greater elevation in PTH, slight improvement in skeletal growth with increased chondrocyte proliferation and PTHrP expression, and further increases in indices of osteoblastic bone formation. Deletion of PTH in CaR(-/-) mice resulted in rescue of early lethality, normocalcemia, increased serum phosphorus, undetectable serum PTH, normalization in skeletal growth with normal chondrocyte proliferation and enhanced PTHrP expression, and dramatic decreases in indices of osteoblastic bone formation. Our results indicate that reductions in hypercalcemia play a critical role in preventing the early lethality of CaR(-/-) mice and that defects in endochondral bone formation in CaR(-/-) mice result from effects of the marked elevation in serum calcium concentration and the decreases in serum phosphorus concentration and skeletal PTHrP levels, whereas the increased osteoblastic bone formation results from direct effects of PTH.
Published: 2011
Full Text: View/download PDF

20. Endogenous PTH deficiency impairs fracture healing and impedes the fracture-healing efficacy of exogenous PTH(1-34).

Author: Yongxin Ren, Bo Liu, Yuxu Feng, Lei Shu, Xiaojian Cao, Andrew Karaplis, David Goltzman, and Dengshun Miao
Subjects: Medicine, Science
Abstract: Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.
Published: 2011
Full Text: View/download PDF

21. An efficient paradigm for genetic epidemiology cohort creation.

Author: Martin Ladouceur, William D Leslie, Zari Dastani, David Goltzman, and J Brent Richards
Subjects: Medicine, Science
Abstract: Development of novel methodologies to efficiently create large genetic epidemiology cohorts is needed. Here we describe a rapid, precise and cost-efficient method for collection of DNA from cases previously experiencing an osteoporotic fracture by identifying cases using and administrative health-care databases. Over the course of 14 months we collected DNA from 1,130 women experiencing an osteoporotic fracture, at a cost of $54 per sample. This cohort is among the larger DNA osteoporotic fracture collections in the world. The novel method described addresses a major unmet health care research need and is widely applicable to any disease that can be identified accurately through administrative data.
Published: 2010
Full Text: View/download PDF

22. Muscle density is associated with fragility fractures in postmenopausal women who are less frail: The CaMOS muscle quality study

Author: Andy Kin On Wong, Courtney Kennedy, George Ioannidis, Karen A. Beattie, Christopher Gordon, Laura Pickard, Alexandra Papaioannou, David Goltzman, and Jerilynn Prior
Subjects: Diseases of the musculoskeletal system, RC925-935
Published: 2014
Full Text: View/download PDF

23. 17β-estradiol plays the anti-osteoporosis role via a novel ESR1-Keap1-Nrf2 axis-mediated stress response activation and Tmem119 upregulation

Author: Renlei Yang, Jie Li, Jing Zhang, Qi Xue, Ran Qin, Rong Wang, David Goltzman, and Dengshun Miao
Subjects: Physiology (medical), Biochemistry
Abstract: Increased oxidative stress and decreased osteoblastic bone formation contribute to estrogen deficiency-induced osteoporosis. However, the role and mechanism of estrogen-deficiency in regulating oxidative stress and osteoblastic activity remain unclear. Here, we showed that estrogen-deficient bone marrow stromal/stem cells (BMSCs) exhibited impaired capacity to combat stress, characterized by increased oxidative stress, shortened cell survival and reduced osteogenic differentiation and bone formation, which were due to a decrease of nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 re-activation induced by the pyrazinyl dithiolethione oltipraz significantly rescued the cell phenotype of estrogen-deficient BMSCs in vitro and ex vivo. Mechanistically, we found that 17β-estradiol/ESR1 (Estrogen Receptor 1) facilitated Nrf2 accumulation, and activated its target genes by competing with Nrf2 for binding to Kelch-like ECH-associated protein 1 (Keap1) via ESR1 containing a highly conserved DLL motif. Of note, oltipraz, an Nrf2 activator, rescued ovariectomy-induced osteoporosis partly by inhibiting oxidative stress and promoting osteoblastic bone formation via Nrf2-induced antioxidant signaling activation and Tmem119 (transmembrane protein 119) upregulation. Conversely, Nrf2 knockout largely blocked the bone anabolic effect of 17β-estradiol in vivo and ex vivo. This study provides insight into the mechanisms whereby estrogen prevents osteoporosis through promoting osteoblastic bone formation via Nrf2-mediated activation of antioxidant signaling and upregulation of Tmem119, and thus provides evidence for Nrf2 as a potential target for clinical prevention and treatment of menopause-related osteoporosis.
Published: 2023

24. 1,25-Dihydroxyvitamin D Deficiency Accelerates Aging-related Osteoarthritis via Downregulation of Sirt1 in Mice

Author: Jie Chen, Jiao Zhang, Jie Li, Ran Qin, Na Lu, David Goltzman, Dengshun Miao, and Renlei Yang
Subjects: Cell Biology, Molecular Biology, Applied Microbiology and Biotechnology, Ecology, Evolution, Behavior and Systematics, Developmental Biology
Published: 2023

25. Race/ethnic differences in the prevalence of osteoporosis, falls and fractures: a cross-sectional analysis of the Canadian Longitudinal Study on Aging

Author: Suzanne N. Morin, Claudie Berger, Alexandra Papaioannou, Angela M. Cheung, Elham Rahme, William D. Leslie, and David Goltzman
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2022

26. A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography

Author: Danielle E. Whittier, Elizabeth J. Samelson, Marian T. Hannan, Lauren A. Burt, David A. Hanley, Emmanuel Biver, Pawel Szulc, Elisabeth Sornay‐Rendu, Blandine Merle, Roland Chapurlat, Eric Lespessailles, Andy Kin On Wong, David Goltzman, Sundeep Khosla, Serge Ferrari, Mary L. Bouxsein, Douglas P. Kiel, and Steven K. Boyd
Subjects: Endocrinology, Diabetes and Metabolism, Orthopedics and Sports Medicine
Published: 2023

27. Inhibition of Nrf2 degradation alleviates age-related osteoporosis induced by 1,25-Dihydroxyvitamin D deficiency

Author: Renlei Yang, Jiao Zhang, Jie Li, Ran Qin, Jie Chen, Rong Wang, David Goltzman, and Dengshun Miao
Subjects: Male, 0303 health sciences, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, 030209 endocrinology & metabolism, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Osteogenesis, Physiology (medical), Animals, Osteoporosis, Receptors, Calcitriol, Vitamin D, 030304 developmental biology
Abstract: Previous studies have shown that 1,25(OH)
Published: 2022

28. Pyrroloquinoline Quinone Alleviates Natural Aging-Related Osteoporosis Via a Novel MCM3-Keap1-Nrf2 Axis-Mediated Stress Response and Fbn1 Upregulation

Author: Jie Li, Jing Zhang, Qi Xue, Ran Qin, Yiping Li, Yue Qiu, Rong Wang, David Goltzman, Dengshun Miao, and Renlei Yang
Published: 2023

29. Mechanisms of action of vitamin D in delaying aging and preventing disease by inhibiting oxidative stress

Author: Dengshun Miao and David Goltzman
Published: 2023

30. Pathophysiology of Hypercalcemia

Author: David Goltzman
Subjects: medicine.medical_specialty, endocrine system diseases, Calcitriol, Endocrinology, Diabetes and Metabolism, Parathyroid hormone, chemistry.chemical_element, Bone Neoplasms, Calcium, Malignancy, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Extracellular, medicine, Vitamin D and neurology, Humans, 030212 general & internal medicine, 030304 developmental biology, 0303 health sciences, Parathyroid hormone-related protein, business.industry, medicine.disease, Pathophysiology, 3. Good health, Calcium, Dietary, chemistry, Parathyroid Hormone, Hypercalcemia, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract: Extracellular calcium is normally tightly regulated by parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, as well as by calcium ion (Ca++) itself. Dysregulated PTH production leading to hypercalcemia occurs most commonly in sporadic primary hyperparathryoidism (PHPT) but may also result from select genetic mutations in familial disorders. Parathyroid hormone-related protein shares molecular mechanisms of action with PTH and is the most common cause of hypercalcemia of malignancy. Other cytokines and mediators may also cause resorptive hypercalcemia once bone metastases have occurred. Less commonly, extrarenal production of calcitriol can occur in malignancies and in infectious and noninfectious inflammatory conditions and can cause hypercalcemia.
Published: 2021

31. Author response for 'A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography'

Author: null Danielle E. Whittier, null Elizabeth J. Samelson, null Marian T. Hannan, null Lauren A. Burt, null David A. Hanley, null Emmanuel Biver, null Pawel Szulc, null Elisabeth Sornay‐Rendu, null Blandine Merle, null Roland Chapurlat, null Eric Lespessailles, null Andy Kin On Wong, null David Goltzman, null Sundeep Khosla, null Serge Ferrari, null Mary L. Bouxsein, null Douglas P. Kiel, and null Steven K. Boyd
Published: 2022

32. Cognitive decline is associated with an accelerated rate of bone loss and increased fracture risk in women: a prospective study from the Canadian Multicentre Osteoporosis Study

Author: Tuan V. Nguyen, David Goltzman, Robert G. Josse, Dana Bliuc, Piet Geusens, Catherine J.M. Stapledon, Roberto Cappai, John A. Eisman, Jerilynn C. Prior, Gerald J. Atkins, Lucian B. Solomon, Christopher S. Kovacs, Thach Tran, Jonathan D. Adachi, Lisa Langsetmo, Claudie Berger, David A. Hanley, Tineke A. C. M. van Geel, Stephanie M. Kaiser, Joop P. W. van den Bergh, Bliuc, D, Tran, T, Adachi, JD, Atkins, GJ, Berger, C, VAN DEN BERGH, Joop, Cappai , R, Eisman, JA, van Geel, T, GEUSENS, Piet, Goltzman, D, Hanley, DA, Josse, R, Kaiser, S, Kovacs, CS, Langsetmo, L, Prior, JC, Nguyen, TV, Solomon, LB, Stapledon, C, Center, JR, Interne Geneeskunde, and RS: NUTRIM - R3 - Respiratory & Age-related Health
Subjects: Male, ELDERLY-WOMEN, medicine.medical_specialty, Longitudinal study, Canada, Endocrinology, Diabetes and Metabolism, Population, Osteoporosis, LONGITUDINAL STUDY, 030209 endocrinology & metabolism, OSTEOPOROSIS, COGNITIVE PERFORMANCE, AGING, 03 medical and health sciences, REPLACEMENT THERAPY, 0302 clinical medicine, Interquartile range, Bone Density, Risk Factors, Internal medicine, Medicine, Humans, Orthopedics and Sports Medicine, Cognitive Dysfunction, 030212 general & internal medicine, Prospective Studies, Cognitive decline, 10. No inequality, education, education.field_of_study, Mini–Mental State Examination, medicine.diagnostic_test, HIP-FRACTURES, Proportional hazards model, business.industry, DEMENTIA, Hazard ratio, MEN, medicine.disease, RELIABLE CHANGE INDEXES, Female, business, BONE MINERAL DENSITY
Abstract: Cognitive decline and osteoporosis often coexist and some evidence suggests a causal link. However, there are no data on the longitudinal relationship between cognitive decline, bone loss and fracture risk, independent of aging. This study aimed to determine the association between: (i) cognitive decline and bone loss; and (ii) clinically significant cognitive decline (>= 3 points) on Mini Mental State Examination (MMSE) over the first 5 years and subsequent fracture risk over the following 10 years. A total of 1741 women and 620 men aged >= 65 years from the population-based Canadian Multicentre Osteoporosis Study were followed from 1997 to 2013. Association between cognitive decline and (i) bone loss was estimated using mixed-effects models; and (ii) fracture risk was estimated using adjusted Cox models. Over 95% of participants had normal cognition at baseline (MMSE >= 24). The annual % change in MMSE was similar for both genders (women -0.33, interquartile range [IQR] -0.70 to +0.00; and men -0.34, IQR: -0.99 to 0.01). After multivariable adjustment, cognitive decline was associated with bone loss in women (6.5%; 95% confidence interval [CI], 3.2% to 9.9% for each percent decline in MMSE from baseline) but not men. Approximately 13% of participants experienced significant cognitive decline by year 5. In women, fracture risk was increased significantly (multivariable hazard ratio [HR], 1.61; 95% CI, 1.11 to 2.34). There were too few men to analyze. There was a significant association between cognitive decline and both bone loss and fracture risk, independent of aging, in women. Further studies are needed to determine mechanisms that link these common conditions. (c) 2021 American Society for Bone and Mineral Research (ASBMR). The Canadian Multicentre Osteoporosis Study was funded by the Canadian Institutes of Health Research (CIHR); Merck Frosst Canada Ltd.; Eli Lilly Canada Inc.; Novartis Pharmaceuticals Inc.; The Alliance: sanofi-aventis & Procter and Gamble Pharmaceuticals Canada Inc.; Servier Canada Inc.; Amgen Canada Inc.; The Dairy Farmers of Canada; and The Arthritis Society. This work was supported by the National Health Medical Research Council Australia Projects 1070187, 1008219, and 1073430. Other funding bodies were an Osteoporosis Australia-Amgen grant; the Bupa Health Foundation (formerly MBF Foundation); the Mrs Gibson and Ernst Heine Family Foundation; and untied grants from Amgen, Merck Sharp & Dohme, Sanofi-Aventis, Servier, and Novartis
Published: 2021

33. The three common polymorphisms p.A986S, p.R990G and p.Q1011E in the calcium sensing receptor (CASR) are not associated with chronic pancreatitis

Author: Lucie Canaff, Claude Férec, Jonas Rosendahl, Katharina Eiseler, Emmanuelle Masson, Peter Bugert, Maren Ewers, Patrick Michl, Vinciane Rebours, Antonia Em. Weh, David Goltzman, Heiko Witt, and Jian-Min Chen
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Genotype, Endocrinology, Diabetes and Metabolism, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Polymorphism (computer science), Pancreatitis, Chronic, Internal medicine, medicine, Humans, Child, Receptor, Allele frequency, Aged, 030304 developmental biology, Calcium metabolism, 0303 health sciences, Polymorphism, Genetic, Hepatology, business.industry, Infant, Newborn, Gastroenterology, Infant, NFAT, Middle Aged, medicine.disease, Endocrinology, Child, Preschool, Mutation, Pancreatitis, Female, 030211 gastroenterology & hepatology, Calcium-sensing receptor, business, Receptors, Calcium-Sensing
Abstract: Background The calcium sensing receptor (CASR) is a G protein-coupled receptor that is responsible for assessing extracellular Ca2+ levels and thus plays a crucial role in calcium homeostasis. Hypercalcemia is a metabolic risk factor for pancreatitis and rare CASR variants have been described in patients with chronic pancreatitis. At the carboxy-terminal tail of CASR, there is a cluster of three common polymorphisms, p.A986S (rs1801725), p.R990G (rs1042636) and p.Q1011E (rs1801726), which have been associated with chronic pancreatitis in various studies, but with conflicting results. Methods We examined 542 German and 339 French patients with chronic pancreatitis as well as 1025 German controls for the 3 common CASR polymorphism by melting curve analysis. For comparison, we used genotype data from 583 French controls from a previous study. In addition, we functionally analyzed the three variants by NFAT and SRE luciferase reporter systems as well as Western blotting and verified cell surface expression by ELISA. Results In both cohorts, neither the genotype nor the allele frequencies differed significantly between patients and controls. In both luciferase assays, p.R990G showed a significant leftward shift, indicating an increased responsiveness of the receptor. p.A986S showed a leftward shift in the SRE but not in the NFAT reporter assay, while the responsiveness of p.Q1011E did not differ from the wild-type. These functional studies therefore do not support the contributions of variant CASR to increasing the risk of pancreatitis. Conclusions The three frequent CASR polymorphisms are unlikely to increase the risk for chronic pancreatitis.
Published: 2021

34. Epigenomic effects of vitamin D in colorectal cancer

Author: Reza Khayami, David Goltzman, Shafaat A Rabbani, and Mohammad Amin Kerachian
Subjects: Epigenomics, Cancer Research, Genetics, Tumor Microenvironment, Humans, Vitamins, Vitamin D, DNA Methylation, Colorectal Neoplasms, Epigenesis, Genetic
Abstract: Vitamin D regulates a plethora of physiological processes in the human body and has been proposed to exert several anticancer effects. Epigenetics plays an important role in regulating vitamin D actions. In this review, we highlight the recent advances in the understanding of different epigenetic factors such as lncRNAs, miRNAs, methylation and acetylation influenced by vitamin D and its downstream targets in colorectal cancer to find more potential therapeutic targets. We discuss how vitamin D exerts anticancer properties through interactions between the vitamin D receptor and genes (e.g.,Vitamin D regulates various physiological processes in the body and could have anticancer effects. These anticancer effects are the result of interactions between many factors such as genes, the environment around the tumors, bacteria in the intestine, etc. in colorectal cancer. Epigenetic factors, including a big network of different molecules in the body that could control our genes without changing DNA, also play a role in regulating vitamin D. This review summarizes the advances in the understanding of different epigenetic factors related to vitamin D and colorectal cancer.
Published: 2022

35. Variation in bone mineral density and fractures over 20 years among Canadians: a comparison of the Canadian Multicenter Osteoporosis Study and the Canadian Longitudinal Study on Aging

Author: Nazila Hassanabadi, Claudie Berger, Alexandra Papaioannou, Angela M. Cheung, Elham Rahme, William D. Leslie, David Goltzman, and Suzanne N. Morin
Subjects: Endocrinology, Diabetes and Metabolism
Abstract: International variations in osteoporosis and fracture rates have been reported, with temporal trends differing between populations. We observed higher BMD and lower fracture prevalence in a recently recruited cohort compared to that of a cohort recruited 20 years ago, even after adjusting for multiple covariates.We explored sex-specific differences in femoral neck bone mineral density (FN-BMD) and in prevalent major osteoporotic fractures (MOF) using two Canadian cohorts recruited 20 years apart.We included men and women aged 50-85 years from the Canadian Multicentre Osteoporosis Study (CaMos, N = 6,479; 1995-1997) and the Canadian Longitudinal Study on Aging (CLSA, N = 19,534; 2012-2015). We created regression models to compare FN-BMD and fracture risk between cohorts, adjusting for important covariates. Among participants with prevalent MOF, we compared anti-osteoporosis medication use.Mean (SD) age in CaMos (65.4 years [8.6]) was higher than in CLSA (63.8 years [9.1]). CaMos participants had lower mean body mass index and higher prevalence of smoking (p 0.001). Adjusted linear regression models (estimates [95%CI]) demonstrated lower FN-BMD in CaMos women (- 0.017 g/cmHigher BMD and lower fracture prevalence were noted in the more recently recruited CLSA cohort compared to CaMos, even after adjusting for multiple covariates. We noted an increase in bisphosphonate use in the recent cohort, but it remained very low in men.
Published: 2022

36. Role of 1,25-dihydroxyvitamin D in alleviating alveolar bone loss and gingival inflammation in ligature-induced periodontitis

Author: Aixiu, Gong, Yining, Liu, Fangrong, Xu, Yiting, Chu, Jun, Wu, David, Goltzman, and Dengshun, Miao
Subjects: Original Article
Abstract: Objectives: The goal of this study was to assess if endogenous 1,25(OH)(2)D deficiency enhanced, whereas exogenous 1,25(OH)(2)D(3) supplementation alleviated alveolar bone loss and gingival inflammation induced by ligature-induced periodontitis. Methods: A model of ligature-induced experimental periodontitis was generated in wild-type (WT) and Cyp27b1-knockout (KO) mice on a rescue diet (RD), and un-ligated genotype-matched littermates as control, or in WT mice on a normal diet (ND) with vehicle treatment or 1,25(OH)(2)D(3) treatment, and un-ligated WT littermates as control. Alveolar bone mass and turnover, T cell infiltration and inflammatory cytokines in gingival tissues were examined. Results: In WT mice, ligature-induced alveolar bone loss occurred by inhibiting alveolar bone formation. This was characterized by reduction of osteoblast numbers, alkaline phosphatase activity and type I collagen synthesis, as well as by augmentation of osteoclastic alveolar bone resorption and gingival inflammation, including increases of osteoclast numbers, inflammatory positive cells and up-regulation of mRNA expression levels of inflammatory cytokines. Alveolar bone destruction and gingival inflammation were more severe in diet-matched Cyp27b1-KO mice than in WT littermates on RD. Supplementation of exogenous 1,25(OH)(2)D(3) alleviated alveolar bone loss and gingival inflammation in ligated WT mice on ND, but those parameters did not reach levels observed in un-ligated WT ones. Conclusions: Endogenous 1,25(OH)(2)D deficiency enhanced, whereas exogenous 1,25(OH)(2)D(3) supplementation alleviated alveolar bone loss and gingival inflammation induced by ligature-induced periodontitis.
Published: 2022

37. A Risk Assessment Tool for Predicting Fragility Fractures and Mortality in the Elderly

Author: Tineke A. C. M. van Geel, David Goltzman, Hanh M Pham, Lisa Langsetmo, Robert G. Josse, Claudie Berger, Jonathan D. Adachi, John A. Eisman, Christopher S. Kovacs, Thach Tran, David A. Hanley, Dana Bliuc, Joop P. W. van den Bergh, Jerilynn C. Prior, Stephanie M. Kaiser, Piet Geusens, Tuan V. Nguyen, Interne Geneeskunde, and RS: NUTRIM - R3 - Respiratory & Age-related Health
Subjects: 0301 basic medicine, Canada, medicine.medical_specialty, MULTISTATE PREDICTION MODEL, SUBSEQUENT FRACTURE, Endocrinology, Diabetes and Metabolism, Osteoporosis, VERTEBRAL FRACTURE, 030209 endocrinology & metabolism, Risk management tools, OSTEOPOROSIS, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Fragility, Bone Density, Risk Factors, Interquartile range, Epidemiology, medicine, Humans, Orthopedics and Sports Medicine, Aged, Bone mineral, Hip fracture, Hip Fractures, business.industry, MORTALITY, Confounding, CANADIAN MULTICENTER OSTEOPOROSIS, HIP FRACTURE, MEN, medicine.disease, CHOICE, CANCER, 3. Good health, 030104 developmental biology, POSTMENOPAUSAL WOMEN, DENSITY, Emergency medicine, MULTISTATE MODELS, business, Osteoporotic Fractures, FRAGILITY FRACTURE
Abstract: Existing fracture risk assessment tools are not designed to predict fracture-associated consequences, possibly contributing to the current undermanagement of fragility fractures worldwide. We aimed to develop a risk assessment tool for predicting the conceptual risk of fragility fractures and its consequences. The study involved 8965 people aged >= 60 years from the Dubbo Osteoporosis Epidemiology Study and the Canadian Multicentre Osteoporosis Study. Incident fracture was identified from X-ray reports and questionnaires, and death was ascertained though contact with a family member or obituary review. We used a multistate model to quantify the effects of the predictors on the transition risks to an initial and subsequent incident fracture and mortality, accounting for their complex interrelationships, confounding effects, and death as a competing risk. There were 2364 initial fractures, 755 subsequent fractures, and 3300 deaths during a median follow-up of 13 years (interquartile range [IQR] 7-15). The prediction model included sex, age, bone mineral density, history of falls within 12 previous months, prior fracture after the age of 50 years, cardiovascular diseases, diabetes mellitus, chronic pulmonary diseases, hypertension, and cancer. The model accurately predicted fragility fractures up to 11 years of follow-up and post-fracture mortality up to 9 years, ranging from 7 years after hip fractures to 15 years after non-hip fractures. For example, a 70-year-old woman with aT-score of -1.5 and without other risk factors would have 10% chance of sustaining a fracture and an 8% risk of dying in 5 years. However, after an initial fracture, her risk of sustaining another fracture or dying doubles to 33%, ranging from 26% after a distal to 42% post hip fracture. A robust statistical technique was used to develop a prediction model for individualization of progression to fracture and its consequences, facilitating informed decision making about risk and thus treatment for individuals with different risk profiles. (c) 2020 American Society for Bone and Mineral Research.
Published: 2020

38. Vertebral Fractures: Which Radiological Criteria Are Better Associated With the Clinical Course of Osteoporosis?

Author: Robert G. Josse, Christopher S. Kovacs, Jerilynn C. Prior, Lisa Langsetmo, David A. Hanley, Jonathan D. Adachi, Linda Probyn, Ian Hammond, Stephanie M. Kaiser, Claudie Berger, William D. Leslie, Jacques P. Brown, Brian C. Lentle, David Goltzman, Andy Kin On Wong, Tanveer Towheed, Angela M. Cheung, and Jeff Hu
Subjects: Male, Canada, medicine.medical_specialty, Osteoporosis, MEDLINE, 030209 endocrinology & metabolism, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Prospective Studies, Aged, Aged, 80 and over, 0303 health sciences, business.industry, Clinical course, General Medicine, Middle Aged, medicine.disease, Spine, Radiography, 030301 anatomy & morphology, Radiological weapon, Vertebral height, Disease Progression, Spinal Fractures, Female, Radiology, business, Osteoporotic Fractures, Follow-Up Studies
Abstract: Study Purpose: Morphometric methods categorize potential osteoporotic vertebral fractures (OVF) on the basis of loss of vertebral height. A particular example is the widely used semiquantitative morphometric tool proposed by Genant (GSQ). A newer morphologic algorithm-based qualitative (mABQ) tool focuses on vertebral end-plate damage in recognizing OVF. We used data from both sexes in the Canadian Multicentre Osteoporosis Study (CaMos) to compare the 2 methods in identifying OVF at baseline and during 10 years of follow-up. Materials and Methods: We obtained lateral thoracic and lumbar spinal radiographs (T4-L4) 3 times, at 5-year intervals, in 828 participants of the population-based CaMos. Logistic regressions were used to study the association of 10-year changes in bone mineral density (BMD) with incident fractures. Results: At baseline, 161 participants had grade 1 and 32 had grade 2 GSQ OVF; over the next 10 years, only 9 of these participants had sustained incident GSQ OVF. Contrastingly, 21 participants at baseline had grade 1 and 48 grade 2 mABQ events; over the next 10 years, 79 subjects experienced incident grade 1 or grade 2 mABQ events. Thus, incident grades 1 and 2 morphologic fractures were 8 times more common than morphometric deformities alone. Each 10-year decrease of 0.01 g/cm2 in total hip BMD was associated with a 4.1% (95% CI: 0.7-7.3) higher odds of having an incident vertebral fracture. Conclusions: This analysis further suggests that morphometric deformities and morphologic fractures constitute distinct entities; morphologic fractures conform more closely to the expected epidemiology of OVF.
Published: 2020

39. SIRT1/FOXO3a axis plays an important role in the prevention of mandibular bone loss induced by 1,25(OH)2D deficiency

Author: Haiyun Chen, David Goltzman, Dengshun Miao, Guoping Wu, Qian Tan, Xiaoqing Hu, and Renlei Yang
Subjects: Genetically modified mouse, Senescence, medicine.medical_specialty, animal structures, antioxidant enzymes peroxiredoxin1, Alveolar Bone Loss, Drug Evaluation, Preclinical, SOD2, Mice, Transgenic, Mandible, medicine.disease_cause, mandibular bone, Applied Microbiology and Biotechnology, Antioxidants, Bone resorption, 03 medical and health sciences, Sirtuin 1, Downregulation and upregulation, Osteogenesis, Internal medicine, medicine, Animals, Humans, Molecular Biology, Cells, Cultured, Cellular Senescence, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, mesenchymal stem cells, 0303 health sciences, Chemistry, Forkhead Box Protein O3, Cell Biology, Vitamin D Deficiency, Endocrinology, medicine.anatomical_structure, Resveratrol, Osteocyte, Receptors, Calcitriol, Sirt1 promoter, Signal transduction, Oxidative stress, Research Paper, Developmental Biology
Abstract: It has been reported that 1,25 dihydroxyvitamin D [1,25(OH)2D] deficiency leads to the loss of mandibular bone, however the mechanism is unclear. We investigated whether the Sirt1/FOXO3a signaling pathway is involved in this process. Using a 1,25(OH)2D deficiency model induced by genetic deletion in mice of 25-hydroxyvitamin D-1α hydroxylase [1α(OH)ase-/- mice]. We first documented a sharp reduction of expression levels of Sirt1 in the 1α(OH)ase-/- mice in vivo. Next, we demonstrated dose-dependent upregulation of Sirt1 by treatment with exogenous 1,25(OH)2D3 in vitro. We then identified a functional VDR binding site in the Sirt1 promoter. By crossing Prx1-Sirt1 transgenic mice with 1α(OH)ase-/- mice we demonstrated that the overexpression of Sirt1 in mesenchymal stem cells (MSCs) greatly improved the 1α(OH)ase-/- mandibular bone loss phenotype by increasing osteoblastic bone formation and reducing osteoclastic bone resorption. In mechanistic studies, we showed, in 1α(OH)ase-/- mice, decreases of Sirt1 and FoxO3a, an increase in oxidative stress as reflected by a reduction of the antioxidant enzymes peroxiredoxin1 (Prdx1), SOD1 and SOD2 expression, and an increase of markers for osteocyte senescence and senescence associated secretory phenotypes (SASP), including β-galactosidase (β-gal), p16, p53 and p21. The targeted overexpression of Sirt1 in the 1α(OH)ase-/- mice restored the expression levels of these molecules. Finally, we demonstrated that a Sirt1 agonist can upregulate FOXO3a activity by increasing deacetylation and nuclear translocation. Overall, results from this study support the concept that targeted increases in Sirt1/FOXO3a signaling levels can greatly improve the bone loss caused by 1,25(OH)2D deficiency.
Published: 2020

40. Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk

Author: Danielle E Whittier, Elizabeth J Samelson, Marian T Hannan, Lauren A Burt, David A Hanley, Emmanuel Biver, Pawel Szulc, Elisabeth Sornay‐Rendu, Blandine Merle, Roland Chapurlat, Eric Lespessailles, Andy Kin On Wong, David Goltzman, Sundeep Khosla, Serge Ferrari, Mary L Bouxsein, Douglas P Kiel, and Steven K Boyd
Subjects: Male, ddc:616, Fracture risk, Endocrinology, Diabetes and Metabolism, High-resolution peripheral computed tomography, Bone and Bones, Article, Absorptiometry, Photon, Phenotype, Bone Density, Machine learning, Humans, Osteoporosis, Orthopedics and Sports Medicine, Female, Bone, Osteoporotic Fractures, Aged
Abstract: Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a "one-size-fits-all" approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).
Published: 2022

41. The Polycomb Protein Bmi1 Plays a Crucial Role in the Prevention of 1,25(OH) 2 D Deficiency‐Induced Bone Loss

Author: Cuicui Yang, Jianliang Jin, Wanxin Qiao, Haijian Sun, Rong Wang, Min Cui, David Goltzman, and Dengshun Miao
Subjects: 2. Zero hunger, 0301 basic medicine, Bone mineral, chemistry.chemical_classification, Genetically modified mouse, Reactive oxygen species, biology, Endocrinology, Diabetes and Metabolism, Osteoporosis, 030209 endocrinology & metabolism, medicine.disease, medicine.disease_cause, Molecular biology, Calcitriol receptor, Bone resorption, 3. Good health, Superoxide dismutase, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, chemistry, medicine, biology.protein, Orthopedics and Sports Medicine, Oxidative stress
Abstract: We analyzed the skeletal phenotypes of heterozygous null Cyp27b1 (Cyp27b1+/- ) mice and their wild-type (WT) littermates to determine whether haploinsufficiency of Cyp27b1 accelerated bone loss, and to examine potential mechanisms of such loss. We found that serum 1,25-dihydroxyvitamin D [1,25(OH)2 D] levels were significantly decreased in aging Cyp27b1+/- mice, which displayed an osteoporotic phenotype. This was accompanied by a reduction of expression of the B lymphoma Moloney murine leukemia virus (Mo-MLV) insertion region 1 (Bmi1) at both gene and protein levels. Using chromatin immunoprecipitation (ChIP)-PCR, electrophoretic mobility shift assay (EMSA) and a luciferase reporter assay, we then showed that 1,25(OH)2 D3 upregulated Bmi1 expression at a transcriptional level via the vitamin D receptor (VDR). To determine whether Bmi1 overexpression in mesenchymal stem cells (MSCs) could correct bone loss induced by 1,25(OH)2 D deficiency, we overexpressed Bmi1 in MSCs using Prx1-driven Bmi1 transgenic mice (Bmi1Tg ) mice. We then compared the bone phenotypes of Bmi1Tg mice on a Cyp27b1+/- background, with those of Cyp27b1+/- mice and with those of WT mice, all at 8 months of age. We found that overexpression of Bmi1 in MSCs corrected the bone phenotype of Cyp27b1+/- mice by increasing osteoblastic bone formation, reducing osteoclastic bone resorption, increasing bone volume, and increasing bone mineral density. Bmi1 overexpression in MSCs also corrected 1,25(OH)2 D deficiency-induced oxidative stress and DNA damage, and cellular senescence of Cyp27b1+/- mice by reducing levels of reactive oxygen species (ROS), elevating serum total superoxide dismutase levels, reducing the percentage of γH2 A.X, p16, IL-1β, and TNF-α-positive cells and decreasing γH2A.X, p16, p19, p53, p21, IL-1β, and IL-6 expression levels. Furthermore, 1,25(OH)2 D stimulated the osteogenic differentiation of MSCs, both ex vivo and in vitro, from WT mice but not from Bmi1-/- mice and 1,25(OH)2 D administration in vivo increased osteoblastic bone formation in WT, but not in Bmi1 -/- mice. Our results indicate that Bmi1, a key downstream target of 1,25(OH)2 D, plays a crucial role in preventing bone loss induced by 1,25(OH)2 D deficiency. © 2019 American Society for Bone and Mineral Research.
Published: 2019

42. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. Santos, Marjeta Majer, Herman Schargrodsky, Bruna Gonçalves Cordeiro da Silva, Ebrahim Eftekhar, Jesús Vioque, Marisa K. Sophiea, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Stefan Söderberg, Isabel O. Oliveira, Joanne Katz, Xingwang Ye, Christophe Tzourio, Marie Zins, Aneta Weres, Ulrich Keil, Haiquan Xu, Akihiro Yoshihara, Rachel Dankner, Gabriella Gruden, Maroje Sorić, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Christa L. Lilly, Veikko Salomaa, Gilad Twig, Senthil K Vasan, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Wilma M. Hopman, Karl-Heinz Jöckel, Ari Voutilainen, Peter Schnohr, Jerzy Chudek, Katia Vergetti Bloch, Vincenzo Capuano, Jyh Eiin Wong, Torben Jørgensen, Anja Schienkiewitz, Nader Saki, Carolina Tarqui-Mamani, Maria Cecília Formoso Assunção, Kazi M. Jamil, Juraci Almeida Cesar, Pedro J Ortiz, Delphine De Smedt, Luciana Zaccagni, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Romana Roccaldo, Sara Magnacca, Peter Stehle, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Tabara Yasuharu, Ali Ghanbari, Gyulli M. Kazakbaeva, Takuro Furusawa, Felicia Cañete, Kari Kuulasmaa, Justina Vaitkeviciute, (NCD-RisC), NCD Risk Factor Collaboration, Imperial College London, Harvard T.H. Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH - Personalized Medicine, AGEM - Endocrinology, metabolism and nutrition, ACS - Diabetes & metabolism, APH - Global Health, ARD - Amsterdam Reproduction and Development, Adult Psychiatry, Global Health, APH - Quality of Care, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, Gómez Santos, Santiago Felipe, NCD Risk Factor Collaboration (NCD-RisC), Faculdade de Desporto, Faculdade de Ciências da Nutrição e Alimentação, Faculdade de Medicina, Tampere University, Clinical Medicine, Department of Clinical Chemistry, Eye Centre, Harvard TH Chan School of Public Health, Middlesex University, World Health Organization, Ministry of Health, University of Lausanne, Eduardo Mondlane University, Victor Babes University of Medicine and Pharmacy Timisoara, University of Sydney, Health and Nutrition, University of Auckland, Seoul National University, ICMR - National Institute of Nutrition, Capital Medical University Beijing An Zhen Hospital, Universidad Peruana Cayetano Heredia, University Tunis El Manar, University of Oulu, University of Zagreb, University of Ljubljana, Caja Costarricense de Seguro Social, Al-Quds University, National Center of Public Healthcare, Qatar University, Birzeit University, Usmanu Danfodiyo University Teaching Hospital, Instituto Mexicano del Seguro Social, Flinders University, Mahidol University, BRAC James P Grant School of Public Health, University of Copenhagen, Copenhagen University Hospital, Food and Nutrition Research Institute, Urmia University of Medical Sciences, Instituto Nacional de Ciencias Médicas y Nutrición, University of Amsterdam, Shahrekord University of Medical Sciences, Non-Communicable Diseases Research Center, University of Oslo, University of Bremen, Republican Center for Health Promotion, Endocrinology and Genetics, Princess Nourah bint Abdulrahman University, Kuwait Institute for Scientific Research, King Abdulaziz University, Dasman Diabetes Institute, Aldara Hospital and Medical Center, King Abdullah International Medical Research Center, Luxembourg Institute of Health, Bispebjerg and Frederiksberg Hospital, Barcelona Institute for Global Health CIBERESP, World Health Organization Regional Office for the Eastern Mediterranean, Bombay Hospital and Medical Research Centre, Research Center for Social Determinants of Health, UMR CNRS-MNHN 7206 Eco-anthropologie, University of Lille, Lille University Hospital, Western Norway University of Applied Sciences, Norwegian School of Sport Sciences, Madras Diabetes Research Foundation, Zahedan University of Medical Sciences, National Institute of Public Health, Institute of Public Health of the University of Porto, Norwegian Institute of Public Health, University of Massachusetts Amherst, Abt Associates, University of Iceland, University of Yaoundé1, Federal University of Pelotas, University of Medicine 1, Oulu University Hospital, Banska Bystrica Regional Authority of Public Health, Tel- Aviv University, Hebrew University of Jerusalem, University of Porto Medical School, Neyshabur University of Medical Sciences, Research Institute for Endocrine Sciences, Non- Communicable Diseases Research Center, Indian Council of Medical Research, University of Science and Technology, Medical University of Lodz, Medical University of Gdansk, Universidad Autónoma de Madrid CIBERESP, University of Rzeszów, University of Palermo, Pan American Health Organization, Mohammed V University de Rabat, University of Pernambuco, Baqai Institute of Diabetology and Endocrinology, Universidade Federal de Santa Catarina (UFSC), Dalhousie University, Jordan University of Science and Technology, Federal University of Maranhao, Al-Farabi Kazakh National University, University College Dublin, Christian Medical College, Care and Consumer Protection, Cafam University Foundation, Kazakh National Medical University, Lithuanian University of Health Sciences, University of Saõ Paulo, B J Medical College, Chirayu Medical College, Sunder Lal Jain Hospital, The Hospital for Sick Children, Aga Khan University, Shandong University of Traditional Chinese Medicine, Jiao-Tong University School of Medicine, Universidad de la República, Institute of Medical Research and Medicinal Plant Studies, Ufa Eye Research Institute, Nepal Health Research Council, University of Montenegro, University of Southern Denmark, University of Gothenburg, Universidade Federal do Rio de Janeiro (UFRJ), National Institute for Public Health and the Environment, University of Turin, University College London, Liverpool John Moores University, Nanyang Technological University Singapore, German Institute of Human Nutrition, Endocrinology Research Centre, Centro de Educación Médica e Investigaciones Clínicas, IRCCS Neuromed, Toulouse University School of Medicine, University of Zurich, University Hospital KU Leuven, Flemish Agency for Care and Health, Ghent University, FrieslandCampina, Universidad Central de Venezuela, Bielefeld University, World Health Organization Regional Office for Europe, German Cancer Research Center, The Fred Hollows Foundation, University of Medicine and Pharmacy Bucharest, Swansea University, University College Copenhagen, Institute of Public Health, Munster Technological University, Universidad de La Laguna, University of Malta, Vanderbilt University, Canadian Fitness and Lifestyle Research Institute, Hospital Santa Maria, Istanbul University - Cerrahpasa, Universidade Federal de Juiz de Fora, Ministry of Public Health, Gaetano Fucito Hospital, University of Groningen, Karolinska Institutet, Centro de Estudios sobre Nutrición Infantil, University of Porto, University of Zaragoza, Santiago de Compostela University, Council for Agricultural Research and Economics, Federal University of Rio Grande, India Diabetes Research Foundation, Duke-NUS Medical School, ICMR - National Institute of Medical Statistics, Singapore Eye Research Institute, Academia Sinica, Capital Institute of Pediatrics, Duke University, Kailuan General Hospital, University of Oxford, Ahvaz Jundishapur University of Medical Sciences, The Gertner Institute for Epidemiology and Health Policy Research, National Centre of Public Health and Analyses, University of Fribourg, Ministry of Health and Welfare, CIBER Epidemiología y Salud Pública, Universidade Estadual Paulista (UNESP), Medical University of Silesia, Charles University, Thomayer Hospital, Primary Health Care, Carol Davila University of Medicine and Pharmacy, Katholieke Universiteit Leuven, Statistics Canada, UMR CNRS- MNHN 7206 Eco-anthropologie, Agency for Preventive and Social Medicine, University of Southampton, Institut Pasteur de Lille, Malawi Epidemiology and Intervention Research Unit, CIBEROBN, University of Debrecen, University of Medicine and Pharmacy Carol Davila, Universidade Federal do Rio Grande do Sul, National Research Council, Eftimie Murgu University Resita, Spanish Agency for Food Safety and Nutrition, Indian Statistical Institute, Tabriz Health Services Management Research Center, Geneva University Hospitals, Sciensano, University Medical Centers, National Research Centre for Preventive Medicine, Innovating Health International, University of Montreal, French National Research Institute for Sustainable Development, French Public Health Agency, Mediterranea Cardiocentro, Universidade do Vale do Rio dos Sinos, Epidemiology and Microbiology, National Council of Scientific and Technical Research, Ministry of Health and Medical Education, University of Novi Sad, National Institute of Nutrition, University of Queensland, Istituto Superiore di Sanita`, Universidad de Cuenca, Helmholtz Zentrum München, Tehran University of Medical Sciences, Ministere de la Santéet de l’Hygiene Publique, University Hospital Düsseldorf, National Institute of Cardiology, Medical University of Lod, Beijing Center for Disease Prevention and Control, UMI 3189 ESS, Beth Israel Deaconess Medical Center, Harvard Medical School, Scuola Superiore Sant’Anna, University of Latvia, Ministry of Health and Medical Services, Hormozgan University of Medical Sciences, University of Benin, University of Skövde, National Institute of Nutrition and Food Technology, The University of the West Indies, University of California Davis, University of Stellenbosch, University of Duisburg- Essen, Karadeniz Technical University, University of Helsinki, Mashhad University of Medical Sciences, Rafsanjan University of Medical Sciences, Queen’s University of Belfast, Tabriz University of Medical Sciences, Fasa University of Medical Sciences, Shiraz University of Medical Sciences, Baqai Medical University, Centro de Salud Villanueva Norte, Hospital Don Benito-Villanueva de la Serena, University of Insubria, Pontificia Universidad Católica de Chile, Institute of Mother and Child, Swiss Tropical and Public Health Institute, University of Basel, University of Tartu, Universiti Sains Malaysia, Umeå University, Federal University of Saõ Paulo, Hospital Universitario Son Espases, Hospital de Clinicas de Porto Alegre, Universitas Sumatera Utara, Kindai University, Kyoto University, Medical University of Warsaw, Jagiellonian University Medical College, Ministero della Salute DG Prevenzione Sanitaria, University of Catania, CIBER en Epidemiología y Salud Pública, Africa Health Research Institute, Geneva University Medical School, Universidade Federal de Minas Gerais (UFMG), Utrecht University, Wageningen University, University of Adelaide, Lund University, Aristotle University of Thessaloniki, Institut National de la Santéet de la Recherche Médicale, Paris University, McGill University, Gasol Foundation, University of Lleida, PASs Hirszfeld Institute of Immunology and Experimental Therapy, Universidad Politécnica de Madrid, St Anne’s University Hospital, Centro de Estudios en Diabetes A.C, Universidad Autónoma de Santo Domingo, Institute for Clinical and Experimental Medicine, Children’s Memorial Health Institute, National Center of Cardiovascular Diseases, University of Ferrara, Authority Sanitaria San Marino, Icelandic Heart Association, Universidad Icesi, State University of Montes Claros, King’s College London, International Agency for Research on Cancer, Capital Medical University, Capital Medical University Beijing Tongren Hospital, Healis-Sekhsaria Institute for Public Health, Eternal Heart Care Centre and Research Institute, University of Ibadan, Institute for Clinical Effectiveness and Health Policy, National Health Insurance Service, Prevention of Metabolic Disorders Research Center, Research and Education Institute of Child Health, Danish Cancer Society Research Center, Kermanshah University of Medical Sciences, University of Eastern Finland, Beijing Institute of Ophthalmology, International Hellenic University, Kyushu University, University of Bergen, Tulane University, National Research Institute for Health and Family Planning, Chinese Center for Disease Control and Prevention, University of Pécs, Danish Health Authority, Joep Lange Institute, Universidade Federal de Pernambuco (UFPE), Universidad Autónoma de Bucaramanga, ETH Zurich, Chronic Diseases Research Center, University of Hong Kong, The Chinese University of Hong Kong, University of Western Australia, University Ramon Llull, Kingston Health Sciences Centre, Fundación Oftalmológica de Santander, University Oran 1, Ministry of Health and Sports, Peking University, VU University Medical Center, American University of Beirut, Cairo University, Erasmus Medical Center Rotterdam, Medical University Varna, The University of Tokyo, Deakin University, Tokyo Metropolitan Institute of Gerontology, Hadassah University Medical Center, Norwegian University of Science and Technology, University of Melbourne, Sports University of Tirana, University Hospital Center Zagreb, University of Zagreb School of Medicine, Heart Foundation, Guangzhou 12th Hospital, Universidad Eugenio Maria de Hostos, University of Duisburg-Essen, Simon Fraser University, Institute of Molecular and Clinical Ophthalmology Basel, University of New South Wales, World Health Organization Country Office, Guilan University of Medical Sciences, University of Opole, Finnish Institute for Health and Welfare, Gulu University, University of Crete, Sri Venkateswara University, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Hellenic Medical Association for Obesity, National and Kapodistrian University of Athens, Maharajgunj Medical Campus, Aarhus University, Johns Hopkins Bloomberg School of Public Health, Pennington Biomedical Research Center, National Institute of Epidemiology, University of Münster, Israel Center for Disease Control, Research Institute for Primordial Prevention of Non- communicable Disease, Amsterdam UMC Public Health Research Institute, South African Medical Research Council, Kyrgyz State Medical Academy, Research Institute of Child Nutrition, Shahid Beheshti University of Medical Sciences, University of Cambridge, Mazandaran University of Medical Sciences, Hypertension Research Center, Medical University of Innsbruck, VASCage, Muhimbili University of Health and Allied Sciences, Yonsei University College of Medicine, National Cancer Center, Sahlgrenska University Hospital, University College South Denmark, Statistics Austria, B P Koirala Institute of Health Sciences, University of Vienna, Oulu Deaconess Institute Foundation, Tartu University Clinics, Kansai Medical University, Hungarian School Sport Federation, Ministry of Health and Quality of Life, University Hospital Ulm, North-West University, University of Jyväskylä, Amrita Institute of Medical Sciences, Institute of Endocrinology, All India Institute of Medical Sciences, African Population and Health Research Center, Hanoi University of Public Health, Hassan First University of Settat, Harokopio University, Sahlgrenska Academy, Endocrinology and Metabolism Research Center, University of Public Health, International Food Policy Research Institute, National University of Singapore, Hong Kong Polytechnic University, Tampere University Hospital, University of Douala, University of Cape Town, National Institute for Health Development, West Virginia University, Oswaldo Cruz Foundation Rene Rachou Research Institute, National Taiwan University, University of Chinese Academy of Sciences, Uppsala University, Taipei Medical University, Sports Medical Center of Minho, Universidad San Martín de Porres, Consejería de Sanidad Junta de Castilla y León, Universidade Federal de Ciências da Saúde de Porto Alegre, Norrbotten County Council, Ilembula Lutheran Hospital, Universidade Federal de Ouro Preto, University of Coimbra, Coimbra University Hospital Center, Institute of Neuroscience of the National Research Council, Baker Heart and Diabetes Institute, Agricultural University of Athens, Hospital Israelita Albert Einstein, SB RAS Federal Research Center Institute of Cytology and Genetics, University of Otago, University of Padua, Hellenic Mediterranean University, Loughborough University, Lausanne University Hospital, Escola Nacional de Saúde Pública Sergio Arouca, CIBERCV, Institut Hospital del Mar d’Investigacions Mediques, Mary Immaculate College, Emory University, Hungarian Society of Sports Medicine, Paracelsus Medical University, Universidade Estadual do Centro-Oeste, Sher-i-Kashmir Institute of Medical Sciences, UiT The Arctic University of Norway, ICMR - National Centre for Disease Informatics and Research, Cape Peninsula University of Technology, Brown University, London School of Hygiene & Tropical Medicine, University of Edinburgh, Shahid Sadoughi University of Medical Sciences, Robert Koch Institute, Universidade de Lisboa, Women’s Social and Health Studies Foundation, Democritus University, Grigore T Popa University of Medicine and Pharmacy, Universita` degli Studi di Firenze, Ain Shams University, Isfahan Cardiovascular Research Center, University of Strasbourg, Strasbourg University Hospital, Mulago Hospital, University of San Carlos of Guatemala, University of Limpopo, University of Medical Sciences of Cienfuegos, Royal College of Surgeons in Ireland, La Trobe University, International Institute of Molecular and Cell Biology, Instituto Conmemorativo Gorgas de Estudios de la Salud, University of Brescia, Ministry of Health and Social Protection, University of Limerick, Croatian Institute of Public Health, Universiti Kebangsaan Malaysia, Bushehr University of Medical Sciences, Ulm University, Kobe University, Suraj Eye Institute, UNICEF, University Medicine Greifswald, National Institute of Hygiene and Epidemiology, University of Medicine and Pharmacy at Ho Chi Minh City, Hanoi Medical University, LifeDoc Health, Heartfile, Eastern Mediterranean Public Health Network, University of Manchester, State University of Medicine and Pharmacy, Tachikawa General Hospital, Korea Centers for Disease Control and Prevention, Japan Wildlife Research Center, Istanbul University, Universidade Federal do Paraná (UFPR), University of Madeira, University of Puerto Rico, Center for Clinical Research and Prevention, MRC Lifecourse Epidemiology Unit, Kwame Nkrumah University of Science and Technology, UniSanté, Prevention and Clinical Network, University of Wisconsin-Madison, Ruprecht-Karls-University of Heidelberg, IRCCS Ente Ospedaliero Specializzato in Gastroenterologia S. de Bellis, Zayed University, Catholic University of Daegu, Science and Technology of Târgu Mures, Jivandeep Hospital, Healis- Sekhsaria Institute for Public Health, National Dental Care Centre Singapore, Universidad de Málaga, University Hospital of Varese, Vietnam National Heart Institute, Clínica de Medicina Avanzada Dr. Abel González, Leibniz Institute for Prevention Research and Epidemiology - BIPS, University of Sarajevo, Cardiovascular Prevention Centre Udine, Pisa University Hospital, Public Health Agency of Catalonia, Ardabil University of Medical Sciences, Centre for Disease Prevention and Control, Alborz University of Medical Sciences, Pure Earth, Institute of Epidemiology Disease Control and Research, University of Turku, Institut Universitari d’Investigacióen AtencióPrima` ria Jordi Gol, Universiti Putra Malaysia, University of Malaya, Sotiria Hospital, University of Valencia, University of the Philippines, Slovak Academy of Sciences, Nutrition Research Foundation, Minas Gerais State Secretariat for Health, CS S. Agustín Ibsalut, Amsterdam Institute for Global Health and Development, National Institute of Health Doutor Ricardo Jorge, Universidade Nove de Julho, Public Health Agency of Canada, Canarian Health Service, Universidad Industrial de Santander, Associazione Calabrese di Epatologia, University of Minho, Fiji National University, Spanish Nutrition Foundation, Public Health Agency of Sweden, Institute of Food Sciences of the National Research Council, Sitaram Bhartia Institute of Science and Research, Kindergarten of Avlonari, National Institute of Health, Catalan Department of Health, Biodonostia Health Research Institute, Instituto de Saúde Ambiental, South Karelia Social and Health Care District, McMaster University, University of Saõ Paulo Clinics Hospital, Hospital Italiano de Buenos Aires, Rigshospitalet, Academic Medical Center of University of Amsterdam, The George Institute for Global Health, Center for Oral Health Services and Research Mid-Norway, Lagos State University College of Medicine, University of Las Palmas de Gran Canaria, Comenius University, National Center for Disease Control and Public Health, Nippon Medical School, Sungkyunkwan University, Finnish Institute of Occupational Health, Public Health Promotion and Development Organization, St Vincent’s Hospital, Nes Municipality, Health Polytechnic Jakarta II Institute, Diponegoro University, University of Bari, Institut Régional de SantéPublique, University of Bordeaux, Oslo Metropolitan University, Ss. Cyril and Methodius University, University of Leuven, Lamprecht und Stamm Sozialforschung und Beratung AG, Bonn University, National Institute of Public Health - National Institute of Hygiene, Kalina Malina Kindergarten, The Jikei University School of Medicine, Fu Jen Catholic University, National Statistical Office, Scientific Research Institute of Maternal and Child Health, University of Lincoln, Central University of Kerala, Amsterdam Public Health Research Institute, Health Service of Murcia, Institut d’Investigacio Sanitaria Illes Balears, University of Bologna, Hellenic Health Foundation, Government Medical College, Sefako Makgatho Health Science University, Addis Ababa University, Universidad Centro-Occidental Lisandro Alvarado, Meharry Medical College, Dokuz Eylul University, University of Tampere Tays Eye Center, Sabiha Gokcen Ilkokulu, Polytechnic Institute of Porto, Icahn School of Medicine at Mount Sinai, Universidad CEU San Pablo, University Miguel Hernandez, Vrije Universiteit Amsterdam, Sunflower Nursery School, North Karelia Center for Public Health, University of the Witwatersrand, Medical University of Vienna, Cork Institute of Technology, Institute for Medical Research, Xinjiang Medical University, Shanghai Educational Development Co. Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing Liu , J Jaime Miranda , Olfa Saidi , Sylvain Sebert , Maroje Sorić , Gregor Starc , Edward W Gregg , Leandra Abarca-Gómez , Ziad A Abdeen , Shynar Abdrakhmanova , Suhaila Abdul Ghaffar , Hanan F Abdul Rahim , Niveen M Abu-Rmeileh , Jamila Abubakar Garba , Benjamin Acosta-Cazares , Robert J Adams , Wichai Aekplakorn , Kaosar Afsana , Shoaib Afzal , Imelda A Agdeppa , Javad Aghazadeh-Attari , Carlos A Aguilar-Salinas , Charles Agyemang , Mohamad Hasnan Ahmad , Noor Ani Ahmad , Ali Ahmadi , Naser Ahmadi , Soheir H Ahmed , Wolfgang Ahrens , Gulmira Aitmurzaeva , Kamel Ajlouni , Hazzaa M Al-Hazzaa , Badreya Al-Lahou , Rajaa Al-Raddadi , Monira Alarouj , Fadia AlBuhairan , Shahla AlDhukair , Mohamed M Ali , Abdullah Alkandari , Ala'a Alkerwi , Kristine Allin , Mar Alvarez-Pedrerol , Eman Aly , Deepak N Amarapurkar , Parisa Amiri , Norbert Amougou , Philippe Amouyel , Lars Bo Andersen , Sigmund A Anderssen , Lars Ängquist , Ranjit Mohan Anjana , Alireza Ansari-Moghaddam , Hajer Aounallah-Skhiri , Joana Araújo , Inger Ariansen , Tahir Aris , Raphael E Arku , Nimmathota Arlappa , Krishna K Aryal , Thor Aspelund , Felix K Assah , Maria Cecília F Assunção , May Soe Aung , Juha Auvinen , Mária Avdicová , Shina Avi , Ana Azevedo , Mohsen Azimi-Nezhad , Fereidoun Azizi , Mehrdad Azmin , Bontha V Babu , Maja Bæksgaard Jørgensen , Azli Baharudin , Suhad Bahijri , Jennifer L Baker , Nagalla Balakrishna , Mohamed Bamoshmoosh , Maciej Banach , Piotr Bandosz , José R Banegas , Joanna Baran , Barbagallo CM, Alberto Barceló , Amina Barkat , Aluisio Jd Barros , Mauro Virgílio Gomes Barros , Abdul Basit , Joao Luiz D Bastos , Iqbal Bata , Anwar M Batieha , Rosangela L Batista , Zhamilya Battakova , Assembekov Batyrbek , Louise A Baur , Robert Beaglehole , Silvia Bel-Serrat , Antonisamy Belavendra , Habiba Ben Romdhane , Judith Benedics , Mikhail Benet , Ingunn Holden Bergh , Salim Berkinbayev , Antonio Bernabe-Ortiz , Gailute Bernotiene , Heloísa Bettiol , Jorge Bezerra , Aroor Bhagyalaxmi , Sumit Bharadwaj , Santosh K Bhargava , Zulfiqar A Bhutta , Hongsheng Bi , Yufang Bi , Daniel Bia , Elysée Claude Bika Lele, Mukharram M Bikbov , Bihungum Bista , Dusko J Bjelica , Peter Bjerregaard , Espen Bjertness , Marius B Bjertness , Cecilia Björkelund , Katia V Bloch , Anneke Blokstra , Simona Bo , Martin Bobak , Lynne M Boddy , Bernhard O Boehm , Heiner Boeing , Jose G Boggia , Elena Bogova , Carlos P Boissonnet , Stig E Bojesen , Marialaura Bonaccio , Vanina Bongard , Alice Bonilla-Vargas , Matthias Bopp , Herman Borghs , Lien Braeckevelt , Lutgart Braeckman , Marjolijn Ce Bragt , Imperia Brajkovich , Francesco Branca , Juergen Breckenkamp , João Breda , Hermann Brenner , Lizzy M Brewster , Garry R Brian , Lacramioara Brinduse , Sinead Brophy , Graziella Bruno , H Bas Bueno-de-Mesquita , Anna Bugge , Marta Buoncristiano , Genc Burazeri , Con Burns , Antonio Cabrera de León , Joseph Cacciottolo , Hui Cai , Tilema Cama , Christine Cameron , José Camolas , Günay Can , Ana Paula C Cândido , Felicia Cañete , Mario V Capanzana , Nadežda Capková , Eduardo Capuano , Vincenzo Capuano , Marloes Cardol , Viviane C Cardoso , Axel C Carlsson , Esteban Carmuega , Joana Carvalho , José A Casajús , Felipe F Casanueva , Ertugrul Celikcan , Laura Censi , Marvin Cervantes-Loaiza , Juraci A Cesar , Snehalatha Chamukuttan , Angelique W Chan , Queenie Chan , Himanshu K Chaturvedi , Nish Chaturvedi , Norsyamlina Che Abdul Rahim , Miao Li Chee , Chien-Jen Chen , Fangfang Chen , Huashuai Chen , Shuohua Chen , Zhengming Chen , Ching-Yu Cheng , Bahman Cheraghian , Angela Chetrit , Ekaterina Chikova-Iscener , Arnaud Chiolero , Shu-Ti Chiou , María-Dolores Chirlaque , Belong Cho , Kaare Christensen , Diego G Christofaro , Jerzy Chudek , Renata Cifkova , Michelle Cilia , Eliza Cinteza , Frank Claessens , Janine Clarke , Els Clays , Emmanuel Cohen , Hans Concin , Susana C Confortin , Cyrus Cooper , Tara C Coppinger , Eva Corpeleijn , Simona Costanzo , Dominique Cottel , Chris Cowell , Cora L Craig , Amelia C Crampin , Ana B Crujeiras , Semánová Csilla , Alexandra M Cucu , Liufu Cui , Felipe V Cureau , Ewelina Czenczek-Lewandowska , Graziella D'Arrigo , Eleonora d'Orsi , Liliana Dacica , María Ángeles Dal Re Saavedra , Jean Dallongeville , Camilla T Damsgaard , Rachel Dankner , Thomas M Dantoft , Parasmani Dasgupta , Saeed Dastgiri , Luc Dauchet , Kairat Davletov , Guy De Backer , Dirk De Bacquer , Giovanni de Gaetano , Stefaan De Henauw , Paula Duarte de Oliveira , David De Ridder , Karin De Ridder , Susanne R de Rooij , Delphine De Smedt , Mohan Deepa , Alexander D Deev , Vincent Jr DeGennaro , Abbas Dehghan , Hélène Delisle , Francis Delpeuch , Stefaan Demarest , Elaine Dennison , Katarzyna Dereń , Valérie Deschamps , Meghnath Dhimal , Augusto F Di Castelnuovo , Juvenal Soares Dias-da-Costa , María Elena Díaz-Sánchez , Alejandro Diaz , Zivka Dika , Shirin Djalalinia , Visnja Djordjic , Ha Tp Do , Annette J Dobson , Maria Benedetta Donati , Chiara Donfrancesco , Silvana P Donoso , Angela Döring , Maria Dorobantu , Ahmad Reza Dorosty , Kouamelan Doua , Nico Dragano , Wojciech Drygas , Jia Li Duan , Charmaine A Duante , Priscilla Duboz , Rosemary B Duda , Vesselka Duleva , Virginija Dulskiene , Samuel C Dumith , Anar Dushpanova , Vilnis Dzerve , Elzbieta Dziankowska-Zaborszczyk , Ricky Eddie , Ebrahim Eftekhar , Eruke E Egbagbe , Robert Eggertsen , Sareh Eghtesad , Gabriele Eiben , Ulf Ekelund , Mohammad El-Khateeb , Jalila El Ati , Denise Eldemire-Shearer , Marie Eliasen , Paul Elliott , Reina Engle-Stone , Macia Enguerran , Rajiv T Erasmus , Raimund Erbel , Cihangir Erem , Louise Eriksen , Johan G Eriksson , Jorge Escobedo-de la Peña , Saeid Eslami , Ali Esmaeili , Alun Evans , David Faeh , Albina A Fakhretdinova , Caroline H Fall , Elnaz Faramarzi , Mojtaba Farjam , Victoria Farrugia Sant'Angelo , Farshad Farzadfar , Mohammad Reza Fattahi , Asher Fawwad , Francisco J Felix-Redondo , Trevor S Ferguson , Romulo A Fernandes , Daniel Fernández-Bergés , Daniel Ferrante , Thomas Ferrao , Marika Ferrari , Marco M Ferrario , Catterina Ferreccio , Eldridge Ferrer , Jean Ferrieres , Thamara Hubler Figueiró , Anna Fijalkowska , Günther Fink , Krista Fischer , Leng Huat Foo , Maria Forsner , Heba M Fouad , Damian K Francis , Maria do Carmo Franco , Ruth Frikke-Schmidt , Guillermo Frontera , Flavio D Fuchs , Sandra C Fuchs , Isti I Fujiati , Yuki Fujita , Matsuda Fumihiko , Takuro Furusawa , Zbigniew Gaciong , Mihai Gafencu , Andrzej Galbarczyk , Henrike Galenkamp , Daniela Galeone , Myriam Galfo , Fabio Galvano , Jingli Gao , Manoli Garcia-de-la-Hera , Marta García-Solano , Dickman Gareta , Sarah P Garnett , Jean-Michel Gaspoz , Magda Gasull , Adroaldo Cesar Araujo Gaya , Anelise Reis Gaya , Andrea Gazzinelli , Ulrike Gehring , Harald Geiger , Johanna M Geleijnse , Ali Ghanbari , Erfan Ghasemi , Oana-Florentina Gheorghe-Fronea , Simona Giampaoli , Francesco Gianfagna , Tiffany K Gill , Jonathan Giovannelli , Glen Gironella , Aleksander Giwercman , Konstantinos Gkiouras , Justyna Godos , Sibel Gogen , Marcel Goldberg , Rebecca A Goldsmith , David Goltzman , Santiago F Gómez , Aleksandra Gomula , Bruna Goncalves Cordeiro da Silva , Helen Gonçalves , David A Gonzalez-Chica , Marcela Gonzalez-Gross , Margot González-Leon , Juan P González-Rivas , Clicerio González-Villalpando , María-Elena González-Villalpando , Angel R Gonzalez , Frederic Gottrand , Antonio Pedro Graça , Sidsel Graff-Iversen , Dušan Grafnetter , Aneta Grajda , Maria G Grammatikopoulou , Ronald D Gregor , Tomasz Grodzicki , Else Karin Grøholt , Anders Grøntved , Giuseppe Grosso , Gabriella Gruden , Dongfeng Gu , Emanuela Gualdi-Russo , Pilar Guallar-Castillón , Andrea Gualtieri , Elias F Gudmundsson , Vilmundur Gudnason , Ramiro Guerrero , Idris Guessous , Andre L Guimaraes , Martin C Gulliford , Johanna Gunnlaugsdottir , Marc J Gunter , Xiu-Hua Guo , Yin Guo , Prakash C Gupta , Rajeev Gupta , Oye Gureje , Beata Gurzkowska , Enrique Gutiérrez-González , Laura Gutierrez , Felix Gutzwiller , Seongjun Ha , Farzad Hadaegh , Charalambos A Hadjigeorgiou , Rosa Haghshenas , Hamid Hakimi , Jytte Halkjær , Ian R Hambleton , Behrooz Hamzeh , Dominique Hange , Abu Am Hanif , Sari Hantunen , Jie Hao , Rachakulla Hari Kumar , Seyed Mohammad Hashemi-Shahri , Maria Hassapidou , Jun Hata , Teresa Haugsgjerd , Jiang He , Yuan He , Yuna He , Regina Heidinger-Felso , Mirjam Heinen , Tatjana Hejgaard , Marleen Elisabeth Hendriks , Rafael Dos Santos Henrique , Ana Henriques , Leticia Hernandez Cadena , Sauli Herrala , Victor M Herrera , Isabelle Herter-Aeberli , Ramin Heshmat , Allan G Hill , Sai Yin Ho , Suzanne C Ho , Michael Hobbs , Michelle Holdsworth , Reza Homayounfar , Clara Homs , Wilma M Hopman , Andrea Rvr Horimoto , Claudia M Hormiga , Bernardo L Horta , Leila Houti , Christina Howitt , Thein Thein Htay , Aung Soe Htet , Maung Maung Than Htike , Yonghua Hu , José María Huerta , Ilpo Tapani Huhtaniemi , Laetitia Huiart , Constanta Huidumac Petrescu , Martijn Huisman , Abdullatif Husseini , Chinh Nguyen Huu , Inge Huybrechts , Nahla Hwalla , Jolanda Hyska , Licia Iacoviello , Jesús M Ibarluzea , Mohsen M Ibrahim , Norazizah Ibrahim Wong , M Arfan Ikram , Violeta Iotova , Vilma E Irazola , Takafumi Ishida , Muhammad Islam , Sheikh Mohammed Shariful Islam , Masanori Iwasaki , Jeremy M Jacobs , Hashem Y Jaddou , Tazeen Jafar , Kenneth James , Kazi M Jamil , Konrad Jamrozik , Imre Janszky , Edward Janus , Juel Jarani , Marjo-Riitta Jarvelin , Grazyna Jasienska , Ana Jelakovic , Bojan Jelakovic , Garry Jennings , Anjani Kumar Jha , Chao Qiang Jiang , Ramon O Jimenez , Karl-Heinz Jöckel , Michel Joffres , Mattias Johansson , Jari J Jokelainen , Jost B Jonas , Jitendra Jonnagaddala , Torben Jørgensen , Pradeep Joshi , Farahnaz Joukar , Dragana P Jovic , Jacek J Jóźwiak , Anne Juolevi , Gregor Jurak , Iulia Jurca Simina , Vesna Juresa , Rudolf Kaaks , Felix O Kaducu , Anthony Kafatos , Eero O Kajantie , Zhanna Kalmatayeva , Ofra Kalter-Leibovici , Yves Kameli , Freja B Kampmann , Kodanda R Kanala , Srinivasan Kannan , Efthymios Kapantais , Argyro Karakosta , Line L Kårhus , Khem B Karki , Marzieh Katibeh , Joanne Katz , Peter T Katzmarzyk , Jussi Kauhanen , Prabhdeep Kaur , Maryam Kavousi , Gyulli M Kazakbaeva , Ulrich Keil , Lital Keinan Boker , Sirkka Keinänen-Kiukaanniemi , Roya Kelishadi , Cecily Kelleher , Han Cg Kemper , Andre P Kengne , Maryam Keramati , Alina Kerimkulova , Mathilde Kersting , Timothy Key , Yousef Saleh Khader , Davood Khalili , Kay-Tee Khaw , Bahareh Kheiri , Motahareh Kheradmand , Alireza Khosravi , Ilse Msl Khouw , Ursula Kiechl-Kohlendorfer , Stefan Kiechl , Japhet Killewo , Dong Wook Kim , Hyeon Chang Kim , Jeongseon Kim , Jenny M Kindblom , Heidi Klakk , Magdalena Klimek , Jeannette Klimont , Jurate Klumbiene , Michael Knoflach , Bhawesh Koirala , Elin Kolle , Patrick Kolsteren , Jürgen König , Raija Korpelainen , Paul Korrovits , Magdalena Korzycka , Jelena Kos , Seppo Koskinen , Katsuyasu Kouda , Viktoria A Kovacs , Sudhir Kowlessur , Slawomir Koziel , Jana Kratenova , Wolfgang Kratzer , Susi Kriemler , Peter Lund Kristensen , Steinar Krokstad , Daan Kromhout , Herculina S Kruger , Ruzena Kubinova , Renata Kuciene , Urho M Kujala , Enisa Kujundzic , Zbigniew Kulaga , R Krishna Kumar , Marie Kunešová , Pawel Kurjata , Yadlapalli S Kusuma , Kari Kuulasmaa , Catherine Kyobutungi , Quang Ngoc La , Fatima Zahra Laamiri , Tiina Laatikainen , Carl Lachat , Youcef Laid , Tai Hing Lam , Christina-Paulina Lambrinou , Edwige Landais , Vera Lanska , Georg Lappas , Bagher Larijani , Tint Swe Latt , Laura Lauria , Maria Lazo-Porras , Gwenaëlle Le Coroller , Khanh Le Nguyen Bao , Agnès Le Port , Tuyen D Le , Jeannette Lee , Jeonghee Lee , Paul H Lee , Nils Lehmann , Terho Lehtimäki , Daniel Lemogoum , Naomi S Levitt , Yanping Li , Merike Liivak , Christa L Lilly , Wei-Yen Lim , M Fernanda Lima-Costa , Hsien-Ho Lin , Xu Lin , Yi-Ting Lin , Lars Lind , Allan Linneberg , Lauren Lissner , Mieczyslaw Litwin , Lijuan Liu , Wei-Cheng Lo , Helle-Mai Loit , Khuong Quynh Long , Luis Lopes , Oscar Lopes , Esther Lopez-Garcia , Tania Lopez , Paulo A Lotufo , José Eugenio Lozano , Janice L Lukrafka , Dalia Luksiene , Annamari Lundqvist , Robert Lundqvist , Nuno Lunet , Charles Lunogelo , Michala Lustigová , Edyta Łuszczki , Guansheng Ma , Jun Ma , Xu Ma , George Ll Machado-Coelho , Aristides M Machado-Rodrigues , Luisa M Macieira , Ahmed A Madar , Stefania Maggi , Dianna J Magliano , Sara Magnacca , Emmanuella Magriplis , Gowri Mahasampath , Bernard Maire , Marjeta Majer , Marcia Makdisse , Päivi Mäki , Fatemeh Malekzadeh , Reza Malekzadeh , Rahul Malhotra , Kodavanti Mallikharjuna Rao , Sofia K Malyutina , Lynell V Maniego , Yannis Manios , Jim I Mann , Fariborz Mansour-Ghanaei , Enzo Manzato , Paula Margozzini , Anastasia Markaki , Oonagh Markey , Eliza Markidou Ioannidou , Pedro Marques-Vidal , Larissa Pruner Marques , Jaume Marrugat , Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta Mišigoj-Durakovic , Antonio Mistretta , Veronica Mocanu , Pietro A Modesti , Sahar Saeedi Moghaddam , Bahram Mohajer , Mostafa K Mohamed , Shukri F Mohamed , Kazem Mohammad , Zahra Mohammadi , Noushin Mohammadifard , Reza Mohammadpourhodki , Viswanathan Mohan , Salim Mohanna , Muhammad Fadhli Mohd Yusoff , Iraj Mohebbi , Farnam Mohebi , Marie Moitry , Drude Molbo , Line T Møllehave , Niels C Møller , Dénes Molnár , Amirabbas Momenan , Charles K Mondo , Michele Monroy-Valle , Eric Monterrubio-Flores , Kotsedi Daniel K Monyeki , Jin Soo Moon , Mahmood Moosazadeh , Leila B Moreira , Alain Morejon , Luis A Moreno , Karen Morgan , Suzanne N Morin , Erik Lykke Mortensen , George Moschonis , Malgorzata Mossakowska , Aya Mostafa , Anabela Mota-Pinto , Jorge Mota , Mohammad Esmaeel Motlagh , Jorge Motta , Marcos André Moura-Dos-Santos , Malay K Mridha , Kelias P Msyamboza , Thet Thet Mu , Magdalena Muc , Boban Mugoša , Maria L Muiesan , Parvina Mukhtorova , Martina Müller-Nurasyid , Neil Murphy , Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria Teresa A Olinto , Isabel O Oliveira , Mohd Azahadi Omar , Altan Onat , Sok King Ong , Lariane M Ono , Pedro Ordunez , Rui Ornelas , Ana P Ortiz , Pedro J Ortiz , Merete Osler , Clive Osmond , Sergej M Ostojic , Afshin Ostovar , Johanna A Otero , Kim Overvad , Ellis Owusu-Dabo , Fred Michel Paccaud , Cristina Padez , Ioannis Pagkalos , Elena Pahomova , Karina Mary de Paiva , Andrzej Pajak , Domenico Palli , Alberto Palloni , Luigi Palmieri , Wen-Harn Pan , Songhomitra Panda-Jonas , Arvind Pandey , Francesco Panza , Dimitrios Papandreou , Soon-Woo Park , Suyeon Park , Winsome R Parnell , Mahboubeh Parsaeian , Ionela M Pascanu , Patrick Pasquet , Nikhil D Patel , Ivan Pecin , Mangesh S Pednekar , Nasheeta Peer , Gao Pei , Sergio Viana Peixoto , Markku Peltonen , Alexandre C Pereira , Marco A Peres , Napoleón Pérez-Farinós , Cynthia M Pérez , Valentina Peterkova , Annette Peters , Astrid Petersmann , Janina Petkeviciene , Ausra Petrauskiene , Emanuela Pettenuzzo , Niloofar Peykari , Son Thai Pham , Rafael N Pichardo , Daniela Pierannunzio , Iris Pigeot , Hynek Pikhart , Aida Pilav , Lorenza Pilotto , Francesco Pistelli , Freda Pitakaka , Aleksandra Piwonska , Andreia N Pizarro , Pedro Plans-Rubió , Bee Koon Poh , Hermann Pohlabeln , Raluca M Pop , Stevo R Popovic , Miquel Porta , Georg Posch , Anil Poudyal , Dimitrios Poulimeneas , Hamed Pouraram , Farhad Pourfarzi , Akram Pourshams , Hossein Poustchi , Rajendra Pradeepa , Alison J Price , Jacqueline F Price , Rui Providencia , Jardena J Puder , Iveta Pudule , Soile E Puhakka , Maria Puiu , Margus Punab , Radwan F Qasrawi , Mostafa Qorbani , Tran Quoc Bao , Ivana Radic , Ricardas Radisauskas , Salar Rahimikazerooni , Mahfuzar Rahman , Mahmudur Rahman , Olli Raitakari , Manu Raj , Ellina Rakhimova , Sherali Rakhmatulloev , Ivo Rakovac , Sudha Ramachandra Rao , Ambady Ramachandran , Jacqueline Ramke , Elisabete Ramos , Rafel Ramos , Lekhraj Rampal , Sanjay Rampal , Vayia Rarra , Ramon A Rascon-Pacheco , Mette Rasmussen , Cassiano Ricardo Rech , Josep Redon , Paul Ferdinand M Reganit , Valéria Regecová , Luis Revilla , Abbas Rezaianzadeh , Lourdes Ribas-Barba , Robespierre Ribeiro , Elio Riboli , Adrian Richter , Fernando Rigo , Natascia Rinaldo , Tobias F Rinke de Wit , Ana Rito , Raphael M Ritti-Dias , Juan A Rivera , Cynthia Robitaille , Romana Roccaldo , Daniela Rodrigues , Fernando Rodríguez-Artalejo , María Del Cristo Rodriguez-Perez , Laura A Rodríguez-Villamizar , Ulla Roggenbuck , Rosalba Rojas-Martinez , Nipa Rojroongwasinkul , Dora Romaguera , Elisabetta L Romeo , Rafaela V Rosario , Annika Rosengren , Ian Rouse , Joel Gr Roy , Adolfo Rubinstein , Frank J Rühli , Jean-Bernard Ruidavets , Blanca Sandra Ruiz-Betancourt , Maria Ruiz-Castell , Emma Ruiz Moreno , Iuliia A Rusakova , Kenisha Russell Jonsson , Paola Russo , Petra Rust , Marcin Rutkowski , Charumathi Sabanayagam , Elena Sacchini , Harshpal S Sachdev , Alireza Sadjadi , Ali Reza Safarpour , Saeid Safiri , Nader Saki , Benoit Salanave , Eduardo Salazar Martinez , Diego Salmerón , Veikko Salomaa , Jukka T Salonen , Massimo Salvetti , Margarita Samoutian , Jose Sánchez-Abanto , Sandjaja , Susana Sans , Loreto Santa Marina , Diana A Santos , Ina S Santos , Lèlita C Santos , Maria Paula Santos , Osvaldo Santos , Rute Santos , Sara Santos Sanz , Jouko L Saramies , Luis B Sardinha , Nizal Sarrafzadegan , Thirunavukkarasu Sathish , Kai-Uwe Saum , Savvas Savva , Mathilde Savy , Norie Sawada , Mariana Sbaraini , Marcia Scazufca , Beatriz D Schaan , Angelika Schaffrath Rosario , Herman Schargrodsky , Anja Schienkiewitz , Sabine Schipf , Carsten O Schmidt , Ida Maria Schmidt , Peter Schnohr , Ben Schöttker , Sara Schramm , Stine Schramm , Helmut Schröder , Constance Schultsz , Aletta E Schutte , Aye Aye Sein , Rusidah Selamat , Vedrana Sember , Abhijit Sen , Idowu O Senbanjo , Sadaf G Sepanlou , Victor Sequera , Luis Serra-Majem , Jennifer Servais , Ludmila Ševcíková , Svetlana A Shalnova , Teresa Shamah-Levy , Morteza Shamshirgaran , Coimbatore Subramaniam Shanthirani , Maryam Sharafkhah , Sanjib K Sharma , Jonathan E Shaw , Amaneh Shayanrad , Ali Akbar Shayesteh , Lela Shengelia , Zumin Shi , Kenji Shibuya , Hana Shimizu-Furusawa , Dong Wook Shin , Majid Shirani , Rahman Shiri , Namuna Shrestha , Khairil Si-Ramlee , Alfonso Siani , Rosalynn Siantar , Abla M Sibai , Antonio M Silva , Diego Augusto Santos Silva , Mary Simon , Judith Simons , Leon A Simons , Agneta Sjöberg , Michael Sjöström , Gry Skodje , Jolanta Slowikowska-Hilczer , Przemyslaw Slusarczyk , Liam Smeeth , Hung-Kwan So , Fernanda Cunha Soares , Grzegorz Sobek , Eugène Sobngwi , Morten Sodemann , Stefan Söderberg , Moesijanti Ye Soekatri , Agustinus Soemantri , Reecha Sofat , Vincenzo Solfrizzi , Mohammad Hossein Somi , Emily Sonestedt , Yi Song , Thorkild Ia Sørensen , Elin P Sørgjerd , Charles Sossa Jérome , Victoria E Soto-Rojas , Aïcha Soumaré , Slavica Sovic , Bente Sparboe-Nilsen , Karen Sparrenberger , Angela Spinelli , Igor Spiroski , Jan A Staessen , Hanspeter Stamm , Maria G Stathopoulou , Kaspar Staub , Bill Stavreski , Jostein Steene-Johannessen , Peter Stehle , Aryeh D Stein , George S Stergiou , Jochanan Stessman , Ranko Stevanovic , Jutta Stieber , Doris Stöckl , Tanja Stocks , Jakub Stokwiszewski , Ekaterina Stoyanova , Gareth Stratton , Karien Stronks , Maria Wany Strufaldi , Lela Sturua , Ramón Suárez-Medina , Machi Suka , Chien-An Sun , Johan Sundström , Yn-Tz Sung , Jordi Sunyer , Paibul Suriyawongpaisal , Boyd A Swinburn , Rody G Sy , Holly E Syddall , René Charles Sylva , Moyses Szklo , Lucjan Szponar , E Shyong Tai , Mari-Liis Tammesoo , Abdonas Tamosiunas , Eng Joo Tan , Xun Tang , Maya Tanrygulyyeva , Frank Tanser , Yong Tao , Mohammed Rasoul Tarawneh , Jakob Tarp , Carolina B Tarqui-Mamani , Radka Taxová Braunerová , Anne Taylor , Julie Taylor , Félicité Tchibindat , William R Tebar , Grethe S Tell , Tania Tello , Yih Chung Tham , K R Thankappan , Holger Theobald , Xenophon Theodoridis , Lutgarde Thijs , Nihal Thomas , Betina H Thuesen , Lubica Tichá , Erik J Timmermans , Anne Tjonneland , Hanna K Tolonen , Janne S Tolstrup , Murat Topbas , Roman Topór-Madry , Liv Elin Torheim , María José Tormo , Michael J Tornaritis , Maties Torrent , Laura Torres-Collado , Stefania Toselli , Giota Touloumi , Pierre Traissac , Thi Tuyet-Hanh Tran , Dimitrios Trichopoulos , Antonia Trichopoulou , Oanh Th Trinh , Atul Trivedi , Lechaba Tshepo , Maria Tsigga , Shoichiro Tsugane , Azaliia M Tuliakova , Marshall K Tulloch-Reid , Fikru Tullu , Tomi-Pekka Tuomainen , Jaakko Tuomilehto , Maria L Turley , Gilad Twig , Per Tynelius , Themistoklis Tzotzas , Christophe Tzourio , Peter Ueda , Eunice Ugel , Flora Am Ukoli , Hanno Ulmer , Belgin Unal , Zhamyila Usupova , Hannu Mt Uusitalo , Nalan Uysal , Justina Vaitkeviciute , Gonzalo Valdivia , Susana Vale , Damaskini Valvi , Rob M van Dam , Johan Van der Heyden , Yvonne T van der Schouw , Koen Van Herck , Hoang Van Minh , Natasja M Van Schoor , Irene Gm van Valkengoed , Dirk Vanderschueren , Diego Vanuzzo , Anette Varbo , Gregorio Varela-Moreiras , Patricia Varona-Pérez , Senthil K Vasan , Tomas Vega , Toomas Veidebaum , Gustavo Velasquez-Melendez , Biruta Velika , Giovanni Veronesi , Wm Monique Verschuren , Cesar G Victora , Giovanni Viegi , Lucie Viet , Salvador Villalpando , Paolo Vineis , Jesus Vioque , Jyrki K Virtanen , Marjolein Visser , Sophie Visvikis-Siest , Bharathi Viswanathan , Mihaela Vladulescu , Tiina Vlasoff , Dorja Vocanec , Peter Vollenweider , Henry Völzke , Ari Voutilainen , Sari Voutilainen , Martine Vrijheid , Tanja Gm Vrijkotte , Alisha N Wade , Aline Wagner , Thomas Waldhör , Janette Walton , Elvis Oa Wambiya , Wan Mohamad Wan Bebakar , Wan Nazaimoon Wan Mohamud , Rildo de Souza Wanderley Júnior , Ming-Dong Wang , Ningli Wang , Qian Wang , Xiangjun Wang , Ya Xing Wang , Ying-Wei Wang , S Goya Wannamethee , Nicholas Wareham , Adelheid Weber , Niels Wedderkopp , Deepa Weerasekera , Daniel Weghuber , Wenbin Wei , Aneta Weres , Bo Werner , Peter H Whincup , Kurt Widhalm , Indah S Widyahening , Andrzej Wiecek , Rainford J Wilks , Johann Willeit , Peter Willeit , Julianne Williams , Tom Wilsgaard , Bogdan Wojtyniak , Roy A Wong-McClure , Andrew Wong , Jyh Eiin Wong , Tien Yin Wong , Jean Woo , Mark Woodward , Frederick C Wu , Jianfeng Wu , Li Juan Wu , Shouling Wu , Haiquan Xu , Liang Xu , Nor Azwany Yaacob , Uruwan Yamborisut , Weili Yan , Ling Yang , Xiaoguang Yang , Yang Yang , Nazan Yardim , Mehdi Yaseri , Tabara Yasuharu , Xingwang Ye , Panayiotis K Yiallouros , Moein Yoosefi , Akihiro Yoshihara , Qi Sheng You , San-Lin You , Novie O Younger-Coleman , Safiah Md Yusof , Ahmad Faudzi Yusoff , Luciana Zaccagni , Vassilis Zafiropulos , Ahmad A Zainuddin , Seyed Rasoul Zakavi , Farhad Zamani , Sabina Zambon , Antonis Zampelas , Hana Zamrazilová , Maria Elisa Zapata , Abdul Hamid Zargar , Ko Ko Zaw , Tomasz Zdrojewski , Kristyna Zejglicova , Tajana Zeljkovic Vrkic , Yi Zeng , Luxia Zhang , Zhen-Yu Zhang , Dong Zhao , Ming-Hui Zhao , Wenhua Zhao , Shiqi Zhen , Wei Zheng , Yingfeng Zheng , Bekbolat Zholdin , Maigeng Zhou , Dan Zhu , Marie Zins , Emanuel Zitt , Yanina Zocalo , Julio Zuñiga Cisneros , Monika Zuziak , Majid Ezzati , Sarah Filippi, Epidemiology, Iurilli, Maria LC, Zhou, Bin, Bennett, James E, Carrillo-Larco, Rodrigo M, Sophiea, Marisa K, Rodriguez-Martinez, Andrea, Bixby, Honor, Solomon, Bethlehem D, Taddei, Cristina, Danaei, Goodarz, Di Cesare, Mariachiara, Stevens, Gretchen A, Riley, Leanne M, Savin, Stefan, Cowan, Melanie J, Bovet, Pascal, Damasceno, Albertino, Chirita-Emandi, Adela, Hayes, Alison J, Ikeda, Nayu, Jackson, Rod T, Khang, Young-Ho, Laxmaiah, Avula, Liu, Jing, Miranda, J Jaime, Saidi, Olfa, Sebert, Sylvain, Sorić, Maroje, Starc, Gregor, Gregg, Edward W, Abarca-Gómez, Leandra, Abdeen, Ziad A, Abdrakhmanova, Shynar, Ghaffar, Suhaila Abdul, Rahim, Hanan F Abdul, Abu-Rmeileh, Niveen M, Garba, Jamila Abubakar, Acosta-Cazares, Benjamin, Adams, Robert J, Aekplakorn, Wichai, Afsana, Kaosar, Afzal, Shoaib, Agdeppa, Imelda A, Aghazadeh-Attari, Javad, Aguilar-Salinas, Carlos A, Agyemang, Charle, Ahmad, Mohamad Hasnan, Ahmad, Noor Ani, Ahmadi, Ali, Ahmadi, Naser, Ahmed, Soheir H, Ahrens, Wolfgang, Aitmurzaeva, Gulmira, Ajlouni, Kamel, Al-Hazzaa, Hazzaa M, Al-Lahou, Badreya, Al-Raddadi, Rajaa, Alarouj, Monira, AlBuhairan, Fadia, AlDhukair, Shahla, Ali, Mohamed M, Alkandari, Abdullah, Alkerwi, Ala'a, Allin, Kristine, Alvarez-Pedrerol, Mar, Aly, Eman, Amarapurkar, Deepak N, Amiri, Parisa, Amougou, Norbert, Amouyel, Philippe, Bo Andersen, Lar, Anderssen, Sigmund A, Ängquist, Lar, Anjana, Ranjit Mohan, Ansari-Moghaddam, Alireza, Aounallah-Skhiri, Hajer, Araújo, Joana, Ariansen, Inger, Aris, Tahir, Arku, Raphael E, Arlappa, Nimmathota, Aryal, Krishna K, Aspelund, Thor, Assah, Felix K, Assunção, Maria Cecília F, Aung, May Soe, Auvinen, Juha, Avdicová, Mária, Avi, Shina, Azevedo, Ana, Azimi-Nezhad, Mohsen, Azizi, Fereidoun, Azmin, Mehrdad, Babu, Bontha V, Jørgensen, Maja Bæksgaard, Baharudin, Azli, Bahijri, Suhad, Baker, Jennifer L, Balakrishna, Nagalla, Bamoshmoosh, Mohamed, Banach, Maciej, Bandosz, Piotr, Banegas, José R, Baran, Joanna, Barbagallo, Carlo M, Barceló, Alberto, Barkat, Amina, Barros, Aluisio JD, Barros, Mauro Virgílio Gome, Basit, Abdul, Bastos, Joao Luiz D, Bata, Iqbal, Batieha, Anwar M, Batista, Rosangela L, Battakova, Zhamilya, Batyrbek, Assembekov, Baur, Louise A, Beaglehole, Robert, Bel-Serrat, Silvia, Belavendra, Antonisamy, Romdhane, Habiba Ben, Benedics, Judith, Benet, Mikhail, Bergh, Ingunn Holden, Berkinbayev, Salim, Bernabe-Ortiz, Antonio, Bernotiene, Gailute, Bettiol, Heloísa, Bezerra, Jorge, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K, Bhutta, Zulfiqar A, Bi, Hongsheng, Bi, Yufang, Bia, Daniel, Lele, Elysée Claude Bika, Bikbov, Mukharram M, Bista, Bihungum, Bjelica, Dusko J, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B, Björkelund, Cecilia, Bloch, Katia V, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M, Boehm, Bernhard O, Boeing, Heiner, Boggia, Jose G, Bogova, Elena, Boissonnet, Carlos P, Bojesen, Stig E, Bonaccio, Marialaura, Bongard, Vanina, Bonilla-Vargas, Alice, Bopp, Matthia, Borghs, Herman, Braeckevelt, Lien, Braeckman, Lutgart, Bragt, Marjolijn CE, Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Breda, João, Brenner, Hermann, Brewster, Lizzy M, Brian, Garry R, Brinduse, Lacramioara, Brophy, Sinead, Bruno, Graziella, Bueno-de-Mesquita, H Ba, Bugge, Anna, Buoncristiano, Marta, Burazeri, Genc, Burns, Con, de León, Antonio Cabrera, Cacciottolo, Joseph, Cai, Hui, Cama, Tilema, Cameron, Christine, Camolas, José, Can, Günay, Cândido, Ana Paula C, Cañete, Felicia, Capanzana, Mario V, Capková, Nadežda, Capuano, Eduardo, Capuano, Vincenzo, Cardol, Marloe, Cardoso, Viviane C, Carlsson, Axel C, Carmuega, Esteban, Carvalho, Joana, Casajús, José A, Casanueva, Felipe F, Celikcan, Ertugrul, Censi, Laura, Cervantes-Loaiza, Marvin, Cesar, Juraci A, Chamukuttan, Snehalatha, Chan, Angelique W, Chan, Queenie, Chaturvedi, Himanshu K, Chaturvedi, Nish, Rahim, Norsyamlina Che Abdul, Li Chee, Miao, Chen, Chien-Jen, Chen, Fangfang, Chen, Huashuai, Chen, Shuohua, Chen, Zhengming, Cheng, Ching-Yu, Cheraghian, Bahman, Chetrit, Angela, Chikova-Iscener, Ekaterina, Chiolero, Arnaud, Chiou, Shu-Ti, Chirlaque, María-Dolore, Cho, Belong, Christensen, Kaare, Christofaro, Diego G, Chudek, Jerzy, Cifkova, Renata, Cilia, Michelle, Cinteza, Eliza, Claessens, Frank, Clarke, Janine, Clays, El, Cohen, Emmanuel, Concin, Han, Confortin, Susana C, Cooper, Cyru, Coppinger, Tara C, Corpeleijn, Eva, Costanzo, Simona, Cottel, Dominique, Cowell, Chri, Craig, Cora L, Crampin, Amelia C, Crujeiras, Ana B, Csilla, Semánová, Cucu, Alexandra M, Cui, Liufu, Cureau, Felipe V, Czenczek-Lewandowska, Ewelina, D'Arrigo, Graziella, d'Orsi, Eleonora, Dacica, Liliana, Re Saavedra, María Ángeles Dal, Dallongeville, Jean, Damsgaard, Camilla T, Dankner, Rachel, Dantoft, Thomas M, Dasgupta, Parasmani, Dastgiri, Saeed, Dauchet, Luc, Davletov, Kairat, De Backer, Guy, De Bacquer, Dirk, de Gaetano, Giovanni, De Henauw, Stefaan, de Oliveira, Paula Duarte, De Ridder, David, De Ridder, Karin, de Rooij, Susanne R, De Smedt, Delphine, Deepa, Mohan, Deev, Alexander D, Jr DeGennaro, Vincent, Dehghan, Abba, Delisle, Hélène, Delpeuch, Franci, Demarest, Stefaan, Dennison, Elaine, Dereń, Katarzyna, Deschamps, Valérie, Dhimal, Meghnath, Di Castelnuovo, Augusto F, Dias-da-Costa, Juvenal Soare, Díaz-Sánchez, María Elena, Diaz, Alejandro, Dika, Zivka, Djalalinia, Shirin, Djordjic, Visnja, Do, Ha TP, Dobson, Annette J, Donati, Maria Benedetta, Donfrancesco, Chiara, Donoso, Silvana P, Döring, Angela, Dorobantu, Maria, Dorosty, Ahmad Reza, Doua, Kouamelan, Dragano, Nico, Drygas, Wojciech, Li Duan, Jia, Duante, Charmaine A, Duboz, Priscilla, Duda, Rosemary B, Duleva, Vesselka, Dulskiene, Virginija, Dumith, Samuel C, Dushpanova, Anar, Dzerve, Vilni, Dziankowska-Zaborszczyk, Elzbieta, Eddie, Ricky, Eftekhar, Ebrahim, Egbagbe, Eruke E, Eggertsen, Robert, Eghtesad, Sareh, Eiben, Gabriele, Ekelund, Ulf, El-Khateeb, Mohammad, El Ati, Jalila, Eldemire-Shearer, Denise, Eliasen, Marie, Elliott, Paul, Engle-Stone, Reina, Enguerran, Macia, Erasmus, Rajiv T, Erbel, Raimund, Erem, Cihangir, Eriksen, Louise, Eriksson, Johan G, la Peña, Jorge Escobedo-de, Eslami, Saeid, Esmaeili, Ali, Evans, Alun, Faeh, David, Fakhretdinova, Albina A, Fall, Caroline H, Faramarzi, Elnaz, Farjam, Mojtaba, Sant'Angelo, Victoria Farrugia, Farzadfar, Farshad, Fattahi, Mohammad Reza, Fawwad, Asher, Felix-Redondo, Francisco J, Ferguson, Trevor S, Fernandes, Romulo A, Fernández-Bergés, Daniel, Ferrante, Daniel, Ferrao, Thoma, Ferrari, Marika, Ferrario, Marco M, Ferreccio, Catterina, Ferrer, Eldridge, Ferrieres, Jean, Figueiró, Thamara Hubler, Fijalkowska, Anna, Fink, Günther, Fischer, Krista, Foo, Leng Huat, Forsner, Maria, Fouad, Heba M, Francis, Damian K, do Carmo Franco, Maria, Frikke-Schmidt, Ruth, Frontera, Guillermo, Fuchs, Flavio D, Fuchs, Sandra C, Fujiati, Isti I, Fujita, Yuki, Fumihiko, Matsuda, Furusawa, Takuro, Gaciong, Zbigniew, Gafencu, Mihai, Galbarczyk, Andrzej, Galenkamp, Henrike, Galeone, Daniela, Galfo, Myriam, Galvano, Fabio, Gao, Jingli, Garcia-de-la-Hera, Manoli, García-Solano, Marta, Gareta, Dickman, Garnett, Sarah P, Gaspoz, Jean-Michel, Gasull, Magda, Gaya, Adroaldo Cesar Araujo, Gaya, Anelise Rei, Gazzinelli, Andrea, Gehring, Ulrike, Geiger, Harald, Geleijnse, Johanna M, Ghanbari, Ali, Ghasemi, Erfan, Gheorghe-Fronea, Oana-Florentina, Giampaoli, Simona, Gianfagna, Francesco, Gill, Tiffany K, Giovannelli, Jonathan, Gironella, Glen, Giwercman, Aleksander, Gkiouras, Konstantino, Godos, Justyna, Gogen, Sibel, Goldberg, Marcel, Goldsmith, Rebecca A, Goltzman, David, Gómez, Santiago F, Gomula, Aleksandra, da Silva, Bruna Goncalves Cordeiro, Gonçalves, Helen, Gonzalez-Chica, David A, Gonzalez-Gross, Marcela, González-Leon, Margot, González-Rivas, Juan P, González-Villalpando, Clicerio, González-Villalpando, María-Elena, Gonzalez, Angel R, Gottrand, Frederic, Graça, Antonio Pedro, Graff-Iversen, Sidsel, Grafnetter, Dušan, Grajda, Aneta, Grammatikopoulou, Maria G, Gregor, Ronald D, Grodzicki, Tomasz, Grøholt, Else Karin, Grøntved, Ander, Grosso, Giuseppe, Gruden, Gabriella, Gu, Dongfeng, Gualdi-Russo, Emanuela, Guallar-Castillón, Pilar, Gualtieri, Andrea, Gudmundsson, Elias F, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idri, Guimaraes, Andre L, Gulliford, Martin C, Gunnlaugsdottir, Johanna, Gunter, Marc J, Guo, Xiu-Hua, Guo, Yin, Gupta, Prakash C, Gupta, Rajeev, Gureje, Oye, Gurzkowska, Beata, Gutiérrez-González, Enrique, Gutierrez, Laura, Gutzwiller, Felix, Ha, Seongjun, Hadaegh, Farzad, Hadjigeorgiou, Charalambos A, Haghshenas, Rosa, Hakimi, Hamid, Halkjær, Jytte, Hambleton, Ian R, Hamzeh, Behrooz, Hange, Dominique, Hanif, Abu AM, Hantunen, Sari, Hao, Jie, Kumar, Rachakulla Hari, Hashemi-Shahri, Seyed Mohammad, Hassapidou, Maria, Hata, Jun, Haugsgjerd, Teresa, He, Jiang, He, Yuan, He, Yuna, Heidinger-Felso, Regina, Heinen, Mirjam, Hejgaard, Tatjana, Hendriks, Marleen Elisabeth, dos Santos Henrique, Rafael, Henriques, Ana, Cadena, Leticia Hernandez, Herrala, Sauli, Herrera, Victor M, Herter-Aeberli, Isabelle, Heshmat, Ramin, Hill, Allan G, Ho, Sai Yin, Ho, Suzanne C, Hobbs, Michael, Holdsworth, Michelle, Homayounfar, Reza, Homs, Clara, Hopman, Wilma M, Horimoto, Andrea RVR, Hormiga, Claudia M, Horta, Bernardo L, Houti, Leila, Howitt, Christina, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Huerta, José María, Huhtaniemi, Ilpo Tapani, Huiart, Laetitia, Petrescu, Constanta Huidumac, Huisman, Martijn, Husseini, Abdullatif, Huu, Chinh Nguyen, Huybrechts, Inge, Hwalla, Nahla, Hyska, Jolanda, Iacoviello, Licia, Ibarluzea, Jesús M, Ibrahim, Mohsen M, Wong, Norazizah Ibrahim, Ikram, M Arfan, Iotova, Violeta, Irazola, Vilma E, Ishida, Takafumi, Islam, Muhammad, Islam, Sheikh Mohammed Shariful, Iwasaki, Masanori, Jacobs, Jeremy M, Jaddou, Hashem Y, Jafar, Tazeen, James, Kenneth, Jamil, Kazi M, Jamrozik, Konrad, Janszky, Imre, Janus, Edward, Jarani, Juel, Jarvelin, Marjo-Riitta, Jasienska, Grazyna, Jelakovic, Ana, Jelakovic, Bojan, Jennings, Garry, Jha, Anjani Kumar, Jiang, Chao Qiang, Jimenez, Ramon O, Jöckel, Karl-Heinz, Joffres, Michel, Johansson, Mattia, Jokelainen, Jari J, Jonas, Jost B, Jonnagaddala, Jitendra, Jørgensen, Torben, Joshi, Pradeep, Joukar, Farahnaz, Jovic, Dragana P, Jóźwiak, Jacek J, Juolevi, Anne, Jurak, Gregor, Simina, Iulia Jurca, Juresa, Vesna, Kaaks, Rudolf, Kaducu, Felix O, Kafatos, Anthony, Kajantie, Eero O, Kalmatayeva, Zhanna, Kalter-Leibovici, Ofra, Kameli, Yve, Kampmann, Freja B, Kanala, Kodanda R, Kannan, Srinivasan, Kapantais, Efthymio, Karakosta, Argyro, Kårhus, Line L, Karki, Khem B, Katibeh, Marzieh, Katz, Joanne, Katzmarzyk, Peter T, Kauhanen, Jussi, Kaur, Prabhdeep, Kavousi, Maryam, Kazakbaeva, Gyulli M, Keil, Ulrich, Boker, Lital Keinan, Keinänen-Kiukaanniemi, Sirkka, Kelishadi, Roya, Kelleher, Cecily, Kemper, Han CG, Kengne, Andre P, Keramati, Maryam, Kerimkulova, Alina, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khaw, Kay-Tee, Kheiri, Bahareh, Kheradmand, Motahareh, Khosravi, Alireza, Khouw, Ilse MSL, Kiechl-Kohlendorfer, Ursula, Kiechl, Stefan, Killewo, Japhet, Kim, Dong Wook, Kim, Hyeon Chang, Kim, Jeongseon, Kindblom, Jenny M, Klakk, Heidi, Klimek, Magdalena, Klimont, Jeannette, Klumbiene, Jurate, Knoflach, Michael, Koirala, Bhawesh, Kolle, Elin, Kolsteren, Patrick, König, Jürgen, Korpelainen, Raija, Korrovits, Paul, Korzycka, Magdalena, Kos, Jelena, Koskinen, Seppo, Kouda, Katsuyasu, Kovacs, Viktoria A, Kowlessur, Sudhir, Koziel, Slawomir, Kratenova, Jana, Kratzer, Wolfgang, Kriemler, Susi, Kristensen, Peter Lund, Krokstad, Steiner, Kromhout, Daan, Kruger, Herculina S, Kubinova, Ruzena, Kuciene, Renata, Kujala, Urho M, Kujundzic, Enisa, Kulaga, Zbigniew, Kumar, R Krishna, Kunešová, Marie, Kurjata, Pawel, Kusuma, Yadlapalli S, Kuulasmaa, Kari, Kyobutungi, Catherine, La, Quang Ngoc, Laamiri, Fatima Zahra, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Lambrinou, Christina-Paulina, Landais, Edwige, Lanska, Vera, Lappas, Georg, Larijani, Bagher, Latt, Tint Swe, Lauria, Laura, Lazo-Porras, Maria, Le Coroller, Gwenaëlle, Le Nguyen Bao, Khanh, Le Port, Agnè, Le, Tuyen D, Lee, Jeannette, Lee, Jeonghee, Lee, Paul H, Lehmann, Nil, Lehtimäki, Terho, Lemogoum, Daniel, Levitt, Naomi S, Li, Yanping, Liivak, Merike, Lilly, Christa L, Lim, Wei-Yen, Lima-Costa, M Fernanda, Lin, Hsien-Ho, Lin, Xu, Lin, Yi-Ting, Lind, Lar, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Liu, Lijuan, Lo, Wei-Cheng, Loit, Helle-Mai, Long, Khuong Quynh, Lopes, Lui, Lopes, Oscar, Lopez-Garcia, Esther, Lopez, Tania, Lotufo, Paulo A, Lozano, José Eugenio, Lukrafka, Janice L, Luksiene, Dalia, Lundqvist, Annamari, Lundqvist, Robert, Lunet, Nuno, Lunogelo, Charle, Lustigová, Michala, Łuszczki, Edyta, Ma, Guansheng, Ma, Jun, Ma, Xu, Machado-Coelho, George LL, Machado-Rodrigues, Aristides M, Macieira, Luisa M, Madar, Ahmed A, Maggi, Stefania, Magliano, Dianna J, Magnacca, Sara, Magriplis, Emmanuella, Mahasampath, Gowri, Maire, Bernard, Majer, Marjeta, Makdisse, Marcia, Mäki, Päivi, Malekzadeh, Fatemeh, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Malyutina, Sofia K, Maniego, Lynell V, Manios, Yanni, Mann, Jim I, Mansour-Ghanaei, Fariborz, Manzato, Enzo, Margozzini, Paula, Markaki, Anastasia, Markey, Oonagh, Ioannidou, Eliza Markidou, Marques-Vidal, Pedro, Marques, Larissa Pruner, Marrugat, Jaume, Martin-Prevel, Yve, Martin, Rosemarie, Martorell, Reynaldo, Martos, Eva, Maruszczak, Katharina, Marventano, Stefano, Mascarenhas, Luis P, Masoodi, Shariq R, Mathiesen, Ellisiv B, Mathur, Prashant, Matijasevich, Alicia, Matsha, Tandi E, Mavrogianni, Christina, Mazur, Artur, Mbanya, Jean Claude N, McFarlane, Shelly R, McGarvey, Stephen T, McKee, Martin, McLachlan, Stela, McLean, Rachael M, McLean, Scott B, McNulty, Breige A, Benchekor, Sounnia Mediene, Medzioniene, Jurate, Mehdipour, Parinaz, Mehlig, Kirsten, Mehrparvar, Amir Houshang, Meirhaeghe, Aline, Meisfjord, Jørgen, Meisinger, Christa, Menezes, Ana Maria B, Menon, Geetha R, Mensink, Gert BM, Menzano, Maria Teresa, Mereke, Alibek, Meshram, Indrapal I, Metspalu, Andre, Meyer, Haakon E, Mi, Jie, Michaelsen, Kim F, Michels, Nathalie, Mikkel, Kairit, Milkowska, Karolina, Miller, Jody C, Minderico, Cláudia S, Mini, GK, Miquel, Juan Francisco, Mirjalili, Mohammad Reza, Mirkopoulou, Daphne, Mirrakhimov, Erkin, Mišigoj-Durakovic, Marjeta, Mistretta, Antonio, Mocanu, Veronica, Modesti, Pietro A, Moghaddam, Sahar Saeedi, Mohajer, Bahram, Mohamed, Mostafa K, Mohamed, Shukri F, Mohammad, Kazem, Mohammadi, Zahra, Mohammadifard, Noushin, Mohammadpourhodki, Reza, Mohan, Viswanathan, Mohanna, Salim, Yusoff, Muhammad Fadhli Mohd, Mohebbi, Iraj, Mohebi, Farnam, Moitry, Marie, Molbo, Drude, Møllehave, Line T, Møller, Niels C, Molnár, Déne, Momenan, Amirabba, Mondo, Charles K, Monroy-Valle, Michele, Monterrubio-Flores, Eric, Monyeki, Kotsedi Daniel K, Moon, Jin Soo, Moosazadeh, Mahmood, Moreira, Leila B, Morejon, Alain, Moreno, Luis A, Morgan, Karen, Morin, Suzanne N, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mostafa, Aya, Mota-Pinto, Anabela, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Moura-dos-Santos, Marcos André, Mridha, Malay K, Msyamboza, Kelias P, Mu, Thet Thet, Muc, Magdalena, Mugoša, Boban, Muiesan, Maria L, Mukhtorova, Parvina, Müller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M, Musa, Kamarul Imran, Milanovic, Sanja Music, Musil, Vera, Mustafa, Norlaila, Nabipour, Iraj, Naderimagham, Shohreh, Nagel, Gabriele, Naidu, Balkish M, Najafi, Farid, Nakamura, Harunobu, Námešná, Jana, Ei K Nang, Ei, Nangia, Vinay B, Nankap, Martin, Narake, Sameer, Nardone, Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, Cristina, Pagkalos, Ioanni, Pahomova, Elena, de Paiva, Karina Mary, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Pan, Wen-Harn, Panda-Jonas, Songhomitra, Pandey, Arvind, Panza, Francesco, Papandreou, Dimitrio, Park, Soon-Woo, Park, Suyeon, Parnell, Winsome R, Parsaeian, Mahboubeh, Pascanu, Ionela M, Pasquet, Patrick, Patel, Nikhil D, Pecin, Ivan, Pednekar, Mangesh S, Peer, Nasheeta, Pei, Gao, Peixoto, Sergio Viana, Peltonen, Markku, Pereira, Alexandre C, Peres, Marco A, Pérez-Farinós, Napoleón, Pérez, Cynthia M, Peterkova, Valentina, Peters, Annette, Petersmann, Astrid, Petkeviciene, Janina, Petrauskiene, Ausra, Pettenuzzo, Emanuela, Peykari, Niloofar, Pham, Son Thai, Pichardo, Rafael N, Pierannunzio, Daniela, Pigeot, Iri, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Pizarro, Andreia N, Plans-Rubió, Pedro, Poh, Bee Koon, Pohlabeln, Hermann, Pop, Raluca M, Popovic, Stevo R, Porta, Miquel, Posch, Georg, Poudyal, Anil, Poulimeneas, Dimitrio, Pouraram, Hamed, Pourfarzi, Farhad, Pourshams, Akram, Poustchi, Hossein, Pradeepa, Rajendra, Price, Alison J, Price, Jacqueline F, Providencia, Rui, Puder, Jardena J, Pudule, Iveta, Puhakka, Soile E, Puiu, Maria, Punab, Margu, Qasrawi, Radwan F, Qorbani, Mostafa, Bao, Tran Quoc, Radic, Ivana, Radisauskas, Ricarda, Rahimikazerooni, Salar, Rahman, Mahfuzar, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rakhimova, Ellina, Rakhmatulloev, Sherali, Rakovac, Ivo, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Elisabete, Ramos, Rafel, Rampal, Lekhraj, Rampal, Sanjay, Rarra, Vayia, Rascon-Pacheco, Ramon A, Rasmussen, Mette, Rech, Cassiano Ricardo, Redon, Josep, Reganit, Paul Ferdinand M, Regecová, Valéria, Revilla, Lui, Rezaianzadeh, Abba, Ribas-Barba, Lourde, Ribeiro, Robespierre, Riboli, Elio, Richter, Adrian, Rigo, Fernando, Rinaldo, Natascia, de Wit, Tobias F Rinke, Rito, Ana, Ritti-Dias, Raphael M, Rivera, Juan A, Robitaille, Cynthia, Roccaldo, Romana, Rodrigues, Daniela, Rodríguez-Artalejo, Fernando, del Cristo Rodriguez-Perez, María, Rodríguez-Villamizar, Laura A, Roggenbuck, Ulla, Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Romeo, Elisabetta L, Rosario, Rafaela V, Rosengren, Annika, Rouse, Ian, Roy, Joel GR, Rubinstein, Adolfo, Rühli, Frank J, Ruidavets, Jean-Bernard, Ruiz-Betancourt, Blanca Sandra, Ruiz-Castell, Maria, Moreno, Emma Ruiz, Rusakova, Iuliia A, Jonsson, Kenisha Russell, Russo, Paola, Rust, Petra, Rutkowski, Marcin, Sabanayagam, Charumathi, Sacchini, Elena, Sachdev, Harshpal S, Sadjadi, Alireza, Safarpour, Ali Reza, Safiri, Saeid, Saki, Nader, Salanave, Benoit, Martinez, Eduardo Salazar, Salmerón, Diego, Salomaa, Veikko, Salonen, Jukka T, Salvetti, Massimo, Samoutian, Margarita, Sánchez-Abanto, Jose, Sandjaja, null, Sans, Susana, Marina, Loreto Santa, Santos, Diana A, Santos, Ina S, Santos, Lèlita C, Santos, Maria Paula, Santos, Osvaldo, Santos, Rute, Sanz, Sara Santo, Saramies, Jouko L, Sardinha, Luis B, Sarrafzadegan, Nizal, Sathish, Thirunavukkarasu, Saum, Kai-Uwe, Savva, Savva, Savy, Mathilde, Sawada, Norie, Sbaraini, Mariana, Scazufca, Marcia, Schaan, Beatriz D, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schipf, Sabine, Schmidt, Carsten O, Schmidt, Ida Maria, Schnohr, Peter, Schöttker, Ben, Schramm, Sara, Schramm, Stine, Schröder, Helmut, Schultsz, Constance, Schutte, Aletta E, Sein, Aye Aye, Selamat, Rusidah, Sember, Vedrana, Sen, Abhijit, Senbanjo, Idowu O, Sepanlou, Sadaf G, Sequera, Victor, Serra-Majem, Lui, Servais, Jennifer, Ševcíková, Ludmila, Shalnova, Svetlana A, Shamah-Levy, Teresa, Shamshirgaran, Morteza, Shanthirani, Coimbatore Subramaniam, Sharafkhah, Maryam, Sharma, Sanjib K, Shaw, Jonathan E, Shayanrad, Amaneh, Shayesteh, Ali Akbar, Shengelia, Lela, Shi, Zumin, Shibuya, Kenji, Shimizu-Furusawa, Hana, Shin, Dong Wook, Shirani, Majid, Shiri, Rahman, Shrestha, Namuna, Si-Ramlee, Khairil, Siani, Alfonso, Siantar, Rosalynn, Sibai, Abla M, Silva, Antonio M, Silva, Diego Augusto Santo, Simon, Mary, Simons, Judith, Simons, Leon A, Sjöberg, Agneta, Sjöström, Michael, Skodje, Gry, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, So, Hung-Kwan, Soares, Fernanda Cunha, Sobek, Grzegorz, Sobngwi, Eugène, Sodemann, Morten, Söderberg, Stefan, Soekatri, Moesijanti YE, Soemantri, Agustinu, Sofat, Reecha, Solfrizzi, Vincenzo, Somi, Mohammad Hossein, Sonestedt, Emily, Song, Yi, Sørensen, Thorkild IA, Sørgjerd, Elin P, Jérome, Charles Sossa, Soto-Rojas, Victoria E, Soumaré, Aïcha, Sovic, Slavica, Sparboe-Nilsen, Bente, Sparrenberger, Karen, Spinelli, Angela, Spiroski, Igor, Staessen, Jan A, Stamm, Hanspeter, Stathopoulou, Maria G, Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D, Stergiou, George S, Stessman, Jochanan, Stevanovic, Ranko, Stieber, Jutta, Stöckl, Dori, Stocks, Tanja, Stokwiszewski, Jakub, Stoyanova, Ekaterina, Stratton, Gareth, Stronks, Karien, Strufaldi, Maria Wany, Sturua, Lela, Suárez-Medina, Ramón, Suka, Machi, Sun, Chien-An, Sundström, Johan, Sung, Yn-Tz, Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A, Sy, Rody G, Syddall, Holly E, Sylva, René Charle, Szklo, Moyse, Szponar, Lucjan, Tai, E Shyong, Tammesoo, Mari-Lii, Tamosiunas, Abdona, Tan, Eng Joo, Tang, Xun, Tanrygulyyeva, Maya, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B, Braunerová, Radka Taxová, Taylor, Anne, Taylor, Julie, Tchibindat, Félicité, Tebar, William R, Tell, Grethe S, Tello, Tania, Tham, Yih Chung, Thankappan, KR, Theobald, Holger, Theodoridis, Xenophon, Thijs, Lutgarde, Thomas, Nihal, Thuesen, Betina H, Tichá, Lubica, Timmermans, Erik J, Tjonneland, Anne, Tolonen, Hanna K, Tolstrup, Janne S, Topbas, Murat, Topór-Madry, Roman, Torheim, Liv Elin, Tormo, María José, Tornaritis, Michael J, Torrent, Matie, Torres-Collado, Laura, Toselli, Stefania, Touloumi, Giota, Traissac, Pierre, Tran, Thi Tuyet-Hanh, Trichopoulos, Dimitrio, Trichopoulou, Antonia, Trinh, Oanh TH, Trivedi, Atul, Tshepo, Lechaba, Tsigga, Maria, Tsugane, Shoichiro, Tuliakova, Azaliia M, Tulloch-Reid, Marshall K, Tullu, Fikru, Tuomainen, Tomi-Pekka, Tuomilehto, Jaakko, Turley, Maria L, Twig, Gilad, Tynelius, Per, Tzotzas, Themistokli, Tzourio, Christophe, Ueda, Peter, Ugel, Eunice, Ukoli, Flora AM, Ulmer, Hanno, Unal, Belgin, Usupova, Zhamyila, Uusitalo, Hannu MT, Uysal, Nalan, Vaitkeviciute, Justina, Valdivia, Gonzalo, Vale, Susana, Valvi, Damaskini, van Dam, Rob M, Van der Heyden, Johan, van der Schouw, Yvonne T, Van Herck, Koen, Van Minh, Hoang, Van Schoor, Natasja M, van Valkengoed, Irene GM, Vanderschueren, Dirk, Vanuzzo, Diego, Varbo, Anette, Varela-Moreiras, Gregorio, Varona-Pérez, Patricia, Vasan, Senthil K, Vega, Toma, Veidebaum, Tooma, Velasquez-Melendez, Gustavo, Velika, Biruta, Veronesi, Giovanni, Verschuren, WM Monique, Victora, Cesar G, Viegi, Giovanni, Viet, Lucie, Villalpando, Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021

43. The diagnosis of osteoporotic vertebral fractures redux

Author: Linda Probyn, Peter L. Munk, David Goltzman, Ian Hammond, Jacques P. Brown, Brian C. Lentle, Jerilynn C. Prior, and William D. Leslie
Subjects: medicine.medical_specialty, business.industry, medicine, Humans, Spinal Fractures, Radiology, Nuclear Medicine and imaging, General Medicine, Redux, business, Osteoporotic Fractures, Spine, Surgery
Published: 2021

44. 1,25-Dihydroxyvitamin D deficiency induces sarcopenia by inducing skeletal muscle cell senescence

Author: Shuxiang, Yu, Biqi, Ren, Haiyun, Chen, David, Goltzman, Jianshe, Yan, and Dengshun, Miao
Subjects: Original Article
Abstract: To determine if 1,25(OH)(2)D deficiency can induce age-related sarcopenia, the skeletal muscular phenotype of male wild-type (WT) and Cyp27b1 knockout (KO) mice were compared at 3 and 6 months of age. We found that muscle mass, grip strength and muscle fiber size were significantly decreased in aging Cyp27b1 KO male mice. The expression levels of genes related to mitochondrial metabolic activity, and antioxidant enzymes including SOD1, catalase, Nqo1 and Gcs were significantly down-regulated in skeletal muscle tissue of Cyp27b1 KO male mice; in contrast, the percentage of p16(+) and p21(+) myofibers, and the expression of p16, p19, p21, p53, TNFα, IL6 and MMP3 at mRNA and/or protein levels were significantly increased. We then injected tibialis anterior muscle of WT and Cyp27b1(+/-) male mice with BaCl(2), and analyzed the regenerative ability of skeletal muscle cells 7 days later. The results revealed that the numbers of newly formed regenerating central nucleated fibers (CNF), the percentage of BrdU(+) cells and the expression of MyoD, MyHC and Myf5 at mRNA levels were significantly down-regulated in the injured skeletal muscle tissue of Cyp27b1(+/-) mice. In summary, our studies indicate that 1,25(OH)(2)D deficiency can result in the development of age-related sarcopenia by inducing oxidative stress, skeletal muscular cell senescence and SASP, and by inhibiting skeletal muscle regeneration. Cyp27b1 KO mice can therefore be used as an animal model of age-related sarcopenia in order to investigate the pathogenesis of age-related sarcopenia and potentially to test intervention measures for treatment of sarcopenia.
Published: 2021

45. A Sonic Hedgehog-Gli-Bmi1 signaling pathway plays a critical role in p27 deficiency induced bone anabolism

Author: Jun Wu, Rong Wang, Xuechun Kan, Jinghan Zhang, Wen Sun, David Goltzman, and Dengshun Miao
Subjects: Polycomb Repressive Complex 1, Osteoblasts, Mesenchymal Stem Cells, Cell Biology, Applied Microbiology and Biotechnology, Mice, Osteogenesis, Proto-Oncogene Proteins, Animals, Hedgehog Proteins, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Developmental Biology, Signal Transduction
Abstract: To explore the mechanism of the bone anabolic action of p27 deficiency, we first confirmed that osteoblast formation and osteogenesis were significantly increased in p27 deficient mice compared with their wild-type littermates. Microarray analysis of differential gene expression profiles, followed by real-time RT-PCR and Western blots revealed that p27 deletion significantly upregulated the expression of Sonic hedgehog (Shh), Gli1 and 2 and their target gene Bmi1 in bone tissue, and significantly down regulated the expression of the negative regulators of the Shh pathway Sufu, Patched 1 and Gli3 in bone tissue. The Shh antagonist KAAD-cyclopamine or vismodegib significantly reduced osteogenesis of bone marrow mesenchymal stem cells (BM-MSCs)
Published: 2021

46. Genetic Deletion of Menin in Mouse Mesenchymal Stem Cells: An Experimental and Computational Analysis

Author: Jad Abi‐Rafeh, Meisam Asgari, Ildi Troka, Lucie Canaff, Ahmed Moussa, Damiano Pasini, and David Goltzman
Subjects: Endocrinology, Diabetes and Metabolism, Orthopedics and Sports Medicine
Abstract: Loss-of-function mutations in the
Published: 2021

47. Reduced Bone Loss Is Associated With Reduced Mortality Risk in Subjects Exposed to Nitrogen Bisphosphonates: A Mediation Analysis

Author: Robert G. Josse, John A. Eisman, Piet Geusens, Dana Bliuc, Lisa Langsetmo, Stephanie M. Kaiser, Thach Tran, Jonathan D. Adachi, Tineke A. C. M. van Geel, Jerilynn C. Prior, Joop P. W. van den Bergh, David A. Hanley, Claudie Berger, Tuan V. Nguyen, Christopher S. Kovacs, David Goltzman, RS: NUTRIM - R3 - Respiratory & Age-related Health, and Interne Geneeskunde
Subjects: Male, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, 0302 clinical medicine, Bone Density, Risk Factors, Orthopedics and Sports Medicine, Bone mineral, education.field_of_study, PROSPECTIVE STUDY, Alendronate, CANADIAN MULTICENTER OSTEOPOROSIS, Hazard ratio, MEN, Middle Aged, Anatomy & Morphology, FRACTURE, Survival Rate, ZOLEDRONIC ACID, Female, Risedronic Acid, BISPHOSPHONATE, medicine.drug, medicine.medical_specialty, SUBSEQUENT FRACTURE, Population, 030209 endocrinology & metabolism, Disease-Free Survival, MORTALITY RISK, 03 medical and health sciences, Internal medicine, medicine, Humans, education, FRAILTY, METAANALYSIS, Aged, Proportional hazards model, business.industry, HIP FRACTURE, Bisphosphonate, EFFICACY, medicine.disease, Confidence interval, 030104 developmental biology, Zoledronic acid, BONE LOSS, 06 Biological Sciences, 09 Engineering, 11 Medical and Health Sciences, OLDER WOMEN, MINERAL DENSITY, business
Abstract: Bisphosphonates, potent antiresorptive agents, have been found to be associated with mortality reduction. Accelerated bone loss is, in itself, an independent predictor of mortality risk, but the relationship between bisphosphonates, bone loss, and mortality is unknown. This study aimed to determine whether the association between bisphosphonates and mortality is mediated by a reduction in the rate of bone loss. Participants from the population-based Canadian Multicentre Osteoporosis Study were followed prospectively between1996 and 2011. Comorbidities and lifestyle factors were collected at baseline and bone mineral density (BMD) at baseline and at years 3 (for those aged 40 to 60 years), 5, and 10. Rate of bone loss was calculated using linear regression. Information on medication use was obtained yearly. Bisphosphonate users grouped into nitrogen bisphosphonates (nBP; alendronate or risedronate) and etidronate and non-users (NoRx) were matched by propensity score, including all baseline factors as well as time of treatment. Cox's proportional hazards models, unadjusted and adjusted for annual rate of bone loss, were used to determine the association between nBP and etidronate versus NoRx. For the treatment groups with significant mortality risk reduction, the percent of mortality reduction mediated by a reduction in the rate of bone loss was estimated using a causal mediation analysis. There were 271 pairs of nBP and matched NoRx and 327 pairs of etidronate and matched NoRx. nBP but not etidronate use was associated with significant mortality risk reduction (hazard ratios [HR] = 0.61 [95% confidence interval 0.39-0.96] and 1.35 [95% CI 0.86-2.11] for nBP and etidronate, respectively). Rapid bone loss was associated with more than 2-fold increased mortality risk compared with no loss. Mediation analysis indicated that 39% (95% CI 7%-84%) of the nBP association with mortality was related to a reduction in the rate of bone loss. This finding provides an insight into the mechanism of the relationship between nBP and survival benefit in osteoporotic patients. (c) 2019 American Society for Bone and Mineral Research.
Published: 2019

48. Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study

Author: Claudie Berger, Tassos Anastassiades, David A. Hanley, Jerilynn C. Prior, Jonathan D. Adachi, Wilma M. Hopman, Lawrence Joseph, Tanveer Towheed, Suzanne N Morin, and David Goltzman
Subjects: Male, 0301 basic medicine, Canada, medicine.medical_specialty, Psychometrics, SF-36, Endocrinology, Diabetes and Metabolism, Osteoporosis, Psychological intervention, 030209 endocrinology & metabolism, Disease, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Bone Density, Surveys and Questionnaires, Internal medicine, medicine, Humans, Longitudinal Studies, Osteoporosis, Postmenopausal, Aged, Aged, 80 and over, Bone mineral, business.industry, Middle Aged, medicine.disease, Health Surveys, Rheumatology, Socioeconomic Factors, Orthopedic surgery, Quality of Life, Physical therapy, Female, Self Report, 030101 anatomy & morphology, business, Osteoporotic Fractures
Abstract: Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.
Published: 2019

49. The Radiology of Osteoporotic Vertebral Fractures Revisited

Author: William D. Leslie, Linda Probyn, Brian C. Lentle, Fernando Rivadeneira, David Goltzman, Jacques P. Brown, Angela M. Cheung, Ian Hammond, Fjorda Koromani, Edwin H.G. Oei, Ling Oei, Leanne M Ward, Jerilynn C. Prior, Epidemiology, Internal Medicine, and Radiology & Nuclear Medicine
Subjects: 0301 basic medicine, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Radiography, Osteoporosis, Gold standard, Structural integrity, 030209 endocrinology & metabolism, Context (language use), medicine.disease, Diagnostic strategy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Increased risk, Clinical diagnosis, medicine, Humans, Spinal Fractures, Orthopedics and Sports Medicine, Radiology, Child, business, Osteoporotic Fractures
Abstract: Until recently there has been little evidence available to validate any method by which to make an accurate diagnosis of an osteoporotic vertebral fractures (OVFs) from plain radiographs. In part this reflects a lack of a completely satisfactory "gold standard," but primarily it relates to the absence of well-designed prospective studies in this context. Historically, OVFs were recognized by evidence of macroscopic structural failure in vertebrae using the criteria applied elsewhere in the skeleton. This comprised altered alignment, fragmentation, cortical disruptions, and breaks, among other changes. However, these morphological criteria were replaced by vertebral morphometry, referring to the use of quantitative or quasi-quantitative measurement tools for fracture diagnosis. Vertebral morphometry emerged as an understanding of and treatment for osteoporosis evolved, mainly in response to the need for expeditious assessments of large numbers of spine images for epidemiological and pharmaceutical purposes. Although most of the descriptions of such morphometric tools have stressed that they were not to be applied to clinical diagnosis with respect to individual patients, this constraint has been widely disregarded. Here we review the major attempts to develop a diagnostic strategy for OVF and describe their characteristics in adults and children. Recent evidence suggests that morphometric (quantitative; ie, based on measurement of dimensions and shape description) criteria are inferior to morphologic (qualitative; ie, based on structural integrity) vertebral damage assessment in identifying people with low bone density and at an increased risk of future fracture. Thus there is now an evidentiary basis for suggesting that morphological assessment is the preferred strategy for use in diagnosing OVF from radiographs. © 2019 American Society for Bone and Mineral Research.
Published: 2019

50. Frailty and Risk of Fractures in Patients With Type 2 Diabetes

Author: David Goltzman, Lehana Thabane, Mitchell Levine, Robert G. Josse, Christopher S. Kovacs, K. Shawn Davison, Tanveer Towheed, Jonathan D. Adachi, Tassos Anastassiades, Alexandra Papaioannou, William D. Leslie, Jerilynn C. Prior, Guowei Li, and Stephanie M. Kaiser
Subjects: Male, Research design, Canada, medicine.medical_specialty, Frail Elderly, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Diabetes Complications, Fractures, Bone, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Prevalence, Internal Medicine, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Risk factor, Prospective cohort study, Aged, Proportional Hazards Models, Advanced and Specialized Nursing, Hip fracture, Frailty, Hip Fractures, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Osteoporosis, Female, business
Abstract: OBJECTIVE We aimed to explore whether frailty was associated with fracture risk and whether frailty could modify the propensity of type 2 diabetes toward increased risk of fractures. RESEARCH DESIGN AND METHODS Data were from a prospective cohort study. Our primary outcome was time to the first incident clinical fragility fracture; secondary outcomes included time to hip fracture and to clinical spine fracture. Frailty status was measured by a Frailty Index (FI) of deficit accumulation. The Cox model incorporating an interaction term (frailty × diabetes) was used for analyses. RESULTS The analysis included 3,149 (70% women) participants; 138 (60% women) had diabetes. Higher bone mineral density and FI were observed in participants with diabetes compared with control subjects. A significant relationship between the FI and the risk of incident fragility fractures was found, with a hazard ratio (HR) of 1.02 (95% CI 1.01–1.03) and 1.19 (95% CI 1.10–1.33) for per-0.01 and per-0.10 FI increase, respectively. The interaction was also statistically significant (P = 0.018). The HR for per-0.1 increase in the FI was 1.33 for participants with diabetes and 1.19 for those without diabetes if combining the estimate for the FI itself with the estimate from the interaction term. No evidence of interaction between frailty and diabetes was found for risk of hip and clinical spine fractures. CONCLUSIONS Participants with type 2 diabetes were significantly frailer than individuals without diabetes. Frailty increases the risk of fragility fracture and enhances the effect of diabetes on fragility fractures. Particular attention should be paid to diabetes as a risk factor for fragility fractures in those who are frail.
Published: 2019

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Category

Publication Type

Journal

Database

Publisher

486 results on '"David Goltzman"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources