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To determine whether 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can exert an anti-osteoporosis role through anti-aging mechanisms, we analyzed the bone phenotype of mice with 1,25(OH) 2 D deficiency due to deletion of the enzyme, 25-hydroxyvitamin D 1α-hydroxylase, while on a rescue diet. 1,25(OH) 2 D deficiency accelerated age-related bone loss by activating the p16/p19 senescence signaling pathway, inhibiting osteoblastic bone formation, and stimulating osteoclastic bone resorption, osteocyte senescence, and senescence-associated secretory phenotype (SASP). Supplementation of exogenous 1,25(OH) 2 D 3 corrected the osteoporotic phenotype caused by 1,25(OH) 2 D deficiency or natural aging by inhibiting the p16/p19 pathway. The proliferation, osteogenic differentiation, and ectopic bone formation of bone marrow mesenchymal stem cells derived from mice with genetically induced deficiency of the vitamin D receptor (VDR) were significantly reduced by mechanisms including increased oxidative stress, DNA damage, and cellular senescence. We also demonstrated that p16 deletion largely rescued the osteoporotic phenotype caused by 1,25(OH) 2 D 3 deficiency, whereas 1,25(OH) 2 D 3 could up-regulate the enzyme Ezh2 via VDR-mediated transcription thereby enriching H3K27me3 and repressing p16/p19 transcription. Finally, we demonstrated that treatment with 1,25(OH) 2 D 3 improved the osteogenic defects of human BM-MSCs caused by repeated passages by stimulating their proliferation and inhibiting their senescence via the VDR-Ezh2-p16 axis. The results of this study therefore indicate that 1,25(OH) 2 D 3 plays a role in preventing age-related osteoporosis by up-regulating Ezh2 via VDR-mediated transcription, increasing H3K27me3 and repressing p16 transcription, thus promoting the proliferation and osteogenesis of BM-MSCs and inhibiting their senescence, while also stimulating osteoblastic bone formation, and inhibiting osteocyte senescence, SASP, and osteoclastic bone resorption., (© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Until recently, randomized controlled trials have not demonstrated convincing evidence that vitamin D, or vitamin D in combination with calcium supplementation could improve bone mineral density (BMD), osteoporosis and fracture. It remains unclear whether vitamin D levels are causally associated with total body BMD. Here, we performed a Mendelian randomization study to investigate the association of vitamin D levels with total body BMD using a large-scale vitamin D genome-wide association study (GWAS) dataset (including 79 366 individuals) and a large-scale total body BMD GWAS dataset (including 66,628 individuals). We selected three Mendelian randomization methods including inverse-variance weighted meta-analysis (IVW), weighted median regression and MR-Egger regression. All these three methods did not show statistically significant association of genetically increased vitamin D levels with total body BMD. Importantly, our findings are consistent with recent randomized clinical trials and Mendelian randomization study. In summary, we provide genetic evidence that increased vitamin D levels could not improve BMD in the general population. Hence, vitamin D supplementation alone may not be associated with reduced fracture incidence among community-dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objective: To obtain descriptive information concerning the extent to which patients taking oral glucocorticoids recall receiving osteoporosis prevention counseling, and to identify factors associated with the practice of 3 behaviors (i.e., calcium intake, vitamin D intake, and bone mineral density [BMD] testing) recommended for patients receiving glucocorticoid therapy., Methods: The study assessed cross-sectional data derived from telephone interviews and mailed questionnaires completed by 227 patients who were currently taking oral prednisone. Questions assessed current calcium and vitamin D intake and history of BMD testing., Results: Approximately one-third of participants (36.3%) reported that they had received osteoporosis prevention counseling. Among those who reported receiving counseling, most (73.2%) remembered being told about the importance of obtaining an adequate amount of calcium. Other topics were remembered less frequently. Slightly more than half of study participants (51.1%) were obtaining the recommended amount of calcium. Fewer were obtaining the recommended amount of vitamin D (35.2%) or had received a BMD test within the past year (33.5%). The most consistent predictors of behavior were counseling status and patients' perceptions of the difficulty associated with performing the behavior., Conclusion: Most patients receiving oral glucocorticoids receive insufficient counseling concerning the prevention of osteoporosis; patients either are not being counseled or they are being counseled in a manner that is not sufficient to promote subsequent recall and behavior change. Research is needed to develop effective strategies to educate patients about the prevention of glucocorticoid-induced osteoporosis.

This study aimed to evaluate the impact of dietary boron on osteoporosis in postmenopausal Jordanian women. Sixty‐six women diagnosed with osteoporosis were recruited and data on personal information, dietary habits, medical history, and lifestyle were collected. Bone mineral density, serum calcium, and serum vitamin D measurements were obtained from patient records. This study showed a strong correlation between boron intake and bone mineral density in these women with osteoporosis and a negative correlation between boron intake and serum calcium (p <.05). However, no significant correlation was found between boron intake and various parameters such as serum vitamin D, dietary habits, body mass index (BMI), waist circumference (WC), age of menopause, cases of hysterectomy or oophorectomy, location of fractures, education level, social status, smoking, and physical activity (p >.05). A significant link was found between boron intake and bone mineral density highlighting the importance of nutritional and lifestyle factors affecting bone health. Further research on the specific impact of boron is warranted to better inform dietary interventions for osteoporosis prevention and management. [ABSTRACT FROM AUTHOR]

Limited guidelines exist regarding osteoporosis prevention in the general population. Despite being a subject of controversy, the majority of research suggests that decreased vitamin D levels correlate with increased bone turnover, that is, an important risk factor for osteoporosis development. In most guidelines, daily vitamin D supplementation is recommended. In persons with epilepsy (PWE), the situation is more complex, as other factors can increase the chance of being vitamin D deficient. Currently, there are no internationally accepted guidelines regarding monitoring bone health in PWE. Our aim was to review the existing evidence in PWE on: (1) risk factors for vitamin D deficiency, (2) the identification of higher risk groups, and (3) the optimal ways to monitor bone health. Our narrative review shows that: (1) anti‐seizure medication (ASM) use, especially enzyme‐inducing ASM (EIASM) and valproic acid, is identified as an important risk factor for impaired bone health (e.g., increased risk for osteoporosis/fractures and/or vitamin D deficiency); (2) higher risk groups within the PWE population are present: intellectual or physical disability, institutionalized patients, puberty, early onset epilepsy and developmental epileptic encephalopathies, postmenopausal women, and use of multiple ASM/concomitant drugs (e.g. corticosteroids); and (3) a monitoring scheme can be suggested including laboratory tests, bone density measurements, managing of risk factors, and/or vitamin D supplementation. Overall, regular vitamin D measurement in PWE is a cost‐effective and practical method for monitoring vitamin D deficiency, whereas in high‐risk patients the combination of vitamin D measurement and bone densitometry is recommended. There is not enough evidence to advocate continuous vitamin D supplementation in all PWE. Children with epilepsy should receive the recommended daily intake of vitamin D for age and additional monitoring and supplementation if at higher risk of deficiency. There is a need for prospective trials exploring the potential benefit of vitamin D supplementation in PWE. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Any pregnant or lactating woman with severe constant back pain, PLO must be kept in mind due to its effect on the quality of life of the mother and her child. A 22‐year‐old woman, who delivered her first child 5 months ago and is now breastfeeding her baby, presented with mid‐back pain. After investigations, including laboratory tests, X‐rays, and bone density measurements, the diagnosis was PLO. The patient is being treated with calcium, vitamin D, and alendronate besides discontinuation of lactation. [ABSTRACT FROM AUTHOR]

Bone remodeling is marked by bone synthesis and absorption balance, and any altered dynamic in this process leads to osteoporosis (OP). The interaction of hormonal, environmental and genetic factors regulate bone metabolism. Since vitamin D displays a classic role in bone metabolism regulation, acting through vitamin D receptor (VDR), the genetic variants within VDR were the first ones associated with bone density and remodelling. Therefore, we investigated whether three single nucleotide polymorphisms (SNPs) within VDR were associated with OP differential susceptibility and clinical profile from postmenopausal versus healthy women from Northeast Brazil. Genetic association study enrolling 146 postmenopausal osteoporotic women as the patient group and 95 healthy age‐matched women as the control group. We assessed three SNPs within VDR (rs11168268, rs1540339 and rs3890733), considering the clinical profile of all patients. Our results showed an association of rs11168268 G/G genotype with higher bone mineral density (BMD) mean for the total hip (A/A = 0.828 ± 0.09; A/G = 0.081 ± 0.13; G/G = 0.876 ± 0.12, p =.039), and the rs3890733 T/T genotype was associated with increased OP risk in patients below 60 years old (odds ratio [OR] = 5.12, 95% confidence interval [CI ]= 1.13–23.27, p =.012). The rs1540339 T/T genotype was associated with protection for individuals with low melanin deposition when compared to the high melanin deposition group (OR = 0.24, 95%CI = 0.06–0.94, p =.029). Additionally, 61% of patients presented deficient vitamin D serum levels. The SNP rs11168268 G/G was associated with a significantly increased mean total hip BMD in patients OP, highlighting this SNP and its relationship with BMD. [ABSTRACT FROM AUTHOR]

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass among winter‐born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long‐term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralization in early childhood in a prespecified, single‐center follow‐up of a double‐blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25‐hydroxyvitamin D level 25–100 nmol/L from three research centers (2008–2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013–2018). Anthropometry and dual‐energy X‐ray absorptiometry (DXA) were performed (yielding whole body less head [WBLH] bone mineral content [BMC], areal bone mineral density [aBMD], bone area [BA], and body composition). Of 723 children, 564 (78.0%) children attended the 4‐year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472–0.481) g/cm2; placebo group: 0.470 (95% CI, 0.466–0.475) g/cm2, p = 0.048). Associations were consistent for BMC and lean mass, and in age‐ and sex‐adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal‐child interactions were observed, with a greater effect size among children with low milk intake and low levels of physical activity. Child weight, height, and body mass index (BMI) were similar by maternal randomization group. These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years, but will require replication in other trials. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Osteoporosis disease is caused by hormonal changes, vitamin D, and calcium deficiency. With current technologies, the identification of osteoporosis requires many tests with the support of medications. Bone mineral density is a typical measure implemented using a DEXA scan which can be very costly. Such high technology equipment is usually not accessible for remote people, and thus a low‐cost screening system is very appealing. This article proposes an osteoporosis prediction system that effectively determines its possibility of occurrence based on essential factors such as smoking habits and calcium level so that the people at high risk can be referred to access the DEXA scanner. Our proposed system is implemented by an improved version of the artificial immune system, enabling care providers to take precautionary measures at the right time to avoid the early development of osteoporosis. The experiments demonstrated a promising result of 94% prediction accuracy that proved its usefulness in identifying people with potential osteoporosis in the future. [ABSTRACT FROM AUTHOR]

High‐dose vitamin D supplementation (4000 or 10,000 IU/d) in vitamin D‐sufficient individuals results in a dose‐dependent decrease in radius and tibia total bone mineral density (Tt.BMD) compared with 400 IU/d. This exploratory analysis examined whether the response to high‐dose vitamin D supplementation depends on imaging modality and skeletal site. Participants were aged 55 to 70 years, not osteoporotic, with serum 25(OH)D 30 to 125 nM. Participants' radius and tibia were scanned on high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to measure Tt.BMD, trabecular bone volume fraction (Tb.BV/TV), trabecular separation (Tb.Sp), cortical thickness (Ct.Th), and finite element analysis (FEA) estimated failure load. Three‐dimensional image registration was used. Dual‐energy X‐ray absorptiometry (DXA) scans of the hip, spine, and radius measured areal BMD (aBMD) and trabecular bone score (TBS). Constrained linear mixed‐effects models determined treatment group‐by‐time and treatment group‐by‐time‐by‐sex interactions. The treatment group‐by‐time interaction previously observed for radial Tt.BMD was observed at both ultradistal (UD, p < 0.001) and 33% (p < 0.001) aBMD sites. However, the treatment group‐by‐time‐by‐sex interaction observed for radial Tt.BMD was not observed with aBMD at either the UD or 33% site, and the 4000 and 400 groups did not differ. Registered radial FEA results mirrored Tt.BMD. An increase in Tb.Sp and decrease in Ct.Th underpinned dose‐dependent changes in radial BMD and strength. We observed no effects in DXA‐based aBMD at the hip or spine or TBS. At the tibia, we observed a time‐by‐treatment group effect for Tb.BV/TV. Given that DXA measures at the radius did not detect sex differences or differences between the 4000 and 400 groups, HR‐pQCT at the radius may be more sensitive for examining bone changes after vitamin D supplementation. Although DXA did not reveal treatment effects at the hip or spine, whether that is a true skeletal site difference or a lack of modality sensitivity remains unclear. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of different intervention measures to prevent falls in elderly osteoporotic patients. Methods: A randomized controlled trial was conducted in our outpatient ward from August 2014 to September 2015. A total of 420 patients over 60 years of age were assigned to four groups. NA VitD group took 800 mg calcium and 800 IU non‐active vitamin D. P‐NA VitD group took 800 mg calcium, 800 IU non‐active vitamin D, and received physical exercise. A VitD group took 800 mg calcium and 0.5 μg active vitamin D. P‐A VitD took 800 mg calcium, 0.5 μg active vitamin D, and received physical exercise. Physical exercise includes guidance in improving muscle strength and balance ability. Short physical performance battery (SPPB), grip strength, modified falls efficacy scale (MFES), blood calcium, and 25‐hydroxyl vitamin D were measured before interventions and at 3, 6, and 12 months after interventions. Bone mineral density (BMD) was detected before interventions and at 12 months after interventions. The incidence of falls and fractures, adverse events, and drug reactions were recorded for 12 months. Results: A total of 420 patients were allocated in the four groups: 98 cases into the NA VitD group (11 males, 87 females), 97 cases into the P‐NA VitD group (13 males, 84 females), 99 cases in the A VitD group (15 males, 84 females), and 98 cases into the P‐A VitD group (11 males, 87 females). At 6 months after interventions, the SPPB of A VitD group significantly increased from 6.9 ± 1.9 to 8.0 ± 2.4 (P < 0.05), and the SPPB of A VitD group significantly increased from 7.2 ± 2.1 to 8.6 ± 1.7 (P < 0.05). At 6 months after interventions, MFES of P‐NA VitD group 7.0 ± 1.6 to 7.6 ± 1.6 (P < 0.05), and MFES of P‐A VitD group significantly increased from 6.7 ± 1.6 to 7.5 ± 1.6 (P < 0.05). At 12 months after interventions, SPPB of all groups, grip strength, and MFES of P‐NA VitD group, A VitD group, P‐A VitD group were significantly improved (P < 0.05). The BMD of lumbar vertebrae of A VitD group significantly increased from 0.742 ± 0.042 to 0.776 ± 0.039, and P‐A VitD group significantly increased from 0.743 ± 0.048 to 0.783 ± 0.042 (P < 0.05). No serious adverse events occurred during the 12 months of follow‐up. Conclusion: Active vitamin D is better than non‐active vitamin D to improve physical ability and the BMD of lumbar vertebrae and reduce the risk of falls. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Three years of high‐dose vitamin D supplementation (400 IU, 4000 IU, 10,000 IU) in healthy vitamin D–sufficient individuals aged 55 to 70 years (serum 25(OH)D 30–125 nmol/L at baseline), resulted in a negative dose‐response relationship for bone density and strength. This study examined whether response differed between males and females. A total of 311 participants (53% male) were randomized to 400 IU (male = 61, female = 48), 4000 IU (male = 51, female = 49), or 10,000 IU (male = 53, female = 49) daily vitamin D3. Participants were scanned with high‐resolution peripheral quantitative computed tomography (HR‐pQCT) to measure total volumetric BMD (TtBMD) at baseline, 6, 12, 24, and 36 months. Finite element analysis estimated bone strength. Balance, physical function, and clinical biochemistry parameters were also assessed. Constrained linear mixed effects models determined time‐by‐treatment group‐by‐sex interactions. Baseline, 3‐month, and 3‐year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L (400 IU); 81.3, 115.3, and 132.2 (4000 IU); and 78.4, 188.0, and 144.4 (10,000 IU), respectively. There were significant time‐by‐treatment group‐by‐sex interactions for TtBMD at the radius (p =.002) and tibia (p =.005). Treatment with 4000 IU or 10,000 IU compared to 400 IU resulted in TtBMD losses in females, but this was not observed with males. After 3 years, females lost 1.8% (400 IU), 3.8% (4000 IU), and 5.5% (10,000 IU), whereas males lost 0.9% (400 IU), 1.3% (4000 IU), and 1.9% (10,000 IU) at the radius. At the tibia, losses in TtBMD were smaller, but followed a similar trend. There were no significant bone strength interactions. Vitamin D supplementation with 4000 IU or 10,000 IU, compared with 400 IU daily, resulted in greater losses of TtBMD over 3 years in healthy vitamin D–sufficient females, but not males. These results are clinically relevant, because vitamin D supplementation is widely administered to postmenopausal females for osteoporosis prevention. Our findings do not support a benefit of high‐dose vitamin D supplementation for bone health, and raise the possibility of harm for females. © 2020 American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Background and Aim: The main clinical relevance of hepatic osteodystrophy is the increased risk of fractures. Dual‐energy X ray absorptiometry (DEXA)‐based assessment of bone mineral density, the current gold standard for diagnosing osteoporosis, is not the sole determinant of fracture risk. Other clinical risk factors also play an important role. This study was carried out to assess the prevalence and risk factors of hepatic osteodystrophy and estimate the entailed fracture risk by using the FRAX tool in a cohort of Indian cirrhotics. Methods: Consecutive patients with cirrhosis (n = 120) were recruited. Etiologic workup, liver function tests, serum calcium, phosphate, 25(OH)D, HbA1c, and DEXA scan were performed. Hepatic osteodystrophy was defined as a T score of < −1. FRAX scores were calculated using the Indian calculator. Results: The study cohort was predominantly male (86.7%) with a median age of 49 (40–65) years. Alcohol was the most common etiology (80%). All patients had Child‐Turcotte‐Pugh class B (63.3%) or class B (36.7%) cirrhosis. Hepatic osteodystrophy was present in 83.3% patients. On multivariate analysis, smoking (odds ratio [OR]: 3.1 [1.76–4.7], P < 0.001) and serum 25(OH)D (OR: 0.23 [0.09–0.94]; P = 0.03) showed significant association with hepatic osteodystrophy. The 10‐year probability of major osteoporotic fracture and hip fracture was 5.7% (2.1–28.9) and 2.5% (1.4–7.4), respectively. Using a FRAX probability cut‐off of 20% for major osteoporotic fracture and 3% for hip fracture, 30% patients qualified for osteoporosis treatment. Conclusion: Hepatic osteodystrophy is widely prevalent among Indian patients with cirrhosis and entails a high risk of fractures. Approximately one‐third of patients with cirrhosis need treatment to reduce the risk of osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Severe vitamin D deficiency may cause rickets. While this point is not disputed, the use of vitamin D in the elderly to prevent fractures has been challenged recently by a meta‐analysis of 81 RCTs, suggesting that the effects of vitamin D were trivial. As is true for any review of the literature, the interpretation of a meta‐analysis can be confounded by the choice of publications to include or exclude. Indeed, the authors excluded RCTs with combined vitamin D and calcium supplementation, included futile studies of very short duration, or studies with high bolus doses known to transiently increase fracture risk. The best available data show that calcium and vitamin D supplementation of elderly subjects can decrease the risk of hip and other non‐vertebral fractures, especially in institutionalized subjects or elderly subjects with poor calcium and vitamin D status. Vitamin D deficiency is associated with many chronic diseases. The VIDA and VITAL trials did not show a protective effect on cardiovascular diseases and cancer. The D2d study also did not influence the progress of prediabetes to diabetes. However, the baseline 25OHD concentrations of the majority of the participants of all these trials were essentially normal. Post‐hoc analysis of these studies suggest some possibly beneficial health outcomes in vitamin D deficient subjects. A meta‐analysis suggested that vitamin D could partly prevent upper respiratory infections. Mendelian randomization studies suggest a causal link between lifelong low vitamin D status and multiple sclerosis. A vitamin D supplement in pregnant women may decrease maternal morbidity and improve the health of their offspring. Better‐designed studies are needed to answer all outstanding questions. However, based on all available data, it seems that correction of vitamin D and/or calcium deficiency of infants, pregnant women and elderly subjects can improve their health. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Objective: Adults aged 50 years and older with epilepsy face an increased risk of fracture associated both with age and with the use of antiepileptic drugs. Lifestyle behaviors, such as physical activity and calcium and vitamin D intake, have been found to be beneficial to bone health. The aim of this study is to investigate these osteoprotective behaviors in people aged 50 years and older with and without epilepsy. Methods: In 2010, the Canadian Community Health Survey (CCHS), a cross‐sectional survey that collects health‐related data nationwide, included a subset of questions related to epilepsy along with the standard items on physical activity, nutrition, and sun exposure. Data on osteoprotective behaviors were extracted and analyzed for adults aged 50 years and older. Results: There were no significant findings related to calcium and vitamin D intake as measured by food choices and sun exposure survey items. People with epilepsy participated in physical activity significantly less often and for significantly shorter duration than people without epilepsy. Significantly fewer people with epilepsy reported intending to increase exercise in the next 12 months as compared to those without epilepsy. Significance: Although adults aged 50 years and older with epilepsy face an increased risk of fracture as compared to those without epilepsy, they do not engage in a higher level of osteoprotective behaviors. In fact, adults with epilepsy are less physically active and report less intention to exercise than adults without epilepsy. [ABSTRACT FROM AUTHOR]

Many older persons lose their mobility and independence due to multiple diseases occurring simultaneously. Geroscience is aimed at developing innovative approaches to better identify relationships among the biological processes of aging. Osteoporosis and sarcopenia are two of the most prevalent chronic diseases in older people, with both conditions sharing overlapping risk factors and pathogenesis. When occurring together, these diseases form a geriatric syndrome termed "osteosarcopenia," which increases the risk of frailty, hospitalizations, and death. Findings from basic and clinical sciences aiming to understand osteosarcopenia have provided evidence of this syndrome as a case of geroscience. Genetic, endocrine, and mechanical stimuli, in addition to fat infiltration, sedentarism, and nutritional deficiencies, affect muscle and bone homeostasis to characterize this syndrome. However, research is in its infancy regarding accurate diagnostic markers and effective treatments with dual effects on muscle and bone. To date, resistance exercise remains the most promising strategy to increase muscle and bone mass, while sufficient quantities of protein, vitamin D, calcium, and creatine may preserve these tissues with aging. More recent findings, from rodent models, suggest treating ectopic fat in muscle and bone marrow as a possible avenue to curb osteosarcopenia, although this needs testing in human clinical trials. [ABSTRACT FROM AUTHOR]

We have previously demonstrated inverse associations between maternal 25(OH)‐vitamin D status and perinatal DNA methylation at the retinoid‐X‐receptor‐alpha (RXRA) locus and between RXRA methylation and offspring bone mass. In this study, we used an existing randomized trial to test the hypothesis that maternal gestational vitamin D supplementation would lead to reduced perinatal RXRA locus DNA methylation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicenter, double‐blind, randomized, placebo‐controlled trial of 1000 IU/day cholecalciferol or matched placebo from 14 weeks' gestation until delivery. Umbilical cord (fetal) tissue was collected at birth and frozen at −80°C (n = 453). Pyrosequencing was used to undertake DNA methylation analysis at 10 CpG sites within the RXRA locus (identified previously). T tests were used to assess differences between treatment groups in methylation at the three most representative CpG sites. Overall, methylation levels were significantly lower in the umbilical cord from offspring of cholecalciferol‐supplemented mothers, reaching statistical significance at four CpG sites, represented by CpG5: mean difference in % methylation between the supplemented and placebo groups was −1.98% (95% CI, −3.65 to −0.32, p = 0.02). ENCODE (Encyclopedia of DNA Elements) evidence supports the functionality of this locus with strong DNase hypersensitivity and enhancer chromatin within biologically relevant cell types including osteoblasts. Enrichment of the enhancer‐related H3K4me1 histone mark is also seen in this region, as are binding sites for a range of transcription factors with roles in cell proliferation, response to stress, and growth factors. Our findings are consistent with previous observational results and provide new evidence that maternal gestational supplementation with cholecalciferol leads to altered perinatal epigenetic marking, informing mechanistic understanding of early life mechanisms related to maternal vitamin D status, epigenetic marks, and bone development. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc. [ABSTRACT FROM AUTHOR]

It is presently unclear whether free serum 25‐hydroxyvitamin D (S‐25(OH)D) better reflects bone health than total S‐25(OH)D. We have previously shown that summer total S‐25(OH)D values are more useful to predict bone mineral density (BMD) than winter values. Our objective was therefore to compare the relative importance of free and total S‐25(OH)D for BMD by season. BMD was measured by dual‐energy X‐ray absorptiometry (DXA) in 5002 Swedish women (mean age 68 years) randomly selected from a large population‐based longitudinal cohort study. Free S‐25(OH)D was analyzed by a commercial ELISA and total S‐25(OH)D by HPLC–tandem mass spectrometry (MS/MS). Free and total S‐25(OH)D co‐varied with season, with 26% and 29% higher values in August compared with those in January–March (nadir). There were no differences in mean BMD between categories of free or total S‐25(OH)D in samples collected during winter. Women with higher total S‐25(OH)D measured during summer had higher BMD at the total hip. Compared with women who had total S‐25(OH)D values above 80 nmol/L during summer, adjusted BMD at the total hip was 6% (95% CI, 1% to 11%) lower for S‐25(OH)D concentrations between 30 and 40 mmol/L, and 11% (95% CI, 3% to 19%) lower for those with total S‐25(OH)D <30 nmol/L. In contrast, free S‐25(OH)D measured during summer was not associated with BMD. Compared with women who had highest free S‐25(OH)D measured during summer (>8.8 pmol/L), those with intermediate (2.4–3.5 pmol/L) and lowest (<2.4 pmol/L) free S‐25(OH)D during summer did not have lower total hip BMD values (3% [95% CI, −2% to 7%] and −2% [95% CI, −8% to 4%]). In addition, we found no added value for the prediction of BMD with the combined measurement of total and free S‐25(OH)D during summer or winter. We conclude that vitamin D status assessed by direct measurements of free S‐25(OH)D does not reflect BMD better than total S‐25(OH)D. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: Most trials of vitamin D supplementation have shown no benefits on bone mineral density (BMD), although severe vitamin D deficiency causes osteomalacia, which is associated with profound BMD deficits. Recently, the ViDA‐BMD study from New Zealand demonstrated a threshold of baseline 25‐hydroxyvitamin D (25OHD; 30 nmol/L) below which vitamin D supplementation did benefit BMD. We have now reexamined data from a similar trial in Aberdeen to determine whether a baseline 25OHD threshold of 30 nmol/L is also observed in that database. The Aberdeen study recruited 305 postmenopausal women in late winter and randomized them to receive placebo, vitamin D 400 IU/d, or vitamin D 1000 IU/d over 1 year. As previously reported, BMD loss at the hip was reduced by vitamin D 1000 IU/d only, and there was no significant treatment effect of either dose at the lumbar spine. In the present analysis, when the trial participants were grouped according to whether their baseline 25OHD was ≤30 nmol/L or above this threshold, significant treatment effects were apparent at both the spine and hip in those with baseline 25OHD ≤30 nmol/L, but no significant effects were apparent in those with baseline 25OHD above this level. There was evidence of a similar threshold for effects on parathyroid hormone, but no groups showed changes in bone turnover markers during the study. It is concluded that vitamin D supplements only increase bone density in adults with nadir 25OHD ≤30 nmol/L. This moves us further toward a trial‐based definition of vitamin D deficiency in adults with adequate calcium intakes and suggests that supplement use should be targeted accordingly. Future trials of vitamin D supplementation should focus on individuals with 25OHD concentrations in this range. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: There is considerable discussion of the importance for increased serum 25‐hydroxyvitamin D (S‐25OHD) concentration associated with adequacy for bone health. Accordingly, whether long‐term high S‐25OHD concentration in general positively affects bone mineral density (BMD) is uncertain. We used a Mendelian randomization design to determine the association between genetically increased S‐25OHD concentrations and BMD. Five single‐nucleotide polymorphisms (SNPs) in or near genes encoding enzymes and carrier proteins involved in vitamin D synthesis or metabolism were used as instrumental variables to genetically predict 1 standard deviation increase in S‐25OHD concentration. Summary statistics data for the associations of the S‐25OHD‐associated SNPs with dual‐energy X‐ray absorptiometry (DXA)‐derived femoral neck and lumbar spine BMD were obtained from the Genetic Factors for Osteoporosis (GEFOS) Consortium (32,965 individuals) and ultrasound‐derived heel estimated BMD from the UK Biobank (142,487 individuals). None of the SNPs were associated with BMD at Bonferroni‐corrected significance level, but there was a suggestive association between rs6013897 near CYP24A1 and femoral neck BMD (p = 0.01). In Mendelian randomization analysis, genetically predicted 1 standard deviation increment of S‐25OHD was not associated with higher femoral neck BMD (SD change in BMD 0.02; 95% confidence interval [CI] –0.03 to 0.07; p = 0.37), lumbar spine BMD (SD change in BMD 0.02; 95% CI –0.04 to 0.08; p = 0.49), or estimated BMD (g/cm2 change in BMD –0.03; 95% CI –0.05 to –0.01; p = 0.02). This study does not support a causal association between long‐term elevated S‐25OHD concentrations and higher BMD in generally healthy populations. These results suggest that more emphasis should be placed on the development of evidence‐based cut‐off points for vitamin D inadequacy rather than a general recommendation to increase S‐25OHD. © 2018 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT: We investigated associations between calcium/vitamin D supplementation and incident cardiovascular events/deaths in a UK population‐based cohort. UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40 to 69 years at recruitment. Supplementation with calcium/vitamin D was self‐reported, and information on incident hospital admission (ICD‐10) for ischemic heart disease (IHD), myocardial infarction (MI), and subsequent death was obtained from linkage to national registers. Cox proportional hazards models were used to investigate longitudinal relationships between calcium/vitamin D supplementation and hospital admission for men/women, controlling for covariates. A total of 475,255 participants (median age 58 years, 55.8% women) had complete data on calcium/vitamin D supplementation. Of that number, 33,437 participants reported taking calcium supplements; 19,089 vitamin D; and 10,007 both. In crude and adjusted analyses, there were no associations between use of calcium supplements and risk of incident hospital admission with either IHD, or subsequent death. Thus, for example, in unadjusted models, the hazard ratio (HR) for admission with myocardial infarction was 0.97 (95% confidence interval [CI] 0.79–1.20, p = 0.79) among women taking calcium supplementation. Corresponding HR for men is 1.16 (95% CI 0.92–1.46, p = 0.22). After full adjustment, HR (95% CI) were 0.82 (0.62–1.07), p = 0.14 among women and 1.12 (0.85–1.48), p = 0.41 among men. Adjusted HR (95% CI) for admission with IHD were 1.05 (0.92–1.19), p = 0.50 among women and 0.97 (0.82–1.15), p = 0.77 among men. Results were similar for vitamin D and combination supplementation. There were no associations with death, and in women, further adjustment for hormone‐replacement therapy use did not alter the associations. In this very large prospective cohort, there was no evidence that use of calcium/vitamin D supplementation was associated with increased risk of hospital admission or death after ischemic cardiovascular events. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Severe vitamin D deficiency causes osteomalacia, yet trials of vitamin D supplementation in the community have not on average demonstrated benefit to bone mineral density (BMD) or fracture risk in adults.Objective: To determine whether monthly high-dose vitamin D supplementation influences BMD in the general population and in those with low 25-hydroxyvitamin D levels.Methods: Two-year substudy of a trial in older community-resident adults. A total of 452 participants were randomized to receive monthly doses of vitamin D3 100 000 IU, or placebo. The primary end-point was change in lumbar spine BMD. Exploratory analyses to identify thresholds of baseline 25-hydroxyvitamin D for vitamin D effects on BMD were prespecified.Results: Intention-to-treat analyses showed no significant treatment effect in the lumbar spine (between-groups difference 0.0071 g cm-2 , 95%CI: -0.0012, 0.0154) or total body but BMD loss at both hip sites was significantly attenuated by ~1/2% over 2 years. There was a significant interaction between baseline 25-hydroxyvitamin D and treatment effect (P = 0.04). With baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 (n = 46), there were between-groups BMD changes at the spine and femoral sites of ~2%, significant in the spine and femoral neck, but there was no effect on total body BMD. When baseline 25-hydroxyvitamin D was >30 nmol L-1 , differences were ~1/2% and significant only at the total hip.Conclusions: This substudy finds no clinically important benefit to BMD from untargeted vitamin D supplementation of older, community-dwelling adults. Exploratory analyses suggest meaningful benefit in those with baseline 25-hydroxyvitamin D ≤ 30 nmol L-1 . This represents a significant step towards a trial-based definition of vitamin D deficiency for bone health in older adults. [ABSTRACT FROM AUTHOR]

Background Serum vitamin D levels have been reported to be associated with individual components of body composition. However, the relationship between serum vitamin D and combined indices of adverse body composition is largely unknown. This cross-sectional study examined the association between serum vitamin D and osteosarcopenic obesity in a nationally representative sample of middle-aged and older adults. Methods We analysed the Korea National Health and Nutrition Examination Surveys (IV and V) conducted in 2008-2010, consisting of 5908 (2485 men, 3423 women) aged ≥ 50 years. Serum vitamin D levels were determined by radioimmunoassay, and body composition was evaluated by dual-energy x-ray absorptiometry. The association between serum vitamin D levels and the number of abnormalities in body composition, including osteosarcopenic obesity, a low bone and muscle mass with concurrent high fat mass, was analysed by multinomial logistic regression adjusting for covariates. Results In men, after controlling for covariates, higher vitamin D levels were associated with a significantly reduced likelihood of the number of phenotypes of adverse body composition ( P for trend < 0.05). Those in the highest tertile group of serum vitamin D levels, compared with those in the lowest tertile, were less likely to have adverse body composition, numbering one (odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.49, 0.92), two (OR = 0.49, 95% CI: 0.33, 0.73), and three (osteosarcopenic obesity; OR = 0.42, 95% CI: 0.26, 0.67). In women, those in the highest tertile group of serum vitamin D levels, compared with those in the lowest tertile, were less likely to have osteosarcopenic obesity (OR = 0.55, 95% CI: 0.33, 0.93). Vitamin D deficiency (<20 ng/mL) in men was significantly associated with an increased likelihood of a higher number of adverse body composition, especially for osteosarcopenic obesity (OR = 2.08, 95% CI: 1.42, 3.03). Vitamin D deficient women, compared with those having normal levels of serum vitamin D, were also more likely to demonstrate osteosarcopenic obesity (OR = 1.99, 95% CI: 1.30, 3.05). Conclusions A high serum vitamin D level in mid- and late-life was associated with reduced odds of multiple adverse body composition, especially osteosarcopenic obesity, suggesting potential health benefits of maintaining adequate levels of vitamin D. [ABSTRACT FROM AUTHOR]

Background: The impact of season when determining a serum 25-hydroxyvitamin D (S-25OHD) cut-off level for optimal bone health is unknown.Objective: To investigate the relative importance of S-25OHD for bone mineral density (BMD) by season.Methods: A subcohort of 5002 Swedish women (mean age 68 years), randomly selected from a large population-based longitudinal cohort study with repeat dietary and lifestyle information, was enrolled during 2003-2009 for a clinical examination, which included dual-energy X-ray absorptiometry and collection of fasting blood samples. Categories of vitamin D status were determined by S-25OHD (measured by HPLC-MS/MS).Results: In samples collected during summer, we found a gradual increase in BMD of the total hip up to a S-25OHD level of 40 nmol L-1 (6% of the cohort). In women with S-25OHD concentrations below 30 nmol L-1 during summer, adjusted BMD was 11% lower [95% confidence interval (CI) 3-19] and in those with S-25OHD levels of 30-40 nmol L-1 BMD was 6% lower (95% CI 1-11), compared with women with S-25OHD levels above 80 nmol L-1 . Low S-25OHD concentrations during summer (<30 nmol L-1 ) were also associated with higher adjusted relative risk of osteoporosis (4.9; 95% CI 2.9-8.4) compared with concentrations above 80 nmol L-1 . By contrast, no differences in mean BMD values between categories of S-25OHD were found during winter.Conclusions: Summer concentrations of S-25OHD appear to be the most useful to predict BMD, whereas winter levels have limited value. To determine a S-25OHD cut-off level for vitamin D deficiency, it may be necessary to take into account the season of blood collection. [ABSTRACT FROM AUTHOR]

Aim: To investigate the impact of new evidence for weight-bearing, bisphosphonates, and vitamin D and calcium interventions, towards updating the systematic review and clinical practice guidelines for osteoporosis in children with cerebral palsy (CP) published in 2011.Method: Computer-assisted literature searches were conducted for articles published from 2010 to 2016. Searches focused on children with CP functioning at Gross Motor Function Classification System levels III to V and limited to weight-bearing activities, bisphosphonates, and vitamin D and/or calcium supplementation. Articles were classified according to the American Academy of Neurology guidelines to update the grading of the evidence for improving bone mineral density (BMD) and decreasing fragility fractures.Results: Six new articles underwent full-text review and data abstraction. These included one weight-bearing, three bisphosphonate, and two mixed intervention studies (bisphosphonate and vitamin D/calcium supplementation). Overall, there continues to be 'probable' evidence for bisphosphonates, 'possible' evidence for vitamin D/calcium, and 'insufficient' evidence for weight-bearing activities as effective interventions to improve low BMD in children with CP. There is 'possible' evidence for bisphosphonates in reducing fragility fractures.Interpretation: The grading of evidence to support the use of weight-bearing activities, bisphosphonates, and vitamin D and calcium supplementation in pediatric CP osteoporosis clinical practice guidelines remained the same. [ABSTRACT FROM AUTHOR]

There is an increasing number of effective therapies for fracture prevention in adults at risk of osteoporosis. However, shortcomings in the evidence underpinning our management of osteoporosis still exist. Evidence of antifracture efficacy in the groups of patients who most commonly use calcium and vitamin D supplements is lacking, the safety of calcium supplements is in doubt, and the safety and efficacy of high doses of vitamin D give cause for concern. Alendronate, risedronate, zoledronate and denosumab have been shown to prevent spine, nonspine and hip fractures; in addition, teriparatide and strontium ranelate prevent both spine and nonspine fractures, and raloxifene and ibandronate prevent spine fractures. However, most trials provide little information regarding long-term efficacy or safety. A particular concern at present is the possibility that oral bisphosphonates might cause atypical femoral fractures. Observational data suggest that the incidence of this type of fracture increases steeply with duration of bisphosphonate use, resulting in concern that the benefit-risk balance may become negative in the long term, particularly in patients in whom the osteoporotic fracture risk is not high. Therefore, reappraisal of ongoing use of bisphosphonates after about 5 years is endorsed by expert consensus, and 'drug holidays' should be considered at this time. Further studies are needed to guide clinical practice in this area. [ABSTRACT FROM AUTHOR]

ABSTRACT Over the past decade, many genome-wide association studies (GWAs) and meta-analyses have identified genes and regions involved in osteoporotic phenotypes. Nevertheless, the large majority of these results were not tested at any functional level. GWA-associated single-nucleotide polymorphisms (SNPs) near candidate genes such as RANK and RANKL suggest that these SNPs and/or other variants nearby may be involved in bone phenotype determination. This study focuses on SNPs along these two genes, which encode proteins with a well-established role in the bone remodeling equilibrium. Thirty-three SNPs, chosen for their location in evolutionary conserved regions or replicated from previous studies, were genotyped in the BARCOS cohort of 1061 postmenopausal women and tested for association with osteoporotic phenotypes. SNP rs9594738, which lies 184 kb upstream of the RANKL gene, was the only SNP found to be associated with a bone phenotype (dominant model: beta coefficient = -0.034, p = 1.5 × 10−4, for lumbar spine bone mineral density). Functional experiments exploring a distal region (DR) of 831 bp that harbors this SNP in a centered position (nt 470) demonstrated its capacity to inhibit the RANKL promoter in reporter gene assays. Remarkably, this DR inhibition was significantly reduced in the presence of vitamin D. In conclusion, the GWA-associated SNP rs9594738 lies in a region involved in transcription regulation through which vitamin D could be regulating RANKL expression and bone mineral density. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ABSTRACT Recently, safety concerns about calcium supplementation have arisen. In this situation, ensuring appropriateness of use is highly important. We aimed to describe the use of calcium and vitamin D supplements, the factors related to it, and to assess the appropriateness of calcium prescription among men and women aged 50 years or older. We performed a cross-sectional study in 2009-2010 including 11,035 adults who belong to the ESOSVAL cohort and attend 272 primary healthcare centers in the Valencia region of Spain. Criteria for the inappropriateness of calcium prescription, based on guidelines and recent evidence, were: excessive or insufficient daily total intake (diet plus supplements), excessive single doses of supplements, excessive or insufficient association with vitamin D, and overall inappropriateness. Calcium and/or vitamin D were prescribed to about 17% of the population. Older age, antiosteoporotic treatment, use of glucocorticoids, and a diagnosis of osteoporosis were related to prescription. The presence of other secondary causes of osteoporosis determined supplementation only in men. Calcium dietary intake was not related to the prescription of supplements. Among calcium users, 85.8% met at least one criterion of inappropriate prescription; 29% had an inappropriate daily total intake mainly resulting from excessive consumption (>2000 mg/day); 53.8% of patients were given calcium supplements in quantities higher than 500 mg per dose; and 38.9% of individuals receiving calcium supplements had inappropriate (absent or below 800 UI/day) vitamin D supplementation (all of them at high risk). In conclusion, we found high inappropriateness of calcium supplementation, mainly because of calcium overdosing, and also to undertreatment and underdosing of vitamin D in high-risk patients. Physicians should be encouraged to assess calcium dietary intakes before supplementation, recommending intake from food whenever possible, and to prescribe low calcium doses and high vitamin D doses when given in fixed-dose combinations, or vitamin D alone when calcium is not necessary. © 2013 American Society for Bone and Mineral Research [ABSTRACT FROM AUTHOR]

Results from previous prospective studies linking serum 25-hydroxyvitamin D (25OHD) with fracture risk have been inconsistent. The present study examined the relationship between serum 25OHD and risk of incident major osteoporotic fracture (hip, spine, radius, and humerus) in older U.S. adults. The study used a pooled cohort of 4749 men and women ages 65 years and older from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) and NHANES 2000-2004. Incident fractures were identified using linked mortality and Medicare records that were obtained for participants from both surveys. Serum 25OHD values were measured by radioimmunoassay in both surveys. Cox proportional hazards models were used to estimate the relative risk (RR) of fracture by serum 25OHD level. There were 525 incident major osteoporotic fractures (287 hip fractures) in the sample. Serum 25OHD was a significant linear predictor of major osteoporotic fracture and significant quadratic predictor of hip fracture in the total sample and among those with less than 10 years of follow-up, but it was not related to risk of either fracture type among those with ≥10 years of follow-up. Major osteoporotic fracture risk was increased by 26% to 27% for each SD decrease in serum 25OHD among those with less than 10 years of follow-up. Serum 25OHD was significantly related to risk of major osteoporotic fractures as a group and to hip fracture alone in this cohort of older U.S. adults from NHANES III and NHANES 2000-2004. However, the predictive utility of serum 25OHD diminished after 10 years. In addition, the relationship appeared to be linear when major osteoporotic fracture risk was considered but quadratic when hip fracture risk was assessed. © 2013 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Osteoporosis is a skeletal disease characterized by a decrease in bone mass and bone quality that predispose an individual to an increased risk of fragility fractures. Evidence demonstrating a positive link between certain dietary patterns (e.g. Mediterranean diet or high consumption of fruits and vegetables) and bone health highlights an opportunity to investigate their potential to protect against the deterioration of bone tissue during ageing. While the list of these phytonutrients is extensive, this review summarizes evidence on some which are commonly consumed and have gained increasing attention over recent years, including lycopene and various polyphenols (e.g. polyphenols from tea, grape seed, citrus fruit, olive and dried plum). Evidence to define a clear link between these phytonutrients and bone health is currently insufficient to generate precise dietary recommendations, owing to mixed findings or a scarcity in clinical data. Moreover, their consumption typically occurs within the context of a diet consisting of a mix of phytonutrients and other nutrients rather than in isolation. Future clinical trials that can apply a robust set of outcome measurements, including the determinants of bone strength, such as bone quantity (i.e. bone mineral density) and bone quality (i.e. bone turnover and bone microarchitecture), will help to provide a more comprehensive outlook on how bone responds to these various phytonutrients. Moreover, future trials that combine these phytonutrients with established bone nutrients (i.e. calcium and vitamin D) are needed to determine whether combined strategies can produce more robust effects on skeletal health. [ABSTRACT FROM AUTHOR]

Key content Osteoporotic fractures are associated with increased morbidity and mortality., Clinical history and bone densitometry can identify individuals at risk for osteoporotic fractures., Treatment is available to prevent and treat osteoporosis., Learning objectives Identify populations at risk for osteoporotic fractures., Make the diagnosis of osteoporosis., Decide appropriate treatment for the prevention or treatment of osteoporosis., Ethical issues Maximising health benefit while minimising financial implications. [ABSTRACT FROM AUTHOR]

Aims Chronic heart failure (CHF) is associated with increased risk of osteoporosis. We investigated the relationship between severity of CHF and bone loss, underlying pathophysiological mechanisms, and the prognostic significance of bone mass changes in heart failure. Methods and results Total body (TB) and femoral (F) bone mineral density (BMD), and T- and Z-scores in the femur were measured in 60 men with CHF (56 ± 11 years) and 13 age-matched men free from CHF. The composite study endpoint was death, implantation of a left ventricular assist device (LVAD), or inotrope dependency during a median 2-year follow-up. Parathyroid hormone (PTH) and vitamin D were measured in all subjects. TBBMD, FBMD, T-score, and Z-score were significantly lower in men with CHF. Their PTH levels were also significantly increased (111 ± 59 vs. 39 ± 14; P < 0.001). Patients in New York Heart Association classes III–IV compared with those in classes I–II demonstrated significantly lower TBBMD, FBMD, T-score, and Z-score, and higher PTH (136 ± 69 vs. 86 ± 31; P= 0.001). Increased PTH levels were correlated with reduced TBBMD (P = 0.003), FBMD (P = 0.002), and femur T-score (P = 0.001), reduced cardiac index (P = 0.01) and VO2 peak (P < 0.0001), and increased wedge pressure (P = 0.001). Low TBBMD [hazard ratio (HR) 0.003, 95% confidence interval (CI) 0.00–0.58; P = 0.03] and Z-score (HR 0.56, 95% CI 0.35–0.90; P = 0.017) were associated with adverse outcome. Conclusions Secondary hyperparathyroidism and reduction in bone density occur in CHF patients and are associated with disease severity. Increased bone mass loss in CHF has prognostic significance. [ABSTRACT FROM PUBLISHER]

In this article the authors highlight the lack of evidence base to support the notion that vitamin D supplementation prevents or reduces rheumatoid arthritis (RA) disease activity while emphasizing on the need for large studies in the area. They note that the observational trials linking low circulating 25-hydroxyvitamin D (25[OH]D) levels to RA and other medical conditions are likely to undergo reverse causality and residual confounding.

Most osteoporosis drugs act by inhibiting bone resorption. A need exists for osteoporosis therapies that stimulate new bone formation. 2-Methylene-19-nor-(20 S)-1α,25-dihydroxyvitamin D (2MD) is a vitamin D analogue that potently stimulates bone formation activity in vitro and in the ovariectomized rat model. In this randomized, double-blind, placebo-controlled study of osteopenic women, the effect of daily oral treatment with 2MD on bone mineral density (BMD), serum markers of bone turnover, and safety were assessed over 1 year. Volunteers were randomly assigned to three treatment groups: placebo ( n = 50), 220 ng of 2MD ( n = 54), and 440 ng of 2MD ( n = 53). In general, 2MD was well tolerated. Although 2MD caused a marked increase in markers of bone formation, it did not significantly increase BMD. Since 2MD also shows marked activity on bone resorption (as revealed by dose-dependent increases in serum C-telopeptide cross-links of type I collagen in this study), 2MD likely stimulated both bone formation and bone resorption, thereby increasing bone remodeling. © 2011 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article presents a study that investigated the effects of a nonsecosteroidal vitamin D receptor (VDR) ligand on hypercalcemia. The results of the study showed that by histomorphometry, it was revealed that VDRM2 caused the growth of the cortical bone area and introduced periosteal bone-formation rate with relation to OVX. The eroded surface of trabecular bone surfaces were suppressed by VDRM2 at normal serum dosage levels of calcium. The data suggest the potency of vitamin D analogues over VDRM2, but the latter has a margin of greater safety.

The article discusses the use of histomorphometric analysis of iliac crest bone biopsies in measuring skeletal health, which is only measurable by the index of the parathyroid hormone. The use of iliac crest bone biopsies is also seen to address the required minimum 25-Hydroxyvitamin D level. In a study that examined 675 male and female iliac crest biopsies, it was found that 36.151% of them was seen with more than 20% of osteoid surface per bone surface while 25.63% of the participants was seen with higher osteoid volume per bone volume.

The article presents a study which suggests that maternal vitamin D insufficiency can influence fetal femoral development as early as 19 weeks' gestation. To determine whether maternal vitamin D insufficiency affects fetal femur growth, the researchers looked at 424 pregnant within a prospective longitudinal study of maternal nutrition and lifestyle before and during pregnancy. They found that lower maternal 25-hydroxyvitamin vitamin D concentration was associated with greater femoral metaphyseal cross-sectional area and higher femoral splaying index.

This article discusses the complementary effects of parathyroid hormone and 1,25(OH)2D in the maintenance of bone metabolism. The effect of parathyroid hormone administration in 1α(OH)ase-/-, that lacked the genetic receptors for 1,25(OH)2D, is considered. These transgenic mice displayed lower levels of bone growth than wild type mice under similar circumstances.

Background Osteoporosis is a recognized complication of inflammatory bowel disease (IBD). Aim To investigate the role of environmental factors and vitamin D receptor (VDR) variants on the prevalence of osteoporosis. Methods DEXA scans and case note review were performed on 440 IBD patients from 1997 to 2006. All the IBD patients and 240 healthy controls were genotyped for VDR variants Taq-1 and Apa-1 using PCR-RFLP. Results Osteoporosis and osteopenia rates were 15% and 18% for IBD, 16% and 18% for Crohn’s disease (CD) and 13% and 19% for ulcerative colitis, respectively. On univariate analysis of the CD patients, low body mass index (BMI, <18.5) and smoking status ( P = 0.008 and 0.005 respectively) were associated with osteoporosis and osteopenia. Low BMI was also associated with osteoporosis on multivariate analysis in CD ( P = 0.021, OR 5.83, CI 1.31–25.94). No difference was observed between Taq-1 and Apa-1 VDR polymorphisms in IBD, CD, ulcerative colitis and healthy controls. However, CD males were more likely to carry the variant Taq-1 polymorphism than healthy controls males ( P = 0.0018, OR 1.94, CI 1.28–2.92) and female CD patients ( P = 0.0061, OR 1.60, CI 1.17–2.44). Conclusions In this well-phenotyped cohort of IBD patients, a relatively low prevalence of osteoporosis was observed. Low BMI was the only independent risk factor identified to be associated with osteoporosis. [ABSTRACT FROM AUTHOR]

The article cites a case study on the implications of Serum 25-Hydroxyvitamin D on the hip fracture risk of older Americans. It used 156 incident hip fracture cases that were presented with lower bone mineral density (BMD) and body mass index with prevalent spine or wrist fractures and weight loss. Serum 25 (OH) D was associated with a significant lower hip fracture risk in the older population, while those values that exceeded 60 nanometers were linked with health benefits.

The article investigates the putative beneficial role of high dietary vitamin K1 (phylloquinone) on bone mineral density (BMD) and the vitamin D3 plus calcium on the bone health of older women in Scotland. The study uses a 2-year double-blind, placebo-controlled trial in several healthy Scottish women aged more than 60 years old. The results showed a significant and sustained increase in both bone mineral density and content at the site of the ultradistal radius.

Introduction. Vitamin D is essential for calcium metabolism as well as for fracture prevention, and a recent review suggested that the optimal serum 25(OH)D lies in the region of 50–80 nmol L−1 (20–32 ng mL−1). A high prevalence of inadequacy has been reported in many studies but the prevalence of inadequacy amongst women with osteoporosis in different regions of the world has not been well characterized. Setting and subjects. A multinational study of 18 countries at various latitudes (range 64N–38S) was conducted in 2004 and 2005 to determine the average levels of serum 25(OH)D and the prevalence of vitamin D inadequacy. A total of 2606 postmenopausal women with osteoporosis (low bone mineral density, history of fragility fracture) seeking routine medical care were enrolled and serum 25(OH)D levels were measured at a single laboratory visit. Results. Mean serum 25(OH)D level was 26.8 ng mL−1 (SE 0.3) and ranged from 7 to 243 ng mL−1. Regional mean values were highest in Latin America (29.6 ng mL−1, SE 0.6) and lowest in the Middle East (20.4 ng mL−1, SE 0.5). Overall, 64% of women had serum levels <30 ng mL−1. Serum parathyroid hormone reached a nadir at serum 25(OH)D levels >35 ng mL−1. In nonequatorial countries, women recruited during the winter months had somewhat lower serum 25(OH)D levels than those recruited during the summer months in some, but not all, countries. Conclusions. Low levels of serum 25(OH)D are common amongst women with osteoporosis. The results underscore the value of assuring vitamin D adequacy in these women. [ABSTRACT FROM AUTHOR]

Combined calcium and vitamin D supplementation is an essential component of the management of osteoporosis, supported by a strong scientific rationale. The types of individuals who should receive calcium and vitamin D supplements are those: (i) patients with documented osteoporosis receiving antiresorptive or anabolic treatment; (ii) patients receiving glucocorticoids; and (iii) individuals with or at high risk of calcium and/or vitamin D insufficiencies, in particular older women and men. This article describes the evidence base that supports targeting these groups. Benefits are most apparent when 800 IU day−1 vitamin D is complemented with a dose of 1000–1200 mg day−1 elemental calcium. Compliance is also key to optimizing clinical efficacy. [ABSTRACT FROM AUTHOR]

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost. The increase in fracture rate with age is believed to result predominantly from age-related increases in the incidence of osteoporosis and falls. This article reviews the evidence for the use of vitamin D and bisphosphonates for the prevention of bone fractures and osteoporosis in elderly patients. [ABSTRACT FROM AUTHOR]

To determine the influence of the vitamin D receptor (VDR) gene FokI and BsmI genotype on bone mineral density response to two exercise training modalities, 206 healthy men and women (50–81 years old) were studied before and after ∼5–6 months of either aerobic exercise training (AT) or strength training (ST). A totla of 123 subjects completed AT (51 men, 72 women) and 83 subjects completed ST (40 men, 43 women). DNA was extracted from blood samples of all subjects and genotyping was performed at the VDR FokI and BsmI locus to determine its association to training response. Total body, greater trochanter and femoral neck bone mineral density (BMD) were measured before and after both training programmes using dual-energy X-ray absorptiometry. VDR BsmI genotype was not significantly related to BMD at baseline or after ST or AT. However, VDR FokI genotype was significantly related to ST- but not AT-induced changes in femoral neck BMD ( P < 0.05). The heterozygotes (Ff) in the ST group approached a significantly greater increase in femoral neck BMD ( P= 0.058) compared to f homozygotes. There were no significant genotype relationships in the AT group. These data indicate that VDR FokI genotype may influence femoral neck BMD response to ST, but not AT. [ABSTRACT FROM AUTHOR]

Presents an index of terms used in the December 2002 issue of 'Ailment Pharmacology Therapeutics.' Alpha-antagonist; Adenosine triphosphate; Ampicillin; Amoxicillin; Antibiotic prophylaxis; Anticonvulsants; Antidepressants; Bisacodyl; Cyclo-oxygenase; Cytosolic hepatic function; Colonic motility; Complementary therapy.

Objectives: The aims of the study were to quantify the prevalence of asymptomatic coeliac disease (CD) in a cohort of osteoporotic females, and to investigate the features of bone loss.Design and Subjects: We studied 255 women (mean age 66.6 +/- 8.5 SD) with primary osteoporosis (WHO diagnostic criteria). After the first CD screening with the measure of serum IgG antigliadin antibodies (IgG-AGA), 53 women showed a positive test: antibodies to tissue transglutaminase (TG-ab) were subsequently determined to confirm the diagnosis of CD. Bone metabolism was evaluated by: serum and urinary calcium, serum and urinary phosphate, serum alkaline phosphatase, urinary crosslaps, serum 25(OH)D and serum parathyroid hormone.Results: High levels of IgG-AGA and TG-ab were observed in 24 patients with a prevalence of serological disease of 9.4%. These women were characterized, in comparison with the other patients, by a statistically significant reduction in serum 25(OH)D (17.8 +/- 7.2 vs. 55.1 +/- 20.3 nmol L(-1), P < 0.01) together with a significant increase of iPTH (65.1 +/- 29.7 vs. 35.1 +/- 20.0 pg mL(-1); P < 0.01). Patients with high TG-ab levels showed also slightly raised values of urinary crosslaps (288 +/- 88 vs. 270 +/- 90 microm mol(-1) Cr). In IgG-AG positive patients a statistically significant inverse correlation was found between 25(OH)D serum levels and log-transformed TG-ab values (r: -0.95, P < 0.001). Intestinal biopsies were obtained in 10 TG-ab positive women and verified CD in six patients.Conclusions: These data support the hypothesis that patients with undiagnosed celiac disease develop high remodelling processes related to calcium malabsorption, secondary hyperparathyroidism and unavailability of vitamin D with a consequent more marked bone loss. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence of hypovitaminosis D [serum 25(OH)D < or = 37 nmol L-1)] in Finnish medical in- and outpatients in a cross-sectional study.Methods: The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured.Results: Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L(-1) or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L(-1) or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males.Conclusion: Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population. [ABSTRACT FROM AUTHOR]

This study examined the association between bone mineral density (BMD) and a T/C polymorphism in the first of the two initiation codons in the vitamin D receptor (VDR) gene. The polymorphism was detected using the restriction enzyme FokI, the F allele indicating absence of the first codon and the f allele its presence. The FokI genotype was determined in 124 postmenopausal osteoporotic French women who were 45–90 years old. The distribution of FokI genotypes in the osteoporotics did not differ significantly from that found in a control group. There were no significant differences by FokI genotype groups in our total sample of osteoporotic women for age, years since menopause, height, weight, and BMD at lumbar spine and femoral neck. However, when only those patients under the age of 75 years are analysed (98 subjects), those with the ff genotype (10% of the population) had a significantly lower BMD at the femoral neck than FF and Ff subjects. This suggests that the ff genotype of the VDR gene correlates with decreased BMD at the femoral neck in French postmenopausal women. [ABSTRACT FROM AUTHOR]