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Summary: This study aimed to investigate the bone impairment in finger joints in PHO patients by HR-pQCT. Results showed distinguished differences in bone architecture and biomechanics parameters at DIPs between PHO patients and healthy controls using HR-pQCT assessment. Besides, serum PGE2, hsCRP and ESR levels were found negatively correlated with total vBMD. Introduction: This study aimed to investigate the bone impairment in finger joints in primary hypertrophic osteoarthropathy (PHO) patients firstly by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: Fifteen PHO patients and 15 healthy controls were enrolled in this study. Bone erosions in hands at distal interphalangeal joints (DIPs) in both PHO patients and controls were evaluated by X-ray. Bone geometry, vBMD, microstructure parameters, and size of individual bone erosion were also measured at the 3rd DIP by HR-pQCT as well. Blood biochemistry levels between the two groups were also compared. Results: Compared to X-ray, HR-pQCT assessment were more sensitive for detection of bone erosions, with 14 PHO patients by HR-pQCT versus ten PHO patients by X-ray judged at the 3rd DIP. The average depth, width, and volume of erosions size in PHO patients were 1.38 ± 0.80 mm, 0.79 ± 0.27 mm, and 1.71 ± 0.52 mm3, respectively. The bone cross-areas including total area (+ 25.3%, p ≤ 0.05), trabecular area (+ 56.2%, p ≤ 0.05), and cortical perimeter (+ 10.7%, p ≤ 0.05) at the defined region of interest of 3rd DIP was significantly larger than controls. Total vBMD was 11.9% lower in PHO patients compared with the controls (p ≤ 0.05). Biochemical test results showed the increased levels of inflammatory cytokines, bone resorption markers, and joint degeneration markers in PHO patients. Serum prostaglandin PGE2, high-sensitive C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) levels were found negatively correlated with total vBMD. Conclusions: This study demonstrated higher sensitivity of the HR-pQCT measurement at DIPs by showing the differences in architecture and biomechanics parameters at DIPs between the PHO patients and healthy controls, which would be of interest clinically to investigate bone deterioration in PHO patients. [ABSTRACT FROM AUTHOR]

Summary: This study aims to detect whether there remains valuable prognostic information in fluctuation of red cell distribution width (RDW) in hip fracture patients. Results show that this readily available parameter may provide a more effective strategy for assessment of mortality risk, therefore providing a reference for clinical planning and decision-making.Introduction: Prognostic values have been found in the fluctuation of some hematologic parameters. The red cell distribution width (RDW) routinely reported with all complete blood cell counts (CBC) has proven to be associated with poor outcomes in various diseases. However, whether the fluctuation in RDW is predictive of long-term mortality in hip fracture patients treated with surgery remains unknown.Methods: One thousand three hundred thirty hip fracture patients who underwent surgery from January 1, 2000 to November 18, 2012 were recruited in this prospective cohort study. Fluctuation in the RDW between admission and discharge was measured, and a Kaplan-Meier (KM) analysis and multivariable Cox regression model were applied to evaluate the relationship between this fluctuation and mortality. Risk factors for a larger fluctuation were detected by using Logistic regression analyses.Results: In addition to the admission RDW, a high RDW level at the time of discharge was also associated with an increased risk of death, while no significant difference was found in the postoperative RDW. Fluctuation in the RDW between admission and discharge was an independent risk predictor for 2-year mortality (HR 1.45 95%CI 1.06-2.00, p = 0.022). Factors affecting the change in the RDW between admission and discharge included both the demographic characteristics of the patients and clinical interventions.Conclusion: Hip fracture patients who experience a greater fluctuation in RDW during the hospital course are at a heightened risk for 2-year all-cause mortality. [ABSTRACT FROM AUTHOR]

Summary: Pregnancy was found to be a skeletal risk factor promoting the initial onset of previously unrecognized monogenic bone disorders, thus explaining a proportion of cases with pregnancy-associated osteoporosis. Therapeutic measures should focus in particular on the normalization of the disturbed calcium homeostasis in order to enable the partial skeletal recovery.Introduction: Pregnancy-associated osteoporosis (PAO) is a rare skeletal condition, which is characterized by a reduction in bone mineral density (BMD) in the course of pregnancy and lactation. Typical symptoms include vertebral compression fractures and transient osteoporosis of the hip. Since the etiology is not well understood, this prospective study was conducted in order to elucidate the relevance of pathogenic gene variants for the development of PAO.Methods: Seven consecutive cases with the diagnosis of PAO underwent a skeletal assessment (blood tests, DXA, HR-pQCT) and a comprehensive genetic analysis using a custom-designed gene panel.Results: All cases showed a reduced BMD (DXA T-score, lumbar spine − 3.2 ± 1.0; left femur − 2.2 ± 0.5; right femur − 1.9 ± 0.5), while the spine was affected more severely (p < 0.05). The trabecular and cortical thickness was overall reduced in HR-pQCT, while the trabecular number showed no alterations in most cases. The genetic analysis revealed three novel mutations in LRP5, COL1A1, and COL1A2.Conclusion: Our data show that previously unrecognized monogenic bone disorders play an important role in PAO. Pregnancy should be considered a skeletal risk factor, which can promote the initial clinical onset of such skeletal disorders. The underlying increased calcium demand is essential in terms of prophylactic and therapeutic measures, which are especially required in individuals with a genetically determined low bone mass. The implementation of this knowledge in clinical practice can enable the partial recovery of the skeleton. Consistent genetic studies are needed to analyze the frequency of pathogenic variants in women with PAO. [ABSTRACT FROM AUTHOR]

Summary: This study explores bone marrow function in patients with defective WNT1 signaling. Bone marrow samples showed increased reticulin and altered granulopoiesis while overall hematopoiesis was normal. Findings did not associate with severity of osteoporosis. These observations provide new insight into the role of WNT signaling in bone marrow homeostasis.Introduction: WNT signaling regulates bone homeostasis and survival and self-renewal of hematopoietic stem cells. Aberrant activation may lead to osteoporosis and bone marrow pathology. We aimed to explore bone marrow findings in a large family with early-onset osteoporosis due to a heterozygous WNT1 mutation.Methods: We analyzed peripheral blood samples, and bone marrow aspirates and biopsies from 10 subjects with WNT1 mutation p.C218G. One subject was previously diagnosed with idiopathic myelofibrosis and others had no previously diagnosed hematologic disorders. The findings were correlated with the skeletal phenotype, as evaluated by number of peripheral and spinal fractures and bone mineral density.Results: Peripheral blood samples showed no abnormalities in cell counts, morphology or distributions but mild increase in platelet count. Bone marrow aspirates (from 8/10 subjects) showed mild decrease in bone marrow iron storages in 6 and variation in cell distributions in 5 subjects. Bone marrow biopsies (from 6/10 subjects) showed increased bone marrow reticulin (grade MF-2 in the myelofibrosis subject and grade MF-1 in 4 others), and an increase in overall, and a shift towards early-phase, granulopoiesis. The bone marrow findings did not associate with the severity of skeletal phenotype.Conclusions: Defective WNT signaling associates with a mild increase in bone marrow reticulin and may predispose to myelofibrosis, while overall hematopoiesis and peripheral blood values are unaltered in individuals with a WNT1 mutation. In this family with WNT1 osteoporosis, bone marrow findings were not related to the severity of osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: Discontinuation of denosumab (Dmab) therapy is associated with lower serum CTX levels in osteoporotic patients previously exposed to bisphosphonates compared to those who were not. Introduction: Discontinuation of Dmab therapy is followed by a transient increase of bone turnover markers (BTMs) above pretreatment values, together with accelerated bone loss, and potentially an increased risk of multiple vertebral fractures. Since a substantial proportion of patients discontinuing Dmab have previously been exposed to bisphosphonates (BPs), we hypothesized that previous BP therapy could attenuate this increase in bone turnover because of the prolonged biological effects of BPs on bone. Methods: In a retrospective observation, we assessed serum CTX levels between 7 and 24 months after the last Dmab injection in 37 patients (33 women and 4 men, aged 50 to 84 years). CTX levels were analyzed according to the number of Dmab injections (1 or multiple) and previous exposure to BPs. Results: In 8 patients who had received only 1 Dmab injection, 7 out of 8 were previously on BPs and none of them showed CTX values above the premenopausal range after Dmab discontinuation. CTX also remained in the premenopausal range in 14 out of 17 patients who discontinued Dmab after multiple (4.1 ± 1.4, range 2-7) injections but were previously exposed to BPs (mean exposure 6.9 ± 5.8 years, range 11 months-15 years; mean time interval between BP exposure and Dmab initiation 25 ± 10 months, range 0-48). In contrast, in 12 patients who discontinued Dmab after multiple (5, range 3-9) injections without prior exposure to BPs, mean CTX levels as measured on average 11.3 months (range 6-23) after the last Dmab injection were above the upper limit of premenopausal range (mean +114%, range 28-320%, p = 0.003-0.005 vs previous BPs). Conclusion: The higher CTX levels occurring after Dmab discontinuation in patients who have received multiple injections may be prevented by prior exposure to BPs. This observation may be related to the persistent effects of BPs on bone that prevent the resorbing activity of newly formed osteoclasts when RANK Ligand is no more antagonized. [ABSTRACT FROM AUTHOR]

Summary: In a random sample of postmenopausal Chinese women, the prevalence of radiographic vertebral fractures increased from 13% between ages 50 and 59 to over 50% after age 80 years. A model with seven clinical risk factors predicted the probability of vertebral fractures as well with as without BMD and better than a model with only three risk factors. More than half an hour of outdoor activity per day might correlate with lower risk of vertebral fracture in this population. Introduction: We aimed to describe the prevalence and develop a model for prediction of radiographic vertebral fractures in a large random sample of postmenopausal Chinese women. Methods: We enrolled 1760 women from an age-stratified random sample of postmenopausal women in Beijing, China. The presence of vertebral fracture was assessed by semi-quantitative grading of lateral thoracolumbar radiographs, risk factors by interview, bone mineral density (BMD) of the proximal femur and lumbar spine by dual x-ray absorptiometry (DXA), and markers of bone turnover from a fasting blood sample. Associations of these factors were analyzed in logistic models and discrimination by areas of receiver operating characteristics curves (AUC). Results: The prevalence of vertebral fracture, ranged from 13.4% ages 50 to 59 years old to 58.1% at age 80 years or older. Older age, a history of non-vertebral fracture, lower femoral neck BMD T-score, body mass index (BMI), height loss, housework, and less than half an hour of outdoor activity were significantly associated with increased probability of having a vertebral fracture. A model with those seven factors had a similar AUC with or without BMD and performed better than a simple model with three factors. Conclusion: This study is from a true random sample of postmenopausal women in urban China with high response rate. The prevalence of vertebral fractures in postmenopausal women in Beijing increases from 13% under age 60 to over 50% by age 80 years. A model with seven clinical risk factors with or without BMD is better than simple models and may guide the use of spine x-rays to identify women with vertebral fractures. More than half an hour of outdoor activity might correlate with lower risk of vertebral fracture in this population. [ABSTRACT FROM AUTHOR]

Summary: In this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms. Introduction: Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP. Methods: We assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients. Results: Clinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP. Conclusion: Adult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms. [ABSTRACT FROM AUTHOR]

Summary: There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis. Introduction: Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators. Methods: Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group. Results: At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes. Conclusions: RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process. [ABSTRACT FROM AUTHOR]

Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with whole-body bone mineral density (WBMD) in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Introduction: This study aims to investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates ( r values ranging from 0.174 to 0.254, all p < 0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. [ABSTRACT FROM AUTHOR]

Summary: The prognostic value of red cell distribution width (RDW) and a combination of RDW and the American Society of Anesthesiologists (ASA) score for long-term hip fracture mortality remains unknown. Our data showed that both RDW and ASA were independent risk predictors. A combination of these two parameters may provide a more powerful strategy for the prediction of hip fracture mortality. Introduction: Red cell distribution width (RDW) has recently been suggested as an independent predictor of prognosis in a variety of disorders. The American Society of Anesthesiologists (ASA) system has been widely used to stratify patients for outcome evaluations. However, the prognostic value of RDW and a combination of RDW and the ASA score for long-term hip fracture mortality has yet to be studied. Methods: This prospective cohort study included 1402 subjects from 2000 to 2011 with a follow-up study over a 2 year period. Cox proportional hazards models with a bootstrap validation were used to evaluate associations of RDW, ASA, and a combination of both with long-term mortality. The global fit and the area under the receiver operating characteristic (ROC) curve (AUC) for model discrimination were further analyzed. Results: Both RDW and ASA exhibited as independent risk predictors of 2-year mortality. The population with elevation of either RDW or ASA increased the risk of mortality (bootstrap validated hazard ratio (HR) 1.971 95 % confidence interval (CI) [1.336-3.005] p < 0.01) while those with an increase in both assessments (bootstrap validated HR 2.667 95 % CI [1.526-4.515] p < 0.01) were at the highest risk for mortality. The addition of the combination of ASA and RDW improved the discrimination power of risk prediction models (AUC increased from 0.700 to 0.723, p < 0.05). Conclusion: Both RDW and ASA exhibited as independent risk predictors of 2-year hip fracture mortality. The combination of these two readily available parameters may provide a more powerful and effective strategy for the assessment of all-cause mortality in hip fracture patients. [ABSTRACT FROM AUTHOR]

Summary: We compared temporal trends in serum 25-hydroxyvitamin D and parathyroid hormone (PTH) in two primary hyperparathyroidism (PHPT) cohorts recruited 20 years apart. The prevalence of 25-hydroxyvitamin D levels <20 and <30 ng/mL declined by 30-50 %, respectively, and was accompanied by lower PTH. In the older cohort, higher PTH may be due to lower 25-hydroxyvitamin D. Introduction: Vitamin D deficiency may exacerbate PHPT. Whether there have been temporal trends in 25-hydroxyvitamin D (25OHD) levels in PHPT is unclear. The prevalence of low vitamin D levels (25OHD <20 and <30 ng/mL) and associated biochemical and bone mineral density (BMD) profiles were assessed in two PHPT cohorts recruited over 20 years apart. Methods: This is a cross-sectional comparison of serum 25OHD levels, calciotropic hormones, and BMD between two PHPT cohorts recruited at the same hospital: the 'old' ( N = 103) and 'new' ( N = 100) cohorts were enrolled between 1984 and 1991 and between 2010 and 2014, respectively. Results: Mean 25OHD levels were 26 % higher in the new cohort (23 ± 10 vs. 29 ± 10 ng/mL, p < 0.0001). Levels of 25OHD <20 and <30 ng/mL declined from 46 and 82 %, respectively, to 19 and 54 % (both p < 0.0001). Supplemental vitamin D use was common in the new (64 %) but not the old cohort (0 %). The new cohort demonstrated 33 % lower serum PTH levels ( p < 0.0001). Neither serum nor urine calcium differed. BMD was higher in the new cohort at all skeletal sites (all p < 0.001). Conclusion: With the rise in vitamin D supplementation over the last two decades, low 25OHD levels are no longer common in PHPT patients in the New York area. Those with 25OHD <20 and <30 ng/mL have declined by over 50 and 30 %, respectively. The lower mean PTH levels in the new cohort are most likely accounted for by higher vitamin D intake. Whether improved vitamin D status also underlies the relatively higher BMD in the more vitamin D replete cohort of PHPT patients is unknown. [ABSTRACT FROM AUTHOR]

Summary: Oxytocin, a neurohypophysial hormone, regulates bone metabolism in animal studies and postmenopausal women. In men, oxytocin is not associated with bone mineral density, bone turnover markers, or prevalent fractures, but weakly negatively with incident fragility fracture requiring further studies. Introduction: We previously showed that serum oxytocin (OT) level is associated with bone mineral density (BMD) and bone turnover rate in postmenopausal women. The aim of our study was to assess the relationship between circulating OT levels and bone status in men. Methods: In 552 men aged 50 and older from the MINOS cohort, we measured serum levels of OT. We assessed the association of serum OT levels with BMD (lumbar, femoral neck, total hip), bone turnover markers (BTM) (serum N-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (bone ALP), and C-terminal telopeptide of type I collagen (CTX-I)) and fracture risk. Results: In the univariate analysis, serum OT level was not associated with BMD at any site, BTM levels, or with prevalent or incident fracture. OT was significantly correlated with body mass index (BMI) ( r = 0.17, p < 0.001), total or bioavalaible 17β-estradiol ( r = 0.09, p = 0.04 and r = 0.20, p < 0.001, respectively), free testosterone ( r = 0.17, p < 0.001), and leptin ( r = 0.16, p < 0.001). Multivariate analysis did not show significant relationship between serum OT and BMD. After adjustment for age, BMI, interaction BMI/age, history of fall in the last year, and BMD, OT and prevalent fracture were not associated. By contrast, the same analysis with additional adjustment for prevalent fracture showed a weakly significant negative association between OT and incident fracture, e.g., after adjustment for femoral neck BMD, HR = 0.73, 95 %CI 0.55-0.99, p = 0.04. Conclusion: In men, serum OT levels are not associated with BMD, bone turnover rate, or prevalent fractures. The weak negative relationship with fracture risk requires further studies. [ABSTRACT FROM AUTHOR]

Summary: In a population of postmenopausal women with a fragility fracture, we found a drastic reduction in the proportion of women with severe (<25 nmol/L) and moderate (25 to 75 nmol/L) hypovitaminosis D, especially from 2009 onwards. These results show that supplementation has been very widely integrated into current practice. Introduction: Vitamin D (25(OH)D) is essential for bone health. In institutionalised osteoporotic women, it reduces the risk of fragility fractures. Numerous articles suggesting the possibility of extraosseous effects have generated a growing number of publications and recommendations on more widespread administration, to limit the risks of moderate or severe hypovitaminosis D. We assessed the impact on clinical practice of these recommendations concerning 25(OH)D supplementation in elderly at-risk populations. Methods: A total of 1486 postmenopausal osteoporotic women were seen in the context of a fracture liaison service (i.e. a rheumatology consultation following a peripheral fragility fracture), between May 2005 and December 2012. Of these, 1107 had a 25(OH)D assay (femur, n = 520; humerus, n = 207; wrist, n = 380). Results: The average age of the total population was 76.7 ± 9.9 years, while for women with an available 25(OH)D assay, the average age was 75.1 ± 11.8 years. The average 25(OH)D (nmol/L) level was similar for the three fracture sites: femur, 30 ± 36.2; humerus, 27.5 ± 24; and wrist, 31 ± 26. A drastic reduction in the proportion of women with severe (<25 nmol/L) and moderate (25 to 75 nmol/L) hypovitaminosis D was observed, especially from 2009 onwards, with a mean prevalence of 69 and 30 % respectively before that year and 35 and 52 % thereafter. Conversely, the proportion of women with 25(OH)D at the threshold value of 75 nmol/L increased from 1.2 to 24 %. Overall, mean serum 25(OH)D levels were significantly higher when comparing the two periods 2005-2008 and 2009-1012 (17.6 ± 14.6 and 48.4 ± 39.2 nmol/L, respectively; p < 0.0001). Conclusion: These results show that supplementation has been very widely integrated into current practice. We can expect it to yield beneficial effects in osseous and extraosseous terms in osteoporotic women, particularly the very elderly. [ABSTRACT FROM AUTHOR]

Summary: African ancestry is associated with low vitamin D levels but high bone density. Fifty percent of African immigrants had low vitamin D levels, but <10 % had evidence of deficiency. The value of providing vitamin D supplementation to African immigrants without evidence of deficiency needs to be determined. Introduction: The Endocrine Society and Institute of Medicine (IOM) have concluded from studies in largely white populations that 25(OH)D is necessary for bone health. However, their definition of vitamin D insufficiency differs. The Endocrine Society recommends a 25(OH)D threshold of <30 ng/mL. The IOM uses a lower threshold of 25(OH)D of <20 ng/mL. As African ancestry is associated with decreased 25(OH)D but increased bone mineral density (BMD), the applicability of these thresholds to Africans is unknown. Therefore, we examined in African immigrants the relationship of 25(OH)D to parathyroid hormone (PTH) and BMD. Methods: One hundred eighty-six African immigrants(69 % male, age 38 ± 10 (mean ± SD), range 20-64 years) living in metropolitan Washington, DC, were enrolled. BMD was determined from whole-body dual-energy X-ray absorptiometry (DXA) scans. Decreased BMD required T-scores ≤−1.0. The threshold for low 25(OH)D was the concentration of 25(OH)D at which PTH became suppressed. This is known as the inflection point. Biochemical deficiency required low 25(OH)D and PTH of >65 pg/mL. Clinical deficiency required low 25(OH)D and T-scores ≤−1.0. Results: 25(OH)D <30 and <20 ng/mL occurred in 83 and 46 % of African immigrants, respectively. PTH inversely correlated with 25(OH)D ( r = −0.31, P = 0.002). The inflection point occurred at a 25(OH)D concentration of 20 ng/mL. Biochemical and clinical deficiency occurred in only 8 and 3 % of immigrants, respectively. Conclusion: As PTH became suppressed at 25(OH)D of 20 ng/mL, the 25(OH)D <20 ng/mL threshold for insufficiency may apply to African immigrants. However, ~50 % of African immigrants have 25(OH)D <20 ng/mL, but only <10 % had evidence of deficiency. The value of providing vitamin D supplementation to the large number of African immigrants with 25(OH)D <20 ng/mL and no detectable evidence of deficiency needs to be determined. [ABSTRACT FROM AUTHOR]

Summary: In this 3-year population-based cohort study, among 1346 subjects, the mean annual change in the serum 25-hydroxyvitamin D levels was 7.6 %/year, which tended to increase during the 3-year period. Multivariate regression analysis indicated that the L2-4 bone mineral density and total daily energy intake were significant independent associated factors. Introduction: The aim of this study was to clarify the change rate of the serum levels of 25-hydroxyvitamin D (25D) and the associated factors in a general Japanese population during a 3-year period. Methods: The baseline survey of Research on Osteoarthritis/osteoporosis Against Disability study (ROAD), a large-scale population-based cohort study, was performed between 2005 and 2007, and a follow-up survey was repeated 3 years later. Among 1690 participants at baseline, the change rate of the serum 25D levels were assessed in 1346 individuals (79.6 %; 458 men and 888 women) who completed measurements of 25D at both the baseline and follow-up examinations. The change rate was calculated, and the factors associated with the changes in the 25D levels were determined using multivariate regression analysis after adjustment for age, gender, body mass index, participated month, and regional differences at baseline. Results: The mean (standard deviation) change rate of the 25D levels in all subjects was 7.6 (13.3) %/year (men, 8.2 [12.4] %/year; women, 7.3 [13.7] %/year). Multivariate regression analysis indicated that higher bone mineral density at lumbar spine L2-4 ( p = 0.05) and total daily energy intake ( p = 0.04) were significantly associated with the change rate of the 25D levels. Conclusions: The serum levels of 25D tended to increase over the 3-year period, and higher lumbar bone mineral density and daily energy intake were found to be associated with increases in the 25D levels over time. [ABSTRACT FROM AUTHOR]

Summary: Scientific interest in vitamin D has greatly risen during the last 10 years. The analysis of the changes in vitamin D prescriptions and related costs in a regional prescription dataset has revealed a profound increase in the period 2006-2013. Further studies on cost-effectiveness of such increase in vitamin D supplementation are needed. Introduction: The aim of this study was to analyze the changes in population-based prescription patterns of vitamin D supplements in the general population in an Italian regional setting during an 8-year period (2006-2013). Methods: Data have been retrieved from the database of reimbursed prescriptions of the Region of Tuscany containing all of the medical reimbursements for the whole regional population (total of 3,619,872 and 3,692,828 inhabitants in 2006 and 2013, respectively). Data referring to adult population (age 20-90+ years) have been considered for this analysis (3,033,530 in 2006 and 3,066,741 in 2013). Two different flows (pharmaceutical distribution dataset and general data flow) were taken into account, using the ATC5 coding system for vitamin D supplements alone or in combination with calcium or alendronate. The number of boxes dispensed was retrieved, the number of patients receiving a specific treatment was calculated, and a cost analysis was performed. Results: An upsurge in the prescriptions of vitamin D compounds was disclosed, mainly sustained by a 75.3-fold increase in cholecalciferol, in all age groups and both sexes. This occurred in parallel to a 4.3-fold rise in prescriptions of oral alendronate in combination with cholecalciferol, a slight decrease in dispensed alendronate alone, and a modest increase in the prescription of the combination of calcium salts and cholecalciferol, and calcium alone. The total cost for reimbursement by the Regional Health System for vitamin D-related compounds rose from €3,242,100 euros in 2006 to €8,155,778 in 2013. Conclusion: The huge increase in vitamin D prescriptions and related costs in the last decade, as revealed by the analysis of a regional pharmaceutical dataset, reflects the increased awareness of the possible consequences of a poor vitamin D status. Further studies on cost-effectiveness of such increase in vitamin D supplementation are needed. [ABSTRACT FROM AUTHOR]

Summary: This review article examines the role of orthogeriatric management for frail older patients with a fragility fracture. The history of orthogeriatrics and its application in clinical practice around the world is reported, and an evidence-based evaluation for the effect of orthogeriatric management on patient morbidity and mortality is also provided. It has been more than 50 years since the role of the geriatrician in the management of patients with a hip fracture was first described. The evidence that supports an orthogeriatric model of care has grown exponentially over the last decade. This evidence base is primarily related to hip fractures and demonstrates reduced morbidity and mortality rates amongst patients managed with a recognised model of orthogeriatric care. The societal and economic burden of hip fracture has led to health economic evaluations within this field, many of which have concluded that orthogeriatric management results in cost-effective clinical practice. Based on existing clinical and economic research, national clinical practice guidelines have been developed in several countries which recommend orthogeriatric participation in the management of older patients with a hip fracture. Compliance with such guidance has already demonstrated improved patient outcomes. Although the pathogenesis and prognosis of other types of fragility fracture may be as poor, there is a dearth of clinical research that evaluates the effect of orthogeriatric management on such injuries. Looking to the future, orthogeriatric management is likely to become more widespread, and the robust collection and reporting of patient outcomes from national registries will provide a greater understanding of the impact of orthogeriatric models in the care of all frail older patients with any type of fragility fracture. [ABSTRACT FROM AUTHOR]

Summary: The present study investigates the effects of vitamin D on muscle function in postmenopausal women. It has been shown that vitamin D supplementation in postmenopausal women with hypovitaminosis D provides significant protective factor against sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass. Introduction: We aimed to evaluate the effect of supplementation of vitamin D (VITD) alone on muscle function in younger postmenopausal women. Methods: In this double-blind, placebo-controlled clinical trial, 160 Brazilian postmenopausal women were randomized into two groups: VITD group consisting of patients receiving vitamin D3 1000 IU/day orally ( n = 80) or placebo group ( n = 80). Women with amenorrhea for more than 12 months and age 50-65 years, with a history of falls (previous 12 months), were included. The intervention time was 9 months, with assessments at two points, start and end. Lean mass was estimated by total-body dual-energy X-ray absorptiometry (DXA) and muscle strength by handgrip strength and chair rising test. The plasma concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance liquid chromatography (HPLC). Statistical analysis was by intention to treat (ITT), using ANOVA, Student's t test, and Tukey's test. Results: After 9 months, average values of 25(OH)D increased from 15.0 ± 7.5 to 27.5 ± 10.4 ng/ml (+45.4 %) in the VITD group and decreased from 16.9 ± 6.7 to 13.8 ± 6.0 ng/ml (−18.5 %) in the placebo group ( p < 0.001). In the VITD group, there was significant increase in muscle strength (+25.3 %) of the lower limbs by chair rising test ( p = 0.036). In women in the placebo group, there was considerable loss (−6.8 %) in the lean mass ( p = 0.030). Conclusion: The supplementation of vitamin D alone in postmenopausal women provided significant protective factor against the occurrence of sarcopenia, with significant increases in muscle strength and control of progressive loss of lean mass. [ABSTRACT FROM AUTHOR]

Summary: Dietary vitamin C intake showed significant positive associations with BMD in postmenopausal women, especially with vitamin D deficiency. Introduction: Although there is a positive role of vitamin C in osteoblastogenesis, debate remains about the contribution of vitamin C to bone mineral density (BMD) in humans. Methods: Data were derived from the Fourth Korean National Health and Nutrition Examination Survey. Dietary information was assessed using a 24-h dietary recall questionnaire. BMD was measured by dual-energy X-ray absorptiometry at the lumbar and hip. Results: A total of 1,196 postmenopausal women aged 50 years and older were stratified into tertiles by daily dietary vitamin C intake. After adjusting for traditional confounders, dietary vitamin C intake tertile was significantly positively associated with BMD at all sites ( R = 0.513 for lumbar spine (LS) and R = 0.657 for femoral neck (FN), P < 0.05 for each). The subjects with osteoporosis had significantly lower dietary vitamin C intake than did subjects without osteoporosis (74.4 ± 66.2 vs 94.1 ± 78.6 mg/day for LS and 65.5 ± 56.6 vs 94.3 ± 79.2 mg/day for FN, respectively, P < 0.001). The multiple-adjusted odds ratio for osteoporosis for dietary vitamin C <100 mg/day was 1.790 (95 % CI 1.333-2.405, P < 0.001). However, the significant association between vitamin C intake and BMD was only observed in subjects with vitamin D deficiency and aged 50-59 years or >70 years. Conclusion: Dietary vitamin C intake was positively associated with BMD in postmenopausal women, and inadequate vitamin C intake could increase the risk of osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: We found for the first time that in maintenance hemodialysis patients, higher sclerostin serum level was associated with severe abdominal aortic calcification (AAC). In addition, cortical bone microarchitecture (density and thickness) assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at tibia was also independently associated with severe AAC. These results suggest that sclerostin may be involved in the association of mineral and bone disorder with vascular calcification in hemodialysis patients. Introduction: Severe abdominal aortic calcifications are predictive of high cardiovascular mortality in maintenance hemodialysis (MHD) patients. In patients with end-stage renal disease, a high aortic calcification score was associated with lower bone turnover on bone biopsies. Thus, we hypothesized that sclerostin, a Wnt pathway inhibitor mainly secreted by osteocytes and acting on osteoblasts to reduce bone formation, may be associated with vascular calcifications in MHD patients. Methods: Fifty-three MHD patients, aged 53 years [35-63] (median [Q1-Q3]) were included. Serum was sampled before the MHD session to assay sclerostin. Framingham score was computed and the abdominal aortic calcification (AAC) score was assessed according to Kauppila method on lateral spine imaging using DEXA. Tibia bone status was evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were distributed into two groups according to their AAC score: patients with mild or without AAC (score below 6) versus patients with severe AAC (score of 6 and above). Results: In multivariate analysis, after adjustment on age, dialysis duration and diabetes, serum sclerostin and cortical thickness were independently associated with severe AAC (odds ratio (OR) = 1.43 for each 0.1 ng/mL increase [95 % confidence interval (CI) 1.10-1.83]; p = 0.006 and 0.16 for 1 SD increase [0.03-0.73]; p = 0.018, respectively). A second cardiovascular model adjusted on Framingham score and the above mentioned confounders showed similar results. Conclusions: Elevated sclerostin serum level and poorer tibia cortical bone structure by HR-pQCT were positively and independently associated with higher odds of severe AAC in MHD patients. Serum sclerostin may become a biomarker of mineral and bone disorder and vascular risk in MHD patients. [ABSTRACT FROM AUTHOR]

Summary: This manuscript describes the role of low vitamin D in bone metabolism of Klinefelter subjects. Low vitamin D is frequent in this condition and seems to be more important than testosterone in inducing low bone mineral density (BMD) and osteoporosis. Supplementation with vitamin D restores BMD after 2 years of treatment, whereas testosterone alone seems to be ineffective. Introduction: Decreased bone mineral density (BMD) in Klinefelter syndrome (KS) is frequent, and it has been traditionally related to low testosterone (T) levels. However, low BMD can be observed also in patients with normal T levels and T replacement therapy does not necessarily increase bone mass in these patients. Nothing is known about vitamin D levels and supplementation in KS. In this study, we determine vitamin D status and bone mass in KS subjects and compare the efficacy of T therapy and vitamin D supplementation on BMD. Methods: A total of 127 non-mosaic KS patients and 60 age-matched male controls were evaluated with reproductive hormones, 25-hydroxyvitamin D, PTH, and bone densitometry by dual-energy X-ray absorptiometry (DEXA). Patients with hypogonadism and/or 25-hydroxyvitamin D deficiency were treated with T-gel 2 % and/or calcifediol and re-evaluated after 24 months of treatment. Results: 25-hydroxyvitamin D levels were significantly lower in KS patients with respect to controls, and they had significantly lower lumbar and femoral BMD. The percentage of osteopenia/osteoporosis in subjects with 25-hydroxyvitamin D deficiency was higher with respect to subjects with normal 25-hydroxyvitamin D and was not related to the presence/absence of low T levels. Subjects treated with calcifediol or T + calcifediol had a significant increase in lumbar BMD after treatment. No difference was found in T-treated group. Conclusions: These data highlight that low 25-hydroxyvitamin D levels seem to have a more critical role than low T levels in inducing low BMD in KS subjects. Furthermore, vitamin D supplementation seems to be more effective than T replacement therapy alone in increasing BMD. [ABSTRACT FROM AUTHOR]

An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery. [ABSTRACT FROM AUTHOR]

Summary: The aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with Paget's disease of bone before and after treatment with bisphosphonates. We found good correlation between the bone turnover marker concentrations and disease activity assessed by bone scintigraphy. Introduction: Paget's disease of bone is a common skeletal disorder of the elderly. Bone turnover marker concentrations are used for diagnosis and follow-up. We aimed to compare the available bone turnover markers and determine their utility in assessing disease activity when compared to quantitative bone scintigraphy. Methods: We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We evaluated total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type 1 amino-terminal propeptide (P1NP), serum, and urine C-terminal telopeptide (uCTx and sCTx, respectively), and urine N-terminal telopeptide (uNTx). The main outcome of interest was the correlation of disease activity with concentrations of bone turnover markers in Paget's disease patients before and after treatment with bisphosphonates. Correlation coefficients were pooled across studies using the random effects model. Results: We included 17 observational studies and one trial reporting on 953 patients. Prior to treatment, all studied bone turnover markers had moderate to strong correlation with scintigraphic indices (correlation coefficients ranging from 0.58 to 0.80) with no statistically significant difference between the bone turnover markers overall ( p = 0.08). P1NP, uNTx, and bone ALP tend to have higher correlation with scintigraphy. After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70). Conclusion: The findings of this meta-analysis suggest the Paget's disease activity is best monitored by following P1NP levels. However, total ALP, bone ALP, and uNTx are good alternatives as markers of disease activity in untreated patients. Total ALP and uNTx can be useful in following patients with Paget's disease after treatment if P1NP is not available. Clinicians, however, should take availability, cost, and the presence of liver disease into consideration when deciding which bone turnover marker is most appropriate when evaluating patients with Paget's disease. [ABSTRACT FROM AUTHOR]

Osteomalacia, a metabolic bone disease characterized by the inability to mineralize new osteoid, can be caused by vitamin D deficiency. We report a patient with symptomatic, biochemical, and imaging evidence of osteomalacia due to vitamin D deficiency, who as a result of work up for bone disease was diagnosed with early primary biliary cirrhosis. Osteomalacia was treated with high-dose vitamin D and serial bone density scans showed evidence of increasing bone mineral density suggesting osteoid mineralization in response to treatment. The diagnosis of cholestatic liver disease should be considered in all patients presenting with osteomalacia due to vitamin D deficiency, particularly if other cholestatic liver enzymes are elevated in addition to alkaline phosphatase. [ABSTRACT FROM AUTHOR]

Summary: We hypothesized that chronic exposures to traffic combustion products may lower bone mineral density (BMD). We found that proximity to freeways was associated with reduced BMD. Our findings suggest that traffic-related pollution may contribute to the occurrence of osteopenia and osteoporosis. Introduction: Adults residing in rural areas have been linked with higher BMD. We aimed to determine if this difference is due in part to air pollution by examining the relationships between traffic metrics and ambient air pollution with total body and pelvic BMD. Methods: Mexican American adults ( n = 1,175; mean 34 years; 72 % female) who had participated in the BetaGene study of air pollution, obesity, and insulin resistance were included in this analysis. Total body and pelvic BMD were estimated using dual-energy X-ray absorptiometry. Traffic and ambient air pollutant exposures were estimated at residences using location and ambient monitoring data. Variance component models were used to analyze the associations between residential distance to the nearest freeway and ambient air pollutants with BMD. Results: Residential proximity to a freeway was associated with lower total body BMD (p-trend = 0.01) and pelvic BMD (p-trend = 0.03) after adjustment for age, sex, weight, and height. The adjusted mean total body and pelvic BMD in participants living within 500 m of a freeway were 0.02 and 0.03 g/cm lower than participants living greater than 1,500 m from a freeway. These associations did not differ significantly by age, sex, or obesity status. Results were similar after further adjustment for body fat and weekly physical activity minutes. Ambient air pollutants (NO, O, and PM) were not significantly associated with BMD. Conclusions: Traffic-related exposures in overweight and obese Mexican Americans may adversely affect BMD. Our findings indicate that long-term exposures to traffic may contribute to the occurrence of osteoporosis and its consequences. [ABSTRACT FROM AUTHOR]

Summary: This study investigated the long-term relationship between the exposure to childhood recreational gymnastics and bone measures and bone strength parameters at the radius and tibia. It was observed that individuals exposed to recreational gymnastics had significantly greater total bone content and area at the distal radius. No differences were observed at the tibia. Introduction: This study investigated the relationship between exposure to early childhood recreational gymnastics with bone measures and bone strength development at the radius and tibia. Methods: One hundred twenty seven children (59 male, 68 female) involved in either recreational gymnastics (gymnasts) or other recreational sports (non-gymnasts) between 4 and 6 years of age were recruited. Peripheral quantitative computed tomography (pQCT) scans of their distal and shaft sites of the forearm and leg were obtained over 3 years, covering the ages of 4-12 years at study completion. Multilevel random effects models were constructed to assess differences in the development of bone measures and bone strength measures between those exposed and not exposed to gymnastics while controlling for age, limb length, weight, physical activity, muscle area, sex, and hours of training. Results: Once age, limb length, weight, muscle area, physical activity, sex, and hours of training effects were controlled, it was observed that individuals exposed to recreational gymnastics had significantly greater total bone area (18.0 ± 7.5 mm) and total bone content (6.0 ± 3.0 mg/mm) at the distal radius ( p < 0.05). This represents an 8-21 % benefit in ToA and 8-15 % benefit to ToC from 4 to 12 years of age. Exposure to recreational gymnastics had no significant effect on bone measures at the radius shaft or at the tibia ( p > 0.05). Conclusions: Exposure to early life recreational gymnastics provides skeletal benefits to distal radius bone content and area. Thus, childhood recreational gymnastics exposure may be advantageous to bone development at the wrist. [ABSTRACT FROM AUTHOR]

Recent studies have noted an increased risk of low energy subtrochanteric and femoral shaft fractures termed 'atypical femur fractures' (AFFs) associated with long-term bisphosphonate use. As such, many clinicians have begun recommending a 'drug holiday' to reduce the risks associated with long-term bisphosphonate use. We present two cases of AFFs occurring during a 4-year or greater drug holiday following long-term bisphosphonate use. These findings highlight the need to reevaluate optimal bisphosphonate therapy duration, dosage, as well as initiation and duration of a drug holiday with continued monitoring in the prevention of AFFs. [ABSTRACT FROM AUTHOR]

Summary: Physicians are indoor workers with low sun exposure. The aim of this study was to compare serum 25-hydroxyvitamin D(25(OH)D) levels among hospitalists and community-based physicians. 25(OH)D levels among hospitalist physicians were significantly lower than those among community-based physicians. Hospitalist physicians should be considered for vitamin D deficiency screening and replacement. Introduction: Vitamin D deficiency is now recognized as a widespread phenomenon, even in a sunny, Mediterranean country such as Israel. Physicians may be vulnerable to low vitamin D levels due to long work hours and lack of sun exposure. Methods: Forty-three physicians employed in a hospital and 38 physicians who work in the community in Jerusalem were enrolled. Their serum 25(OH)D levels were measured, and a questionnaire was filled to assess the risk of vitamin D deficiency. Results: Mean serum levels of 25(OH)D among hospitalist physicians were significantly lower than those among community-based physicians (15 ± 6 vs. 19.7 ± 6 ng/ml, respectively; p < 0.00 l). Arab physicians had a lower 25(OH)D level compared to Jewish physicians (18.2 ± 6.6 vs. 11.4 ± 2.7 ng/ml; p < 0.001). After exclusion of Arab physicians from the analysis, 25(OH)D levels remained higher in hospitalist compared to community-based physicians (15.9 ± 6 vs. 20.4 ± 6 ng/ml; p < 0.004). The variables that were significantly linked to low mean serum levels of 25(OH)D were as follows: age, night shifts, daily sun exposure, and ethnic origin. Conclusion: Hospitalist physicians are at greater risk for low vitamin D levels than community-based physicians. [ABSTRACT FROM AUTHOR]

Summary: In the large community-based Hordaland Health Study, low plasma dimethylglycine was associated with low bone mineral density in both middle-aged and elderly subjects and to an increased risk of subsequent hip fracture among the elderly. These associations seemed to be particularly strong among subjects exposed to nicotine. Introduction: Dimethylglycine (DMG) is a product of the choline oxidation pathway and formed from betaine during the folate-independent remethylation of homocysteine (Hcy) to methionine. Elevated plasma DMG levels are associated with atherosclerotic cardiovascular disease and inflammation, which in turn are related to osteoporosis. High plasma total Hcy and low plasma choline are associated with low bone mineral density (BMD) and hip fractures, but the role of plasma DMG in bone health is unknown. Methods: We studied the associations of plasma DMG with BMD among 5315 participants (46-49 and 71-74 years old) and with hip fracture among 3310 participants (71-74 years old) enrolled in the Hordaland Health Study. Results: In age and sex-adjusted logistic regression models, subjects in the lowest versus highest DMG tertile were more likely to have low BMD (odds ratio [OR] 1.68, 95 % confidence interval [CI] 1.43-1.99). The association was stronger in participants exposed compared to those unexposed to nicotine (OR 2.31, 95 % CI 1.73-3.07 and OR 1.43, 95 % CI 1.16-1.75, respectively, p interaction = 0.008). In the older cohort, Cox regression analyses adjusted for sex showed that low plasma DMG was associated with an increased risk of hip fracture (hazard ratio [HR] 1.70, 95 % CI 1.28-2.26). A trend toward an even higher risk was found among women exposed to nicotine (HR 3.41, 95 % CI 1.40-8.28). Conclusion: Low plasma DMG was associated with low BMD and increased risk of hip fractures. A potential effect modification by nicotine exposure merits particular attention. [ABSTRACT FROM AUTHOR]

Summary: In this population-based, cross-sectional study in Italian postmenopausal females not affected by diabetes, we showed a link between serum C-peptide and lumbar bone mineral density, suggesting that C-peptide exerts an insulin-independent effect on bone mass. Introduction: It is well known that type 1 (T1) diabetes, characterized by insulin and C-peptide deficiency, is associated with a low lumbar bone mineral density and an increased risk for fracture. While a role for insulin in the pathogenesis of osteoporosis has been demonstrated, the association between C-peptide and the bone mineral density has not been investigated. We conducted a study in a cohort of 84 postmenopausal women without diabetes to clarify the association between serum C-peptide and the lumbar bone mineral density. Methods: Participants underwent a bone mineral density evaluation by DXA and biochemical analysis including the C-peptide assay. Results: rteen percent of the population had osteoporosis and 38 % had osteopenia. With ANOVA test, we showed that women with the lowest C-peptide concentration had lower lumbar mineral density in comparison to those in all other C-peptide concentration group ( p = 0.02 among groups after adjustment). The univariate and multivariate analysis showed that C-peptide was positively associated with both lumbar T-score and Z-score besides other well-known factors like age (with T-score p < 0.001; beta = −0.38) and BMI (with T-score p = 0.009; beta = 0.34), while insulin was not correlated with the lumbar bone mineral density. The area under the receiver operating characteristic (ROC) curve for C-peptide to predict the absence of lumbar osteoporosis was 0.74 (SE = 0.073; p = 0.013). Conclusions: These results suggest that C-peptide may exert an insulin- and BMI-independent effect on lumbar bone mineral density and that further large-scale studies are needed in order to clarify its role in bone mineralization especially in subjects without diabetes. [ABSTRACT FROM AUTHOR]

Summary: Patients with axial spondyloarthritis (axSpA) have an increased risk of osteoporosis related to inflammation. We evaluate the performance of low bone mineral density (BMD) in diagnosis of axSpA for patients with symptoms suggestive of the disease. A low BMD (T ≤ −2) could be an additional tool for the diagnosis of axSpA. Introduction: Diagnosis of axial spondyloarthritis (axSpA) can be challenging, especially in the absence of radiographic abnormalities. Patients with axSpA have an increased risk of osteoporosis related to inflammation. This study evaluated the performance of low bone mineral density (BMD) in diagnosis of axSpA for patients with symptoms suggestive of the disease. Methods: Medical files of patients that visited a tertiary centre for symptoms suggestive of axSpA were reviewed. Two hundred and sixty-seven patients were classified in confirmed axSpA or unconfirmed axSpA according to the diagnosis of a senior rheumatologist. BMD measurements results and percentage of patients with a low BMD (T ≤ −2) at either spine or hip were compared between the two groups. Diagnostic performances of low BMD (specificity, sensitivity, positive, negative predictive values and positive likelihood ratio (LR+)) were assessed. Results: Compared to patients with unconfirmed axSpA ( n = 74), patients with confirmed axSpA ( n = 193) had similar age, were more frequently male, with positive HLA B27, higher disease duration and higher C-reactive protein (CRP). Low BMD was more frequent at spine and hip, in patients with confirmed (40.3 %) than unconfirmed axSpA (24.6 %, p = 0.021). The LR+ of low BMD for an axSpA diagnosis was 2.60 and 3.12 at the spine and hip. In the subgroup of patients without any radiographic abnormalities ( n = 128), the LR+ of low BMD for an axSpA diagnosis was 2.90 and 2.54 at the spine and hip. Conclusion: In patients with symptoms suggestive of axSpA, a low BMD (T ≤ −2) could be an additional tool for the diagnosis of axSpA. [ABSTRACT FROM AUTHOR]

A bone biopsy specimen in a long-term hemodialysis patient with sarcoidosis coexisting with severe hypoparathyroidism has demonstrated that a persistent near physiological level of 1,25-dihydroxyvitamin D contributes to the preservation of bone remodeling and has the potential to retard the development of vascular calcification and atherosclerosis. Sarcoidosis-related hypercalcemia and hypoparathyroidism, which is characterized by 1,25-dihydroxyvitamin D (1,25(OH)D) overproduction, is rarely seen in hemodialysis patients. Herein, we describe a 60-year-old Japanese woman on hemodialysis for 35 years who presented with malaise and hypercalcemia. Severe hypoparathyroidism without parathyroidectomy and a preserved 1,25(OH)D level were detected. Computed tomography showed bilateral axillary lymphadenopathy and minimal aortic and soft tissue calcification. The axillary node biopsy led to a definite diagnosis of sarcoidosis. A bone biopsy specimen obtained from the right iliac crest showed remodeling of normal lamellar bone with scalloped cement lines and clear double labeling by tetracycline on fluorescence microscopy. Histomorphometric analysis revealed that the bone formation rate was preserved (30.0 %/year), together with a decrease of osteoid volume (5.75 %) and fibrous volume (0 %), indicating that the patient did not have adynamic bone disease and only showed mild disease. This is the first documented case of sarcoidosis-related hypercalcemia associated with severe hypoparathyroidism in a long-term hemodialysis patient who underwent bone histomorphometry. Our findings suggest that, in hemodialysis patients with sarcoidosis coexisting with severe hypoparathyroidism, a persistent near physiological level of 1,25(OH)D contributes to the preservation of bone remodeling and has the potential to retard the development of vascular calcification and atherosclerosis. [ABSTRACT FROM AUTHOR]

Summary: While type 2 diabetes (T2D) is associated with higher skeletal fragility, specific risk stratification remains incompletely understood. We found volumetric bone mineral density, geometry, and serum sclerostin differences between low-fracture risk and high-fracture risk T2D women. These features might help identify T2D individuals at high fracture risk in the future. Introduction: Diabetic bone disease, an increasingly recognized complication of type 2 diabetes mellitus (T2D), is associated with high skeletal fragility. Exactly which T2D individuals are at higher risk for fracture, however, remains incompletely understood. Here, we analyzed volumetric bone mineral density (vBMD), geometry, and serum sclerostin levels in two specific T2D subsets with different fracture risk profiles. We examined a T2D group with prior history of fragility fractures (DMFx, assigned high-risk group) and a fracture-free T2D group (DM, assigned low-risk group) and compared their results to nondiabetic controls with (Fx) and without fragility fractures (Co). Methods: Eighty postmenopausal women ( n = 20 per group) underwent quantitative computed tomography (QCT) to compute vBMD and bone geometry of the proximal femur. Additionally, serum sclerostin, vitamin D, parathyroid hormone (PTH), HbA1c, and glomerular filtration rate (GFR) levels were measured. Statistical analyses employed linear regression models. Results: DMFx subjects exhibited up to 33 % lower femoral neck vBMD than DM subjects across all femoral sites (−19 % ≤ ΔvBMD ≤ −33 %, 0.008 ≤ p ≤0.021). Additionally, DMFx subjects showed significantly thinner cortices (−6 %, p = 0.046) and a trend toward larger bone volume (+10 %, p = 0.055) relative to DM women and higher serum sclerostin levels when compared to DM (+31.4 %, p = 0.013), Fx (+25.2 %, p = 0.033), and control (+22.4 %, p = 0.028) subjects. Conclusion: Our data suggest that volumetric bone parameters by QCT and serum sclerostin levels can identify T2D individuals at high risk of fracture and might therefore show promise as clinical tools for fracture risk assessment in T2D. However, future research is needed to establish diabetes-specific QCT- and sclerostin-reference databases. [ABSTRACT FROM AUTHOR]

Summary: No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. Methods: The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. Results: After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group ( p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months ( p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study. Conclusion: The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium. [ABSTRACT FROM AUTHOR]

Summary: Ethnic differences in renal calcium and phosphate excretion exist, which may depend on differences in their dietary intakes and regulatory factors. We report highly significant differences in urinary calcium and phosphate excretion between white British and Gambian adults after statistical adjustment for mineral intakes, indicating an independent effect of ethnicity. Introduction: Populations vary in their risk of age-related osteoporosis. There are racial or ethnic differences in the metabolism of the bone-forming minerals calcium (Ca) and phosphate (P), with a lower renal Ca and P excretion in African-Americans compared to white counterparts, even at similar intakes and rates of absorption. Also, Africans in The Gambia have a lower Ca excretion compared to white British subjects, groups known to differ in their dietary Ca intake. Here, we report on differences in urinary Ca and P excretion between Gambian and white British adults while allowing for known predictors, including dietary intakes. Methods: Participants were healthy white British ( n = 60) and Gambian ( n = 61) men and women aged 60-75 years. Fasting blood and 2-h urine samples were collected. Markers of Ca and P metabolism were analysed. Dietary intake was assessed with country-specific methods. Results: White British older adults had higher creatinine-corrected urinary Ca and P excretion (uCa/uCr, uP/uCr) and lower tubular maximum of Ca and P compared to Gambian counterparts. The predictors of urinary Ca and P differed between groups. Multiple regression analysis showed that dietary Ca and Ca/P were predictors of uCa/uCr and uP/uCr, respectively. Ethnicity remained a significant predictor of uCa/uCr and uP/uCr after adjustment for diet and other factors. Conclusions: Gambian older adults have higher renal Ca conservation than British counterparts. Dietary mineral intakes were predictors of the differences in urinary Ca and P excretion, but ethnicity remained a highly significant predictor after statistical adjustment. This suggests that ethnicity has an independent effect on renal Ca and P handling. [ABSTRACT FROM AUTHOR]

Compared with numerous encouraging reports of percutaneous kyphoplasty (PKP) in treatment of painful osteoporotic vertebral compression fractures, there have been fewer reports on the role of PKP in the treatment of nonunion of osteoporotic vertebral compression fractures. Even less is known about the use of PKP in treating nonunion of osteoporotic vertebral compression fractures with severe spinal stenosis. We reported an 87-year-old man presented with half a year back pain and numbness of both legs after back sprain 6 months ago. Nonunion of L3 with severe spinal stenosis was recognized in the preoperative films. Bone mineral analysis showed severe osteoporosis with a T-score of −4.7. He refused to receive the decompression surgery. As a result, PKP was introduced to him as an alternative option. The patient experienced complete pain relief after PKP without any complication. Meanwhile, it was an interesting finding that numbness of both legs disappeared. After 12 months follow-up, the patient was asymptomatic. This case illustrated that PKP could be considered as one of the options for nonunion of osteoporotic vertebral compression fractures with severe spinal stenosis. [ABSTRACT FROM AUTHOR]

Summary: The association between hyponatremia and osteoporosis was evaluated in humans. A significant association was found between low sodium levels, lower bone mineralization in the hip, and with several common conditions. Hyponatremia could be used as a marker of osteoporosis and systemic disease. Introduction: The objective of this study was to evaluate the association between hyponatremia and osteoporosis in humans through a cross-sectional study. Methods: Patient information was gathered from regional and national Danish patient databases, both in- and outpatient settings, from 2004 to 2011. Patients with dual-energy x-ray absorptiometry (DXA) scans performed within this time were included if accompanied [Na+] was measured within 14 days prior or past the scan date. A total of 1575 patients were included. Results: A total of 104 patients were hyponatremic (6.6 %). Total hip and lumbar spine bone mineral content (BMC) and densities (BMD) and T-scores were all significantly lower with hyponatremia. The odds ratio (OR) of osteoporosis significantly increased among hyponatremic patients at both total hip (unadjusted OR = 2.17, 95 % CI = [1.40-3.34], p < .05) and lumbar spine (unadjusted OR = 1.83, 95 % CI = [1.20-2.80], p < .05) regions. Dose-response found between increasing [Na+] and increasing total hip BMC (slope .174, adjusted p < .05), BMD (slope .004, adjusted p < .05), and T-score (slope .034, adjusted p < .05). Systemic disease was more prevalent in hyponatremia. Conclusion: The presence of hyponatremia increases the risk of concurrent osteoporosis at both the total hip and lumbar spine in humans. Hyponatremia could be used a screening tool and marker of secondary osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: We studied bone turnover markers (BTM) and bone microarchitecture (using high-resolution peripheral quantitative computed tomography (HR-pQCT)) in 171 postmenopausal women and their 210 premenopausal daughters. BTM levels correlated positively between mothers and daughters. The mother-daughter pairs with high BTM levels had lower cortical density than those with low BTM levels. Introduction: We assessed the correlation of serum bone turnover markers (BTM) between postmenopausal mothers and their premenopausal daughters as well as possible determinants of this association and its impact on resemblance of bone microarchitecture between mothers and their daughters. Methods: Cross-sectional analysis was performed in 171 untreated postmenopausal mothers (54 sustained fragility fractures) and their 210 premenopausal daughters. Intact N-terminal propeptide of type I collagen (PINP) and β-isomerized C-terminal crosslinking telopeptide of type I collagen (CTX-I) were measured in the fasting status. Bone microarchitecture was assessed using HR-pQCT. Results: After adjustment for age, weight, lifestyle factors, hormones, and mother's fracture status, BTM levels correlated positively between mothers and daughters (Intraclass Correlation Coefficient = 0.22-0.27, p <0.005). Average BTM levels were ∼0.6 SD higher among daughters of mothers in the highest BTM quartile vs. the ones in the lowest BTM quartile. The variability of BTM levels explained ≤10 and ≤14 % of variability of bone microarchitecture in the daughters and mothers, respectively. Cortical density was lower by 2.3-2.9 % (0.6 SD, p <0.05 to <0.005) in the daughters from the mother-daughter pairs with high BTM levels (defined by generation-specific quartiles) than in the daughters from the pairs with low BTM levels. Corresponding differences for the mothers were 4.5-4.8 % (0.5 SD, p <0.05 to <0.01). Conclusion: BTM levels correlated between postmenopausal mothers and their premenopausal daughters after adjustment for age, weight, mother's fracture status, lifestyle, and hormonal factors. Family resemblance of BTM levels may contribute to family resemblance of some bone microarchitectural parameters, especially of cortical density. [ABSTRACT FROM AUTHOR]

Summary: Predictors of bone mineral density (BMD) loss are additional tools in the management of osteoporosis in premenopausal women with systemic lupus erythematosus (SLE). This study provides original evidence that N-terminal propeptide of type 1 collagen (P1NP), the most specific bone formation marker, is a predictor of BMD loss in this group of women. Introduction: SLE is associated with a high risk of low bone mass/fractures but this risk is still controversial in premenopausal women. Our aim was to determine the 1 year incidence of BMD loss in premenopausal SLE women and the value of bone turnover markers as predictors of this complication. Methods: This study enrolled a convenience sample of 63 premenopausal SLE patients. BMD was evaluated by dual X-ray absorptiometry at lumbar spine and hip at baseline and after 12 months. BMD changes above the least significant change were considered significant. Serum levels of P1NP and CTX (electrochemiluminescence), OPG, and RANKL (ELISA) were determined at baseline. Results: Mean age was 31.1 ± 6.8 years, and disease duration was 5.25 ± 3.8 years. 36.5 % of patients presented BMD loss and 17.5 % BMD gain at lumbar spine and/or hip. Patients were divided in three groups: BMD loss (BL), no BMD change (NC), and BMD gain (BG). Patients with BL and NC received similar cumulative/mean/maximum glucocorticoid doses during the study, but patients with BG received lower doses ( p < 0.05). Baseline P1NP levels were different in the groups (BL: 36.95 ± 23.37 vs. NC: 54.63 ± 30.82 vs. BG: 84.09 ± 43.85 ng/mL; p = 0.031 BL vs. NC, p < 0.001 BL vs. BG, and p = 0.039 NC vs. BG). There was no difference in CTX, OPG, or RANKL levels. After multivariate analysis, P1NP remained as an independent risk factor for BMD loss ( p < 0.03). Conclusions: This study provides original evidence that lower levels of P1NP, the most specific bone formation marker, are predictive of BMD loss over 12 months in premenopausal SLE patients. [ABSTRACT FROM AUTHOR]

Summary: This prospective study showed that the incidence of acute anterior uveitis, confirmed by ophthalmic examination, in patients receiving intravenous zoledronate infusions as part of a randomized controlled trial for fracture prevention is 1.1 %. Introduction: We prospectively investigated the incidence of ocular side effects after a single intravenous zoledronate infusion. Methods: In a secondary analysis of a double-blind, placebo-controlled trial in which early post-menopausal women ( N = 1054) with normal bone density or osteopenia were randomized to infusion of zoledronate 5 mg ( N = 703) or placebo ( N = 351), we analyzed significant adverse ocular events occurring within 3 months. Results: Fourteen participants reported ocular symptoms after the infusion. All were examined by an ophthalmologist and eight were diagnosed with acute anterior uveitis (AAU) and one with sectoral episcleritis. The incidence of AAU and episcleritis was 1.1 % (95 % CI 0.5-2.1) and 0.1 % (95 % CI 0.0-0.7), respectively, in the zoledronate group and 0 % for both conditions in the placebo group (95 % CI 0.0-0.8). The mean time from infusion to symptom onset for AAU was 3 days (range 2-4). Three cases were bilateral. AAU was mild-moderate in seven participants and severe in one. All affected eyes were treated with topical cyclopentolate 1 % (to break, or minimize, posterior synechiae), and intensive, potent, topical corticosteroids with a tapering regime based on treatment response. The mean duration of topical corticosteroid was 26 ± 10 days (range 17-44). The mean, best corrected visual acuity was 20/20 (range 20/20-20/40) at presentation, which remained unchanged after AAU resolution. None of the participants lost vision, and no long-term sequelae were reported at last follow-up (range 3-13 months post-infusion). Conclusions: Prescribers should inform patients about the possibility of ocular side effects with zoledronate infusions and refer promptly to an ophthalmologist if symptoms develop. [ABSTRACT FROM AUTHOR]

Summary: This 7-year prospective observational study determined the predictors of re-fracture amongst 234 patients managed within a Secondary Fracture Prevention programme. Poor compliance, multiple co-morbidities, corticosteroid therapy, low hip bone mineral density (BMD) or low body weight were all significantly associated with re-fracture in patients commenced on long-term anti-resorptive therapy. Introduction: Risk factors for osteoporotic fracture amongst treatment-naïve patients are well established. In contrast, predictors of re-fracture in patients optimally managed within a Secondary Fracture Prevention (SFP) programme are ill-defined. Methods: This prospective observational study included 234 subjects with incident osteoporotic fractures managed long-term by the Concord SFP programme. Using Cox proportional hazards models, predictors of re-fracture were analysed separately for patients commenced on specific pharmacotherapy (group 1, N = 171) and subjects receiving calcium and/or vitamin D supplements only (group 2, N = 63). Relevant anthropometric, clinical and technical data were documented at each visit. Compliance and persistence were analysed as time-varying covariates. Results: During a mean follow-up of 5.2 (range 3.5-7.3) years, 20.9 % of all subjects re-fractured (26.3 % in group 1, 6.3 % in group 2). Multivariate predictors of re-fracture in group 1 were significant co-morbidity (HR 2.04 if >3, 95 % CI 1.10-3.79, p = 0.024), corticosteroid use (HR 1.75, 95 % CI 1.12-2.73, p = 0.013) and total hip BMD (HR 1.36 per 0.1 g/cm decrease, 95 % CI 1.08-1.70, p = 0.008). In contrast, gender, prevalent fractures and lumbar spine BMD were not associated with re-fracture. Amongst patients with complete compliance data, a medication possession ratio of ≤ 50 % (HR 3.36, 95 % CI 1.32-8.53, p = 0.011) and low body weight (HR 1.04 per 1-kg decrease, 95 % CI 1.003-1.08, p = 0.032) were significantly associated with re-fracture. Conclusions: Amongst patients managed within a dedicated SFP programme, poor compliance, multiple co-morbidities, corticosteroid therapy, low hip BMD or low body weight are all associated with increased risk of re-fracture. This subgroup of patients therefore require intensive management including strategies to improve compliance. [ABSTRACT FROM AUTHOR]

Summary: In patients with systemic lupus erythematosus (SLE), low bone mineral density (BMD) is associated with increased age, prolonged disease, low body mass index (BMI), and overlap with rheumatoid arthritis (RA). Elevated fibroblast growth factor (FGF)-23 in cyclosporine A (CsA) users with SLE are associated with decreased active vitamin D and osteocalcin. Introduction: The objective of this study was to investigate the steroid and CsA effect on bone metabolism and serum FGF-23 in SLE patients. Methods: Seventy-two SLE patients and 10 age- and sex-matched healthy individuals underwent blood tests for bone metabolic biomarkers and FGF-23, and lumbar spine dual-energy X-ray absorptiometry for BMD. Results: Comparisons between patients and controls were made in premenopausal women/men younger than 50 years and postmenopausal women/men older than 50 years separately. SLE patients had more frequent low Z-score (≤ − 2.0, 8.5 vs. 0 %), osteopenia (−2.5 < T-score < −1.0, 52 vs. 50 %), and osteoporosis (T-score ≤ −2.5, 12 vs. 0 %), than the healthy age-compatible counterparts. BMD was significantly lower in patients with advanced age, longer disease duration, lower BMI, and overlap with RA (all p < 0.05 by multiple linear regression analyses). Serum FGF-23 was significantly higher and 1,25-dihydroxyvitamin D (1,25(OH)D) lower in SLE patients treated with glucocorticoid and CsA than in those not taking both of them ( p = 0.027 and 0.002, respectively). The cumulative dose of glucocorticoid was inversely correlated with serum intact parathyroid hormone ( r = −0.299, p = 0.011), C-terminal telopeptide of type I collagen ( r = −0.581, p < 0.001), and osteocalcin ( r = −0.648, p < 0.001). FGF-23 and the cumulative dose of CsA were positively correlated ( r = 0.38, p = 0.001) and both were negatively correlated with 1,25(OH)D ( r = −0.266, p = 0.016 and r = −0.55, p < 0.001) and osteocalcin ( r = −0.234, p = 0.034 and r = −0.274, p = 0.02). Conclusion: SLE patients treated with glucocorticoid and CsA exhibited markedly decreased bone turnover. Those taking CsA had higher serum FGF-23 associated with suppression of 1,25(OH)D and bone formation. Such high-risk patients necessitate regular screening of osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: Odanacatib is a cathepsin K inhibitor investigated for the treatment of postmenopausal osteoporosis. Phase 2 data indicate that 50 mg once weekly inhibits bone resorption and increases bone mineral density, with only a transient decrease in bone formation. We describe the background, design and participant characteristics for the phase 3 registration trial. Introduction: Odanacatib (ODN) is a selective cathepsin K inhibitor being evaluated for the treatment of osteoporosis. In a phase 2 trial, ODN 50 mg once weekly reduced bone resorption while preserving bone formation and progressively increased BMD over 5 years. We describe the phase III Long-Term ODN Fracture Trial (LOFT), an event-driven, randomized, blinded placebo-controlled trial, with preplanned interim analyses to permit early termination if significant fracture risk reduction was demonstrated. An extension was planned, with participants remaining on their randomized treatment for up to 5 years, then transitioning to open-label ODN. Methods: The three primary outcomes were radiologically determined vertebral, hip, and clinical non-vertebral fractures. Secondary end points included clinical vertebral fractures, BMD, bone turnover markers, and safety and tolerability, including bone histology. Participants were women, 65 years or older, with a BMD T-score ≤−2.5 at the total hip (TH) or femoral neck (FN) or with a prior radiographic vertebral fracture and a T-score ≤−1.5 at the TH or FN. They were randomized to ODN or placebo tablets. All received weekly vitamin D (5600 international units (IU)) and daily calcium supplements as needed to ensure a daily intake of approximately 1200 mg. Results: Altogether, 16,713 participants were randomized at 387 centers. After a planned interim analysis, an independent data monitoring committee recommended that the study be stopped early due to robust efficacy and a favorable benefit/risk profile. Following the base study closeout, 8256 participants entered the study extension. Conclusions: This report details the background and study design of this fracture end point trial and describes the baseline characteristics of its participants. [ABSTRACT FROM AUTHOR]

Summary: Data gathered from a nationally representative cohort demonstrated that subject with low skeletal muscle mass had consistently low femoral neck composite strength indices for compression, bending, and impact, especially in older women, supporting the highly integrated nature of skeletal muscle and bone. Introduction: Skeletal muscle and bone interact mechanically and functionally. The present study was performed to investigate the association between muscle mass and femoral neck composite strength indices using a nationally representative cohort. Methods: This is a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys, including 1,275 Koreans (674 women and 601 men) aged 50 years or older. Femoral neck axis length and width were measured by hip DXA scans and were combined with BMD, body weight, and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. Presarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by body weight that was less than 1 SD below the sex-specific mean for young adults. Results: After adjusting for confounders, women with presarcopenia had consistently lower indices for compression strength (CSI), bending strength (BSI), and impact strength (ISI) than women without this condition. Men with presarcopenia had a lower ISI value than men without presarcopenia. Multiple regression analyses revealed that lower relative skeletal muscle mass (ASM/weight) associated significantly with lower values for all three femoral neck composite indices in women and with lower CSI and ISI in men. Conclusions: These findings provide the first clinical evidence for the notion that age-related low muscle mass may increase the risk of osteoporotic hip fractures by decreasing femoral neck strength relative to load, especially in older women, and support the highly integrated nature of skeletal muscle and bone. [ABSTRACT FROM AUTHOR]

Summary: This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indicator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased. Introduction: Inflammation may contribute to the pathophysiology underlying impaired bone metabolism. This study investigates the association between CRP, BMD, bone loss, fracture risk, and mortality in women aged 75 and above. Methods: This longitudinal study is based on 1044 women, all age 75 at inclusion, reassessed at ages 80 and 85, with a mean follow-up time of 11.6 years (maximum 16.9 years). Results: Women in the lowest CRP quartile (mean 0.63 mg/L) had lower BMD compared to those in the highest CRP quartile (mean 5.74 mg/L) at total hip (TH) (0.809 vs. 0.871 g/cm, p < 0.001) and femoral neck (FN) (0.737 vs. 0.778 g/cm, p = 0.007). A single measurement of CRP was not associated with bone loss; however, women with persistently elevated CRP, i.e., ≥3 mg/L at ages 75 and 80 had significantly higher bone loss compared to women with CRP <3 mg/L (TH −0.125 vs. −0.085 g/cm, p = 0.018 and FN −0.127 vs. −0.078 g/cm, p = 0.005) during 10 years of follow-up. Women in the highest CRP quartile had a lower risk of osteoporotic fractures (hazard ratios (HR) 0.76 (95 % confidence intervals (CI) 0.52-0.98)) compared to those in the lowest, even after adjusting for weight and BMD. Mortality risk was only increased among women with the highest CRP levels. Conclusion: CRP was not an indicator for low BMD, bone loss, or fracture in elderly women in this study. Persistently elevated CRP however seemed to be detrimental to bone health and may be associated with a higher rate of bone loss. Only the highest CRP levels were associated with mortality. [ABSTRACT FROM AUTHOR]

Summary: Lower bone mineral density, vitamin D deficiency, lower lean body mass, greater loss of excess weight, and increased bone turnover are complications found after bariatric surgery correlated in the literature with increased risk of fractures. The prevention and treatment of such complications should begin immediately after surgery. Introduction: The aims of the study were to evaluate bone mass in patients undergoing bariatric surgery by the Wittgrove technique after 1 year of the procedure and correlate it with body composition, weight loss, 25OH vitamin D levels, and markers of bone metabolism. Methods: The operated group (OG) participated in a clinical consultation; a blood sample taken and a body composition; and bone mineral density assessment by dual energy X-ray absorptiometry (DXA). The results were compared with a control group (CG). Results: Fifty-six subjects in the OG and 27 in the CG were included. The bone mineral density (BMD), after the surgery, at the lumbar spine (LS) was lower in the OG than in the CG. There was a positive correlation between total body (TB) BMD with 25OHD, body mass index (BMI), and lean mass and an inverse correlation with percentage of excess weight loss (%EWL). Vitamin D deficiency was seen in 60.41 % (OG) and in 16.6 % (CG). PTH was higher in the OG, with secondary hyperparathyroidism in 41.7 %. In 26.5 % and 14.2 % of the OG, ALP and OC levels were above the reference values. In <50 years, elevated values of carboxy-terminal telopeptide (CTX) were found in 66.7 % of patients. A difference was observed in the variation of CTX between 12 and 18 months when compared to over 24 months. Conclusions: Lower BMD was observed, correlated with lower lean body mass and greater loss of excess weight. Vitamin D deficiency with high prevalence of secondary hyperparathyroidism and high bone turnover was detected. The prevention of bone loss should be initiated in the first months after surgery, which is a period associated with severe muscle loss and increased bone turnover. [ABSTRACT FROM AUTHOR]

Summary: Cortical porosity is increasingly recognized as an important risk for fracture in DM patients. The present study demonstrated that decreased cortical thickness, assessed using a newly developed quantitative ultrasonic bone densitometry, is a significant risk factor for vertebral fractures in type 2 diabetes mellitus patients with stage 3 or higher chronic kidney disease, but not in those without. Introduction: Cortical porosity is increasingly recognized as an important risk factor for fracture in type 2 diabetes mellitus (T2DM) patients as well as in stage 3 chronic kidney disease (CKD) patients in whom serum parathyroid hormone (PTH) starts to increase. The present study aimed to clarify whether the coexistence of CKD might affect the relationship of decreased cortical thickness (CoTh) in the development of vertebral fractures (VF) in T2DM patients. Methods: In this cross-sectional study, trabecular bone mineral density (TrBMD), elastic modulus of trabecular bone (EMTb), and CoTh were estimated with a new quantitative ultrasound bone densitometry in 173 T2DM patients. VFs were identified radiographically. Results: Thirty-nine patients (22.5 %) had VF. Those with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m (low eGFR) showed a significantly higher VF rate (32.4 %) than those with eGFR ≥60 mL/min/1.73 m (high eGFR, 16.2 %). Serum PTH was significantly higher with low eGFR than with high eGFR. In those with high eGFR, EMTb was significantly lower in VF(+) than VF(−). In those with low eGFR, TrBMD, EMTb, and CoTh were significantly lower in VF(+) than in VF(−). In a multivariate logistic regression analysis, EMTb was independently and significantly associated with VF in T2DM patients with a high eGFR, in contrast to those with only CoTh with VF in T2DM with low eGFR. Conclusion: This study demonstrated CoTh as a factor independently associated with VF in T2DM patients with low eGFR and increasing serum PTH levels. [ABSTRACT FROM AUTHOR]

Summary: Assessment of serum 25-hydroxyvitamin D levels in association with the occurrence of musculoskeletal diseases using a population-based cohort study design revealed that serum 25-hydroxyvitamin D levels could predict the occurrence of osteoporosis at the femoral neck within 3 years, but not the occurrence of knee osteoarthritis or lumbar spondylosis. Introduction: The aim of this study is to clarify the association between serum 25-hydroxyvitamin D (25D) levels and occurrence of osteoporosis and osteoarthritis in the general population. Methods: The Research on Osteoarthritis/Osteoporosis Against Disability study, a large-scale population-based cohort study, was performed during 2005-2007. Serum 25D levels were measured in 1,683 participants. Of these, 1,384 individuals (81.9 %) completed a second follow-up survey 3 years later. Osteoporosis was defined according to World Health Organization criteria, in which osteoporosis is diagnosed by T-scores of bone mineral density (BMD) that are 2.5 standard deviations (SD) less than normal BMD. Knee osteoarthritis and lumbar spondylosis were defined as Kellgren-Lawrence grade ≥2, using paired X-ray films. Cumulative incidences were determined according to changes in measurements using World Health Organization criteria for osteoporosis or Kellgren-Lawrence grades for osteoarthritis between the baseline and second survey. Results: The mean (SD) serum 25D level of the 1,384 participants in both surveys was 23.4 ng/mL (6.5). The annual cumulative incidences of osteoporosis at L2-4 and the femoral neck were 0.76 and 1.83 %/year, respectively. The incidences of knee osteoarthritis and lumbar spondylosis were 3.3 and 11.4 %/year, respectively. After adjusting for potential associated factors, logistic regression analyses revealed that the odds ratio for the occurrence of femoral neck osteoporosis significantly decreased as serum 25D levels increased (+1 SD; odds ratio 0.67; 95 % confidence interval 0.49-0.92; p = 0.014). Conclusions: Higher serum 25D levels may prevent the occurrence of osteoporosis at the femoral neck, but not knee osteoarthritis, lumbar spondylosis, or osteoporosis at L2-4. [ABSTRACT FROM AUTHOR]

Summary: We examined the association of alcoholic cirrhosis in 33 patients with areal bone mineral density (BMD) and the assessed bone geometric strength of their proximal femora. Lower areal BMD, cross-sectional area and section modulus, thinner cortex, and higher buckling ratio suggest that the alcoholic liver cirrhosis is associated with lower measures of bone strength. Introduction: Hepatic bone disease is an important complication of chronic liver disease and is associated with significant morbidity through fractures resulting in pain, deformity, and immobility. In this study, we examined the association of alcoholic cirrhosis and liver insufficiency stage with areal bone mineral density (aBMD) and additionally employed hip structure analysis (HSA) as an advanced method to assess bone geometric strength of the proximal femur in men with alcoholic liver cirrhosis. Methods: The study included 33 male patients with alcoholic liver cirrhosis and a control group of 36 healthy patients. Laboratory testing included the following biochemical markers of bone turnover: serum levels of osteocalcin and C-telopeptide of type 1 collagen. Areal BMD was measured by dual x-ray absorptiometry on the proximal femora. Structural parameters were then derived from these scans using hip structure analysis software. Results: After adjusting for age, body height, and weight, we found lower cross-sectional area ( p = 0.005) and section modulus ( p = 0.005), thinner cortex ( p = 0.012), and higher buckling ratio ( p = 0.043) in the neck region among patients with cirrhosis. The findings suggest that alcoholic liver cirrhosis is associated with lower measures of bone strength. These findings were consistent with decreased osteocalcin values and increased C-telopeptide of type 1 collagen in patients with cirrhosis, indicating reduction in bone formation and increased bone resorption. Conclusion: Our results emphasize that HSA-derived structural indices of proximal femoral structure may be an important index of greater fragility in patients with alcoholic cirrhosis. [ABSTRACT FROM AUTHOR]

Summary: Fibroblast growth factor 23(FGF23) is a bone-derived hormone which regulates mineral homeostasis but may also have a role in cardiovascular disease. Here, we found that higher plasma FGF23 was independently associated with decreased heart rate variability in stage 5 CKD patients and parathyroidectomy may reverse these abnormal indicators. Introduction: Lower heart rate variability (HRV) in patients with chronic kidney disease (CKD) compared with healthy controls is associated with increased risk of cardiovascular disease (CVD). Higher levels of plasma FGF23 also predict higher risk of CVD. Here, we aimed to evaluate the relationship between plasma FGF23 levels and HRV in patients with stage 5 CKD and to investigate longitudinal changes of them together with the correlation between their changes in two severe secondary hyperparathyroidism (SHPT) subgroups with successful parathyroidectomy (PTX) and persistent SHPT. Methods: This cross-sectional study included 100 stage 5 CKD patients, 78 controls, and a prospective study in two PTX subgroups classified as successful PTX ( n = 24) and persistent SHPT ( n = 4) follow-up. Blood examination and 24-h Holter monitoring for HRV were measured. Results: Most HRV indices were lower in stage 5 CKD patients than in healthy controls, and plasma FGF23 levels were higher. In multivariate stepwise regression models, levels of plasma FGF23 and serum parathyroid hormone (PTH) were correlated with HRV. The successful PTX subgroup had significant improvements over baseline in HRV indices. Persistent SHPT subgroup had numerically similar changes in HRV indices. However, plasma FGF23 levels decreased in both subgroups. Conclusions: Plasma FGF23 levels were higher in CKD patients than in controls, much higher in patients with severe SHPT. FGF23 was independently associated with decreased HRV in stage 5 CKD. Successful PTX may reverse these abnormal indicators and contribute to decreases in the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]