FN BMD Research Articles

Osteoporosis and coronary heart disease: a bi-directional Mendelian randomization study.

Osteoporosis (OP) and cardiovascular disease (CVD) are major global public health issues, especially exacerbated by the challenges of an aging population. As these problems intensify, the associated burden on global health is expected to increase significantly. Despite extensive epidemiological investigations into the potential association between OP and CVD, establishing a clear causal relationship remains elusive. Instrumental variables were selected from summary statistics of the IEU GWAS database. Five different components of BMD (heel BMD, LS BMD, FA BMD, FN BMD, and TB BMD) were used as OP phenotypes. CHD, MI, and stroke were selected to represent CVD. Multiple analysis methods were used to evaluate the causal relationship between CVD and OP comprehensively. In addition, sensitivity analyses(Cochran's Q test, MR-Egger intercept test, and "leave one out" analysis) were performed to verify the reliability of the results. The MR showed a significant causal relationship between CHD on heel BMD and TB BMD; in the reverse analysis, there was no evidence that OP has a significant causal effect on CVD. The reliability of the results was confirmed through sensitivity analysis. The study results revealed that CHD was causally associated with Heel BMD and TB BMD, while in the reverse MR analysis, the causal relationship between OP and CVD was not supported. This result posits CHD as a potential etiological factor for OP and prompts that routine bone density assessment at traditional sites (forearm, femoral neck, lumbar spine) using DAX may inadequately discern underlying osteoporosis issues in CHD patients. The recommendation is to synergistically incorporate heel ultrasound or DAX for total body bone density examinations, ensuring clinical diagnostics are both precise and reliable. Moreover, these findings provide valuable insights for public health, contributing to the development of pertinent prevention and treatment strategies.

Pre-treatment bone mineral density and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into FN BMD T-score subgroups (≤-2.5, > -2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ -2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ -2.5 and > -2.5 subgroups. Compared to those with FN BMD T-score > -2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ -2.5, but only the all-fracture outcome reached statistical significance (interaction P = .001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all, and all clinical fractures in the lower BMD quintiles (all interaction P ≤ .03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above -2.5, though effects tended to be larger and more significant in those with baseline T-scores <-2.5.

Are associations between physical activity and bone mineral density in adults sex- and age-dependent? An analysis of the UK Biobank study.

Although physical activity (PA) is recognized as a key bone mass determinant across life, athlete studies suggest that it may be less effective in women and older individuals. This has not been explored within the general population. We aimed to address this knowledge gap using data from the UK Biobank Study, a large population-based study of middle-aged and older adults. Free-living PA data collected at 100Hz for 7 d using wrist-worn accelerometers were classified as sedentary behavior (0-29 milligravities [mg]), light (30-124mg), or moderate-to-vigorous PA (125 + mg). LS and FN-BMD were assessed using DXA. The associations between PA and BMD were assessed using linear regression models, with formal assessments of sex and age interactions undertaken and adjustments made for accelerometer wear time, height, body mass index, education, ethnicity, disability, and (in women only) menopausal status. In total, 15 133 UK Biobank participants (52% women) had complete PA, bone, and covariate data. In this sample, greater overall and moderate-to-vigorous PA was associated with higher LS BMD. In women, these associations were typically weaker in older individuals, for example, regression coefficients in women aged 70 yr or older were ~50% lower than at 45-54 yr (age-by-PA interactions P< .01 in all models). Similar associations were observed in basic but not full models for FN BMD. Greater sedentary time was associated with lower LS BMD in men only, and greater light PA and sedentary time were associated with higher and lower FN BMD, respectively, in both sexes. These results suggest that associations between PA and bone health at clinically-relevant sites are weaker in older than younger women. That positive associations are evident between overall and moderate-vigorous PA and FN BMD even in women ≥70 yr suggests that PA for bone health should still be promoted in older women.

Response rates for lumbar spine, total hip, and femoral neck bone mineral density in men treated with abaloparatide: results from the ATOM study.

Osteoporosis in men is an underappreciated public health issue, accounting for approximately 30% of the societal burden of osteoporosis. Although the prevalence of osteoporosis in men is lower, fracture-related morbidity and mortality rates exceed those of women. Abaloparatide is a synthetic, 34-amino acid peptide with homology to human parathyroid hormone-related protein (PTHrP), which favors bone formation by selective activation of PTH receptor type 1. In the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM; NCT03512262) trial, 228 men with primary or hypogonadism-associated osteoporosis were randomized to receive subcutaneous injections of abaloparatide 80μg or placebo. Abaloparatide significantly improved LS, TH, and FN BMD when compared with placebo. In this prespecified analysis, the proportion of men with a percent change from baseline of >0%, >3%, and > 6% in BMD at the LS, TH, and FN at 3, 6, and 12mo and/or a shift in T-score category (based on LS and TH T-scores) at 12mo was compared between the abaloparatide and placebo groups in ATOM. There were significantly more men with a BMD gain of >3% at all 3 anatomical sites in the abaloparatide than placebo group at month 6 (18/122 [14.8%] vs 1/70 [1.4%], P = .002) and at month 12 (38/119 [31.9%] vs 1/66 [1.5%], P < .0001). At month 3, more men treated with abaloparatide than placebo had a > 3% BMD increase at the LS (82/134 [61.2%] vs 21/68 [30.9%], P < .0001). A greater proportion of men treated with abaloparatide had an improvement in T-score category from osteoporosis to low BMD or normal when compared with placebo. In conclusion, use of abaloparatide compared with placebo for 12mo resulted in significant and rapid improvements in BMD in men with osteoporosis from the ATOM study.

The nonlinear association between triglyceride glucose-body mass index and femoral neck BMD in nondiabetic elderly men: NHANES 2005-March 2020.

The triglyceride glucose-body mass index (TyG-BMI) has been considered a surrogate marker for assessing insulin resistance. We aimed to correlate the TyG-BMI, triglyceride glucose combined with body mass index, with femoral neck bone mineral density (FN BMD) in non-diabetic elderly men. Using data from the National Health and Nutrition Examination Survey (NHANES) database, totally, 1182 eligible men aged ≥ 50 years without diabetes were included in the current study. Smoothed curves were obtained by a two-piecewise linear regression model and the threshold effects were explored by using a smoothing function. TyG-BMI was positive related with and FN BMD with or without adjustment for confounders. However, no typical dose-dependent positive association between TyG-BMI and FN BMD was observed across the TyG-BMI tertiles, indicating a non-linear association. Further analysis by the weighted two-piecewise linear regression model and recursive algorithm suggested that per SD increase in TyG-BMI increased FN BMD by 0.266 gm/cm2 when TyG-BMI lower than 168.20. However, when TyG-BMI is higher than 168.20, FN BMD only increased 0.046 gm/cm2 for per SD increase of TyG-BMI after fully adjustment (OR = 11.258, 95%CI: 6.034, 16.481). Moreover, subgroup analyses showed that higher TyG-BMI levels were related to elevated FN BMD in all groups, suggesting the consistency of the positive association within these stratas. This study demonstrated that TyG-BMI is positively associated with FN BMD in a nonlinear fashion among elderly men without diabetes, which may be a reliable marker for the early identification of individuals with lower FN BMD.

Height Loss Is an Independent Predictor of Fracture Incidence in Postmenopausal Women: The Results from the Gliwice Osteoporosis Study (GO Study).

The aim of a longitudinal, retrospective study was to establish variables predicting fracture incidence over a decade. The study sample comprises a group of 457 postmenopausal women aged over 55 years, recruited from the database of an outpatient osteoporotic clinic. Several variables with potential influence on bone status, including the measurement of body height and hip bone densitometry, were collected. BMD at the femoral neck (FN BMD) was established using a Prodigy device (Lunar, GE, USA). Current body height was compared with the maximal historical body height in early adulthood, as reported by the patient. Three hundred and ninety-four women did not have fractures during the follow up, and 63 subjects presented fractures. Subjects with fracture had lower FN BMD with a T-score of -1.86 ± 1.04 compared to -1.44 ± 0.89 in those without fractures (p < 0.001). Mean height loss (HL) was 3.47 ± 2.11 cm in fractured subjects and 2.50 ± 2.47 cm in unfractured ones, and differed significantly, p < 0.01. Fracture incidence was significantly related to age, rheumatoid arthritis, falls, and previous fractures. In the multivariable analysis using logistic regression, FN BMD, baseline fracture, and HL were identified as the significant predictors of fractures of follow up. Osteoporotic fractures in postmenopausal women were predicted by FN BMD, prior fracture(s), and HL easily established during physical examination.

Association of C-peptide level with bone mineral density in type 2 diabetes mellitus.

To explore the relationship between C-peptide and BMD and fracture risk in T2DM patients. 530 T2DM patients were enrolled and divided into three groups by FCP tertiles, and the clinical data were collected. BMD was measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of major osteoporotic fractures (MOFs) and hip fractures (HFs) was evaluated by adjusted fracture risk assessment tool (FRAX). In the FCP ≤ 1.14ng/ml group, FCP level was positively correlated with WB, LS, and FN BMD, while FCP was negatively correlated with fracture risk and osteoporotic fracture history. However, FCP was not correlated with BMD and fracture risk and osteoporotic fracture history in the 1.14 < FCP ≤ 1.73ng/ml and FCP > 1.73ng/ml groups. The study has shown that FCP was an independent factor influencing BMD and fracture risk in the FCP ≤ 1.14ng/ml group. There is no significant linear relationship between FCP level and BMD or fracture risk in T2DM patients. In the FCP ≤ 1.14ng/ml group, FCP is positively correlated with WB, LS, and FN BMD and negatively correlated with fracture risk, and FCP is an independent influencing factor of BMD and fracture risk. The findings suggest that FCP may predict the risk of osteoporosis or fracture in some T2DM patients, which has a certain clinical value.

Cross-sectional study and bioinformatics analysis to reveal the correlations of osteoporosis in patients with Parkinson's disease

ObjectivesOsteoporosis and Parkinson's disease (PD) are both aging-related diseases. PD patients with comorbid osteoporosis are vulnerable to the risk of fracture, which leads to a serious public health burden to the whole society. Therefore, this study sought to reveal the clinical and genetic correlations between PD and osteoporosis based on a cross-sectional study and bioinformatics analysis. MethodsA cross-sectional study of 95 PD patients and 99 healthy controls was conducted. Ordinal logistic regression analysis was utilized to investigate the clinical correlations between PD and osteoporosis. Two microarray datasets (GSE20292, GSE35958) including PD, osteoporosis and normal control samples were retrieved from the GEO database for GO analysis, KEGG pathway analysis and PPI network. ResultsPD patients had lower 25(OH)VitD, FN BMD, BMD and T-score of the LS and TH, as well as poorer bone mass diagnosis, yet higher PINP compared to healthy controls. Both age and UPDRS II score of PD patients were adversely correlated with BMD of LS and TH. PD diagnosis acted as an independent risk factor of osteoporosis, and PD patients had approximately double risk for osteoporosis. Bioinformatics analysis further revealed that SNAP25, AQP4, SV2B, KCND3, and ABCA2 had important diagnostic value and risk prediction value for both PD and osteoporosis. ConclusionsPD diagnosis can be used as an independent risk factor for osteoporosis. Moreover, SNAP25, AQP4, SV2B, KCND3 and ABCA2 as the top 5 hub genes have important diagnostic and risk predictive value for both PD and osteoporosis.

Osteoporosis and sarcopenia-related traits: A bi-directional Mendelian randomization study.

BackgroundWith the advancement of world population aging, age-related osteoporosis (OP) and sarcopenia (SP) impose enormous clinical and economic burden on society. Evidence from accumulating studies indicates that they mutually influence one another. However, an observational study may be affected by potential confounders. Meanwhile, a Mendelian randomization (MR) study can overcome these confounders to assess causality.ObjectivesThe aim of this study was to evaluate the causality between OP and SP, informing new strategies for prevention, diagnosis, and treatment of osteosarcopenia.MethodsInstrumental variables (IVs) at the genome‐wide significance level were obtained from published summary statistics, and the inverse variance weighted method and several other MR methods were conducted to evaluate the bi-directional causality between SP and OP. Myopia was analyzed as a negative control outcome to test the validity of IVs.ResultsFemoral neck bone mineral density (FN BMD), lumbar spine BMD (LS BMD), and forearm BMD (FA BMD) had a direct causal effect on appendicular lean mass (ALM) [FA BMD-related analysis: odds ratio (OR) = 1.028, 95% confidence interval (CI) = (1.008,1.049), p = 0.006; FN BMD-related analysis: OR (95% CI) = 1.131 (1.092,1.170), p = 3.18E-12; LS BMD-related analysis: OR (95% CI) = 1.080 (1.062,1.098), p = 2.86E-19]. ALM had a significant causal effect on LS BMD [OR (95% CI) = (1.033,1.147), p = 0.001]. There was no evidence for causal association between BMD and low grip strength.ConclusionsOP and SP might mutually have a significant causal effect on each other. Our results supported the idea that the patient with severe OP was more susceptible to lose ALM and severe ALM loss might reduce LS BMD.

The Effects of Exercise on Bone Mineral Density in Men: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aim of this systematic review and meta-analysis was to provide an updated analysis, including the use of more robust methods, on the effects of exercise on bone mineral density in men. Randomised Control Trials of > 24weeks and published in English up to 01/05/20 were retrieved from 3 electronic databases, cross-referencing, and expert review. The primary outcome measures were changes in FN, LS, and lower limb BMD Standardised effect sizes were calculated from each study and pooled using the inverse heterogeneity model. A statistically significant benefit of exercise was observed on FN BMD [g = 0.21 (0.03, 0.40), Z = 2.23 p = 0.03], with no observed statistically significant benefit of exercise on LS BMD [g = 0.10 (-0.07, 0.26), Z = 1.15 p = 0.25]. This analysis provided additional evidence to recommend ground- and/or joint-reaction force exercises for improving or maintaining FN, but not LS BMD. Additional well-designed RCTs are unlikely to alter this evidence, although interventions that include activities that directly load the lumbar spine are needed to ensure this is not a potential method of improving LS BMD.

The significance of height loss in postmenopausal women. The results from GO Study.

The aim of the study was the assessment of clinical significance of height loss (HL) in female population. The study cohort was recruited from GO Study. Data from 1735 postmenopausal women aged over 55years (mean age 68.15±8.16years) were analysed. Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a device Prodigy (GE, USA). Height was established using stadiometer and was compared with maximal height in early adulthood. The mean HL was 3.9±3.2cm. HL was significantly higher in women with fractures in comparison with those without fracture (4.9±3.6cm vs 3.4±2.8cm; P<.0001). HL increased with the number of fractures, and was 4.1±3.2cm, 5.3±3.5cm and 6.7±4.1cm in women with one, two and three or more fractures respectively. Women with spine fractures presented with HL higher in comparison with all the other subjects (6.3±4.0 vs 3.6±2.9cm, P<.0001) and women with all non-spine fractures (6.3±4.0 vs 4.0±3.0cm, P<.0001). In women with steroid use and falls, HL was significantly greater than in subjects without this factor. HL correlated significantly with age and BMI (positively) and current height (negatively). Mean T-score for FN BMD was -1.75±0.9 and correlate significantly with HL (r=-.21, P<.0001). For the HL threshold above 4cm, the fracture incidence was above 50%. Height loss value is a simple and very informative measure describing fracture risk and functional status in postmenopausal women. HL exceeding 4cm is related to fracture probability above 50%.

Muscle Strength and Physical Performance Are Associated With Risk of Postfracture Mortality But Not Subsequent Fracture in Men.

ABSTRACTMuscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low‐trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed‐effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow‐up of 3.7 (interquartile range [IQR], 1.3–8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8–9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1‐SD) decrement in grip strength: HR 1.12 (95% CI, 1.01–1.25) and gait speed: HR 1.14 (95% CI, 1.02–1.27), and 1‐SD increment in chair stands time: HR 1.08 (95% CI, 0.97–1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1‐SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01–1.33) and in gait speed: HR 1.38 (95% CI, 1.13–1.68), and 1‐SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07–1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%–109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Clinical effectiveness of denosumab, raloxifene, romosozumab, and teriparatide for the prevention of osteoporotic fragility fractures: A systematic review and network meta-analysis.

To determine the clinical effectiveness of denosumab (DEN), raloxifene (RLX), romosozumab (ROMO) and teriparatide (TPTD), within their licensed (or anticipated licensed) indications, for the treatment of osteoporosis. A systematic review was conducted. Nine electronic databases and trial registries were searched up to the end of July 2018. Studies were eligible for inclusion if they were randomised controlled trials (RCT) in a population at risk of osteoporotic fracture, comparing these four non-bisphosphonates DEN, RLX, ROMO, or TPTD with each other, a non-active treatment, or the bisphosphonates alendronate (ALN), risedronate (RIS), ibandronate (IBN) and zoledronic acid (ZOL). Quality of included studies was assessed using the Cochrane Risk of Bias tool. Network meta-analyses (NMA) were used to determine the relative effectiveness of treatments. The systematic review identified 7898 citations. Forty-six RCTs of non-bisphosphonates met the inclusion criteria for the review and provided data for analyses. Additionally 49 RCTs of bisphosphonates were used in the NMAs. Forty-six RCTs were included in the NMA of vertebral fracture data, 23 RCTs for hip fractures and 73 RCTs in the NMA of femoral neck bone mineral density (FN BMD). For vertebral fractures, all four non-bisphosphonates showed statistically significant benefit relative to placebo: TPTD HR 0.23 (95% credible internal (CrI) 0.16, 0.32); ROMO followed by ALN 0.25 (95% CrI 0.15, 0.43); DEN HR 0.30 (95% CrI 0.21, 0.43); RLX HR 0.61 (95% CrI 0.44, 0.80). The four non-bisphosphonates interventions studied also showed statistically significant benefit relative to placebo for FN BMD, and for hip fractures TPTD, ROMO followed by ALN, and DEN showed statistically significant benefit relative to placebo. The four non-bisphosphonate interventions studied were all statistically significantly clinically effective for reducing vertebral fractures when compared to placebo, and were beneficial for change in FN BMD compared to placebo. All reduced hip fractures, and this was statistically significant for TPTD, ROMO followed by ALN, and DEN.

SAT-532 Bisphosphonates Prevent Bone Loss Associated with Denosumab Treatment Discontinuation

Denosumab (DMAb) is a soluble inhibitor of RANKL and, therefore, does not incorporate into the bone matrix. Consistently, DMAb discontinuation is associated with the reversal of the effects attained with treatment. Concerns have been raised regarding possible increased vertebral fragility following denosumab discontinuation due to a rebound in bone turnover to values above pretreatment levels and accompanying rapid bone loss. Bisphophonates administration has been recommended to avoid rapid bone loss but few studies have addressed this question.Aim: Compare BMD and bone turnover markers between patients who had received bisphosphonates after stopping DMab and those who had not.Material &Methods: Postmenopausal women who had received at least two consecutive doses and had discontinued DMab were invited to this prospective and observational study. They were divided into two groups according to whether they had received bisphosphonates or not (Treated Group vs Non-treated Group). Treatment´s decisions were made by each patient and their primary physician.All patients had a DXA scan done (LS and FN) (Lunar Prodigy Advance, software 13.6), spine RX and bone turnovers markers evaluated (C-telopeptide (CTx) (electrochemiluminescence ) and osteocalcin (electrochemiluminescence) baseline (+ 6 months after last DMab ) and annually (+18 months after DMab).Results: 33 postmenopausal women completed the first year of follow up: 23 from the Non-treated Group and 10 from the Treated one. After 18 months of the last DMab dose, in the first group we observed a significant reduction in LS BMD (- 6.4 ± 6.6 %; p < 0.01) and FN BMD (- 6 ± 5.4 %; p <0.01). In the Treated Group, LS BMD was 3.6 ± 4.5% lower than baseline (p=0.05) and FN 1 ± 3.7 % lower (P=0.29). Comparing both groups, there was no significant difference in LS BMD (p= 0.19) but a significant one in FN BMD (p =0.02).CTx values increased 1063 ± 738 % (P < 0.01) in the Non- treated Group and 373 ± 333.5 % in the Treated Group (P <0.01), with a significant difference between them (P< 0.01). Osteocalcin increased 264 ± 200 % (P <0.01) and 131 ± 102 % (p <0.01) respectively, with no significant differences between groups (P 0.06). No new vertebral fractures were found in any patient ´s spine RX.Conclusion: In this study,we showed that bisphosphonates decreased bone loss both in LS and FN after DMab discontinuation and prevented the rebound of bone remodeling markers.More studies are needed to confirm the role of bisphosphonates in the long term and the best strategy to give them. Meanwhile, it is important to enhance physicians’ awareness of the need to start bisphosphonates after discontinuing DMab.

Bone Variables in Active Overweight/Obese Men and Sedentary Overweight/Obese Men

The aim of this study was to compare bone variables in active overweight/obese men and sedentary overweight/obese men. Thirty-seven active overweight/obese men and 45 sedentary overweight/obese men participated in this study. Weight and height were measured, and body mass index was calculated. Body composition and bone variables (bone mineral content [BMC], bone mineral density [BMD], geometric indices of hip bone strength, and trabecular bone score) were measured by DXA. Physical activity level, daily calcium intake, daily protein intake, and sleep duration were measured by validated questionnaires. Maximum oxygen consumption (VO2 max) was determined by direct measurement while exercising on a medical treadmill. One-repetition-maximum half-squat of the lower limbs was measured using a validated protocol. Body weight and body mass index were higher in sedentary overweight/obese men than in active overweight/obese men. In the whole population (n = 82), VO2 max (in liter per minute), lean mass, and one-repetition-maximum half-squat were positively correlated to BMC, BMD, and geometric indices of hip bone strength (cross-sectional area and section modulus [Z] of the femoral neck [FN]). After adjusting for body weight using a 1-way analysis of covariance, active overweight/obese men displayed higher whole-body BMC, lumbar spine BMD, total hip BMD, FN BMD, FN cross-sectional area, and FN Z values than sedentary overweight/obese men. In conclusion, the current study suggests that physical activity level positively affects bone variables in overweight/obese men. Optimizing lean mass and muscular strength of the lower limbs can help to prevent osteoporosis in overweight and obese men.

Muscle mass is associated with incident fracture in postmenopausal women: The OFELY study

The relationships between body composition and bone mineral density are well established but the contribution of body composition to the risk of fracture (Fx) has rarely been evaluated prospectively. We analyzed the risk of Fx by body composition in 595 postmenopausal women (mean age 66±8years) from a longitudinal cohort study (Os des Femmes de Lyon). We assessed the risk of the first incident fragility Fx according to body composition obtained from whole-body DXA: abdominal visceral (VFAT) and subcutaneous fat mass (SFAT), total body fat mass (FM), lean mass index (LMI) and appendicular skeletal muscle mass index (ASMI).During a median [IQ] follow-up of 13.1years [1.9], 138 women sustained a first incident Fx, including 85 women with a major osteoporotic Fx (MOP Fx: hip, clinical spine, humerus or wrist). After adjustment for age, women who sustained Fx had lower BMI (−4%, p=0.01), LMI (−6%, p=0.002) and ASMI (−3%, p=0.003), compared with women without Fx. After adjustment for age, prevalent Fx, physical activity, incident falls and FN BMD, each SD increase of baseline values of LMI and ASMI was associated with decreased Fx risk with adjusted hazard ratios of 0.76 for both of p≤0.02. Those associations were similar after accounting for the competing risk of death. VFAT and SFAT were associated with Fx risk in the multivariate model only for MOP Fx and the association did not persist after consideration of competing mortality.We conclude that lean mass and appendicular muscle mass indexes are associated with the risk of fracture in postmenopausal women independently of BMD and clinical risk factors.

DXA-based variables and osteoporotic fractures in Lebanese postmenopausal women

IntroductionThe aim of this study was to assess DXA-based variables (bone mineral density, bone mineral apparent density, compressive strength index of the femoral neck and trabecular bone score) in Lebanese postmenopausal women having presented a previous fracture. Materials and methodsOne thousand Lebanese postmenopausal women between 45 and 89 years participated in this study. The women were recruited by advertisements offering bone mineral density measurements at a reduced cost. Subjects with previous history of radiotherapy or chemotherapy were excluded. Informed written consent was obtained from all the participants. ResultsFemoral neck compressive strength index (FN CSI) was significantly (P<0.001) associated with the presence of fracture using a simple logistic regression (odds ratio=0.51 [0.385–0.653]). When a multivariate logistic regression analysis was performed with the presence of fracture as a dependent variable and each of age, FN BMD and FN CSI as independent variables, only FN BMD (P=0.005) and FN CSI (P=0.004) were found to be associated with the presence of fracture. ConclusionThis study suggests that FN CSI is associated with history of osteoporotic fractures in postmenopausal women. The use of FN CSI in clinical practice may help to identify patients with high risk of fracture. Level of evidenceEpidemiological study, level IV.

Type of Fracture Is an Independent Determinant of Long-Term Mortality in Older Patients With Hip Fracture: Systematic Review and Meta-Analysis of Longitudinal Studies

s 423 Results: In our study group, mean age was 61.1 11.7 years and mean BMI was 27.9 5.3 kg/m. At the time of baseline DXA scan, women with incident fracture (n5164) were shorter (1.527 0.065 m vs. 1.560 0.078 m; P!0.001), were older (65.0 11.5 years vs. 60.4 11.6 years; P!0.001), had a higher BMI (29.4 5.3 kg/m vs. 27.6 5.3 kg/m; P!0,001), had a lower femoral neck BMD (0.736 0.120 g/cm vs. 0.796 0.158 g/cm; P!0.001) and had a lower FN CSI (3.55 0.74 g/kg m vs. 3.88 0.81 g/kg m; P!0.001) than women without fracture (n5836). Body weight was not significantly different between women with incident fracture and women without simple logistic regression (odds ratio [95%CI]50.51 [0.385-0.653]). Femoral neck BMD was significantly (P!0.001) associated with the presence of fracture using a simple logistic regression (odds ratio [95%CI]50.041 [0.011-0.152]). Age, height and BMI were also significantly associated with the presence of fracture using simple logistic regressions (P! 0.001). When a multivariate logistic regression analysis was performed with the presence of fracture as a dependent variable and each age, FN BMD and FN CSI as independent variables, only FN BMD (P50.005) and FN CSI (P50.004) were found to be associated with the presence of fracture. Conclusion: This study suggests that FN CSI is an independent predictor of osteoporotic fractures in postmenopausal women. Further research is needed to determine the relative importance of FN CSI on fracture risk prediction in postmenopausal women.

E-15 Thematic Poster - Aging and Skeletal Muscle

PURPOSE: The Bone-Specific Physical Activity Questionnaire (BPAQ) was designed to provide researchers with a tool to control the previous bone-relevant exercise history of participants enrolled in bone-targeted exercise intervention trials. We sought to determine whether short-term changes in BPAQ score induced by a 9-month bone-targeted intervention would correspond to changes in markers of bone strength in premenopausal women. METHODS: 391 women (age 23.4±4.5 y, BMI 22.7±2.7 kg/m2) were randomized into 9 jumping groups representing three jump heights (4, 8, or 12-inch step) and three jump repetition schemes (10, 50, 100 jumps per session) or a control group. Subjects stepped up and jumped off of a step for their required reps 3 d/wk for 9 months. Femoral neck bone mineral density (FN BMD) and Femoral Strength Index (FSI) (a computed surrogate of bone strength that takes into account bone geometry and BMD of the hip) of bilateral proximal femurs using DXA (Lunar Prodigy Advance) and BPAQ scores were measured at baseline and after the 9-month intervention. Ground reaction force and loading rate were determined every 3 months via force platform (Kistler). An average effective load stimulus for each step height used for jumping was determined using the BPAQ algorithms described by Weeks & Beck (2008). PPM correlation coefficients were determined for percent change in BMD and FSI vs percent change in BPAQ score. RESULTS: The 211 subjects (54%) who jumped at least 2 days/wk and completed all measurements were included in the analyses. Bone at the proximal femur responds well to low loading volume in that as few as 25 jumps/wk at a magnitude of 3 times body weight improves FSI by 9% although higher impacts may negatively impact bone (details presented elsewhere). While the pre- and post-test values for FN BMD and FSI correlated positively with BPAQ scores (r=0.18, r=0.14 and r=0.17, respectively, p<0.05), percent change in FN BMD and FSI was not related to percent change in BPAQ score during the intervention. CONCLUSIONS: Absolute BPAQ score was related to FN BMD and FSI before and after the intervention, but percent change in BPAQ score was not related to percent change in bone parameters. The BPAQ may be insufficiently sensitive to detect very modest short term change in parameters of bone strength. Supported by NIH SC3GM08705

Circulating irisin is associated with osteoporotic fractures in postmenopausal women with low bone mass but is not affected by either teriparatide or denosumab treatment for 3 months

In vitro data suggest that myokine irisin may affect bone metabolism by promoting osteoblast differentiation while inhibiting osteoclast differentiation. In this study, circulating irisin levels were associated with previous osteoporotic fractures but not with bone mass and were not affected by denosumab or teriparatide treatment for 3months. This study aimed to evaluate predictors of circulating irisin in postmenopausal women with low bone mass and to assess a potential effect of denosumab or teriparatide treatment for 3months. Serum samples for irisin measurement were obtained from (a) postmenopausal women with low bone mass (lumbar spinal [LS] or femoral neck [FN] bone mineral density [BMD] T-score ≤-2.0) and their age-matched controls at baseline and 3months after denosumab (Dmab) injection (Dmab group, n = 50; Dmab control group, n = 25) and (b) women with more severe disease (LS or FN BMD T-score ≤-2.8) and their age-matched controls at the above-mentioned time points after teriparatide (TPTD) initiation (TPTD group, n = 25; TPTD control group, n = 25). At baseline, irisin levels were inversely correlated with age (partial coefficient (r p ) = -0.24; p = 0.009), parathyroid hormone (PTH) (r p = -0.30; p = 0.001), and creatinine (r p = -0.23; p = 0.016) in univariate analysis, and were lower in women with (n = 26; 41.6 ± 2.7ng/dL) than without previous osteoporotic fracture(s) (n = 99; 51.0 ± 1.6ng/dL; p = 0.007). In multiple linear regression, previous osteoporotic fracture(s) and PTH were independently negatively associated with irisin [p = 0.04, CI -16.1 to -0.4 and p = 0.002, CI -0.3 to -0.07, respectively], but only the association with PTH remained after controlling for creatinine levels. Serum irisin levels were not different between women with or without low bone mass and were not affected by either Dmab or TPTD treatment for 3months. Circulating irisin levels were associated with previous osteoporotic fracture(s); whether this association is independent or is due to confounding by lower muscle mass, potentially reflected by lower creatinine levels, remains to be fully clarified.