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Summary Determinants of trabecular bone score (TBS) and vertebral fractures assessed semiquantitatively (SQ1–SQ3) were studied in 496 women with fragility fractures. TBS was associated with age, parental hip fracture, alcohol intake and BMD, not SQ1–SQ3 fractures. SQ1–SQ3 fractures were associated with age, prior fractures, and lumbar spine BMD, but not TBS. Introduction Trabecular bone score (TBS) and vertebral fractures assessed by semiquantitative method (SQ1–SQ3) seem to reflect different aspects of bone strength. We therefore sought to explore the determinants of and the associations between TBS and SQ1–SQ3 fractures. Methods This cross-sectional sub-study of the Norwegian Capture the Fracture Initiative included 496 women aged ≥ 50 years with fragility fractures. All responded to a questionnaire about risk factors for fracture, had bone mineral density (BMD) of femoral neck and/or lumbar spine assessed, TBS calculated, and 423 had SQ1–SQ3 fracture assessed. Results Mean (SD) age was 65.6 years (8.6), mean TBS 1.27 (0.10), and 33.3% exhibited SQ1–SQ3 fractures. In multiple variable analysis, higher age (βper SD = − 0.26, 95% CI: − 0.36,− 0.15), parental hip fracture (β = − 0.29, 95% CI: − 0.54,− 0.05), and daily alcohol intake (β = − 0.43, 95% CI − 0.79, − 0.08) were associated with lower TBS. Higher BMD of femoral neck (βper SD = 0.34, 95% CI 0.25–0.43) and lumbar spine (βper SD = 0.40, 95% CI 0.31–0.48) were associated with higher TBS. In multivariable logistic regression analyses, age (ORper SD = 1.94, 95% CI 1.51–2.46) and prior fragility fractures (OR = 1.71, 95% CI 1.09–2.71) were positively associated with SQ1–SQ3 fractures, while lumbar spine BMD (ORper SD = 0.75 95% CI 0.60–0.95) was negatively associated with SQ1–SQ3 fractures. No association between TBS and SQ1–SQ3 fractures was found. Conclusion Since TBS and SQ1–SQ3 fractures were not associated, they may act as independent risk factors, justifying the use of both in post-fracture risk assessment.

Altres ajuts: The present study was supported by the Allgemeine Unfallversicherungsanstalt (AUVA), research funds of the Austrian workers compensation board, and the Wiener Gebietskrankenkasse (WGKK), Viennese sickness insurance funds. Long-term antiresorptives use has been linked to atypical subtrochanteric and diaphyseal femoral fractures (AFF), the pathogenesis of which is still unknown. In the present case report we present the results of analysis of bone chips from a 74-year old female patient that had been on alendronate, ibandronate and denosumab treatment, and who sustained an atypical femoral fracture, by histology, quantitative backscattered electron imaging, and Raman spectroscopic analysis. The results indicate ongoing osteoclastic resorption, but also several abnormalities: 1) an altered arrangement of osteons; 2) impaired mineralization; 3) the presence of pyrophosphate, which might contribute to the impaired mineralization evident in the present case. Taken together, these changes may contribute to the focally reduced bone strength of this patient.

Importance Fragility fracture is a major health issue because of the accompanying morbidity, mortality, and financial cost. Despite the high cost to society and personal cost to affected individuals, secondary fracture prevention is suboptimal in Norway, mainly because most patients with osteoporotic fractures do not receive treatment with antiosteoporotic drugs after fracture repair. Objectives To improve secondary fracture prevention by introducing a standardized intervention program and to investigate the effect of the program on the rate of subsequent fractures. Design, Setting, and Participants Trial protocol of the Norwegian Capture the Fracture Initiative (NoFRACT), an ongoing, stepped wedge cluster randomized clinical trial in 7 hospitals in Norway. The participating hospitals were cluster randomized to an intervention starting date: May 1, 2015; September 1, 2015; and January 1, 2016. Follow-up is through December 31, 2019. The outcome data were merged from national registries of women and men 50 years and older with a recent fragility fracture treated at 1 of the 7 hospitals. Discussion The NoFRACT trial is intended to enroll 82 000 patients (intervention period, 26 000 patients; control period, 56 000 patients), of whom 23 578 are currently enrolled by January 2018. Interventions include a standardized program for identification, assessment, and treatment of osteoporosis in patients with a fragility fracture that is led by a trained coordinating nurse. The primary outcome is rate of subsequent fracture (per 10 000 person-years) based on national registry data. Outcomes before (2008-2015; control period) and after (2015-2019; intervention period) the intervention will be compared, and each hospital will act as its own control. Use of outcomes from national registry data means that all patients are included in the analysis regardless of whether they are exposed to the intervention (intention to treat). A sensitivity analysis with a transition window will be performed to mitigate possible within-cluster contamination. Results Results are planned to be disseminated through publications in peer-reviewed journals and presented at local, national, and international conferences. Conclusions By introducing a standardized intervention program for assessment and treatment of osteoporosis in patients with fragility fractures, we expect to document reduced rates of subsequent fractures and fracture-related mortality. This is an open access article distributed under the terms of the CC-BY License.

Elevated plasma homocysteine levels are associated with increased risk of fractures in observational studies. However, it is unsettled whether homocysteine-lowering treatment affects fracture risk. The aim of this study was to investigate the effect of an intervention with B vitamins on the risk of hip fracture in a secondary analysis of combined data from two large randomized controlled trials originally designed to study cardiovascular diseases. Both trials had identical design, intervention, and primary objective. Based on a two-by-two factorial design, the intervention consisted of a daily capsule with either (1) folic acid (0.8 mg) plus vitamin B12 (0.4 mg) and vitamin B6 (40 mg); (2) folic acid (0.8 mg) plus vitamin B12 (0.4 mg); (3) vitamin B6 alone (40 mg); or (4) placebo. The participants were followed with respect to hip fracture during the trial or during an extended follow-up (from the trial start for each patient until the end of 2012). No statistically significant association was found between folic acid plus vitamin B12 treatment and the risk of hip fracture, neither during the trial (median 3.3 years; hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.48 to 1.59) nor during the extended follow-up (median 11.1 years; HR 1.08; 95% CI, 0.84 to 1.40). Nor were there significant differences in the risk of hip fracture between groups receiving versus not receiving vitamin B6 during the trial (HR 1.42; 95% CI, 0.78 to 2.61). However, during the extended follow-up, those receiving vitamin B6 showed a significant 42% higher risk of hip fracture (HR 1.42; 95% CI, 1.09 to 1.83) compared to those not receiving vitamin B6. In conclusion, treatment with folic acid plus vitamin B12 was not associated with the risk of hip fracture. Treatment with a high dose of vitamin B6 was associated with a slightly increased risk of hip fracture during the extended follow-up (in-trial plus post-trial follow-up). © 2017 American Society for Bone and Mineral Research. This is the pre-peer reviewed version of the following article: [B Vitamins and Hip Fracture: Secondary Analyses and Extended Follow-Up of Two Large Randomized Controlled Trials], which has been published in final form at [http://onlinelibrary.wiley.com/doi/10.1002/jbmr.3189/abstract]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

To determine the efficacy of once-yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women.A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial.Multicenter, randomized, double-blind, placebo-controlled trials.Postmenopausal women (agedor =75) with documented osteoporosis (T-scoreor =-2.5 at femoral neck or/=1 prevalent vertebral or hip fracture) or a recent hip fracture.Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n=1,961) or placebo (n=1,926) at baseline and 12 and 24 months.Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment.At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR)=0.65, 95% confidence interval (CI)=0.54-0.78, P.001; HR=0.34, 95% CI=0.21-0.55, P.001; and HR=0.73, 95% CI=0.60-0.90, P=.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups.Once-yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis.