Romosozumab efficacy and safety in European patients enrolled in the FRAME trial.

In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density. INTRODUCTION: In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study. METHODS: In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME. RESULTS: In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p < 0.001), new vertebral fracture (0.4% versus 2.1%; p < 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p < 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups. CONCLUSIONS: Among European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab.

Zoledronic acid reduces the rate of clinical fractures after surgical repair of a hip fracture regardless of the Pretreatment bone mineral density.

In patients with surgical repair of a low-trauma hip fracture, zoledronic acid (ZA) reduced the risk of subsequent fractures regardless of pretreatment femoral neck and total hip bone mineral density (BMD). INTRODUCTION: Zoledronic acid reduces the risk of subsequent fractures after repair of a hip fracture. It is still unclear whether the benefits in fracture reduction with ZA depend upon hip bone mineral density at the time of fracture. METHODS: We preformed additional post hoc analyses of data from the HORIZON Recurrent Fracture Trial to determine if ZA treatment reduced the risk of new clinical fractures regardless of pretreatment BMD. We modeled femoral neck and total hip BMD as both continuous and dichotomous variables (BMD T-score above and below -2.5). RESULTS: There are no evidence that baseline femoral neck and total hip BMD modified the anti-fracture efficacy of ZA when pretreatment BMD was analyzed as a continuous or a dichotomous variable (interaction p-values > 0.20). The clinical fracture efficacy of ZA was similar among patients with pretreatment femoral neck BMD values above and below -2.5 (relative hazards = 0.60 and 0.67, respectively, interaction p-value = 0.95). A similar result was obtained using pretreatment total hip BMD values (relative hazards = 0.72 and 0.57, respectively, interaction p-value = 0.41). CONCLUSION: There data should provide more comfort in prescribing ZA after surgical repair of a hip fracture, regardless of pretreatment BMD.

Bisphosphonate drug holidays in postmenopausal osteoporosis: effect on clinical fracture risk.

A cohort of 183 postmenopausal women, who had either discontinued or continued bisphosphonates (BPs) after first-line therapy, was used to investigate the relationships between "drug holiday" and clinical fracture. The risk of new clinical fractures was found to be 40% higher in women who had taken a BP "drug holiday." INTRODUCTION: BPs are the most widely used treatment for postmenopausal osteoporosis. The optimal treatment duration, however, remains unclear. The purpose of this study was to evaluate the fracture risk in postmenopausal women with osteoporosis after discontinuing BP treatment (BP "drug holiday"). METHODS: A retrospective analysis was performed at Lille University Hospital (LUH) on postmenopausal women with osteoporosis who had taken a "drug holiday" or continued treatment after first-line BP therapy (3 to 5 years). The occurrence of new clinical fractures during follow-up was also explored. Cox proportional hazards models were used to investigate the relationships between BP "drug holiday" and the occurrence of clinical fractures, while controlling for confounding factors. Survival without new clinical fractures was analyzed using Kaplan-Meier curves and log-rank tests. RESULTS: One hundred eighty-three women (mean age: 61.8 years; SD: 8.7) who had previously undergone BP treatment for 3 to 5 years were enrolled in our study. The patients had received alendronate (n = 81), risedronate (n = 73), zoledronic acid (n = 20), and ibandronate (n = 9). In 166 patients ("drug holiday" group: n = 31; continuous-treatment group: n = 135), follow-up ranged from 6 to 36 months (mean duration: 31.8 months; SD: 8.2). The incidences of new clinical fractures during follow-up were 16.1% (5/31) and 11.9% (16/135). After full adjustment, the hazard ratio of new clinical fractures among "drug holiday" patients was 1.40 (95% CI: 1.12-1.60; p = 0.0095). CONCLUSIONS: After first-line BP therapy in postmenopausal women with osteoporosis, the risk of new clinical fractures was 40% higher in subjects who took a bisphosphonate drug holiday.

Exercise and fractures in postmenopausal women. Final results of the controlled Erlangen Fitness and Osteoporosis Prevention Study (EFOPS).

UNLABELLED: The EFOPS trial clearly established the positive effect of long-term exercise on clinical low-trauma fractures in postmenopausal women at risk. Bearing in mind that the complex anti-fracture exercise protocols also affect a large variety of diseases of increased age, we strongly encourage older adults to perform multipurpose exercise programs. INTRODUCTION: Physical exercise may be an efficient option for autonomous fracture prevention during increasing age. The aim of the study was to evaluate the effect of exercise on clinical overall fracture incidence and bone mineral density (BMD) in elderly subjects at risk. METHODS: In 1998 initially, 137 early-postmenopausal, osteopenic women living in Erlangen-Nuremberg, Germany, were included in the EFOPS trial. Subjects of the exercise group (EG; n = 86) conducted two supervised group and two home exercise sessions/week while the control group (CG; n = 51) was requested to maintain their physical activity. Primary study endpoints were clinical overall low-trauma fractures determined by questionnaires, structured interviews, and BMD at the lumbar spine and femoral neck assessed by dual-energy X-ray absorptiometry. RESULTS: In 2014, 105 subjects (EG: n = 59 vs. CG: n = 46) representing 1680 participant-years were included in the 16-year follow-up analysis. Risk ratio in the EG for overall low-trauma fractures was 0.51 (95% confidence interval (95% CI) 0.23 to 0.97, p = .046), rate ratio was 0.42 (95% CI 0.20 to 0.86, p = .018). Based on comparable baseline values, lumbar spine (MV -1.5%, 95% CI -0.1 to -2.8 vs. -5.8%, -3.3 to -7.2%) and femoral neck (-6.5%, -5.2 to -7.7 vs. -9.6%, -8.2 to 11.1%) BMD decreased in both groups; however, the reduction was more pronounced in the CG (p ≤ .001). CONCLUSION: This study clearly evidenced the high anti-fracture efficiency of multipurpose exercise programs. Considering furthermore the favorable effect of exercise on most other risk factors of increasing age, we strongly encourage older adults to perform multipurpose exercise programs.

Association of serum uric acid with bone mineral density and clinical fractures in Chinese type 2 diabetes mellitus patients: A cross-sectional study.

BACKGROUND: We evaluate the associations of serum uric acid (UA) with bone mineral density (BMD) and prevalence of clinical fractures in type 2 diabetes mellitus (T2DM) patients. METHODS: 1562 T2DM patients undergoing BMD measurement and clinical fractures assessment were enrolled andserum UA concentrations were measured. RESULTS: T2DM patients with osteoporosis had lower serum UA concentrations compared with those with normal BMD values and osteopenia. Serum UA concentration was significantly correlated with BMD values at the lumbar spine, femoral neck, and total hip in postmenopausal women, and serum UA concentration was positively associated with BMD values at the lumbar spine in men. Moreover, patients with clinical fractures had lower serum UA than those without. Multiple logistic regression analysis showed that serum UA concentrations were significantly and inversely associated with the presence of clinical fractures after adjustment for age, BMI, diabetes duration, fasting blood glucose (FBG), Glycated hemoglobin A1c (HbA1c), alkaline phosphatase (ALP), creatinine (Cr), neutrophil to lymphocyte ratio (NLR), diabetic vascular complications [men: OR = 0.996, 95% CI = 0.993-1.000, P = 0.039; women: OR = 0.996,95% CI = 0.994-0.998, P = 0.001]. The results were not statistically significant when models were further adjusted for BMD values at each site. CONCLUSIONS: Lower serum UA concentrations may be associatedwith lower BMD values and higher prevalence of clinical fractures independent of potential confounders except for BMD values at each site. These findings need to be confirmed by further prospective studies.

Real-world effectiveness of daily teriparatide in Japanese patients with osteoporosis at high risk for fracture: final results from the 24-month Japan Fracture Observational Study (JFOS).

OBJECTIVE: The Japan Fracture Observational Study (JFOS), a prospective observational study, investigated the real-world effectiveness of daily teriparatide to reduce clinical fracture risk in osteoporotic patients. METHODS: In routine clinical practice, Japanese patients initiated on teriparatide 20 µg/day by subcutaneous injection were enrolled. The primary end-point was the rate of clinical fractures at 6-month intervals over 24 months. Bone mineral density (BMD), procollagen type 1 aminoterminal propeptide (P1NP), back pain, and health-related quality-of-life (HRQoL) information was collected. RESULTS: Of 1,996 patients at baseline, 90.1% were female, and mean age was 76.9 years. Teriparatide persistence at 12 and 24 months was 68.0% and 51.6%, respectively. Compared to the first 6-month treatment interval, the odds ratio of fractures decreased by 56.4% during 6-12 months, 51.6% during 12-18 months, and 58.8% during 18-24 months (all p < .01). After 24 months, BMD increased by 17.2% (lumbar spine) and 7.9% (total hip). After 6 months, P1NP levels increased by 259.3%. A reduction in back pain (100 mm visual analog scale) of 16.1 mm at 3 months was maintained through 24 months. HRQoL (pain, daily living activities, general health) improved by ≥10% at each post-baseline time point. Of 279 (14.6%) patients with ≥1 adverse event (AE), 71 (3.7%) experienced ≥1 drug-related AE (investigator assessed), including nausea (0.7%), dizziness (0.4%), and decreased appetite (0.3%). Osteosarcoma was not reported; there were no new safety signals. CONCLUSIONS: JFOS demonstrated effectiveness of teriparatide 20 µg/day to reduce the risk of clinical fractures in Japanese patients in a real-world setting.