Search

Summary: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82 %, with 66 patients (7 %) reporting serious adverse events and 19 patients (2 %) reporting fractures. Introduction: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. Methods: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). Results: Among 935 patients (mean age 71 years), mean baseline T-scores were −2.18 (femoral neck) and −2.00 (lumbar spine); 50 % of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly ( p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > −2.5, and treatment by female physicians (US). Lower persistence was associated ( p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7 %); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2 %) reported osteoporotic fractures. Conclusions: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: The Safe Functional Motion test (SFM) was developed to document movement strategies used to perform everyday activities that may increase the risk for osteoporotic fracture. After adjusting for variables known to predict vertebral compression fracture (VCF), baseline score on the SFM was a significant independent predictor of incident VCF at 1- and 3-year follow-ups. Introduction: Functional movements may contribute to risk for VCF. We hypothesize that scores on the SFM, a performance-based test of physical function, are associated with incident VCF. Methods: An osteoporosis clinic database was queried for men and women ≥50 years with an initial SFM and corresponding data for prevalent VCF, history of injurious falls, femoral neck bone mineral density (fnBMD), osteoporosis medication use, and incident morphometric VCF at 1-year ( n = 878) and 3-year follow-ups ( n = 503). Multiple logistic regressions, adjusted for gender, age, injurious fall(s), fnBMD, prevalent VCF at baseline, and osteoporosis medication use, were used to determine whether SFM score was associated with incident VCF at follow-up visits. Results: Baseline SFM score was a significant independent predictor of incident VCF at 1-year follow-up (adjusted odds ratio (95 % confidence intervals (CI)) = 0.818 (0.707, 0.948); p < 0.008) and 3-year follow-up (adjusted odds ratio (95 % CI) = 0.728 (0.628, 0.844); p < 0.0001). Baseline fnBMD and osteoporosis medication use were significant predictors at 1-year ( p = 0.05 and < 0.0001, respectively) and 3-year ( p < 0.01 and 0.001, respectively) follow-ups. At 3-year follow-up, gender and prevalent VCF were also significant predictors ( p = 0.003 and 0.007, respectively). Conclusions: For every 10-point increase in SFM score, the odds of future VCF decreases by 18 % at 1 year and 27 % at 3 years after adjusting for known covariates. The SFM may aid in the identification of modifiable functional risk factors for VCF. [ABSTRACT FROM AUTHOR]

Summary: The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. Introduction: This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. Methods: In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 μg/day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. Results: At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine ( p = 0.001) and femoral neck ( p = 0.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral fractures were less severe ( p = 0.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. Conclusions: Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate. [ABSTRACT FROM AUTHOR]

Summary: Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Introduction: Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. Methods: In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia ( n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol ( n = 135), ibuprofen ( n = 137) or placebo ( n = 137), or placebo + placebo ( n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. Results: The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. Conclusion: Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg. [ABSTRACT FROM AUTHOR]

Summary: Patients in the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Recurrent Fracture Trial were assessed for evidence of delayed hip fracture healing. No association was observed between zoledronic acid (ZOL) and delayed healing. We conclude that ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. Introduction: Intravenous zoledronic acid 5 mg (ZOL) given after a hip fracture reduces secondary fracture rates and mortality. It has been postulated that bisphosphonates may affect healing if given soon after a fracture. We sought to determine whether the timing of ZOL infusion affected the risk of delayed hip fracture healing. Methods: In the HORIZON Recurrent Fracture Trial, patients were randomized within 90 days of a low-trauma hip fracture to receive either once-yearly ZOL ( n = 1,065) or placebo ( n = 1,062). Clinical symptoms of delayed hip fracture healing were sought at randomization, 6 months and 12 months after fracture; if present, a central adjudication committee blinded to treatment assignment reviewed radiographs and clinical records. Median follow-up was 1.9 years. Results: The overall incidence of delayed healing was 3.2% (ZOL) and 2.7% (placebo; odds ratio [OR], 1.17; 95% confidence interval [CI], 0.72-1.90; p = 0.61). Logistic regression models revealed no association between ZOL and delayed healing even after adjusting for other risk factors (OR, 1.21; 95% CI, 0.74-1.99; p = 0.44). There was no interaction by timing of infusion, and nonunion rates were similar even when ZOL was given within 2 weeks of hip fracture repair. NSAID use was significantly associated with delayed fracture healing (OR, 2.55; 95% CI, 1.49-4.39; p < 0.001). Conclusions: ZOL has no clinically evident effect on fracture healing, even when the drug is infused in the immediate postoperative period. [ABSTRACT FROM AUTHOR]