Time to Benefit of Bisphosphonate Therapy for the Prevention of Fractures Among Postmenopausal Women With Osteoporosis

Abstract

IMPORTANCEThe clinical decision to initiate bisphosphonate therapy for the treatment of osteoporosis requires balancing shorter-term harms and burdens (eg, gastroesophageal irritation or severe musculoskeletal pain) with longer-term benefits in reducing potential fractures.OBJECTIVE To assess the time to benefit (TTB) of bisphosphonate therapy for the prevention of nonvertebral and other fractures among postmenopausal women with osteoporosis.DATA SOURCES Randomized clinical trials (RCTs) were identified from systematic reviews commissioned by the US Preventive Services Task Force (1 review), the Agency for Healthcare Research and Quality (1 review), the Cochrane Library (2 reviews), and the Endocrine Society (1 review).STUDY SELECTION Studies selected were RCTs involving postmenopausal women with a diagnosis of osteoporosis based on existing vertebral fractures or bone mineral density T scores of −2.5 or lower. The selection process was focused on studies of alendronate, risedronate, and zoledronic acid because they are guideline-recommended first-line agents for reducing nonvertebral fractures. Studies were excluded if they did not focus on women with a primary diagnosis of osteoporosis, had no placebo arm, or had a lack of data on time to fracture.DATA EXTRACTION AND SYNTHESIS Random-effects Weibull survival curves were fitted and Markov chain Monte Carlo methods were used to estimate the absolute risk reduction (ARR) and TTB for each study. These estimates were pooled using a random-effects meta-analysis model. MAIN OUTCOMES AND MEASURESThe primary outcome was the time to 3 different ARR thresholds (0.002, 0.005, and 0.010) for the first nonvertebral fracture. Secondary outcomes included the time to 4 ARR thresholds (0.001, 0.002, 0.005, and 0.010) for hip fracture, any clinical fracture, and clinical vertebral fracture. RESULTSOf 67 full-text articles identified, 10 RCTs comprising 23 384 postmenopausal women with osteoporosis were included either as the original RCT or part of subsequently published pooled analyses. Among the studies, the number of participants ranged from 994 to 7765, with mean (SD) age ranging from 63 (7) years to 74 (3) years and follow-up duration ranging from 12 to 48 months. The pooled meta-analysis found that 12.4 months (95% CI, 6.3-18.4 months) were needed to avoid 1 nonvertebral fracture per 100 postmenopausal women receiving bisphosphonate therapy at an ARR of 0.010. To prevent 1 hip fracture, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 20.3 months (95% CI, 11.0-29.7 months) at an ARR of 0.005. In addition, 200 postmenopausal women with osteoporosis would need to receive bisphosphonate therapy for 12.1 months (95% CI, 6.4-17.8 months) to avoid 1 clinical vertebral fracture at an ARR of 0.005. CONCLUSIONS AND RELEVANCEThis meta-analysis found that the TTB of bisphosphonate therapy was 12.4 months to prevent 1 nonvertebral fracture per 100 postmenopausal women with osteoporosis. These results suggest that bisphosphonate therapy is most...

Subsequent hip fractures in patients identified by a Fracture Liaison Service (FLS) in England and Wales – linkage of the national FLS and Hip Fracture databases

“…Pharmacological aspects of the AOM include time to treatment onset and size of treatment fracture risk reduction. Bisphosphonates vary in their time to maximal fracture reduction with a weak effect from 4 months and a maximal effect requiring at least 12 months in general [39] with differences by fracture type and type of bisphosphonate [40]. A head-to-head trial with fracture end points has demonstrated the superiority of anabolic to anti-resorptive AOMs [41,42].…”

Multidisciplinary Care of a Vertebral Fracture in a Patient with Hematopoietic Stem Cell Transplant: Safety Appropriateness in Interventional Pain Management and Rehabilitation Considerations

“…A systematic review reported high-certainty evidence that bisphosphonates are beneficial for reducing the risk of VFs with data extending to 2 years, in particular with moderate-certainty evidence that these medications are beneficial for preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck, with little to no harm [ 22 ]. Similarly, a more recent meta-analysis revealed that bisphosphonate therapy is most likely to benefit postmenopausal women with osteoporosis who have a life expectancy greater than 12.4 months, but this may be a limiting factor in this population [ 23 ]. All patients with a high risk of corticosteroid induced bone loss should be counseled on lifestyle measures to maintain bone strength including nutrition and weight-bearing exercise.…”

Ann Robinson’s research reviews—3 December 2021

“…We know that the optimal maximum time to stay on bisphosphonates is 3-5 years, but how long does it take for the benefits to kick in? The answer is just over a year, according to this meta-analysis involving over 23 000 postmenopausal women with osteoporosis, which found that it took 12.4 months to avoid one non-vertebral fracture per 100 women who took bisphosphonates 1. To prevent one hip fracture, 200 women would need to be taking bisphosphonates for 20.3 months, and 200 women would need to be on them for one year to avoid one clinical vertebral fracture.…”