Time to Benefit of Bisphosphonate Therapy for the Prevention of Fractures Among Postmenopausal Women With Osteoporosis: A Meta-analysis of Randomized Clinical Trials.
Level 1 - systematic review of randomized trials
Meta-analysis of randomized controlled trials
PubMed 34807231 · doi:10.1001/jamainternmed.2021.6745
What was done
Meta-analysis of 10 randomized clinical trials (extracted from systematic reviews from USPSTF, AHRQ, Cochrane, and the Endocrine Society) encompassing 23,384 postmenopausal women with osteoporosis (BMD T-score ≤ -2.5 or existing vertebral fractures). The study evaluated first-line bisphosphonates (alendronate, risedronate, zoledronic acid) versus placebo. Random-effects Weibull survival curves and Markov chain Monte Carlo methods modeled absolute risk reduction (ARR) and time to benefit (TTB) for nonvertebral, hip, and clinical vertebral fractures.
What was found
The pooled time to benefit across studies (mean age 63 to 74 years, follow-up 12 to 48 months) was: - Nonvertebral fracture (ARR = 0.010, preventing 1 fracture per 100 women): 12.4 months (95% CI, 6.3-18.4 months). - Hip fracture (ARR = 0.005, preventing 1 fracture per 200 women): 20.3 months (95% CI, 11.0-29.7 months). - Clinical vertebral fracture (ARR = 0.005, preventing 1 fracture per 200 women): 12.1 months (95% CI, 6.4-17.8 months).
Why it matters
These findings provide explicit time horizons (roughly 12 to 20 months) to help clinicians decide whether patients have adequate life expectancy to benefit from initiating bisphosphonate therapy.
Limits
Restricted to postmenopausal women and three specific bisphosphonates. Studies without placebo controls or lacking time-to-fracture data were excluded. Generalizability to men, premenopausal women, or secondary causes of osteoporosis is unknown.
Cited by
- supports Bisphosphonates are considered first-line pharmacological therapy for osteoporosis.