Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 36592455 · doi:10.7326/M22-0684
What was done
A living systematic review and network meta-analysis searched MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov (2014 to February 2022). The review evaluated treatments for low bone mass or osteoporosis to prevent fractures in adults. Randomized controlled trials (RCTs) were assessed for fracture outcomes, and RCTs alongside large observational studies (n ≥ 1000) were assessed for harms. Risk of bias and certainty of evidence were independently assessed in duplicate.
What was found
The review included 34 RCTs (100 publications) and 36 observational studies. The abstract reports no numerical effect sizes or confidence intervals. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high certainty). Bisphosphonates for ≥36 months were associated with increased risk for atypical femoral fractures and osteonecrosis of the jaw, though absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased withdrawals due to adverse events (moderate to high certainty). Raloxifene and bazedoxifene for ≥36 months reduced radiographic vertebral but not clinical fractures (low to moderate certainty). Abaloparatide, teriparatide, and sequential romosozumab followed by alendronate may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate certainty). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low certainty) and radiographic vertebral fractures in males with osteoporosis (low to moderate certainty).
Why it matters
This review synthesizes comparative efficacy across major osteoporosis drug classes to inform clinical guidelines, clarifying fracture risk reduction alongside class-specific harms and treatment duration effects.
Limits
The abstract provides no quantitative point estimates or confidence intervals. Evidence was limited for males, individuals with low bone mass, Black-identifying populations, sequential regimens, and treatments beyond 3 years.
Cited by
- supports Bisphosphonates are associated with abnormal femoral fractures.