Screening for Osteoporosis to Prevent Fractures: A Systematic Evidence Review for the US Preventive Services Task Force

Importance: Fragility fractures result in significant morbidity. Objective: To review evidence on osteoporosis screening to inform the US Preventive Services Task Force. Data Sources: PubMed, Embase, Cochrane Library, and trial registries through January 9, 2024; references, experts, and literature surveillance through July 31, 2024. Study Selection: Randomized clinical trials (RCTs) and systematic reviews of screening; pharmacotherapy studies for primary osteoporosis; predictive and diagnostic accuracy studies. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, study quality, and extracted data; when at least 2 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Hip, clinical vertebral, major osteoporotic, and total fractures; mortality; harms; accuracy. Results: Three RCTs and 3 systematic reviews reported benefits of screening in older, higher-risk women. Two RCTs used 2-stage screening: Fracture Risk Assessment Tool estimate with bone mineral density (BMD) testing if risk threshold exceeded. One RCT used BMD plus additional tests. Screening was associated with reduced hip (pooled relative risk [RR], 0.83 [95% CI, 0.73-0.93]; 3 RCTs; 42009 participants) and major osteoporotic fracture (pooled RR, 0.94 [95% CI, 0.88-0.99]; 3 RCTs; 42009 participants) compared with usual care. Corresponding absolute risk differences were 5 to 6 fewer fractures per 1000 participants screened. The discriminative accuracy of risk assessment instruments to predict fracture or identify osteoporosis varied by instrument and fracture type; most had an area under the curve between 0.60 and 0.80 to predict major osteoporotic fracture, hip fracture, or both. Calibration outcomes were limited. Compared with placebo, bisphosphonates (pooled RR, 0.67 [95% CI, 0.45-1.00]; 6 RCTs; 12055 participants) and denosumab (RR, 0.60 [95% CI, 0.37-0.97] from the largest RCT [7808 participants]) were associated with reduced hip fractures. Compared with placebo, no statistically significant associations were observed for adverse events. Conclusions and Relevance: Screening in higher-risk women 65 years or older was associated with a small absolute risk reduction in hip and major fractures compared with usual care. No evidence evaluated screening with BMD alone or screening in men or younger women. Risk assessment instruments, BMD alone, or both have poor to modest discrimination for predicting fracture. Osteoporosis treatment with bisphosphonates or denosumab over several years was associated with fracture reductions and no meaningful increase in adverse events.