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

Abstract

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; 42 009 participants) and major osteoporotic fracture (pooled RR, 0.94 [95% CI, 0.88-0.99]; 3 RCTs; 42 009 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; 12 055 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.

Figure 1.. Analytic Framework: Screening for Osteoporosis to Prevent Fractures

Evidence reviews for the USPSTF use an analytic framework to visually display the key questions that the review will address in order to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes. For further details see the USPSTF Procedure Manual. DXA indicates dual energy X-ray absorptiometry.

Figure 2.. Literature Search Flow Diagram: Screening for Osteoporosis

HDI indicates human development index; KQ, key question; RCT, randomized clinical trial; SR, systematic review.

Figure 3.. Results of Randomized Clinical Trials of Screening vs Usual Care (KQ1)

Note: This analysis used the first per-protocol data from the ROSE trial for the fracture outcomes because these data reflect a similar study design as the intention-to-treat (ITT) data reported for SCOOP and SOS. See the full evidence report for a sensitivity analysis using the ITT data from the ROSE trial for the fracture outcomes. The data for mortality is the ITT population for ROSE because per-protocol data for ROSE was not reported. ^a SCOOP reported an outcome entitled “Osteoporotic Fractures,” which were defined as clinical fractures excluding hand, foot, skull, or cervical vertebrae. This definition differs from the definition of MOF used by the other 2 studies (hip, clinical vertebral, distal forearm, and humerus); as such, SCOOP data was included for both “Osteoporotic Fractures” and for “MOF” in this figure. The RR estimate for MOF without SCOOP included is 0.93 (95% CI, 0.86 to 1.00); Absolute Effect: 6 fewer (from 12 fewer to 0 fewer). It is also not clear that fractures associated with trauma were excluded from SCOOP. CI indicates confidence interval; DL, DerSimonian & Laird estimator for pooling estimates; FRAX, Fracture Risk Assessment Tool; F/U, follow-up; ITT, inention to treat; KQ, key question; MOF, major osteoporotic fracture; N, number; PriorFx, prior fracture; ROSE, Risk-stratified Osteoporosis Strategy Evaluation; SCOOP, Screening in the Community to Reduce Fractures in Older Women; SOS, Stichting Artsen Laboratorium en Trombosedienst Osteoporosis Study; vs, versus; y, year.

Figure 4.. Results of Randomized, Placebo-Controlled Trials of Treatment for Osteoporosis (KQs 4 and 5)

^a Although multiple studies reported, evidence base is dominated by 1 large (N = 7808) study. ^b Sensitivity analysis was conducted limiting to studies reporting clinical vertebral fractures ( 4 studies) and the pooled RR was 0.44 (95% CI, 0.24 to 0.79; 2373 participants, I² = 0%). AE indicates adverse event; ARD, absolute risk difference; CI, confidence interval; GI, gastrointestinal; KQ, key question; N, number; RR, relative risk.