Meera Viswanathan1,2, Shivani Reddy1,2, Nancy Berkman1,2, Katie Cullen1,2, Jennifer Cook Middleton2,3, Wanda K Nicholson4, Leila C Kahwati1,2. 1. RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center. 2. RTI International, Research Triangle Park, North Carolina. 3. Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill. 4. Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill.
Abstract
Importance: Osteoporotic fractures cause significant morbidity and mortality. Objective: To update the evidence on screening and treatment to prevent osteoporotic fractures for the US Preventive Services Task Force. Data Sources: PubMed, the Cochrane Library, EMBASE, and trial registries (November 1, 2009, through October 1, 2016) and surveillance of the literature (through March 23, 2018); bibliographies from articles. Study Selection: Adults 40 years and older; screening cohorts without prevalent low-trauma fractures or treatment cohorts with increased fracture risk; studies assessing screening, bone measurement tests or clinical risk assessments, pharmacologic treatment. Data Extraction and Synthesis: Dual, independent review of titles/abstracts and full-text articles; study quality rating; random-effects meta-analysis. Main Outcomes and Measures: Incident fractures and related morbidity and mortality, diagnostic and predictive accuracy, harms of screening or treatment. Results: One hundred sixty-eight fair- or good-quality articles were included. One randomized clinical trial (RCT) (n = 12 483) comparing screening with no screening reported fewer hip fractures (2.6% vs 3.5%; hazard ratio [HR], 0.72 [95% CI, 0.59-0.89]) but no other statistically significant benefits or harms. The accuracy of bone measurement tests to identify osteoporosis varied (area under the curve [AUC], 0.32-0.89). The pooled accuracy of clinical risk assessments for identifying osteoporosis ranged from AUC of 0.65 to 0.76 in women and from 0.76 to 0.80 in men; the accuracy for predicting fractures was similar. For women, bisphosphonates, parathyroid hormone, raloxifene, and denosumab were associated with a lower risk of vertebral fractures (9 trials [n = 23 690]; relative risks [RRs] from 0.32-0.64). Bisphosphonates (8 RCTs [n = 16 438]; pooled RR, 0.84 [95% CI, 0.76-0.92]) and denosumab (1 RCT [n = 7868]; RR, 0.80 [95% CI, 0.67-0.95]) were associated with a lower risk of nonvertebral fractures. Denosumab reduced the risk of hip fracture (1 RCT [n = 7868]; RR, 0.60 [95% CI, 0.37-0.97]), but bisphosphonates did not have a statistically significant association (3 RCTs [n = 8988]; pooled RR, 0.70 [95% CI, 0.44-1.11]). Evidence was limited for men: zoledronic acid reduced the risk of radiographic vertebral fractures (1 RCT [n = 1199]; RR, 0.33 [95% CI, 0.16-0.70]); no studies demonstrated reductions in clinical or hip fractures. Bisphosphonates were not consistently associated with reported harms other than deep vein thrombosis (raloxifene vs placebo; 3 RCTs [n = 5839]; RR, 2.14 [95% CI, 0.99-4.66]). Conclusions and Relevance: In women, screening to prevent osteoporotic fractures may reduce hip fractures, and treatment reduced the risk of vertebral and nonvertebral fractures; there was not consistent evidence of treatment harms. The accuracy of bone measurement tests or clinical risk assessments for identifying osteoporosis or predicting fractures varied from very poor to good.
Importance: Osteoporotic fractures cause significant morbidity and mortality. Objective: To update the evidence on screening and treatment to prevent osteoporotic fractures for the US Preventive Services Task Force. Data Sources: PubMed, the Cochrane Library, EMBASE, and trial registries (November 1, 2009, through October 1, 2016) and surveillance of the literature (through March 23, 2018); bibliographies from articles. Study Selection: Adults 40 years and older; screening cohorts without prevalent low-trauma fractures or treatment cohorts with increased fracture risk; studies assessing screening, bone measurement tests or clinical risk assessments, pharmacologic treatment. Data Extraction and Synthesis: Dual, independent review of titles/abstracts and full-text articles; study quality rating; random-effects meta-analysis. Main Outcomes and Measures: Incident fractures and related morbidity and mortality, diagnostic and predictive accuracy, harms of screening or treatment. Results: One hundred sixty-eight fair- or good-quality articles were included. One randomized clinical trial (RCT) (n = 12 483) comparing screening with no screening reported fewer hip fractures (2.6% vs 3.5%; hazard ratio [HR], 0.72 [95% CI, 0.59-0.89]) but no other statistically significant benefits or harms. The accuracy of bone measurement tests to identify osteoporosis varied (area under the curve [AUC], 0.32-0.89). The pooled accuracy of clinical risk assessments for identifying osteoporosis ranged from AUC of 0.65 to 0.76 in women and from 0.76 to 0.80 in men; the accuracy for predicting fractures was similar. For women, bisphosphonates, parathyroid hormone, raloxifene, and denosumab were associated with a lower risk of vertebral fractures (9 trials [n = 23 690]; relative risks [RRs] from 0.32-0.64). Bisphosphonates (8 RCTs [n = 16 438]; pooled RR, 0.84 [95% CI, 0.76-0.92]) and denosumab (1 RCT [n = 7868]; RR, 0.80 [95% CI, 0.67-0.95]) were associated with a lower risk of nonvertebral fractures. Denosumab reduced the risk of hip fracture (1 RCT [n = 7868]; RR, 0.60 [95% CI, 0.37-0.97]), but bisphosphonates did not have a statistically significant association (3 RCTs [n = 8988]; pooled RR, 0.70 [95% CI, 0.44-1.11]). Evidence was limited for men: zoledronic acid reduced the risk of radiographic vertebral fractures (1 RCT [n = 1199]; RR, 0.33 [95% CI, 0.16-0.70]); no studies demonstrated reductions in clinical or hip fractures. Bisphosphonates were not consistently associated with reported harms other than deep vein thrombosis (raloxifene vs placebo; 3 RCTs [n = 5839]; RR, 2.14 [95% CI, 0.99-4.66]). Conclusions and Relevance: In women, screening to prevent osteoporotic fractures may reduce hip fractures, and treatment reduced the risk of vertebral and nonvertebral fractures; there was not consistent evidence of treatment harms. The accuracy of bone measurement tests or clinical risk assessments for identifying osteoporosis or predicting fractures varied from very poor to good.