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Screening for Osteoporosis: An Update for the U.S. Preventive Services Task Force (continued)
Table 3 summarizes the evidence reviewed for this update, and an outcomes table providing an illustration of the clinical application of the evidence is described in the Appendix and Appendix Table 5 (Also Appendix Figures 3 and 4). No RCTs evaluated the overarching questions of the effectiveness and harms of screening for osteoporosis in reducing fractures and fracture-related outcomes for postmenopausal women and men. Therefore, no direct evidence that screening improves outcomes is available. Support for population screening would be based on evidence that individual risk for fracture can be estimated and fractures can be significantly reduced for persons at risk.
Although many different risk-assessment instruments have been developed, most include similar variables, such as age and weight. Studies that report AUC estimates for validated instruments demonstrate that they are modest predictors of low bone density or fracture, and simpler models perform as well as more complex ones, such as FRAX. No studies determined the effectiveness of these instruments in improving fracture outcomes.
Data from large population-based cohorts indicate that the predictive performance of DEXA is similar for men and women. Calcaneal QUS using various types of devices can predict fractures of the femoral neck, hip, or spine in men and women, although variation exists across studies. Quantitative ultrasonography has low correlation with DEXA, and it is not clear how QUS can be used to select persons for medications that were proven efficacious on the basis of DEXA criteria. Data are lacking to determine how frequently to obtain bone measurements, although 1 study indicated no advantage to repeated measures that were 8 years apart (79).
No trials of medications report effects on fracture-related morbidity and mortality. For postmenopausal women, bisphosphonates, parathyroid hormone, raloxifene, and estrogen reduce primary vertebral fractures. Bisphosphonates significantly reduce nonvertebral fractures in sensitivity analyses that used alternative pooling methods or broadened our definition of primary prevention—consistent with meta-analyses of secondary prevention trials of alendronate and risedronate (109,111). Estrogen also reduces nonvertebral fractures in trials when using unadjusted estimates, but results are not statistically significant when estimates are adjusted. In the only primary prevention trial that stratified results according to baseline BMD, benefits were observed only in patients with T-scores of -2.5 or less (82). For men, no primary prevention trials of bisphosphonates exist, and results from a single trial of parathyroid hormone did not reach statistical significance.
Trials and safety reviews have not supported consistent associations with serious upper gastrointestinal adverse events, atrial fibrillation, or osteonecrosis of the jaw in otherwise healthy patients taking bisphosphonates for fracture prevention. The FDA has recently highlighted case reports of esophageal cancer and severe musculoskeletal pain. An analysis of data from 3 trials published after our searches found no association between bisphosphonate use and atypical fractures of the subtrochanteric or diaphyseal femur, with an event rate of 2.3 per 10,000 patient-years (138). Evidence on harms associated with calcitonin and parathyroid hormone for treatment of osteoporosis is limited. Raloxifene and estrogen with and without progestin increase thromboembolic events; estrogen with and without progestin increases stroke; and estrogen with progestin increases coronary heart disease among older users and breast cancer.
Osteoporotic fractures result from several factors, and this review is limited by its focus on only some of them. Consideration of vision, physical function, risk for falls, and secondary causes of osteoporosis, for example, is also important in reducing fractures. However, these conditions are beyond the scope of this review.
Available evidence is also limited. Trials of medications vary in size, duration, quality, and applicability and have few fracture outcomes. Primary prevention trials and trials that enroll men or persons with low BMD (that is, baseline BMD T-scores from -1.0 to -2.5) are lacking. Applying the results of clinical trials to patient care is especially difficult when selection criteria are rigid and study participants do not represent the community population. This is particularly true in older populations, in which comorbid conditions and use of several medications are common and would disqualify patients from enrolling in most trials.
Osteoporosis and osteoporosis-related fractures are common in aging men and women in the United States. Fractures cause premature mortality, loss of independence and function, reduced quality of life, and substantial financial costs. Although methods to identify persons at risk for osteoporotic fractures are available and medications to reduce fractures are effective, no trials directly evaluate screening effectiveness, harms, and intervals.
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