Summary of Review Findings

Table 10 summarizes the evidence reviewed for this update, and an outcomes table providing an illustration of the clinical application of the evidence is described in Table 11 and Figure 2 and Figure 3. 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 those at risk.

Table 10

Summary of the Evidence.

Table 11

Screening Outcomes for Women Without Prior Vertebral Fractures.

Figure 2

Number of Women Needed to Screen to Prevent One Fracture in 5 Years.

Figure 3

10-year Risks for Major Osteoporotic and Hip Fractures for Women from the FRAX Calculator. Abbreviations: BMI = body mass index; FRAX = online risk calculator (http://www.shef.ac.uk/FRAX/). *Normal BMI=25.0 (more...)

Although many different risk-assessment instruments have been developed and tested, 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 DXA 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 ultrasound has low correlation with DXA, and it is not clear how QUS can be used to select individuals for medications that were proven efficacious on the basis of DXA criteria.

Data are lacking to determine how frequently to obtain bone measurements, although one study indicated no advantage to repeated measures that were 8 years apart.¹³⁸

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.^{161, 162} 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 only observed in patients with T-scores ≤ −2.5.⁵⁰ 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 three trials published after our searches found no association between bisphosphonate use and atypical fractures of the subtrochanteric of diaphyseal femur, with an event rate of 2.3 per 10,000 patient-years.²¹⁶ 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.

Limitations

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.

Studies of risk-assessment instruments are limited by their lack of inclusion of men, and for many, by their study designs (cross-sectional analysis, consecutive rather than population-based recruitment). Several instruments include history of previous fracture, which is more relevant to case-finding than screening. Comparing AUC estimates of instruments is an imprecise method, and may not lend itself as the best method for assessing which instrument has better discriminate ability.

Studies of DXA and peripheral bone measurement tests are limited by their study designs and use of various measures. In general, however, the large population-based prospective studies provide a good method for evaluating the predictive performance of these tests. Studies that report both men and women and adjust for important confounders are the most robust. The consistency of findings across studies also attests to the reliability of the results. The biggest limitation relates to the applicability of estimates derived from populations to an individual in a clinical setting.

Trials of drug therapies vary in size, duration, quality, and applicability. The most important limitations to this evidence include the lack of primary prevention trials and trials that enroll men or enroll patients with mild bone loss (i.e., baseline BMD T-scores between −10 and −2.5). Applying the results of clinical trials to patient care is especially difficult when selection criteria are rigid and study subjects do not represent the community population. This is particularly true in older populations where co-morbidities and use of multiple medications are common would disqualify them for most RCTs.

Future Research

Future research needs to focus on critical evidence gaps. Trials of the efficacy and harms of screening in reducing fractures and fracture-related outcomes are needed. Initial studies of screening effects support a benefit, but require collaborative evidence from large RCTs.^217–221 In addition, studies about acceptability and barriers to screening and treatment, harms, optimal intervals, and starting and stopping ages would inform screening approaches. Screening will most likely detect many individuals with secondary causes of osteoporosis or prior fragility fractures who were not appropriately identified previously. Although they are not part of the true screening pool, identifying them and initiating appropriate management is important also. Studies capturing this aspect of detection would also be useful. Research that includes all types of interventions would provide a more comprehensive approach to fracture prevention. These include not only drug therapies, but also functional assessment, safety evaluations, vision examinations, nutrition, and others. Fracture registries that track individuals over time would be useful in determining effective prevention approaches, and evaluate if screening-detected individuals benefit over the long-term compared to those not screened.

Conclusions

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 individuals with increased risk for osteoporotic fractures are available, and medications to reduce fractures are effective, no trials directly evaluate screening effectiveness, harms, and intervals.