Purpose of Review and Prior USPSTF Recommendation

This systematic evidence review is an update for the U.S. Preventive Services Task Force (USPSTF) recommendation on screening for osteoporosis. In 2002, based on results of a previous review,^{1, 2} the USPSTF recommended bone density screening for women age ≥65 years and women age 60–64 years at increased risk for osteoporotic fractures (B Recommendation).^{3, 4} They made no recommendations for or against screening postmenopausal women age <60 years or women age 60–64 years without increased risk (C Recommendation). Men were not considered in the prior recommendation. (See Appendix A1 for a list of all abbreviations included in this report.)

The USPSTF made additional conclusions about the state of the evidence in 2002 including:

• The risk for osteoporosis and fractures increases with age and other factors.
• Although there are many risk factors for low bone density and fractures, female sex, older age, and lower body weight (<70 kg) are the strongest predictors of low bone density. There is less evidence to support the use of other individual risk factors as a basis for identifying high-risk women (for example, smoking, weight loss, family history, decreased physical activity, alcohol or caffeine use, or low calcium and vitamin D intake).
• At any given age, black women on average have higher bone mineral density than white women and are thus less likely to benefit from screening.
• Bone density measurements accurately predict the risk for fractures in the short term.
• Among different bone measurement tests performed at various anatomical sites, bone density measured at the femoral neck by dual-energy x-ray absorptiometry (DXA) is the best predictor of hip fracture and is comparable to forearm measurements for predicting fractures at other sites.
• The likelihood of being diagnosed with osteoporosis varies greatly depending on the site and type of bone measurement test; the number of sites tested; the brand of densitometer used; and the relevance of the reference range.
• Treating asymptomatic women with osteoporosis reduces their risk for fractures.

Several evidence gaps were identified including:

• No trials have evaluated the effectiveness of screening on reducing fractures or fracture-related morbidity or mortality; therefore, there is no direct evidence that screening improves outcomes.
• No studies have evaluated the optimal intervals for repeated screening.
• There are no data to determine the appropriate age to stop screening, and few data on osteoporosis treatment in women age ≥85 years.
• Few published studies address screening and treatment for younger postmenopausal women.
• No bone density studies or treatment trials include large numbers of non-white women.
• Although there are several methods to estimate risk for osteoporosis and fractures using risk factors, the accuracy and clinical applicability of these methods in identifying high risk individuals in practice have not been demonstrated.
• Peripheral bone density tests have not been extensively studied for screening. Further research is needed to define the appropriate use of these technologies.
• It is unknown whether women who have a similar overall risk for fracture, but different bone densities, will benefit similarly from treatment.
• There is little empirical data on potential harms of screening.
• Data for men are lacking.

This update focuses on new studies and evidence gaps that were unresolved at the time of the 2002 recommendation. These include the effectiveness and harms of osteoporosis screening in reducing fractures and fracture-related health outcomes for men as well as postmenopausal women without known previous fractures; the performance of risk-assessment instruments and bone measurement tests in identifying individuals with osteoporosis; optimal screening intervals; and efficacy and harms of medications to reduce primary fractures in a screening-detected population.

The USPSTF considers the value of clinical interventions to prevent the onset of a condition or to treat asymptomatic individuals who have developed important risk factors or preclinical disease.⁵ For osteoporosis, the focus is on the identification of individuals with low bone mass and risk factors in order to prevent fractures. The target populations for this review include postmenopausal women and men age >50 years without known previous osteoporosis related fragility fractures or secondary causes of osteoporosis (e.g., corticosteroid users, transplant recipients, cancer patients). Individuals with these conditions undergo a different course of evaluation and management and are not considered screening candidates. This distinction becomes somewhat blurred for the large number of individuals with undiagnosed vertebral fractures who are included in the screening pool because their fractures have been undetected. Also, many individuals with previous fractures have never been appropriately evaluated for osteoporosis and may be diagnosed during the course of routine screening.

The USPSTF has a U.S. perspective and focuses on technologies, therapies, and practices that are feasible in primary care clinical settings across the United States. Recommendations are based on the strength of evidence of benefits and harms. Costs are not considered in the recommendation, but may be used contextually by the USPSTF.

Condition Definition

Osteoporosis is a systemic skeletal condition characterized by low bone mass and microarchitectural deterioration of bone tissue that increases bone fragility and risk for fractures.⁶ Osteoporosis may occur without a known cause, or secondary to another condition. These include corticosteroid therapy, excessive alcohol use, primary or secondary hypogonadism, low calcium intake, vitamin D deficiency, smoking, antiepileptic drug use, thyrotoxicosis, primary hyperparathyroidism, chronic liver or kidney disease, rheumatoid arthritis, diabetes, human immunodeficiency virus, organ transplantation, multiple myeloma, and others.

Osteoporosis is diagnosed in individuals on the basis of presence of a fragility fracture or by bone mass measurement criteria. A fragility fracture results from forces that would not normally cause a fracture, such as a hip or wrist fracture from falling from standing height or a vertebral compression fracture. Although specific fracture sites have been considered more characteristic of osteoporosis, fractures occurring at nearly every anatomical site have been associated with osteoporosis.

Bone mineral density (BMD) criteria were developed by the World Health Organization (WHO) from epidemiologic data that describe the normal distribution of BMD in a young healthy reference population.⁷ Osteoporosis is diagnosed when the BMD at the spine, hip, or wrist is 2.5 or more standard deviations (SD) below the reference mean. Low bone density or mass (sometimes referred to as osteopenia) is diagnosed when BMD is between 1.0–2.5 SD below the reference mean. BMD criteria for osteoporosis identify only one aspect of the condition. Other important components, such as rate of bone loss and quality of bone, are not well characterized clinically.

The number of standard deviation units above or below the young healthy mean is called the T-score. A Z-score is the number of standard deviation units above or below the mean for one’s own age group. Although intended for epidemiologic purposes, T-scores have been used as selection criteria for trials of therapies. They are now used to identify individuals with low BMD and to make treatment decisions.

Prevalence and Burden of Disease

Estimates indicate that as many as 50 percent of Americans age >50 years will be at risk for osteoporotic fractures during their lifetimes.⁶ This translates to 12 million individuals with osteoporosis by 2012.⁶ Specific prevalence rates depend on how bone density is measured and characteristics of the population. Rates for women are higher than for men; rates vary by race, with the highest rates in whites; and rates for all demographic groups increase with age.^8–10 Despite differences between demographic groups, osteoporosis is common in all of them.

Fracture rates are particularly sensitive to increasing age because fractures are multi-factorial outcomes. For example, 5 percent of 50-year-old women and 25 percent of 80-year-old women have had at least one vertebral fracture.¹¹ Older individuals have much higher fracture rates than younger individuals with the same bone density because of increasing risks from other factors such as bone quality and tendency to fall.¹²

All types of fractures are associated with higher mortality rates.^13–16 Men are more likely than women to die in the year after a hip fracture, with mortality rates for men estimated up to 37.5 percent.¹⁷ Although less often causing death, fractures at other sites can adversely impact function and quality of life, resulting in chronic pain, disability, and high costs. These include direct care expenditures estimated to be 12.2 to 17.9 billion per year in 2002 dollars⁶ in addition to lost productivity of patients and their caregivers.

Risk Factors

Several risk factors for osteoporosis and fractures have been identified from an extensive research base. Large prospective population-based studies, such as the Study of Osteoporotic Fractures (SOF) for women in the United States, provide well-developed multivariable models of risk factors for osteoporosis and fractures.¹⁸ These factors have been incorporated into risk assessment instruments to identify candidates for BMD testing or drug therapy. This report includes a review of these instruments (Key Question 2).

Rationale for Screening/Screening Strategies

Bone measurement tests are used to predict fractures, to diagnose osteoporosis, and to select patients for treatment. Among bone measurement tests at various sites, DXA of the hip is the strongest predictor of hip fracture.^19–21 Most DXA testing includes measurements at the hip and lumbar spine (central DXA). Diagnostic criteria are based on these DXA measurements, most randomized controlled trials of drug therapies have used them as inclusion criterion, and they have become the gold standard. It is, therefore, difficult for clinicians to make decisions for patients identified as having osteoporosis by other tests, even if they are also equally predictive of BMD and fractures.

Several other types of bone measurement tests are available, and many studies have been done to determine their advantages and disadvantages compared to central DXA. The most clinically applicable procedures measure bone mass at peripheral anatomic sites. Currently, the most commonly used non-DXA test in the United States is quantitative ultrasound (QUS) of the calcaneus (heel). QUS avoids ionizing radiation, and is inexpensive, portable, and feasible for primary care settings. DXA uses radiation, is hospital-based, more costly, and requires interpretation of results. QUS measures ultrasound waves across the bone using different parameters (broadband ultrasound attenuation ²², speed of sound [SOS], velocity of sound [VOS], quantitative ultrasound index [QUI], and stiffness). These parameter values are lower in osteoporotic bone than in healthy bone. This report includes a review of QUS (Key Question 3).

Interventions/Treatment

Current Clinical Practice

Despite increased awareness of the magnitude and consequences of osteoporosis and recommendations for screening and treatment from multiple groups, osteoporosis is under detected and inadequately treated in the United States.^{30, 31} Reasons for this are unclear, although the differing recommendations for identifying candidates for testing and treatment, confusion in interpreting results of testing, and fragmentation of health care may contribute.³² Usually the fracture itself is treated by an acute care team in hospital emergency departments and orthopedic services, while screening, prevention, and treatment are addressed in another context.

Recommendations of Other Groups

Recommendations of other groups are summarized in Table 1.

Table 1

Recommendations of Other Groups.