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Viswanathan M, Reddy S, Berkman N, et al. Screening to Prevent Osteoporotic Fractures: An Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Jun. (Evidence Synthesis, No. 162.)

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Screening to Prevent Osteoporotic Fractures: An Evidence Review for the U.S. Preventive Services Task Force [Internet].

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Scope and Purpose

The U.S. Preventive Services Task Force (USPSTF or Task Force) will use this report to update its 2011 recommendation on screening for osteoporosis.1 This report evaluates the evidence on the accuracy, reliability, and harms of screening approaches, appropriate screening intervals, and the benefits and harms of pharmacotherapy.

This report focuses on populations without known comorbidities or medication use associated with secondary osteoporosis because the detection and management of secondary osteoporosis falls outside the purview of the Task Force. The report also excludes younger populations (<40 years of age) because increasing age is the single most important risk for osteoporosis and fragility fractures. Further, a diagnosis of osteoporosis among those under age 40 is extremely rare in the absence of an underlying medical comorbidity or use of medications associated with bone loss. The scope of this review includes screening strategies related to fracture risk assessment, with or without bone mineral density testing; other types of screening (e.g., functional assessment, safety evaluations, vision examinations, nutrition assessments) are not included. Because the focus of this review is on primary prevention of osteoporotic fractures, the management of osteoporosis in populations characterized primarily by prevalent fractures and comparative effectiveness of osteoporosis treatments are also outside the scope of this review.

Condition Background

Condition Definition

Osteoporosis is a skeletal disorder characterized by loss of bone mass, microarchitectural deterioration of bone tissue, and decline in bone quality leading to increased bone fragility and risk of fractures.2-4 Although bone mass (expressed by bone mineral density [BMD]) is only one factor contributing to fracture risk, and new tools measuring bone quality are under development, osteoporosis has been defined operationally on the basis of BMD assessments or the history of a fragility fracture.5

The World Health Organization (WHO) defines osteoporosis as a bone density at the hip or spine that is 2.5 standard deviations or lower (T-score ≤−2.5) than the mean bone density of a reference population of young healthy women, presumably at peak bone mass. This definition was established originally for postmenopausal women using BMD of the proximal femur, but guidelines from the International Society for Clinical Densitometry indicate that they can also be used for men 50 years or older.6 The WHO definition is currently used for lumbar spine, distal radius, and total hip.7 Of note, U.S. bone density machines report T-scores using a reference group matched on race and sex, whereas the WHO uses a reference group of young white women only using normative data from the National Health and Nutrition Examination Survey (NHANES) reference database.8 Low bone mass, sometimes referred to as osteopenia, is operationally defined as a T-score between -1 and -2.5.

Osteoporotic fractures, also known as fragility, “low-energy,” or “low-trauma” fractures, are those sustained from a fall from standing height or lower and that would not give rise to a fracture in most healthy individuals.9 Osteoporotic fractures occur as a result of bone fragility resulting from bone loss or structural changes.10 Major osteoporotic fractures include fractures of the hip, spine, wrist, or shoulder. Because osteoporosis itself is asymptomatic, preventing osteoporotic fractures is the main goal of any osteoporosis screening strategy.

Prevalence and Burden of Disease

In the United States, the prevalence rates of osteoporosis and low bone mass at the femoral neck or lumbar spine among the noninstitutionalized population 50 years of age or older (adjusted by age, sex, and race and ethnicity) was estimated to be 10.3 percent and 43.9 percent, respectively, based on the NHANES.11 In 2010, these estimates equated to 10.2 million older adults with osteoporosis and 43.4 million with low bone mass.

In the group that is 50 years of age or older, the prevalence of osteoporosis is greater in women (15.4%) than men (4.3%). The prevalence also varies by race and ethnicity: 10.2 percent in non-Hispanic whites, 4.9 percent in non-Hispanic blacks, and 13.4 percent in Mexican Americans. Prevalence increases dramatically with age: 50 to 59 years, 5.1 percent; 60 to 69 years, 8.0 percent; 70 to 79 years, 16.4 percent; and 80 years or older, 26.2 percent.

Researchers applying the NHANES data to 2020 and 2030 Census population projections estimated that the population that is 50 years of age or older with osteoporosis or low bone mass is forecast to increase from an estimated 53 million in 2010 to 63.9 million in 2020 and 70.6 million in 2030.11

In 2005, approximately 2 million osteoporotic fractures occurred in the United States.12 Most fractures (71%) occur among women, and more than three-quarters of the total costs of incident fractures (more than $16.9 billion) were among women. Hip fractures account for a large portion of the mortality and morbidity related to osteoporotic fractures. Estimates based on Medicare claims data from 1986 to 2005 suggest an annual rate of hip fractures of 957.3 per 100,000 in women and 414.4 per 100,000 in men.13 The excess mortality due to hip fracture in the first year after fracture ranges from 8 percent to 36 percent, more than twice that of age and sex matched controls.14 Men have greater excess mortality compared to women at all ages, for unclear reasons. The greatest risk of death occurs in the first 3 to 6 months after fracture and may be due to post-operative events associated with corrective hip surgery, comorbid medical conditions, or inadequate treatment of risk factors for fracture including osteoporosis.14, 15 The extent to which these factors contribute to excess mortality is unclear. Mortality from hip fracture decreases over time, but does not return to that of age- and sex-matched controls.15All types of fractures are associated with higher rates of mortality.16-19

Etiology and Natural History

Osteoporosis may occur either without a known cause or secondary to another condition. Bone loss is associated with certain medical conditions: various endocrine conditions of the pituitary, thyroid, parathyroid, or reproductive organs; eating disorders; disorders of the gastrointestinal or biliary tract; renal disease; bone marrow disorders; and cancer.20 Secondary osteoporosis can also result after organ transplantation. It can also arise from chronic use of medications with known deleterious effects on bone mass, such as glucocorticosteroids, immunosuppressants, antiepileptic medications, heparin, gonadotropin-releasing hormone agonists, and some long-acting progesterone agents used as contraceptives.

Although osteoporosis is related to an increased risk of fracture,3 most fractures occur in those with nonosteoporotic T-scores.21-23 Similarly, fragility fractures can occur in persons with normal bone mass.24 Older adults have much higher fracture rates than younger adults with the same bone density because of concurrent increasing risk from declining bone quality and an increasing tendency to fall.25

Clinical Risk Factors

For both men and women, advancing age was found to be a more critical determinant of fracture than bone mass.26 Additional risk factors include menopausal status in women,27 previous osteoporotic fracture, long-term glucocorticoid therapy, low body weight (less than 58 kg [127 lbs.]), parental history of hip fracture, cigarette smoking, excess alcohol consumption, and use of anti-convulsants or benzodiazepines.28,29

A systematic review and meta-analysis identified risk factors associated with osteoporotic fractures in men.30 The review found statistically significant associations between fractures and increasing age, low body mass index, excessive alcohol intake (daily intake or greater than 10 servings per week), current smoking, chronic corticosteroid use, history of prior fractures, history of falls within the past year, hypogonadism, history of cerebrovascular accident, and history of diabetes. A large multiethnic study, the National Osteoporosis Risk Assessment Cohort, compared fracture risk among races and ethnicities, and found that Black women and Asian American women had a lower risk of fracture when compared with white women, whereas Hispanic and Native American women had risks similar to white women.31 Genetic, anthropometric, lifestyle, comorbidities all contribute to fracture risk and the relative contribution of these factors to fracture risk is likely to differ between races and ethnicities.31

Rationale for Screening

The rationale for screening for osteoporosis is to identify those at risk of fracture and provide treatment to increase bone mass and prevent further losses. These actions can prevent fractures and related morbidity. Screening for osteoporosis traditionally involves bone measurement testing (e.g., bone density). More recently, fracture risk assessment (with or without bone measurement testing) have been proposed as alternative strategies to identify individuals who may benefit from treatment. Numerous risk assessment instruments have been developed to either (1) identify low bone density or (2) predict the risk of fracture.2, 3 These instruments vary in the number and weight assigned to risk factors, but the USPSTF 2010 systematic review found that instruments with fewer risk factors often had similar or higher areas under the curve than instruments with more risk factors.2, 3 Several instruments had not been developed using prospective cohorts or validated in men. The most studied risk assessment instrument is the Fracture Risk Assessment Tool (FRAX), which WHO developed in 2008. FRAX uses an algorithm for predicting the 10-year probability of hip fracture or major osteoporotic fractures (hip, spine, wrist, shoulder) using clinical risk factors and bone mineral density at the femoral neck when available. It was derived from nine cohorts in Europe, the United States, Japan, and Canada and has been applied to men.9, 32 Country-specific versions of FRAX are available that have been calibrated for use in each country using country-specific fracture incidence and mortality data. For the US non-Hispanic white population, the FRAX model was calibrated using national mortality data and fracture incidence rates from the population of Olmsted County, Minnesota between 1989 and 1991.33 For non-white US populations, race-specific fracture incidence and mortality was used to calibrate the model. In response to declining fracture incidence, the US FRAX model was recalibrated in 2009. In countries or settings without access to bone density testing, the FRAX score (without BMD) can be used to make treatment decisions.

Bone density can be measured using various methods and at various bone sites. Dual-energy X-ray absorptiometry (DXA) measures bone mass at either central (e.g., hip and lumbar spine) or peripheral bone sites; both central and peripheral DXA can identify patients with low bone mass at increased fracture risk.2, 34 Centrally measured DXA serves as the standard machine-based test for identifying osteoporosis because trials of treatment for osteoporosis to prevent fracture have been conducted with study populations assessed with centrally measured DXA.2 Other machine-based tests include quantitative ultrasound (QUS), peripheral DXA, quantitative computed tomography (QCT), and radiograph absorptiometry. Further, the lack of a single population-based reference for determining T-scores, required because of technical differences among tests, has limited the ability to use noncentrally measured DXA tests for diagnostic and treatment decisions.

QUS is used at peripheral bone sites, such as the heel, and it avoids the risk of radiation inherent in DXA. However, QUS does not actually measure BMD, so it cannot be used in risk prediction instruments that use BMD. Peripheral DXA and QUS use portable devices and may be more accessible than central DXA measurement. QCT provides a volumetric measure of bone density, which may improve detection of osteoporosis compared to areal BMD by DXA.35, 36 However, reproducibility is poor in community settings, and few data are available on how T-scores generated from QCT predict fracture risk compared with those based on DXA.7 The most recent version of FRAX allows providers to enter bone mineral density from Mindways QCT (Mindways Software, Austin, Texas).37 Finally, radiograph absorptiometry, which uses computerized processing of radiographs from peripheral sites such as hand or heel, and dental radiographs can also be used to assess low bone mass.38

Current Drug Therapies

The U.S. Food and Drug Administration (FDA) has approved various medications from different drug classes to prevent osteoporosis (adults with T-scores between -1.0 and -2.5) and to treat osteoporosis (adults with T-scores <-2.5 or history of fragility fractures regardless of bone mass). These drugs work either to inhibit osteoclastic bone resorption (antiresorptive agents) or to stimulate osteoblastic new bone formation (anabolic agents).39 Drugs classified primarily as antiresorptive include bisphosphonates, estrogens, selective estrogen receptor modulators, calcitonin, and denosumab, a monoclonal antibody targeting the receptor activator of nuclear factor kappa-B ligand (RANKL) approved by the FDA in 2010. In addition, in 2013 the FDA approved the first combination estrogen-estrogen agonist/antagonist (Duavee®) to prevent osteoporosis in postmenopausal women. The FDA-approved therapeutic agent with an anabolic mechanism of action are teriparatide (human recombinant parathyroid hormone [PTH] fragment [1-34 N-terminal amino acid sequence]) and abaloparatide (synthetic peptide analog of human PTH-related protein). Abaloparatide is indicated for women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.40

Emerging Drug Therapies

A human recombinant PTH (full length 1 to 84 sequence) has been studied for use in osteoporosis. It is approved for use in Europe, but in the United States it is available only for patients with chronic hypoparathyroidism. In addition, alternative PTH fragments and delivery mechanisms, including intermittent, transdermal, oral, and inhalational, are under investigation.41 Several other potential targets for increasing bone mass have been identified and several drug candidates are in phase III trials.42 These new drugs include romosozumab and blosozumab, which are sclerostin human monoclonal antibodies that enhance the wingless-int signaling pathway to prevent the inhibition of bone formation. The sponsors of odanacatib, a cathepsin-K inhibitor that is involved in bone resorption, stopped a Phase III trial after evidence of increased risk of stroke.43

Adjunctive Therapies

Typical adjunctive treatments, in addition to medication for preventing or treating osteoporosis, include adequate dietary intake of calories (to avoid underweight), calcium, and vitamin D, with supplemental calcium or vitamin D (or both) if dietary intake is insufficient. Additionally, exercise of various types may reduce the risk of fracture, for example through small increases in bone density and beneficial changes in bone architecture; they may also decrease the risk of falls.44

Current Clinical Practice

Screening and primary prevention of osteoporosis in asymptomatic adults without known risks for secondary osteoporosis is within the scope of practice for most primary care providers (e.g., internal medicine, family medicine). It may also be in scope for gynecologic practices that serve as primary care providers for women during perimenopause. Recommendations for screening developed by various organizations and specialty societies continue to differ. This is especially true with respect to who should be screened, how to screen (i.e., bone density testing vs. fracture risk assessment), when to start or stop screening, and the frequency of screening (see Table 1).

Table 1. Recommendations About Screening and Treatment of Osteoporosis From Various Professional and Health Organizations.

Table 1

Recommendations About Screening and Treatment of Osteoporosis From Various Professional and Health Organizations.

Although all currently approved medications for osteoporosis are labeled for use based on BMD or history of fragility fracture, a shift toward treatment based on absolute fracture risk has received increasing consideration. A systematic review of osteoporotic fracture risk assessment guidelines using FRAX identified 120 such guidelines.45 Of these, 38 did not provide a rationale for the use of fracture probabilities in setting intervention thresholds. The authors categorized the others as offering fixed-probability threshold (N=58, a group that includes the USPSTF 2011 recommendation), an age-dependent threshold (N=22), or a combination (N=2). Of the guidelines referencing fixed-probability thresholds, over half (N=39) reference an absolute fracture risk of 20 percent or greater for major osteoporotic fractures as the threshold for treatment in those with low bone mass. In the United States, this threshold, along with a threshold of 3 percent or greater absolute fracture risk for hip fractures, is based on a cost-effectiveness analysis of treatment relying on 2005 cost data.46 The 2011 USPSTF recommendation,1 along with a small minority of other guidelines (Scottish Intercollegiate Guidelines Network,47 the Michigan Quality Improvement Consortium,48 the American Academy of Family Physicians,49 and the Institute for Clinical Systems Improvement)50 uses a fixed-probability FRAX threshold as a gateway to further assessment with bone density testing rather than treatment. Specifically, the 2011 USPSTF recommendation relied on the U.S. FRAX tool for identifying risk in women younger than 65 and establishes a threshold for bone density testing for women at an absolute fracture risk of 9.3 percent or greater, which is the 10-year probability of a major osteoporotic fracture for a 65-year old white woman of average body mass index of 25 kg/m2 with no other risk factors.

In 2006, the National Committee for Quality Assurance introduced the Healthcare Effectiveness Data and Information Set measure assessing the percentage of women 65 to 85 years of age who report ever having received a bone density test to screen for osteoporosis. The rate of receipt of bone density tests rose in the ensuing decade.51 In 2006, 64.4 percent of women 65 to 85 years of age in a Medicare health maintenance organization plan and 71.3 percent in a Medicare preferred provider organization reported ever having a bone density test. By 2014, these numbers had risen to 74.2 percent and 78.5 percent, respectively. At the same time, some studies have identified inappropriate use of bone mineral density screening. Overuse is defined as a diagnostic test or treatment that is commonly used but that offers limited benefits or carries risks that outweigh its benefits)52 For BMD tests, the Good Stewardship Working Group defines overuse as DXA screening in women under age 65 years or men under 70 years with no risk factors. Findings from the National Ambulatory Medical Care Survey indicated that overuse of DXA in primary care accounted for $527 million in expenditures;53 a study in a large regional health care system suggested that about one-half of women under age 65 without risk factors received DXA screening over a 7-year period.54 The Choosing Wisely® Campaign, which is endorsed by multiple medical societies, lists bone density testing as a test that should be considered carefully before ordering in women younger than 65 and in men younger than 70 with no risk factors.

Previous Review and USPSTF Recommendations

In 2011, the USPSTF recommended screening for osteoporosis in women age 65 or older and in younger women whose fracture risk is equal to or greater than that of a 65-year old white women who has no additional risk factors (B grade). The USPSTF also concluded that the evidence was insufficient to assess the balance of benefits and harms of screening for osteoporosis in men.

Use and Accuracy of Fracture Risk Instruments for Identifying Patients for Further Evaluation

Modeling studies raise concerns regarding the clinical value of the USPSTF-recommended fracture risk threshold for bone density testing in younger women. In 2011, the USPSTF recommended screening with DXA in women 55 to 64 years of age whose fracture risk is equal to or greater than that of a 65-year old white woman who has no additional risk factors, which is equivalent to a FRAX calculated risk of ≥9.3 percent for major osteoporotic fracture. Table 2 reflects fracture risk probabilities by age, race, and sex for men and women in the United States at mean height and weight, with no other risk factors.55 Notably, FRAX calculates the risk of a fracture, not the risk of osteoporosis defined operationally by a T-score ≤−2.5.

Table 2. FRAX-Generated 10-Year Fracture Risk Probabilities by Age, Race, and Sex for U.S. Populations of Average Height and Weight.

Table 2

FRAX-Generated 10-Year Fracture Risk Probabilities by Age, Race, and Sex for U.S. Populations of Average Height and Weight.

The 2011 USPSTF recommendation used FRAX as a risk stratification tool for screening for osteoporosis for women younger than 65 to try to identify higher-risk women who may benefit from earlier screening (women older than 65 are to be routinely screened). The use of FRAX in younger women is then intended to lead to cascade of interventions that results in lower future risk of fractures. An implicit assumption of the recommendation is that FRAX is a reasonable risk stratification tool for osteoporosis. Studies published after the recommendation do not support the assumption that FRAX predicts osteoporosis as defined by T-score accurately. A retrospective application of the FRAX threshold of ≥9.3 percent to a series of women 50 to 64.5 years of age undergoing DXA found sensitivity and specificity of 37 and 74 percent, respectively, for the detection of osteoporosis.56 The study found that lowering the FRAX risk threshold to 5.5 percent would increase the sensitivity from 37 to 80 percent while reducing the specificity from 74 to 27 percent.

Another study compared FRAX, Osteoporosis Self-Assessment Tool (OST), and the Simple Calculated Osteoporosis Risk Estimate (SCORE) among 5,165 Women’s Health Initiative participants 50 to 64 years of age from 1994 to 2012. The study found that the FRAX threshold of ≥9.3 percent was modestly better than chance, and inferior to OST and SCORE in identifying women with osteoporosis (femoral neck T-score ≤−2.5).57 Using the same database, the authors also examined the sensitivity and specificity of FRAX, SCORE, and OST in predicting the incidence of major osteoporotic fracture. The findings of low sensitivity and specificity and thus very low area under the curve scores ranging from 0.52 to 0.56 suggested that none of these tools are suitable for predicting fractures in younger postmenopausal women.58

Clinical Considerations for the Update

Numerous comments received during workplan development for the current update noted the limitations of focusing on screening for osteoporosis with BMD alone. Commenters requested that the analytic framework include consideration of the full spectrum of risk beyond bone mineral density measurement, and focus on screening for osteoporotic fracture risk rather than osteoporosis. As a result, the analytic framework was expanded to address the full spectrum of risk related to osteoporotic fractures beyond low BMD. The current update also reviews continuing uncertainties regarding the overarching question of effectiveness and harms of screening and treatment, risk assessment thresholds, efficacy of screening and treatment for subgroups, and screening intervals.


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