62.1

Introduction

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture . Because osteoporotic fractures result in loss of independence, chronic pain, decreased quality of life, and increased risk of death , it is important to detect osteoporosis prior to the occurrence of fracture, that is, by screening.

The primary purpose of screening tests is to detect early disease or risk factors for disease in large numbers of asymptomatic, but potentially at risk, individuals . The goal of screening is to detect disease in a preclinical phase, based on the assumption that the treatment of earlier (screen-detected) disease is more beneficial than later treatment of disease that is detected without screening . General principles of screening include, but are not limited to, the following: the condition should be an important health problem, there should be a treatment for the condition, there should be a latent stage of the disease, and there should be a test for the condition that is acceptable to the population . Osteoporosis meets these criteria because osteoporosis is an important health problem, several osteoporosis treatments exist, there is a detectable latent stage (prior to the development of symptomatic fracture), and there are available screening tests. In this chapter, we use the term bone mineral density (BMD) to refer to BMD assessed by duel-energy X-ray absorptiometry (DXA). BMD (expressed as a 1 SD decrease) has a higher gradient of risk for prediction of hip fracture than does serum cholesterol (expressed as a 1 SD increase) for the prediction of cardiovascular disease events .

The potential harms of screening for osteoporosis include costs and adverse effects, such as the burden of financial cost and time required for the patient to undergo the screening process and discuss results, and the downstream harms (financial costs, adverse effects) of subsequently treating individuals who would not ever experience fracture without osteoporosis medication therapy. An important concept regarding the utility of osteoporosis screening among women aged under 65 years is that, at a given level of BMD, the absolute risk of fracture is much lower among women younger than 65 years-old than that of older women. Although this chapter is focused on screening, we note that the paucity of data about treatment efficacy in reducing clinical fractures in younger women and men has important ramifications in decision-making regarding screening.

Screening is distinct from case-finding. Case-finding refers to the process of performing tests on individuals who are already suspected to be at risk for a disease and/or already have signs or symptoms of disease. Case-finding is a strategy for targeting resources at individuals or groups who are suspected to be at risk for a particular disease . It involves actively searching systematically for at-risk people, rather than waiting for them to present with symptoms or signs of active disease. It is an example of “diagnostic testing.” For example, bone density testing of persons taking glucocorticoid medication or aromatase inhibitors over a prolonged period of time would qualify as case-finding, not screening. Many countries advocate selective bone density testing based on case-finding strategies instead of broad population-based screening strategies.

This chapter does not focus on patients who already have an existing vertebral or hip fracture, because individuals with existing vertebral or hip fractures are not candidates for screening. A prevalent vertebral or hip fracture is an indication for pharmacologic treatment, and BMD testing in that population is not required prior to treatment initiation.

We begin this chapter on osteoporosis screening by discussing the tools that are often used to identify candidates for osteoporosis screening. We then provide a suggested approach to decision-making regarding whom to screen, when to initiate screening, how frequently to order BMD testing, and when to stop screening for osteoporosis.

62.2

Bone mineral density testing

In the absence of fracture, osteoporosis is diagnosed in persons over age 50 years based on a DXA BMD T -score ≤−2.5 at the hip or lumbar spine, and low bone mass (previously called osteopenia) is diagnosed based on BMD T -score between −1 and −2.5 . For both men and women the referent group for BMD T -score is the young white female referent . The recommended reference ranges are the National Health and Nutrition Examination Survey III database for femoral neck measurements in women aged 20–29 years . More than 43 million adults (10% of adults) in the United States alone have osteoporosis or low bone mass, based on the National Health and Nutrition Examination Survey data . These numbers vary by sex. Among women, 8.2 million have osteoporosis and 27.3 million have low bone mass; among men, 2 million have osteoporosis and 16.1 million have low bone mass .

There are two types of formal risk assessment tools available: tools designed to estimate absolute risk of fracture during a specified time frame [such as the fracture risk assessment tool (FRAX), QFracture, and the Garvan fracture risk calculator], and tools designed to identify individuals with a DXA BMD T -score ≤−2.5 at the hip or lumbar spine [e.g., the Osteoporosis Self-Assessment Tool (OST) calculator]. Both types of tools have been advocated for osteoporosis screening because they identify potential treatment candidates, that is, those with a higher estimated probability of fracture and/or those with a BMD T -score in the osteoporosis range. These two types of formal risk assessment tool are discussed next.

62.3

Formal risk assessment tools

62.4

Who should be screened?

62.5

Younger postmenopausal women aged 50–64 years

The risk assessment strategy to select younger postmenopausal women for osteoporosis screening is uncertain. Despite rapid rates of bone loss at the lumbar spine during the menopausal transition, the absolute fracture risk for any given BMD is much lower in younger postmenopausal women compared with older women. In particular, the absolute 5-year probability of hip fracture is <1.0% until age 70–79 when the probability begins to rise exponentially with increasing age . Data are unavailable on the benefits versus harms of drug treatment beginning at age 50–64 years and continuing over the next three decades of life. The use of drug treatment in younger women leaves them with fewer options for pharmacotherapy in their eighth decade of life, when hip fracture risk accelerates.

Some guidelines encourage BMD testing in this age group among women with risk factors for fracture. However, there is no consensus regarding all the specific risk factors that should be considered in this decision. In 2011 the USPSTF recommended BMD testing in this age group among women with elevated FRAX-predicted 10-year risk of fracture (i.e., predicted risk of MOF ≥9.3%) . Subsequently, in 2018, the USPSTF recommended screening for osteoporosis with BMD testing in postmenopausal women younger than aged 65 years at increased risk of osteoporosis, as determined by a formal clinical risk assessment tool. Several tools are available to assess the presence of low BMD: the SCORE, ORAI, OSIRIS, and the OST. Of note, the OST ( Box 62.1 ) is a simple calculator based on age and weight that is feasible to use in the busy primary care practice setting. Studies have suggested that an OST score <2 is an appropriate cutoff to select younger postmenopausal women for BMD testing. An alternative strategy noted by the USPSTF is to estimate absolute long-term fracture probability to assist in the clinical decision-making regarding whether or not to recommend BMD testing in younger postmenopausal women. The USPSTF suggested selecting younger postmenopausal women for BMD testing who have a 10-year fracture probability as calculated by the FRAX tool that is equal or greater than that of a 65-year-old white woman without additional risk factors [i.e., 10-year probability of major osteoporotic (hip, clinical vertebral, distal forearm, or humerus) fracture estimated without BMD of ≥8.4%]. Direct comparisons of the OST approach versus FRAX-based strategy suggested by the USPSTF have reported superior combined sensitivity and specificity and better discrimination for identification of women with low BMD with the OST approach . Thus if there is consensus from the clinician and patient that drug treatment will be initiated for low BMD (e.g., BMD T -score ≤−2.5), evidence at present suggests that use of OST cutoff <2 is a preferable strategy compared with the use of FRAX for identifying younger postmenopausal women for BMD testing.

Additional investigations have compared the performance of tools in predicting fracture risk among younger postmenopausal women. Prospective studies have reported poor performance of OST, FRAX, and Garvan in identification of younger postmenopausal women who will experience incident fractures during a 10-year follow-up period . These findings indicate that fracture risk prediction in younger postmenopausal requires an assessment of risk factors not included in currently available strategies.

62.6

Men

Osteoporosis screening in older men has been proposed because organizations and professional societies in many countries recommend universal screening in older women. However, osteoporosis is less common in men; the prevalence of BMD-defined osteoporosis among US men aged ≥65 years is 5.6% (and 10.3% in men aged ≥80 years) . Data on the efficacy of pharmacotherapy in preventing fractures in men are limited; randomized trials in osteoporotic men have only evaluated radiographic vertebral fracture as an endpoint.

Some guidelines recommend BMD testing in all older men (e.g., age ≥70 years) and in men 50–69 years with risk factors. Other research has suggested using the OST tool to identify men for screening . The USPSTF made no recommendation about osteoporosis screening in men citing insufficient evidence. A study that compared proposed strategies for selecting men 70 years for osteoporosis screening reported that the OST (cutoff <2) performed modestly better than a more complex FRAX-based strategy (BMD testing in men with a 10-year FRAX probability of MOF equal or greater than that of a 65-year-old white woman without additional risk factors) in identifying men with BMD T -score ≤−2.5. The use of either tool substantially reduced the proportion of men referred for BMD testing compared to universal screening. The major concern regarding osteoporosis screening recommendations in men is the lack of randomized controlled trials of pharmacotherapy demonstrating a reduction in risk of clinical fractures in men. Future research in older men on the development and validation of osteoporosis risk assessment tools and randomized trials with clinical fracture endpoints are needed to clarify whether targeted screening strategies or universal screening are warranted in this patient population.

62.7

When to stop screening?

Life expectancy and treatment burden related to the number and severity of comorbid conditions are important considerations to take into account in clinical decision making regarding whether or not to recommend osteoporosis rescreening with BMD testing in older adults in late life. However, the age at which to stop or decrease BMD testing and the impacts of comorbidity burden and prognosis on screening decisions in late life have not been examined in research studies. In addition, these issues are not addressed in the current guidelines. Older women (i.e., those 65 years and older) with higher BMD T -scores (e.g., >−1.5) have a very low risk of disabling fracture before their estimated time to death and these women may benefit less from rescreening. In contrast, older women with lower BMD T -scores (e.g., <−2.0) have a high risk of disabling fracture before their estimated time to death so they (assuming willingness to initiate drug treatment for fracture prevention) may benefit more from rescreening. The age to stop screening may be lower in men as compared with women due to their higher competing risk of mortality.

62.8

How often to screen?

Evidence is inadequate to inform the optimal frequency of serial BMD testing to screen for osteoporosis among untreated individuals. Recent studies summarized next have established that a single BMD test predicts fracture risk over many years. Moreover, baseline age and BMD are likely to have a strong influence on the optimal frequency of repeated BMD testing in the screening setting in older women, older men, and younger postmenopausal women.

For example, among women aged ≥67 years in the Study of Osteoporotic Fractures, a single femoral neck BMD measurement strongly predicted long-term hip fracture risk to 25 years (30% risk in the lowest BMD quartile vs 8% in the highest BMD quartile) , and a repeat BMD measurement up to 8 years after baseline provided little additional value over initial BMD measurement for predicting incident nonspine fracture fractures . In that same cohort, among women who had normal baseline BMD or BMD T -score slightly below normal (between −1.01 and −1.49), osteoporosis-range BMD developed in less than 10% of women during a rescreening interval of 15 years . Among older men aged ≥65 years in the MrOS cohort, men with femoral neck, total hip, and lumbar spine BMD T -scores ≥−1.50 on a first BMD test were very unlikely to develop osteoporosis during a mean follow-up of 8.7 years . Among men with BMD T -score between −1.50 and −1.99, it took 8.5 years for 10% of men to develop BMD in the osteoporotic range . Therefore additional BMD testing in older men may be most informative in those with BMD T -score ≤−1.50. Among untreated older individuals (mean age 75 years) in the Framingham study, a second BMD measure after 4 years did not meaningfully improve the prediction of hip or MOF, suggesting that repeating a BMD measure within 4 years to improve fracture risk stratification may not be necessary among untreated individuals in this age group . Finally, in the Dubbo Osteoporosis Epidemiology Study conducted in persons over age 60, the time needed for 10% of persons to reach osteoporosis level BMD or experience a low-trauma fracture depended on baseline BMD and age, ranging from 1.5 years (for 80-year-old women with baseline BMD T -score −2.2) to 11 years (for 60-year-old men with baseline BMD T -score of 0) .

Similar data exist for younger postmenopausal women from the Women’s Health Initiative study. Among women without baseline osteoporosis (and without a prevalent fracture), the estimated time for 1% of women to have a hip or clinical vertebral fracture was 13 years for women aged 50–54 years and women aged 55–59 years, but 8 years among women 60–64 years . Because of very low rates of MOF in postmenopausal women aged 50–64 years, the authors concluded that women in this age group, who do not have osteoporosis on their first BMD test, are unlikely to benefit from rescreening until the age of 65 years.

Based on these results, we suggest consideration of age and baseline BMD to determine the appropriate time interval for repeat BMD testing.

62.9

Guideline statements

The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in women 65 years and older (B recommendation) . The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in postmenopausal women younger than 65 years who are at increased risk of osteoporosis, as determined by a formal clinical risk assessment tool (B recommendation). For postmenopausal women aged less than 65 years with at least one risk factor, the USPSTF states, “a reasonable approach to determine who should be screened with bone measurement testing is to use a clinical risk assessment tool.” Suggested tools include OST, ORAI, OSIRIS, SCORE, and FRAX . The USPSTF concluded that there is insufficient evidence regarding screening for osteoporosis in men. Although BMD tests are accurate for detecting osteoporosis in men, the USPSTF found that current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men .

Regarding screening intervals, the USPSTF says “Some observational and modeling studies have suggested screening intervals based on age, baseline BMD, and calculated projected time to transition to osteoporosis… Two good-quality studies found no benefit in predicting fractures from repeating bone measurement testing 4 to 8 years after initial screening.”

The Osteoporosis Canada guidelines recommend BMD testing among all men and women aged ≥65 years, with selective testing in younger adults based on the presence of individual clinical risk factors (e.g., prolonged glucocorticoid use, parental hip fracture, high alcohol intake, current smoking, low body weight, or disorders or medications strongly associated with osteoporosis) . For individuals who have not experienced minimal trauma fracture, the Royal Australian College of General Practitioners recommends BMD testing for all individuals aged ≥70 years and selective testing among women aged 50–69 years who have one or more clinical risk factors (the presence of disease, condition, or medication use that is associated with bone loss) . The UK strategy has recommended age-specific assessment thresholds and age-specific treatment thresholds to select candidates for BMD testing . Specifically, postmenopausal women aged ≥50 years with prior fragility fracture should be considered for treatment without the need for BMD testing, whereas men and postmenopausal women aged ≥50 years without fragility fracture should undergo FRAX risk assessment . Based on the FRAX assessment, persons with 10-year predicted risk of MOF below the age-specific assessment threshold would receive reassurance without BMD testing (along with lifestyle advice), and those above the age-specific treatment threshold would be offered treatment without BMD testing. Under the UK strategy, BMD testing would be recommended only among those who have intermediate FRAX-predicted MOF risk, that is, above the age-specific assessment threshold and below the age-specific treatment threshold . Key clinical guidelines recommendations are summarized in Box 62.3 .

Box 62.3

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