Final Research Plan
Osteoporosis to Prevent Fractures: Screening
November 18, 2021
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Abbreviation: DXA=dual energy X-ray absorptiometry
1. Does screening for fracture risk or osteoporosis reduce fractures and fracture-related morbidity and mortality in adults?
2a. What is the predictive accuracy of risk assessment tools for identifying adults who are at increased risk for hip fractures or major osteoporotic fractures?
2b. What is the predictive accuracy of bone mineral density testing with dual X-ray absorptiometry at central skeletal sites for identifying adults who are at increased risk for hip or major osteoporotic fractures?
2c. What is the diagnostic accuracy of risk assessment tools for identifying adults with osteoporosis?
2d. What is the evidence to determine screening intervals, and how do these intervals vary by baseline or current individual fracture risk?"
3. What are the harms of screening for fracture risk or osteoporosis?
4. What is the effectiveness of pharmacotherapy with selected Food and Drug Administration (FDA)–approved medications on fracture incidence and fracture-related morbidity and mortality?
5. What are the harms associated with selected FDA-approved medications?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- What is the evidence from modeling studies about the effectiveness of risk screening strategies that use different ages at which to start and stop screening and different screening intervals?
- How do various fracture risk assessment tools use race and ethnicity in fracture risk calculations?
- What is the incidence of fractures among persons of different races and ethnicities in the United States in the last 10 to 15 years, and what factors might explain differences in incidence among different races and ethnicities?
- What are the differences in rates of screening or treatment initiation among persons of different races and ethnicities, and what might explain these differences?
- What are the implications of using fixed fracture-risk thresholds for decisions regarding stepwise screening or treatment?
- What is the evidence for rare harms of bisphosphonate treatment (i.e., osteonecrosis of the jaw, atypical femur fractures) from observational studies that use noneligible control groups or are uncontrolled?
- What is the evidence for rebound fractures after discontinuation of denosumab?
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the evidence review. Criteria are overarching as well as specific to each of the key questions (KQs).
|Population||KQs 1–3 (Screening benefits, accuracy, harms): Adults age 40 years or older without known osteoporosis or history of fragility fractures
KQs 4, 5 (Treatment benefits and harms): Adults age 40 years or older with osteoporosis, osteopenia, or increased fracture risk (as defined by study authors)
Studies in which less than 50% of the enrolled population includes persons with conditions or medications listed as excluded will be included, and results will be stratified if possible.
Subpopulations of interest include men, women age 65 years or older, and postmenopausal women younger than 65 years.*
|All KQs: Studies that exclusively enroll adults younger than age 40 years
KQs 1–3: Studies that exclusively enroll:
|Screening Interventions||KQs 1–3 (Screening benefits, accuracy, and harms):
|Screening Comparators||KQs 1, 3 (Screening benefits and harms):
KQ 2 (Accuracy):
|KQs 1, 3:
KQ 2: Any comparator not specifically identified as included.
|Treatment Interventions||KQs 4, 5 (Treatment benefits and harms):
Bisphosphonates with FDA-approved indications for the treatment of osteoporosis (i.e., alendronate, ibandronate, risedronate, zoledronic acid), denosumabMales only: Teriparatide, abaloparatide, and romosozumab are also eligible†
|KQs 4, 5:
|Treatment Comparators||KQs 4, 5 (Treatment benefits and harms): Placebo, vitamin D or calcium or both, no treatment||
|Outcomes||KQs 1, 4 (Screening and treatment benefits):
KQ 2 (Accuracy):
KQ 3 (Screening harms):
KQ 5 (Treatment harms):
|KQs 1, 4:
KQs 2, 3, 5: Outcomes not specifically identified as included
|Timing||KQs 1, 4 (Screening and treatment benefits): Followup for at least 1 year
KQ 2 (Accuracy):
|Timing that does not meet inclusion criteria|
|Study Design||KQs 1, 3 (Screening benefits and harms): RCTs, clinical controlled trials, or systematic reviews of RCTs or controlled trials. Cohort studies and systematic reviews of cohort studies are also eligible for KQ 3 only.
KQ 2 (Accuracy): Recent (published in the last 5 years) systematic reviews of cohort or test accuracy studies, cohort studies designed for evaluating predictive accuracy (i.e., prognosis for fracture risk) or diagnostic accuracy (for identification of osteoporosis), comparative studies in which a single group is treated as a cohort for purposes of evaluating predictive or diagnostic accuracy are also eligible.KQs 4, 5 (Treatment benefits and harms): RCTs and controlled trials (including those in which participants serve as their own controls); controlled cohort studies are also eligible for KQ 5 only
|All KQs: Case series; case reports; case-control studies; conference abstracts, posters, or proceedings without data or information available to assess risk of bias; unpublished data; editorials; commentaries; narrative reviews
KQs 4, and 5: Systematic reviews are not eligible but will be hand searched to identify studies potentially missed by our search
|Settings||KQs 1, 3, 4, 5 (Screening and treatment benefits and harms): Primary care settings in countries designated as “very high” on the 2020 Human Development Index (as defined by the United Nations Development Programme)
KQ 2 (Accuracy): Predictive accuracy: United States or countries with similar hip fracture incidence as the United States§ for synthesis of any primary research studies
|KQs 1, 3, 4, 5: Long-term care settings such as nursing homes, inpatient settings
KQs 1, 3: Specialty medical settings (e.g., endocrinology, rheumatology)KQ 2: Predictive accuracy: studies in single countries with high or low fracture incidence
|Study Quality||All KQs: Good or fair quality as determined by standard risk of bias instruments and existing USPSTF criteria tailored to study design||All KQs: Poor quality|
* For the purposes of this review, we will use the terms men and women consistent with how they are typically used in the underlying evidence base for this topic. Men refers to persons assigned male sex at birth. Women refers to persons assigned female sex at birth. Studies that include gender-diverse individuals, including those who have undergone gender-affirming therapy (e.g., transmen, transwomen), are not excluded from the scope of this review. However, studies that exclusively enrolled populations who take hormone therapy that affects bone density are excluded from this review, consistent with our criteria that exclude studies that focus on populations with secondary osteoporosis or who take chronic medications that have known effects on bone metabolism. For such populations, individualized clinical decisions about bone density testing in the context of condition and medication management are required.
† This review is not intended as a comprehensive review of all available pharmacologic therapies. Second-line therapies (abaloparatide, teriparatide, romosozumab) are excluded for women because the USPSTF is likely to have sufficient evidence to determine the net benefit of treatment based on the evidence for FDA-approved bisphosphonates and denosumab, as determined by the most recent review before this update. We will only consider these drugs for men given the paucity of treatment studies generally available for men. Although romosozumab is not currently FDA-approved for men, it is currently in Phase 3 studies for men, so it will be included in this update. Hormone therapy and selective estrogen receptor modulators are reviewed in a separate USPSTF review on hormone therapy, so they will not be included in this update.
‡ Major osteoporotic fracture is typically defined as fractures of the hip, wrist, and humerus and clinical vertebral fractures.
§ Countries with “moderate” hip fracture incidence in addition to the United States include Finland, France, Canada, New Zealand, Lithuania, Malaysia, South Korea, Portugal, Japan, Israel, Australia, Russia, The Netherlands, Kuwait, Spain, Mexico, Estonia, Poland, Chile, and Thailand.1
Abbreviations: BMD=bone mineral density; CT=computerized tomography; DXA=dual-energy X-ray absorptiometry; FDA=Food and Drug Administration; FRA=fracture risk assessment; KQ=key question; NHANES=National Health and Nutrition Examination Survey; ORA=osteoporosis risk assessment; RCT=randomized, controlled trial; USPSTF=U.S. Preventive Services Task Force.
The draft Research Plan was posted for public comment on the USPSTF website from August 12, 2021, to September 8, 2021. In response to comments, the USPSTF included additional outcomes, added two contextual questions regarding rare but serious harms, and specified subpopulations of interest. The USPSTF also made several minor additions and wording changes to improve the clarity and specificity of the research approach.
Kanis JA, Oden A, McCloskey EV, et al. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int. 2012;23(9):2239-2256.