Final Research Plan

Osteoporosis to Prevent Fractures: Screening

November 05, 2015

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.

The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from June 18 until July 15, 2015 at 5:00 p.m., ET.

Abbreviation: KQ = key question.

Text Description.

This figure is the analytic framework depicting the five key questions (KQs) that will guide the evidence review. In general, the figure illustrates the overarching question of whether screening for osteoporosis to prevent fractures in adults without low-trauma fractures, endocrinopathies, or steroid use reduces fractures and fracture-related morbidity and mortality (KQ 1). The framework starts on the left with the patient population of interest. Moving from left to right, the figure depicts an initial risk assessment, after which some individuals may be classified as being at increased risk for osteoporotic fractures or not. Those at increased risk may undergo a comprehensive risk assessment, including bone density measurement. Following the comprehensive risk assessment, individuals may be classified again as being at increased risk for osteoporotic fractures or not (KQ 2). Screening may result in harms (KQ 3). For adults with increased risk for osteoporotic fractures, treatment may reduce the likelihood of fractures or fracture-related morbidity and mortality (KQ 4). Treatment may result in harms (KQ 5).

1. Does screening (clinical risk assessment, bone density measurement, or both) for osteoporotic fracture risk in adults reduce fractures and fracture-related morbidity and mortality?

2a. What is the accuracy and reliability of screening approaches to identify adults who are at increased risk for osteoporotic fracture?

2b. What is the evidence to determine screening intervals, and do they vary by baseline fracture risk?

3. What are the harms of screening for osteoporotic fracture risk?

4a. What is the effectiveness of treatment with pharmacotherapy for the reduction of fractures and fracture-related morbidity and mortality?

4b. Does the effectiveness of treatment with pharmacotherapy for the reduction of fractures and fracture-related morbidity and mortality vary by subgroup, specifically in postmenopausal women, premenopausal women, men, younger age groups (<65 years), and older age groups (≥65 years) or by baseline bone mineral density and fracture risk?

5. What are the harms associated with treatment with pharmacotherapy?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What is the evidence from modeling studies about different fracture risk thresholds for identifying patients for further evaluation or treatment?
  2. What is the evidence from modeling studies about the effectiveness of screening strategies (screening, clinical risk assessment, or bone density measurement) that use a) different ages at which to start and stop screening and b) different screening intervals?

The Proposed 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).

  Include Exclude
Populations KQs 1–3: Adults in general primary care age ≥40 years without history of a low-trauma fracture; endocrine disorder likely to be related to metabolic bone disease, such as premature ovarian failure, hypogonadism, untreated hyperthyroidism, hyperparathyroidism, adrenal insufficiency, or Cushing’s syndrome; or chronic use of glucocorticoid medications (>5 mg/day oral prednisone [or equivalent] for ≥3 months)

KQs 4, 5: Adults age ≥40 years with increased fracture risk

KQs 1–5:
  • Majority of study population has underlying medical condition likely to be related to metabolic bone disease, is already receiving treatment for osteoporosis, or has experienced a low-trauma fracture
  • Nonhuman populations
  • Majority of study population is comprised of adults age <40 years

KQs 4, 5: Adults without increased fracture risk

Interventions KQs 1–3: Risk assessment tools for low bone mass and/or high fracture risk, bone density measurement tests (including vertebral fracture assessment), or both (intervention must be available in the United States). Eligible bone density measurement tests include dual-energy x-ray absorptiometry (central or peripheral measurement) and quantitative ultrasound.

KQs 4, 5: Pharmacotherapy approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis (including bisphosphonates, estrogen agonists/antagonists, hormone therapy, calcitonin, parathyroid hormone, and RANKL inhibitors)

KQs 1–3:
  • Interventions that are not risk assessment tools or bone density measurement tests
  • Tests that are not in routine clinical use in the United States

KQs 2, 3: Screening tests not approved by the U.S. Food and Drug Administration; biomarkers of bone metabolism, quantitative computed tomography, magnetic resonance imaging, hip structural analysis, structural engineering models, and finite element analysis

KQs 4, 5: Interventions other than those described in the inclusion criteria

Comparators KQ 1 (control intervention): No screening group

KQs 2, 3 (control intervention): Other risk assessment/testing approach, threshold, or interval

KQ 4 (control intervention): Placebo

KQ 5 (control intervention): Placebo or no treatment

KQ 1a (control intervention): Lack of a nonscreening group (active comparator)

KQ 2 (control intervention): Not an active comparator

KQ 3: None

KQs 4, 5 (control intervention): Active comparator

Outcomes All KQs: Fractures, fracture-related morbidity and mortality, or all-cause mortality

KQs 2, 3:

  • Screening test characteristics of risk assessment tools, bone density measurement tests, or both (e.g., sensitivity, specificity, reliability)
  • Fracture risk prediction (measures of discrimination and calibration)

KQ 3: Harms (e.g., unnecessary radiation, labeling, anxiety, false-positive results)

KQ 5: Harms (e.g., cardiovascular events, hot flashes, esophageal cancer, gastrointestinal events, osteonecrosis of the jaw, atypical fractures of the femur, rashes)

KQ 1:
  • Nonvalidated fractures and their related morbidity and mortality
  • Bone density measures (t-score, z-score)

KQs 2–4: Outcomes other than those described in the inclusion criteria

KQ 5: None

Timing KQ 1: ≥6 months following screening

KQs 2, 3: Any time

KQs 4, 5: ≥6 months following initiation of treatment

KQ 1: Within 6 months of screening

KQs 2, 3: None

KQs 4, 5: Within 6 months of initiation of treatment

Settings All KQs: U.S. adult population or comparable populations (i.e., those categorized as “Very High” on the Human Development Index, as defined by the United Nations Development Programme)

KQ 1: Primary care or primary care–like settings

KQs 2–5: Primary care or primary care–like settings, specialists

All KQs: Settings not comparable or applicable to U.S. adult population

KQ 1: Inpatient, medical specialty (e.g., endocrinology), or nursing home settings

KQs 2–5: Inpatient or nursing home settings

Study designs KQs 1–3:
  • Randomized, controlled trials
  • Controlled clinical trials
  • Systematic reviews of trials

KQs 2, 3: Observational studies other than case series and case reports

KQ 4: Systematic reviews and randomized, controlled trials; controlled trials published since any recent, relevant review

KQ 5: Systematic reviews and randomized, controlled trials; controlled trials; and observational studies published since any recent, relevant review

KQ 1: Nonrandomized, controlled trials; noncontrolled clinical trials, or nonsystematic reviews

KQs 2, 3: Case series, case reports

KQs 4, 5: Nonsystematic reviews, case series, case reports

Quality Good and fair quality Poor quality
Language English Languages other than English
Publication type Published or unpublished original research Nonsystematic review article, letter, or editorial; articles in which results are reported elsewhere; articles with no original data
Date of search November 1, 2009 onward for all searches; additional expanded searches for terms missing in prior review Before November 1, 2009 unless otherwise specified

Abbreviation: RANKL = receptor activator of nuclear factor kappa-B ligand.

A draft version of the research plan was posted for public comment on the USPSTF Web site from June 18, 2015 to July 15, 2015. The USPSTF received several comments requesting that the analytic framework include consideration of the full spectrum of risk beyond bone mineral density measurement. As a result, the analytic framework was expanded to address the full spectrum of risk. It now incorporates bone mineral density measurement as a component of comprehensive risk assessment. Search dates were also expanded to capture all relevant literature.