Table 1 Eligibility criteria for each key question
Key question 1 a & b (a) Benefits and harms of screening vs no screening (b) Comparative benefits and harms of different screening approaches/tools | Key question 2 Predictive accuracy of screening tests | Key question 3 a & b (a) Benefits of pharmacologic treatments (b) Harms of pharmacologic treatments | Key question 4 Acceptability of screening and/or treatment | ||
|---|---|---|---|---|---|
Population | Include | Asymptomatic adults ≥40 years in the general population (≥80% of the sample or mean age -1 standard deviation is ≥40 years) Subgroups for decision-making: age, sex, menopausal status Methods subgroups: diabetes, presence of prior fractures, baseline predicted fracture risk, length of follow-up | Asymptomatic adults ≥40 years in the general population Subgroups for decision-making: age, sex, menopausal status Methods subgroups: treatment with anti-osteoporosis drugs, baseline predicted fracture risk, length of follow-up | KQ3a: Adults ≥40 years in the general population who are at risk of fragility fracture KQ3b: Adults ≥40 years who are at risk of fragility fracture Subgroups for decision-making: age, sex, menopausal status Methods subgroups (KQ3a): prior fracture, predicted fracture risk, length of follow-up | Adults aged ≥40 years Population subgroups: absolute fracture risk (perceived or actual), prior screening, history of fracture, prior use of anti-osteoporotic medication, prior diagnosis of osteoporosis, level of concern or perceived severity of fractures |
Exclude | - Adults <40 years - Treatment with anti-osteoporosis drugs - >50% with prior diagnosis of osteoporosis, prior fragility fracture, endocrine or other disorders related to metabolic bone disease, chronic use of glucocorticoid medications, cancer | - Adults <40 years - >50% with prior diagnosis of osteoporosis, prior fragility fracture, endocrine or other disorders related to metabolic bone disease, chronic use of glucocorticoid medications, cancer | KQ3a: - Adults <40 years - > 50% with with prior fragility fracture, endocrine or other disorders related to metabolic bone disease, chronic use of glucocorticoid medications, cancer KQ3b: - Adults <40 years - Endocrine or other disorders related to metabolic bone disease, cancer | - Adults <40 years - Current use of anti-osteoporosis drugs (>10% of population) - >50% with prior fragility fracture, endocrine or other disorders related to metabolic bone disease, chronic use of glucocorticoid medications, cancer | |
Intervention/ Exposure | Include | Screeninga to prevent fragility fracture with any of the following: -Fracture risk assessment alone (validated or non-validated tools) -Bone mineral density (BMD) alone by dual x-ray absorptiometry ± vertebral fracture assessment (VFA)/spinal radiography - Fracture risk assessment followed by BMD if indicated ± vertebral fracture assessment/spinal radiography Treatment is offered for participants meeting “high risk” threshold | Screening tool to prevent fragility fracture using any of the following: - Fracture risk assessment alone (validated or nonvalidated tools) - Bone mineral density (BMD) alone by dual X-ray absorptiometry ± vertebral fracture assessment/spinal radiography - Fracture risk assessment followed by/incorporating BMD ± vertebral fracture assessment (VFA)/spinal radiography Risk assessment tools must be available to clinicians and have been externally validated to predict fragility fractures in a population within a very high human development index country with a fracture rate similar to Canada (i.e., moderate) | Pharmacotherapy currently approved by Health Canada for the treatment of osteoporosis or prevention of fragility fractures that is commonly used in Canada as a first-line treatment: - Bisphosphonates (alendronate, risedronate, zoledronic acid); harms of bisphosphonates as a class will be included when no or very low certainty evidence is available for individual bisphosphonates - Denosumab (exposure is discontinuation of denosumab for rebound fracture outcome) Adjunct calcium and/or vitamin D (but not other drugs) will be included if it is used identically in both the intervention and comparison group | Population may or may not have knowledge of their own fracture risk but must have at least some general scenario or background information on the possible magnitude of benefits and/or harms from screening (same tools as KQ1) or treatment (bisphosphonates or denosumab) for fragility fractures or osteoporosis. OR Investigators solicit the magnitude of benefits and/or harms where screening or treatment is acceptable. Exposure subgroups: different presentation of information |
Exclude | - Other screening tests - VFA without BMD | - Tools not externally validated - Tools not available to clinicians - Tools that do not provide absolute fracture risk (CAROC retained due to relevance to Canada) - Other countries (see inclusion) - Other BMD or osteoporosis-related screening tests | - Pharmacotherapies not commonly used in Canada: hormone therapy, etidronate, raloxifene, teriparatide, calcitonin - Drugs used in combination - Off-label pharmaceuticals and dosages - Natural health products, dietary supplements (e.g., vitamins, minerals) - Complex interventions (e.g., pharmacotherapy + exercise) | - Context of screening using other BMD or osteoporosis screening tests - Benefit and harm information about treatments | |
Comparator | Include | KQ1a: no screening KQ1b: another screening strategy or screening using a different risk assessment tool | Not applicable | KQ3a: Placebo KQ3b: Placebo or no treatment; continuation of denosumab for rebound fracture outcome | − None - Non-active exposure: intervention without information about the possible magnitude of benefits and/or harms of screening or treatment - Information on alternative screening or treatment strategy |
Exclude | - Other screening tests - Fracture liaison services | Not applicable | All other comparators | See exposure | |
Outcome | Include | Benefits: hip fractures, clinical fragility fracturesb, fracture-related mortality, functionality and disability, quality of life or wellbeing, all-cause mortality Harms: serious adverse eventsc (all serious cardiovascular events, serious cardiac rhythm disturbances, serious gastrointestinal adverse events, gastrointestinal cancer, atypical fractures, osteonecrosis of the jaw, overdiagnosis (defined in Additional file 3), discontinuation due to adverse events, non-serious adverse events (including “any” adverse events) | Calibration (total/average and by differing estimated risks) for 5- and 10-year risk of hip and clinical fragility fractures | KQ3a: hip fractures, clinical fragility fracturesb, fracture-related mortality, functionality and disability, quality of life or wellbeing, all-cause mortality KQ3b: serious adverse eventsc (all serious cardiovascular events, serious cardiac rhythm disturbances, serious gastrointestinal adverse events, gastrointestinal cancer, atypical fractures, osteonecrosis of the jaw, rebound fractures i.e. multiple vertebral fractures, discontinuation due to adverse events, non-serious adverse events (including “any” adverse events; non-serious gastrointestinal adverse events, musculoskeletal pain, dermatologic adverse events, infections) | - Willingness or intentions to screen or initiate treatment - Acceptability of screening or initiating treatment - Uptake of screening or treatment - Absolute risk for fracture to make treatment acceptable - Others as suitable, as reported by authors |
Exclude | All other outcomes | Discrimination (we will supplement with findings from 2018 USPSTF systematic review) | All other outcomes | All other outcomes | |
Follow-up | Include | ≥6 months | Any length of follow-up; to make predictions for 5- or 10-year fracture | ≥6 months | Any |
Exclude | <6 months | Not applicable | <6 months | Not applicable | |
Setting | Include | Primary health care | Primary health care | KQ3a: primary health care KQ3b: primary health care or long-term care | Primary health care |
Exclude | Long-term care | Long-term care | KQ3a: long-term care KQ3b: all other settings | Long-term care or hospital | |
Study design | Include | Randomized controlled trials, clinical controlled trials (if needed)d; manuscripts, reports, abstracts, dissertations, clinical trials registers if data are available | Prospective or retrospective cohort studies; single arms of randomized trials; manuscripts, reports, abstracts, dissertations, clinical trials registers if data are available | KQ3a: randomized controlled trials; manuscripts, reports, abstracts, dissertations, clinical trials registers if data are available KQ3b: systematic reviews of randomized trials or observational studiese; primary studies for rebound fractures after denosumab discontinuation | Any quantitative primary study design, quantitative data from mixed methods studies |
Exclude | Systematic reviews, meta-analyses and pooled analyses; all other primary study designs; non-research; studies only available as gray literature if data are inadequate to assess study design and risk of bias | Systematic reviews, meta-analyses and pooled analyses; all other primary study designs; non-research; studies only available as gray literature if data are inadequate to assess study design and risk of bias | KQ3a: Systematic reviews, meta-analyses and pooled analyses; all other primary study designs; non-research; studies only available as gray literature if data are inadequate to assess study design and risk of bias KQ3b: primary research, overviews of reviews | Systematic reviews, meta-analyses and pooled analyses; qualitative studies; non-research; studies only available as gray literature if data are inadequate to assess study design and risk of bias | |
Language | Include | English or French | English or French | English or French | English or French |
Exclude | All other languages | All other languages | All other languages | All other languages | |
Date of publication | Include | Any | Any | KQ3a: any KQ3b: 2015–present; 2020 for primary studies of rebound fractures | 1995–present (introduction of bisphosphonates) |
Exclude | Not applicable | Not applicable | KQ3a: not applicable KQ3b: pre-2015 (with exception of previously identified AHRQ review) | Pre-1995 | |