Draft Research Plan
Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Falls and Fractures in Community-Dwelling Adults: Preventive Medication
January 12, 2023
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.
* Measures of whole body calcium status do not exist; thus, the indirect evidence pathway for calcium cannot be evaluated.
Abbreviation: KQ=key question.
- Does supplementation with vitamin D, calcium, or both prevent fractures and falls or reduce fracture- and fall-related morbidity and mortality?
- What are the harms of supplementation with vitamin D, calcium, or both?
To the extent that it is reported in the studies, we will describe the population and intervention characteristics of the included studies. Based on available data, we will explore variation in effectiveness and harms of supplementation by age, sex, race, and ethnicity. To explore variation by subpopulation, we will rely on the approach developed for USPSTF reviews described by Whitlock et al,1 which involves identifying and assessing credibility of within-study subgroup analyses and examining between-study variability (with quantitative assessment if appropriate). We will also explore variation in effectiveness and harms by dosage and duration of supplementation where data are available by stratifying results based on dosage groupings derived from the empiric evidence available.
|Population||Community-dwelling adults with no known disorders related to vitamin D, calcium, or bone metabolism.
Mixed populations will be included if no more than 20% of the study population has any of the excluded conditions. Study populations with 20% to 50% having a known condition will be considered in sensitivity analyses.
|Children or adolescents age 18 years or younger; pregnant or lactating persons; studies for which patient eligibility is determined by testing to identify vitamin D deficiency or bone measurement testing, with selection based on low vitamin D or bone density level; studies with inclusion criteria designed to assemble populations with a specific condition or a group of closely related conditions, such as those with:
|Setting||Community and primary care–relevant settings, including assisted and independent living facilities.||Inpatient, skilled nursing facilities; postacute care and rehabilitation facilities.|
||Short-term supplementation use (less than 1 month); vitamin D preparations or metabolites designed for treatment not supplementation (e.g., calcitriol, alphacalcitriol, calcifediol); synthetic vitamin D analogs (i.e., doxercalciferol, paricalcitol, falecalcitriol, oxacalcitriol, alfacalcidol); multivitamin supplements that include vitamin D or calcium, unless the independent effects of vitamin D, calcium, or both can be evaluated; foods or beverages fortified with vitamin D, calcium, or both; and vitamin D obtained through natural or artificial ultraviolet light exposure.|
|Comparators||Placebo or no treatment.||Alternative dosages of vitamin D, calcium, or both.
Intervention and comparison arms that do not allow for the evaluation of the independent contribution of vitamin D, calcium, or both (e.g., studies assessing a multicomponent intervention that includes vitamin D as one of several components compared with no intervention would not be eligible unless the comparison arm included all of the other intervention components except vitamin D).
||KQ 1: Morphometric vertebral fractures; BMD; laboratory or functional measures of bone or muscle strength or quality; fall efficacy measures; and basic activities of daily living.
KQ 2: Incident cancer or cardiovascular disease or events; asymptomatic renal outcomes (soft-tissue calcification, nephrocalcinosis, artery calcification, hypercalcemia, hypercalciuria); and nonserious adverse events.
|Study design||KQ 1: RCTs, controlled clinical trials.
KQ 2: RCTs; prospective cohort studies with contemporaneous comparison groups with a primary study aim to evaluate the use of vitamin D or calcium supplementation.
|Study designs not listed as specifically included (e.g., case reports, case series, case-control studies, studies without a comparison group). Recent systematic reviews will not be included but will be handsearched to ensure that no relevant studies have been missed.|
|Timing||KQ 1: Intervention duration of 1 month or longer.
KQ 2: Any duration.
|KQ 1: Intervention duration of less than 1 month.
KQ 2: No exclusions.
|Language||Full-text articles published in English.||Full-text articles not published in English.|
|Quality||Fair or good quality according to design-specific criteria.||Poor-quality according to design-specific criteria.|
Abbreviations: BMD=bone mineral density; ED=emergency department; KQ=key question; RCT=randomized, controlled trial.