Screening for Vitamin D Deficiency in Adults

Updated Evidence Report and Systematic Review for the US Preventive Services Task Force

Kahwati, Leila C. MD; MPH
LeBlanc, Erin MD; MPH
Weber, Rachel Palmieri PhD
Giger, Kayla BS
Clark, Rachel BA
Suvada, Kara BS
Guisinger, Amy BS
Viswanathan, Meera PhD

¹RTI International–University of North Carolina at Chapel Hill Evidence-based Practice Center, Chapel Hill, North Carolina
²RTI International, Research Triangle Park, North Carolina
³Kaiser Permanente Center for Health Research, Portland, Oregon
⁴Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill
⁵Gillings School of Global Public Health and Eshelman School of Pharmacy, University of North Carolina at Chapel Hill

Article Information

Corresponding Author: Leila C. Kahwati, MD, MPH, RTI International, 3040 E Cornwallis Rd, Research Triangle Park, NC 27709 ([email protected]).

Accepted for Publication: December 21, 2020.

Author Contributions: Dr Kahwati had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kahwati, LeBlanc, Palmieri Weber, Clark, Viswanathan.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kahwati, LeBlanc, Giger, Clark, Suvada, Guisinger.

Critical revision of the manuscript for important intellectual content: Kahwati, LeBlanc, Palmieri Weber, Suvada, Viswanathan.

Statistical analysis: Kahwati, Weber, Clark, Suvada.

Obtained funding: Kahwati, Viswanathan.

Administrative, technical, or material support: Kahwati, Palmieri Weber, Giger, Clark, Suvada, Guisinger, Viswanathan.

Supervision: Kahwati.

Conflict of Interest Disclosures: None reported.

Funding/Support: This research was funded under contract HHSA-290-2015-00011-I, Task Order 11, from the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the US Preventive Services Task Force (USPSTF).

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings.

Disclaimer: The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.

Additional Contributions: We acknowledge the following individuals for their contributions to this project: AHRQ staff Howard Tracer, MD, andTracy Wolff, MD, MPH; former AHRQ staff Quyen Ngo-Metzger, MD, MPH; current and former members of the USPSTF who contributed to topic deliberations; and RTI International–University of North Carolina Evidence-based Practice Center staff B. Lynn Whitener, DrPH, Carol Woodell, BSPH, Sharon Barrell, MA, and Loraine Monroe. USPSTF members, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of the full evidence report underwent external peer review from 4 content experts (John Aloia, MD, New York University Winthrop Bone Mineral Research Center; JoAnn E. Manson, MD, MPH, DrPH, Harvard Medical School; Clifford Rosen, MD, Maine Medical Center Research Institute; and Christopher Sempos, PhD, Vitamin D Standardization Program LLC) and 4 individuals from 3 federal partner reviewers (2 from the National Institutes of Health, 1 from the Centers for Disease Control and Prevention). Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF Recommendation Statement. It did not undergo additional peer review after submission to JAMA.

Received September 15, 2020

Accepted December 21, 2020

JAMA: The Journal of the American Medical Association 325(14):p 1443-1463, April 13, 2021. | DOI: 10.1001/jama.2020.26498

Importance

Low serum vitamin D levels have been associated with adverse clinical outcomes; identifying and treating deficiency may improve outcomes.

Objective

To review the evidence about screening for vitamin D deficiency in adults.

Data Sources

PubMed, EMBASE, the Cochrane Library, and trial registries through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020.

Study Selection

Fair- or good-quality, English-language randomized clinical trials (RCTs) of screening with serum 25-hydroxyvitamin D (25[OH]D) compared with no screening, or treatment with vitamin D (with or without calcium) compared with placebo or no treatment conducted in nonpregnant adults; nonrandomized controlled intervention studies for harms only. Treatment was limited to studies enrolling or analyzing participants with low serum vitamin D levels.

Data Extraction and Synthesis

Two reviewers assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; when at least 3 similar studies were available, meta-analyses were conducted.

Main Outcomes and Measures

Mortality, incident fractures, falls, diabetes, cardiovascular events, cancer, depression, physical functioning, and infection.

Results

Forty-six studies (N = 16 205) (77 publications) were included. No studies directly evaluated the health benefits or harms of screening. Among community-dwelling populations, treatment was not significantly associated with mortality (pooled absolute risk difference [ARD], 0.3% [95% CI, −0.6% to 1.1%]; 8 RCTs, n = 2006), any fractures (pooled ARD, −0.3% [95% CI, −2.1% to 1.6%]; 6 RCTs, n = 2186), incidence of diabetes (pooled ARD, 0.1% [95% CI, −1.3% to 1.6%]; 5 RCTs, n = 3356), incidence of cardiovascular disease (2 RCTs; hazard ratio, 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs; hazard ratio, 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58], or depression (3 RCTs, various measures reported). The pooled ARD for incidence of participants with 1 or more falls was −4.3% (95% CI, −11.6% to 2.9%; 6 RCTs). The evidence was mixed for the effect of treatment on physical functioning (2 RCTs) and limited for the effect on infection (1 RCT). The incidence of adverse events and kidney stones was similar between treatment and control groups.

Conclusions and Relevance

No studies evaluated the direct benefits or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the effect of treatment on physical functioning and infection.