Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial
Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK
JAMA · 240 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Funding not disclosed
Publication
- Published
- 2019-08-27 · JAMA · vol. 322 · issue 8 · p. 736
- Publisher
- American Medical Association
- Cited
- 334 citations · more than 100% of similar papers · 25.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 44 works
- Access
- Free to read
- Research areas
- Vitamin D Research Studies · Bone health and osteoporosis research · Nutrition and Health in Aging
- Keywords
- Medicine, Vitamin D and neurology, Bone mineral, Osteoporosis, Quantitative computed tomography, Bone density, Randomized controlled trial, Vitamin, Tibia, Internal medicine, Surgery
- MeSH
- radius, tibia, humans, cholecalciferol, vitamins, vitamin d, absorptiometry, photon, treatment failure, administration, oral, double-blind method, bone density, dose-response relationship, drug, finite element analysis, dietary supplements, aged, middle aged, female, male, flexural strength
6 authors
From CA
- Lauren A. BurtUniversity of Calgary; Alberta Bone and Joint Health Institute
- Emma Olive BillingtonUniversity of Calgary; Alberta Bone and Joint Health Institute
- Marianne S RoseAlberta Health Services
- Duncan A. RaymondUniversity of Calgary; Alberta Bone and Joint Health Institute
- David A. HanleyUniversity of Calgary; Alberta Bone and Joint Health Institute
- Steven K. Boyd · correspondingUniversity of Calgary; Alberta Bone and Joint Health Institute
Abstract
Importance
Few studies have assessed the effects of daily vitamin D doses at or above the tolerable upper intake level for 12 months or greater, yet 3% of US adults report vitamin D intakes of at least 4000 IU per day.
Objective
To assess the dose-dependent effect of vitamin D supplementation on volumetric bone mineral density (BMD) and strength.
Design, setting, and participants
Three-year, double-blind, randomized clinical trial conducted in a single center in Calgary, Canada, from August 2013 to December 2017, including 311 community-dwelling healthy adults without osteoporosis, aged 55 to 70 years, with baseline levels of 25-hydroxyvitamin D (25[OH]D) of 30 to 125 nmol/L.
Interventions
Daily doses of vitamin D3 for 3 years at 400 IU (n = 109), 4000 IU (n = 100), or 10 000 IU (n = 102). Calcium supplementation was provided to participants with dietary intake of less than 1200 mg per day.
Main outcomes and measures
Co-primary outcomes were total volumetric BMD at radius and tibia, assessed with high resolution peripheral quantitative computed tomography, and bone strength (failure load) at radius and tibia estimated by finite element analysis.
Results
Of 311 participants who were randomized (53% men; mean [SD] age, 62.2 [4.2] years), 287 (92%) completed the study. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L for the 400-IU group; 81.3, 115.3, and 132.2 for the 4000-IU group; and 78.4, 188.0, and 144.4 for the 10 000-IU group. There were significant group × time interactions for volumetric BMD. At trial end, radial volumetric BMD was lower for the 4000 IU group (-3.9 mg HA/cm3 [95% CI, -6.5 to -1.3]) and 10 000 IU group (-7.5 mg HA/cm3 [95% CI, -10.1 to -5.0]) compared with the 400 IU group with mean percent change in volumetric BMD of -1.2% (400 IU group), -2.4% (4000 IU group), and -3.5% (10 000 IU group). Tibial volumetric BMD differences from the 400 IU group were -1.8 mg HA/cm3 (95% CI, -3.7 to 0.1) in the 4000 IU group and -4.1 mg HA/cm3 in the 10 000 IU group (95% CI, -6.0 to -2.2), with mean percent change values of -0.4% (400 IU), -1.0% (4000 IU), and -1.7% (10 000 IU). There were no significant differences for changes in failure load (radius, P = .06; tibia, P = .12).
Conclusions and relevance
Among healthy adults, treatment with vitamin D for 3 years at a dose of 4000 IU per day or 10 000 IU per day, compared with 400 IU per day, resulted in statistically significant lower radial BMD; tibial BMD was significantly lower only with the 10 000 IU per day dose. There were no significant differences in bone strength at either the radius or tibia. These findings do not support a benefit of high-dose vitamin D supplementation for bone health; further research would be needed to determine whether it is harmful.
Trial registration
ClinicalTrials.gov Identifier: NCT01900860.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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