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Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial.
JAMA 2019; 322(8):736-745JAMA

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.

Authors+Show Affiliations

McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.Research Facilitation, Alberta Health Services, Calgary, Canada.McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31454046

Citation

Burt, Lauren A., et al. "Effect of High-Dose Vitamin D Supplementation On Volumetric Bone Density and Bone Strength: a Randomized Clinical Trial." JAMA, vol. 322, no. 8, 2019, pp. 736-745.
Burt LA, Billington EO, Rose MS, et al. Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA. 2019;322(8):736-745.
Burt, L. A., Billington, E. O., Rose, M. S., Raymond, D. A., Hanley, D. A., & Boyd, S. K. (2019). Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. JAMA, 322(8), pp. 736-745. doi:10.1001/jama.2019.11889.
Burt LA, et al. Effect of High-Dose Vitamin D Supplementation On Volumetric Bone Density and Bone Strength: a Randomized Clinical Trial. JAMA. 2019 08 27;322(8):736-745. PubMed PMID: 31454046.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of High-Dose Vitamin D Supplementation on Volumetric Bone Density and Bone Strength: A Randomized Clinical Trial. AU - Burt,Lauren A, AU - Billington,Emma O, AU - Rose,Marianne S, AU - Raymond,Duncan A, AU - Hanley,David A, AU - Boyd,Steven K, PY - 2020/02/27/pmc-release PY - 2019/8/28/entrez PY - 2019/8/28/pubmed PY - 2019/9/24/medline SP - 736 EP - 745 JF - JAMA JO - JAMA VL - 322 IS - 8 N2 - 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/31454046/Effect_of_High_Dose_Vitamin_D_Supplementation_on_Volumetric_Bone_Density_and_Bone_Strength:_A_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2019.11889 DB - PRIME DP - Unbound Medicine ER -