TY - JOUR
T1 - The effect of monthly vitamin D supplementation on fractures
T2 - a tertiary outcome from the population-based, double-blind, randomised, placebo-controlled D-Health trial
AU - Waterhouse, Mary
AU - Ebeling, Peter R.
AU - McLeod, Donald S.A.
AU - English, Dallas
AU - Romero, Briony Duarte
AU - Baxter, Catherine
AU - Armstrong, Bruce K.
AU - Hartel, Gunter
AU - Kimlin, Michael
AU - O'Connell, Rachel L.
AU - van der Pols, Jolieke C.
AU - Venn, Alison J.
AU - Webb, Penelope M.
AU - Whiteman, David C.
AU - Neale, Rachel E.
N1 - Funding Information:
We thank the D-Health Trial staff and members of the data and safety monitoring board (Patricia Valery [QIMR Berghofer Medical Research Institute], Ie-Wen Sim [University of Melbourne, Monash Health, Eastern Health], and Kerrie Sanders [Department of Medicine, University of Melbourne]). We also extend our thanks to the D-Health Trial participants who committed to this research. We acknowledge Services Australia for supplying Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data, and the staff of the State and Territory health departments (Western Australia, Victoria, South Australia & Northern Territory, New South Wales, Queensland, and Tasmania) for the provision of hospital data and data linkage. Furthermore, we thank the data custodians from The State Registries of Births, Deaths and Marriages. The D-Health Trial is funded by National Health and Medical Research Council (NHMRC) project grants (GNT1046681 and GNT1120682). REN, PMW, DCW, and PRE are or were supported by fellowships from the NHMRC (GNT1060183, GNT1173346, GNT1155413, and GNT1197958). DSAM is supported by a Metro North Clinician Research Fellowship and a Queensland Advancing Clinical Research Fellowship. The vitamin D assays were done at the University of Western Australia, supported by infrastructure funding from the Western Australian State Government in partnership with the Australian Federal Government, through Bioplatforms Australia and the National Collaborative Research Infrastructure Strategy.
Funding Information:
We thank the D-Health Trial staff and members of the data and safety monitoring board (Patricia Valery [QIMR Berghofer Medical Research Institute], Ie-Wen Sim [University of Melbourne, Monash Health, Eastern Health], and Kerrie Sanders [Department of Medicine, University of Melbourne]). We also extend our thanks to the D-Health Trial participants who committed to this research. We acknowledge Services Australia for supplying Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data, and the staff of the State and Territory health departments (Western Australia, Victoria, South Australia & Northern Territory, New South Wales, Queensland, and Tasmania) for the provision of hospital data and data linkage. Furthermore, we thank the data custodians from The State Registries of Births, Deaths and Marriages. The D-Health Trial is funded by National Health and Medical Research Council (NHMRC) project grants (GNT1046681 and GNT1120682). REN, PMW, DCW, and PRE are or were supported by fellowships from the NHMRC (GNT1060183, GNT1173346, GNT1155413, and GNT1197958). DSAM is supported by a Metro North Clinician Research Fellowship and a Queensland Advancing Clinical Research Fellowship. The vitamin D assays were done at the University of Western Australia, supported by infrastructure funding from the Western Australian State Government in partnership with the Australian Federal Government, through Bioplatforms Australia and the National Collaborative Research Infrastructure Strategy.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/5
Y1 - 2023/5
N2 - Background: Low serum 25-hydroxy vitamin D concentration is associated with increased fracture risk. It is uncertain whether vitamin D supplementation reduces fractures, or whether intermittent doses are harmful. We aimed to investigate if supplementing adults living in Australia with monthly doses of 60 000 international units (IU) vitamin D3 for 5 years or less altered the rate of fractures. Methods: We did a population-based, double-blind, randomised, placebo-controlled trial of oral vitamin D3 supplementation (60 000 IU per month) for up to 5 years in adults aged 60–84 years living in Australia. We randomly assigned (1:1) 21 315 participants to either vitamin D or placebo. We ascertained fractures through linkage with administrative datasets. The main outcome was total fractures. Additional outcomes were non-vertebral, major osteoporotic (hip, wrist, proximal humerus, and spine), and hip fractures. We excluded participants (989 [4·6%]) without linked data, and estimated hazard ratios (HRs) and 95% CIs using flexible parametric survival models. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763, and the trial intervention ended in February, 2020. Findings: Between Feb 14, 2014, and June 17, 2015, we recruited 21 315 participants. For the current analysis, we included 20 326 participants (vitamin D 10 154 [50·0%]; placebo 10 172 [50·0%]). 9295 (45·7%) of 20 326 participants were women and the mean age was 69·3 years (SD 5·5). Over a median follow-up of 5·1 years (IQR 5·1–5·1), 568 (5·6%) participants in the vitamin D group and 603 (5·9%) in the placebo group had one or more fractures. There was no effect on fracture risk overall (HR 0·94 [95% CI 0·84–1·06]), and the interaction between randomisation group and time was not significant (p=0·14). However, the HR for total fractures appeared to decrease with increasing follow-up time. The overall HRs for non-vertebral, major osteoporotic, and hip fractures were 0·96 (95% CI 0·85–1·08), 1·00 (0·85–1·18), and 1·11 (0·86–1·45), respectively. Interpretation: These findings do not support concerns that bolus doses of vitamin D administered monthly increase fracture risk. Long-term supplementation might reduce the incidence of total fractures, but additional research is needed to clarify this effect. Funding: Australian National Health and Medical Research Council.
AB - Background: Low serum 25-hydroxy vitamin D concentration is associated with increased fracture risk. It is uncertain whether vitamin D supplementation reduces fractures, or whether intermittent doses are harmful. We aimed to investigate if supplementing adults living in Australia with monthly doses of 60 000 international units (IU) vitamin D3 for 5 years or less altered the rate of fractures. Methods: We did a population-based, double-blind, randomised, placebo-controlled trial of oral vitamin D3 supplementation (60 000 IU per month) for up to 5 years in adults aged 60–84 years living in Australia. We randomly assigned (1:1) 21 315 participants to either vitamin D or placebo. We ascertained fractures through linkage with administrative datasets. The main outcome was total fractures. Additional outcomes were non-vertebral, major osteoporotic (hip, wrist, proximal humerus, and spine), and hip fractures. We excluded participants (989 [4·6%]) without linked data, and estimated hazard ratios (HRs) and 95% CIs using flexible parametric survival models. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763, and the trial intervention ended in February, 2020. Findings: Between Feb 14, 2014, and June 17, 2015, we recruited 21 315 participants. For the current analysis, we included 20 326 participants (vitamin D 10 154 [50·0%]; placebo 10 172 [50·0%]). 9295 (45·7%) of 20 326 participants were women and the mean age was 69·3 years (SD 5·5). Over a median follow-up of 5·1 years (IQR 5·1–5·1), 568 (5·6%) participants in the vitamin D group and 603 (5·9%) in the placebo group had one or more fractures. There was no effect on fracture risk overall (HR 0·94 [95% CI 0·84–1·06]), and the interaction between randomisation group and time was not significant (p=0·14). However, the HR for total fractures appeared to decrease with increasing follow-up time. The overall HRs for non-vertebral, major osteoporotic, and hip fractures were 0·96 (95% CI 0·85–1·08), 1·00 (0·85–1·18), and 1·11 (0·86–1·45), respectively. Interpretation: These findings do not support concerns that bolus doses of vitamin D administered monthly increase fracture risk. Long-term supplementation might reduce the incidence of total fractures, but additional research is needed to clarify this effect. Funding: Australian National Health and Medical Research Council.
UR - https://www.scopus.com/pages/publications/85152394730
U2 - 10.1016/S2213-8587(23)00063-3
DO - 10.1016/S2213-8587(23)00063-3
M3 - Article
C2 - 37011645
AN - SCOPUS:85152394730
SN - 2213-8587
VL - 11
SP - 324
EP - 332
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 5
ER -