TY - JOUR
T1 - Vitamin D supplementation and risk of falling: outcomes from the randomized, placebo-controlled D-Health Trial
AU - Waterhouse, Mary
AU - Sanguineti, Emma
AU - Baxter, Catherine
AU - Duarte Romero, Briony
AU - McLeod, Donald S.A.
AU - English, Dallas R.
AU - Armstrong, Bruce K.
AU - Ebeling, Peter R.
AU - Hartel, Gunter
AU - Kimlin, Michael G.
AU - O'Connell, Rachel L.
AU - Pham, Hai
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:
Penelope Webb has funding from AstraZeneca for an unrelated study of ovarian cancer. Peter Ebeling reports grants and other from Amgen, other from Sanofi, grants and other from Novartis, grants from Eli‐Lilly and grants from Alexion. Mary Waterhouse, Emma Sanguineti, Catherine Baxter, Briony Duarte Romero, Donald McLeod, Dallas English, Bruce Armstrong, Gunter Hartel, Michael Kimlin, Rachel O'Connell, Hai Pham, Jolieke van der Pols, Alison Venn, David Whiteman and Rachel Neale declare that they have no conflict of interest.
Funding Information:
The D-Health Trial is funded by National Health and Medical Research Council (NHMRC) project grants (GNT1046681 and GNT1120682). PMW and DCW are supported by fellowships from the NHMRC (GNT1173346 and GNT1155413). DSAM is supported by a Metro North Clinician Research Fellowship and a Queensland Advancing Clinical Research Fellowship. HP is supported by a University of Queensland PhD Scholarship. We would like to acknowledge the D-Health Trial staff and members of the Data and Safety Monitoring Board (Patricia Valery, Ie-Wen Sim, Kerrie Sanders). We also extend our thanks to the D-Health Trial participants who committed to this research. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle.32
Funding Information:
The D‐Health Trial is funded by National Health and Medical Research Council (NHMRC) project grants (GNT1046681 and GNT1120682). PMW and DCW are supported by fellowships from the NHMRC (GNT1173346 and GNT1155413). DSAM is supported by a Metro North Clinician Research Fellowship and a Queensland Advancing Clinical Research Fellowship. HP is supported by a University of Queensland PhD Scholarship.
Publisher Copyright:
© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.
PY - 2021/12
Y1 - 2021/12
N2 - Background: Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high-dose vitamin D supplementation reduces risk and incidence of falls.Methods: We used data from the randomized, double-blind, placebo-controlled D-Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25-hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3-month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention-to-treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013. Results: Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) (P-interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. Conclusions: Monthly high-dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
AB - Background: Falls cause considerable morbidity and mortality in older people. It is unclear how vitamin D supplementation affects falls risk, particularly when taken at high doses. We sought to determine whether monthly high-dose vitamin D supplementation reduces risk and incidence of falls.Methods: We used data from the randomized, double-blind, placebo-controlled D-Health Trial conducted in Australia. Between February 2014 and May 2015, 21 315 participants aged 60–84 years were randomized (1:1) to monthly doses of either 60 000 IU of colecalciferol or placebo for a maximum of 5 years. People who reported a history of osteomalacia, sarcoidosis, hyperparathyroidism, hypercalcaemia or kidney stones or who were taking >500 IU/day supplementary vitamin D were ineligible. Each year, we collected blood samples from ~450 randomly sampled participants from each trial arm and measured 25-hydroxyvitamin D [25(OH)D]. Falls, a prespecified tertiary outcome, were ascertained using annual surveys and, for a subset of participants, 3-month falls diaries. The primary outcome for this analysis was any fall in the month before completing an annual survey. As part of our process to maintain blinding, we used random samples of participants (surveys, n = 16 000; diaries, n = 2400), with equal numbers per group. Participants with no outcome data were excluded. Following an intention-to-treat approach, we analysed outcomes using logistic, ordinal and negative binomial regression. Registration: Australian New Zealand Clinical Trials Registry (ACTRN12613000743763); registered 4 July 2013. Results: Mean treatment duration was 4.3 years (standard deviation [SD] = 1.4 years). Mean serum 25(OH)D concentrations during the trial were 114.8 (SD 30.3) nmol/L and 77.5 (SD 25.2) nmol/L in the vitamin D and placebo groups, respectively. Survey and diary analytic sets included 15 416 and 2200 participants, respectively; approximately half were randomized to vitamin D (surveys: 50.1%; diaries: 50.4%). Vitamin D had no effect on falling in the past month (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.95–1.10). There was an interaction with body mass index (BMI) (P-interaction = 0.001); vitamin D increased risk in participants with BMI < 25 kg/m2 (OR 1.25, 95% CI 1.09–1.43), but there was no effect in those with BMI ≥ 25 kg/m2 (OR 0.95, 95% CI 0.87–1.04). Analyses of diary data were consistent with these findings. The incidence of hypercalcaemia and kidney stones did not differ between groups. Conclusions: Monthly high-dose vitamin D supplementation did not reduce risk of falling. A possible increased risk of falling with vitamin D supplementation in people with normal BMI warrants further investigation.
UR - http://www.scopus.com/inward/record.url?scp=85111795078&partnerID=8YFLogxK
U2 - 10.1002/jcsm.12759
DO - 10.1002/jcsm.12759
M3 - Article
C2 - 34337905
AN - SCOPUS:85111795078
SN - 2190-6009
VL - 12
SP - 1428
EP - 1439
JO - Journal of Cachexia, Sarcopenia and Muscle
JF - Journal of Cachexia, Sarcopenia and Muscle
IS - 6
ER -