Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

David A Jolliffe, Averalda van Graan, Nicholas C Harvey, Cyrus Cooper, Amy E Mendham, Jonathan C Y Tang, Adrian R Martineau, William D Fraser, Anna K Coussens, Lisa K Micklesfield, Linda-Gail Bekker, Robert J Wilkinson, Richard L Hooper, James Nuttall, Carmen Delport, Neil Walker, Justine Stewart, Keren Middelkoop

Journal: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2024;39(3):211-221

PMID: 38477739

Abstract

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.

Address: Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, Cape Town 7925, Western Cape, South Africa.; Department of Medicine, University of Cape Town, Observatory, Cape Town 7925, Western Cape, South Africa.; Division of Physiological Sciences, Department of Human Biology, Faculty of Health Sciences, Health through Physical Activity, Lifestyle and Sport Research Centre (HPALS), University of Cape Town, Newlands, Cape Town 7700, Western Cape, South Africa.; Department of Paediatrics, SAMRC/Wits Developmental Pathways for Health Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg 2193, Gauteng, South Africa.; Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, United Kingdom.; Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, Cape Town 7925, Western Cape, South Africa.; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, United Kingdom.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town 7925, Western Cape, South Africa.; Infectious Diseases and Immune Defence Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.; Biostatistics Unit, SAFOODS Division, South African Medical Research Council, Tygerberg, Cape Town 7505, Western Cape, South Africa.; Division of Human Nutrition, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town 7505, Western Cape, South Africa.; Department of Paediatrics and Child Health, Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital, Rondebosch, Cape Town 7700, Western Cape, South Africa.; Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom.; Departments of Laboratory Medicine, Clinical Biochemistry and Departments of Diabetes and Endocrinology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich NR4 7UY, United Kingdom.; MRC Lifecourse Epidemiology Centre, University of Southampton, Southampton SO16 6YD, United Kingdom.; NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton SO16 6YD, United Kingdom.; University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, United Kingdom.; Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, Cape Town 7925, Western Cape, South Africa.; The Francis Crick Institute, London NW1 1AT, United Kingdom.; Imperial College London, London W12 0NN, United Kingdom.
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