@article{Middelkoop2023,
abstract = {BACKGROUND Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. METHODS We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial. FINDINGS 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. 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, P{\textless}0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95{\%} CI -0.94 to -0.17, P=0.005). 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 for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95{\%} CI 0.27 to 1.85, P=0.48). INTERPRETATION Weekly vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk. FUNDING Medical Research Council {\#}{\#}{\#} Competing Interest Statement ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton {\&} Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref [NCT04641195][1]); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests. {\#}{\#}{\#} Clinical Trial NCT02880982 {\#}{\#}{\#} Funding Statement This study was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1) {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymised data may be requested from the corresponding author to be shared subject to terms of research ethics committee approval. [1]: /lookup/external-ref?link{\_}type=CLINTRIALGOV{\&}access{\_}num=NCT04641195{\&}atom={\%}2Fmedrxiv{\%}2Fearly{\%}2F2023{\%}2F05{\%}2F19{\%}2F2023.05.18.23290153.atom},
author = {Middelkoop, Keren and Micklesfield, Lisa and Walker, Neil and Stewart, Justine and Delport, Carmen and Jolliffe, David and Mendham, Amy and Coussens, Anna K and van Graan, Averalda and Nuttall, James and Tang, Jonathan and Fraser, William and Cooper, Cyrus and Harvey, Nicholas and Hooper, Richard and Wilkinson, Robert J and Bekker, Linda-Gail and Martineau, Adrian},
doi = {10.1101/2023.05.18.23290153},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Middelkoop et al. - 2023 - Influence of vitamin D supplementation on bone mineral content, bone turnover markers and fracture risk in So.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {may},
pages = {2023.05.18.23290153},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Influence of vitamin D supplementation on bone mineral content, bone turnover markers and fracture risk in South African schoolchildren: multicentre double-blind randomised placebo-controlled trial (ViDiKids)}},
url = {https://www.medrxiv.org/content/10.1101/2023.05.18.23290153v1 https://www.medrxiv.org/content/10.1101/2023.05.18.23290153v1.abstract},
year = {2023}
}

{"_id":"h5nfkStCuKrRJwFiq","bibbaseid":"middelkoop-micklesfield-walker-stewart-delport-jolliffe-mendham-coussens-etal-influenceofvitamindsupplementationonbonemineralcontentboneturnovermarkersandfractureriskinsouthafricanschoolchildrenmulticentredoubleblindrandomisedplacebocontrolledtrialvidikids-2023","author_short":["Middelkoop, K.","Micklesfield, L.","Walker, N.","Stewart, J.","Delport, C.","Jolliffe, D.","Mendham, A.","Coussens, A. K","van Graan, A.","Nuttall, J.","Tang, J.","Fraser, W.","Cooper, C.","Harvey, N.","Hooper, R.","Wilkinson, R. J","Bekker, L.","Martineau, A."],"bibdata":{"bibtype":"article","type":"article","abstract":"BACKGROUND Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. METHODS We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial. FINDINGS 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. 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, P\\textless0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17, P=0.005). 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 for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95% CI 0.27 to 1.85, P=0.48). INTERPRETATION Weekly vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk. FUNDING Medical Research Council ### Competing Interest Statement ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref [NCT04641195][1]); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests. ### Clinical Trial NCT02880982 ### Funding Statement This study was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymised data may be requested from the corresponding author to be shared subject to terms of research ethics committee approval. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04641195&atom=%2Fmedrxiv%2Fearly%2F2023%2F05%2F19%2F2023.05.18.23290153.atom","author":[{"propositions":[],"lastnames":["Middelkoop"],"firstnames":["Keren"],"suffixes":[]},{"propositions":[],"lastnames":["Micklesfield"],"firstnames":["Lisa"],"suffixes":[]},{"propositions":[],"lastnames":["Walker"],"firstnames":["Neil"],"suffixes":[]},{"propositions":[],"lastnames":["Stewart"],"firstnames":["Justine"],"suffixes":[]},{"propositions":[],"lastnames":["Delport"],"firstnames":["Carmen"],"suffixes":[]},{"propositions":[],"lastnames":["Jolliffe"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Mendham"],"firstnames":["Amy"],"suffixes":[]},{"propositions":[],"lastnames":["Coussens"],"firstnames":["Anna","K"],"suffixes":[]},{"propositions":["van"],"lastnames":["Graan"],"firstnames":["Averalda"],"suffixes":[]},{"propositions":[],"lastnames":["Nuttall"],"firstnames":["James"],"suffixes":[]},{"propositions":[],"lastnames":["Tang"],"firstnames":["Jonathan"],"suffixes":[]},{"propositions":[],"lastnames":["Fraser"],"firstnames":["William"],"suffixes":[]},{"propositions":[],"lastnames":["Cooper"],"firstnames":["Cyrus"],"suffixes":[]},{"propositions":[],"lastnames":["Harvey"],"firstnames":["Nicholas"],"suffixes":[]},{"propositions":[],"lastnames":["Hooper"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]},{"propositions":[],"lastnames":["Bekker"],"firstnames":["Linda-Gail"],"suffixes":[]},{"propositions":[],"lastnames":["Martineau"],"firstnames":["Adrian"],"suffixes":[]}],"doi":"10.1101/2023.05.18.23290153","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Middelkoop et al. - 2023 - Influence of vitamin D supplementation on bone mineral content, bone turnover markers and fracture risk in So.pdf:pdf","journal":"medRxiv","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"may","pages":"2023.05.18.23290153","publisher":"Cold Spring Harbor Laboratory Press","title":"Influence of vitamin D supplementation on bone mineral content, bone turnover markers and fracture risk in South African schoolchildren: multicentre double-blind randomised placebo-controlled trial (ViDiKids)","url":"https://www.medrxiv.org/content/10.1101/2023.05.18.23290153v1 https://www.medrxiv.org/content/10.1101/2023.05.18.23290153v1.abstract","year":"2023","bibtex":"@article{Middelkoop2023,\r\nabstract = {BACKGROUND Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. METHODS We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial. FINDINGS 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. 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, P{\\textless}0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95{\\%} CI -0.94 to -0.17, P=0.005). 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 for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95{\\%} CI 0.27 to 1.85, P=0.48). INTERPRETATION Weekly vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk. FUNDING Medical Research Council {\\#}{\\#}{\\#} Competing Interest Statement ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton {\\&} Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref [NCT04641195][1]); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests. {\\#}{\\#}{\\#} Clinical Trial NCT02880982 {\\#}{\\#}{\\#} Funding Statement This study was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1) {\\#}{\\#}{\\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The trial was approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Anonymised data may be requested from the corresponding author to be shared subject to terms of research ethics committee approval. 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