The role of vitamin D metabolism in regulating bone turnover in adolescents with perinatally-acquired HIV in Southern Africa: A cross-sectional study in Zimbabwe and Zambia

Madanhire, Tafadzwa, Ward, Kate A., Macdougall, Amy, Mohammed, Nuredin, Filteau, Suzanne, Kasona, Lackson, Mabuda, Hilda B., Chisenga, Molly, Tang, Jonathan C. Y., Fraser, William D., Bandason, Tsitsi, Dzavakwa, Nyasha. V., Simms, Victoria, Ferrand, Rashida. A. and Gregson, Celia L. (2025) The role of vitamin D metabolism in regulating bone turnover in adolescents with perinatally-acquired HIV in Southern Africa: A cross-sectional study in Zimbabwe and Zambia. Journal of Bone and Mineral Research, 40 (1). 59–68. ISSN 0884-0431

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Abstract

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis, and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in Southern Africa. A pre-planned secondary analysis was performed of baseline data from the vitamin D for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology trial (PACTR20200989766029) which enrolled ALWH (11-19 yr) taking antiretroviral therapy for ≥6 mo, and recorded socio-demographic, clinical and dietary data. After over-night fasting, vitamin D metabolites (25(OH)D, 1,25(OH) 2D, and 24,25(OH) 2D), intact parathyroid hormone (PTH), and bone turnover markers (BTMs) (C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)) were measured. Tandem Mass Spectrometry measured vitamin D metabolites, while intact PTH and BTMs were analyzed by electrochemiluminescence immunoassay. Stratified by 25(OH)D (<75 vs ≥75 nmol/L), associations between standardized concentrations (β = standard deviations) of vitamin D metabolites, intact PTH and BTMs were assessed using structural equations modelling (SEM) adjusted for age, sex, and country (Zimbabwe/Zambia). Among the 842 ALWH enrolled, the median dietary calcium intake was 100 mg (IQR: 55-145). The SEM showed PTH was positively associated (β: 0.21; 95% CI, 0.1, 0.32) with 1,25(OH) 2D, only when 25(OH)D was <75 vs ≥75 nmol/L (β: 0.23; 95%CI, -0.13, 0.59), with evidence of an interaction (β: -0.11; 95%CI, -0.20, -0.02). A positive relationship between 25(OH)D and 24,25(OH) 2D was seen irrespective of 25(OH)D concentration. 24,25(OH) 2D was inversely related to BTMs, particularly when 25(OH)D was <75 nmol/L (CTX: β: -0.15; 95% CI, -0.24, -0.06 and P1NP: β: -0.14; 95%CI, -0.22, -0.06). There was interaction between dietary calcium and 25(OH)D on PTH (β: -0.15; 95% CI, -0.22, -0.07) suggesting an interaction between low 25(OH)D and low dietary calcium which increases PTH. In conclusion, associations between 25(OH)D, PTH, 1,25(OH) 2D, and BTMs in ALWH appear dependent upon 25(OH)D concentrations <75 nmol/L and calcium intake. A novel, potentially causal pathway between 25(OH)D, 24,25(OH) 2D, and BTMs was seen. Findings enhance understanding of vitamin D metabolism in people living with HIV.

Item Type:	Article
Additional Information:	Data availability statement: The datasets used and/or analysed during the current study are available at the London School of Hygiene and Tropical Medicine (LSHTM) DataCompass repository (DOI: 10.17037/DATA.00003868) upon reasonable request to the corresponding author. Funding information: This project is part of the EDCTP2 programme supported by the European Union (Grant number RIA2018CO-2512) The research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW011326 to TM. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. CLG is funded by the National Institute for Health and Care Research (NIHR302394). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
Uncontrolled Keywords:	adolescents,africa,hiv,parathyroid hormone,vitamin d,endocrinology, diabetes and metabolism,orthopedics and sports medicine,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700/2712
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	27 Nov 2024 10:45
Last Modified:	06 Feb 2025 12:26
URI:	https://ueaeprints.uea.ac.uk/id/eprint/97765
DOI:	10.1093/jbmr/zjae190

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