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. 2024 Dec 31;40(1):59-68.
doi: 10.1093/jbmr/zjae190.

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

Tafadzwa Madanhire  1   2 , Kate A Ward  3   4 , Amy Macdougall  2 , Nuredin Mohammed  4   5 , Suzanne Filteau  6 , Lackson Kasonka  7 , Hilda B Mabuda  7 , Molly Chisenga  7 , Jonathan Tang  8   9 , William D Fraser  8   9 , Tsitsi Bandason  1 , Nyasha V Dzavakwa  1   5 , Victoria Simms  1   5 , Rashida A Ferrand  1   10 , Celia L Gregson  1   11
Affiliations

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

Tafadzwa Madanhire et al. J Bone Miner Res. .

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.

Keywords: Africa; HIV; adolescents; parathyroid hormone; vitamin D.

Plain language summary

Vitamin D plays an important role in regulating calcium and supporting bone health particularly during puberty when the body needs extra nutrients to support rapid growth. However, many people living with HIV often have low vitamin D, which may be because HIV disrupts how the body processes vitamin D, or because of certain HIV treatments like tenofovir-disoproxil-fumarate, or, in Africa people have low calcium diets. We researched adolescents, age 11-19 yr, living with HIV in Zimbabwe and Zambia, with low calcium diets. We investigated how important hormones control vitamin D and how this relates to bone activity, and growth. The findings suggest adolescents living with HIV need higher levels of vitamin D than has traditionally been thought. Our research also discovered a new link between a vitamin D breakdown product (called 24,25(OH)2D), and suggests this might play its own role influencing bone activity and development. These findings provide new understanding of vitamin D and its actions in people living with HIV in Africa. In addition the study findings might inform vitamin D supplementation programs in adolescents living with HIV to target achieving higher vitamin D levels to see improvements in bone health.

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