Potential value of vitamin D as adjunctive therapy in osteoarticular tuberculosis: a comprehensive review
- 1Gong An County People’s Hospital, Gong’an, 434300 Hubei China
- 2Jianli People’s Hospital, Jianli, 433300 Hubei China
- 3Yichang Third People’s Hospital, Yichang, 443000 Hubei China
Abstract
Osteoarticular tuberculosis (OATB) is one of the most common clinical types of extrapulmonary tuberculosis (EPTB), characterized primarily by progressive bone destruction and high morbidity. Standard anti-tuberculous chemotherapy has limited efficacy in reversing established bone damage. Vitamin D, a fat-soluble steroid hormone with immunomodulatory and bone-metabolic properties, shows promise as an adjunctive therapeutic agent. Mechanistically, vitamin D enhances anti-tuberculous immunity through multiple pathways: inducing antimicrobial peptide LL-37 expression, activating autophagic flux, and modulating Th1/Th17/regulatory T cell balance. At the bone level, vitamin D counteracts Mtb-induced destruction via the OPG/RANKL axis, Wnt/β-catenin signaling activation, and correction of secondary hyperparathyroidism. However, rifampicin—a cornerstone chemotherapy agent—accelerates vitamin D catabolism by inducing CYP3A4/CYP24A1, creating a clinically significant drug-nutrient interaction that exacerbates vitamin D depletion. Evidence supporting vitamin D supplementation remains predominantly derived from pulmonary tuberculosis (PTB) patients in randomized controlled trials (RCTs), with only one small-sample study specific to OATB (n = 41, 8 weeks). These PTB-derived trials employed single high-dose bolus regimens with 3–6 months follow-up, demonstrating modest benefits (HR 0.58–0.89) primarily in vitamin D-deficient subgroups, with negligible effects in replete populations. Direct applicability to OATB remains unverified. This review systematizes vitamin D’s immunological and bone-metabolic mechanisms in OATB, critically appraises existing evidence quality and extrapolation limitations, and proposes an RCT framework with bone structural repair and functional recovery as primary endpoints. Our aim is to guide theoretical development and future clinical investigation of vitamin D as adjunctive therapy for OATB.
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BibTeX
@article{zhang2026potential,
title = {{Potential value of vitamin D as adjunctive therapy in osteoarticular tuberculosis: a comprehensive review}},
author = {Chenglong Zhang and Kai Xu and Yang Chen and Zhe Dong and Xiao Wu},
journal = {Infection},
year = {2026},
month = jun,
doi = {10.1007/s15010-026-02860-5},
url = {https://doi.org/10.1007/s15010-026-02860-5},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Potential value of vitamin D as adjunctive therapy in osteoarticular tuberculosis: a comprehensive review
AU - Chenglong Zhang
AU - Kai Xu
AU - Yang Chen
AU - Zhe Dong
AU - Xiao Wu
PY - 2026
DA - 2026/06/12
JO - Infection
DO - 10.1007/s15010-026-02860-5
UR - https://doi.org/10.1007/s15010-026-02860-5
AB - Osteoarticular tuberculosis (OATB) is one of the most common clinical types of extrapulmonary tuberculosis (EPTB), characterized primarily by progressive bone destruction and high morbidity. Standard anti-tuberculous chemotherapy has limited efficacy in reversing established bone damage. Vitamin D, a fat-soluble steroid hormone with immunomodulatory and bone-metabolic properties, shows promise as an adjunctive therapeutic agent. Mechanistically, vitamin D enhances anti-tuberculous immunity through multiple pathways: inducing antimicrobial peptide LL-37 expression, activating autophagic flux, and modulating Th1/Th17/regulatory T cell balance. At the bone level, vitamin D counteracts Mtb-induced destruction via the OPG/RANKL axis, Wnt/β-catenin signaling activation, and correction of secondary hyperparathyroidism. However, rifampicin—a cornerstone chemotherapy agent—accelerates vitamin D catabolism by inducing CYP3A4/CYP24A1, creating a clinically significant drug-nutrient interaction that exacerbates vitamin D depletion. Evidence supporting vitamin D supplementation remains predominantly derived from pulmonary tuberculosis (PTB) patients in randomized controlled trials (RCTs), with only one small-sample study specific to OATB (n = 41, 8 weeks). These PTB-derived trials employed single high-dose bolus regimens with 3–6 months follow-up, demonstrating modest benefits (HR 0.58–0.89) primarily in vitamin D-deficient subgroups, with negligible effects in replete populations. Direct applicability to OATB remains unverified. This review systematizes vitamin D’s immunological and bone-metabolic mechanisms in OATB, critically appraises existing evidence quality and extrapolation limitations, and proposes an RCT framework with bone structural repair and functional recovery as primary endpoints. Our aim is to guide theoretical development and future clinical investigation of vitamin D as adjunctive therapy for OATB.
SN - 0300-8126
SN - 1439-0973
ER -