Potential value of vitamin D as adjunctive therapy in osteoarticular tuberculosis: a comprehensive review

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.