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<p>Bone tuberculosis (BTB) remains a diagnostic and therapeutic challenge despite advances in molecular medicine, accounting for 10–15% of extrapulmonary tuberculosis cases with disproportionate morbidity in immunocompromised populations. This comprehensive review synthesizes current understanding of BTB pathogenesis, diagnostic innovations, and therapeutic strategies while highlighting critical knowledge gaps. At the molecular level, <i>Mycobacterium tuberculosis</i> exploits bone-specific niches through granuloma formation, immune evasion mechanisms involving autophagy inhibition and cytokine dysregulation, and direct disruption of RANKL/OPG signaling that drives osteoclastic bone destruction. Clinically, BTB exhibits distinct phenotypes, with vertebral (spinal) disease characterized by delayed diagnosis, higher relapse rates, and frequent need for surgical intervention, whereas peripheral joint and long bone involvement often presents with indolent synovitis and diagnostic overlap with inflammatory or degenerative disorders. Pediatric BTB represents a distinct entity, frequently involving growth plates, displaying marked paucibacillary disease that limits microbiological confirmation, and carrying substantial risk of long-term skeletal deformity. Multi-omics approaches have identified novel biomarkers, including microRNAs (miR-29, miR-125b), long non-coding RNAs (MALAT1, NEAT1), and protein signatures (calprotectin, lipocalin-2) with diagnostic potential, though clinical validation remains limited. Conventional imaging modalities are complemented by emerging molecular diagnostics, such as GeneXpert MTB/RIF Ultra, which promise earlier and more accurate diagnoses. Standard anti-tuberculosis regimens face substantial challenges in skeletal tissues due to avascular lesions, granuloma microenvironments, and rising drug resistance, necessitating prolonged treatment durations with suboptimal outcomes. Novel therapeutic paradigms encompass bone-targeted nanotechnology-enabled drug delivery systems. Critical barriers to clinical translation include technical limitations in bone tissue multi-omics analysis, significant gaps in genetic diversity across research cohorts, regulatory hurdles to combination therapies, and healthcare inequities in resource-limited settings. The future roadmap integrates AI-assisted multimodal data integration to enable personalized BTB management that simultaneously addresses pathogen elimination, immune restoration, and bone regeneration.</p>

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Bone tuberculosis: molecular pathogenesis, diagnostic advances, therapeutic challenges, and emerging strategies for effective management

  • 期刊论文

  • 发表日期：

    2026年3月14日

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  • Xueli Du,
  • Xin Gu,
  • Nan Li,
  • Tao Ji,
  • Wei Fu,
  • Shuai Cao,
  • Meirong Wang,
  • Tao Peng

摘要

Bone tuberculosis (BTB) remains a diagnostic and therapeutic challenge despite advances in molecular medicine, accounting for 10–15% of extrapulmonary tuberculosis cases with disproportionate morbidity in immunocompromised populations. This comprehensive review synthesizes current understanding of BTB pathogenesis, diagnostic innovations, and therapeutic strategies while highlighting critical knowledge gaps. At the molecular level, Mycobacterium tuberculosis exploits bone-specific niches through granuloma formation, immune evasion mechanisms involving autophagy inhibition and cytokine dysregulation, and direct disruption of RANKL/OPG signaling that drives osteoclastic bone destruction. Clinically, BTB exhibits distinct phenotypes, with vertebral (spinal) disease characterized by delayed diagnosis, higher relapse rates, and frequent need for surgical intervention, whereas peripheral joint and long bone involvement often presents with indolent synovitis and diagnostic overlap with inflammatory or degenerative disorders. Pediatric BTB represents a distinct entity, frequently involving growth plates, displaying marked paucibacillary disease that limits microbiological confirmation, and carrying substantial risk of long-term skeletal deformity. Multi-omics approaches have identified novel biomarkers, including microRNAs (miR-29, miR-125b), long non-coding RNAs (MALAT1, NEAT1), and protein signatures (calprotectin, lipocalin-2) with diagnostic potential, though clinical validation remains limited. Conventional imaging modalities are complemented by emerging molecular diagnostics, such as GeneXpert MTB/RIF Ultra, which promise earlier and more accurate diagnoses. Standard anti-tuberculosis regimens face substantial challenges in skeletal tissues due to avascular lesions, granuloma microenvironments, and rising drug resistance, necessitating prolonged treatment durations with suboptimal outcomes. Novel therapeutic paradigms encompass bone-targeted nanotechnology-enabled drug delivery systems. Critical barriers to clinical translation include technical limitations in bone tissue multi-omics analysis, significant gaps in genetic diversity across research cohorts, regulatory hurdles to combination therapies, and healthcare inequities in resource-limited settings. The future roadmap integrates AI-assisted multimodal data integration to enable personalized BTB management that simultaneously addresses pathogen elimination, immune restoration, and bone regeneration.