Comprehensive review of osteoarticular tuberculosis: from epidemiology to emerging therapies
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20252594Keywords:
Osteoarticular tuberculosis, Extrapulmonary tuberculosis, Multidrug-resistant tuberculosis, Antitubercular agents, Molecular diagnostic techniques, Surgical procedures, Immunotherapy, Regenerative medicineAbstract
Osteoarticular tuberculosis (OATB) remains a significant global health challenge with high morbidity and potential for permanent disability. Recent advancements in diagnostics, pharmacotherapy, and adjunctive treatments have shown promise for improving the outcomes of patients with OATB. This review summarizes the latest developments in the field, focusing on epidemiology, pathogenesis, diagnostic innovations, novel anti-tuberculosis drugs, combination therapy approaches, surgical interventions, adjunctive therapies, and the importance of multidisciplinary approaches. Emerging diagnostic technologies such as advanced imaging modalities, molecular assays, and nanotechnology-based tests have enhanced the speed and accuracy of OATB detection. Newer anti-tuberculosis drugs, including bedaquiline, delamanid, and pretomanid, have demonstrated efficacy in multidrug-resistant (MDR) and extensively drug-resistant (XDR) cases, whereas DprE1 inhibitors and oxazolidinone alternatives show promise in early phase trials. Minimally invasive surgical techniques, joint-preserving procedures, and reconstructive methods using 3D-printed implants and antibiotic-loaded materials have improved functional outcomes. Immunomodulators, bone grafts, and regenerative medicine have been explored as adjunctive therapies. Effective management of OATB requires collaboration among various specialists, and integrated care models facilitate personalized treatment plans. Challenges remain, including drug resistance, and the need for further research to establish optimal regimens and durations specific to OATB. By highlighting key advancements and their potential impact on patient outcomes, this review underscores the importance of a multidisciplinary evolving paradigm for treating OATB in the era of precision medicine.
Metrics
References
Tuli S. Tuberculosis of the skeletal system (bones, joints, spine, and bursal sheaths). In Jaypee Brothers Medical Publishers (P) Ltd. eBooks. 2016. DOI: https://doi.org/10.5005/jp/books/12726
WHO. Global Tuberculosis Report 2023. World Health Organization; 2023. Available at: https://www.who.int/publications/i/item/9789240077660. Accessed on 12 April 2025.
Garg RK, Somvanshi DS. Spinal tuberculosis: a review. J Spinal Cord Med. 2011;34(5):440-54.
Arathi N, Ahmad F, Huda N. Osteoarticular tuberculosis-a three years’ retrospective study. J Clin Diagnost Res. 2013;7(10):2189.
Moon MS. Tuberculosis of the spine: controversies and a new challenge. Spine. 1997;22(15):1791-7. DOI: https://doi.org/10.1097/00007632-199708010-00022
Jain AK. Tuberculosis of the spine: a fresh look at an old disease. J Bone Joint Surg Brit. 2010;92(7):905-13. DOI: https://doi.org/10.1302/0301-620X.92B7.24668
Ahmad N, Ahuja SD, Akkerman OW, Alffenaar JW, Anderson LF, Baghaei P, et al. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis. Lancet. 2018;392(10150):821-34. DOI: https://doi.org/10.1016/S0140-6736(18)31644-1
Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Eng J Med. 2020;382(10):893-902.
Makarov V, Lechartier B, Zhang M, Neres J, van der Sar AM, Raadsen SA, et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Molecular Med. 2014;6(3):372-83. DOI: https://doi.org/10.1002/emmm.201303575
Zhang X, Xie Q, Ye Z, Li Y, Che Z, Huang M, et. al. Mesenchymal stem cells and tuberculosis: clinical challenges and opportunities. Front Immunol. 2021;12:695278. DOI: https://doi.org/10.3389/fimmu.2021.695278
Moskowitz NC, Moskowitz MT, Sugalski E, Moskowitz AD, inventors; Moskowitz Family LLC, assignee. 3-d printed spinal implant. United States patent application US 17/471,667. 2022.
Wallis RS, Hafner R. Advancing host-directed therapy for tuberculosis. Nature Rev Immunol. 2015;15(4):255-63. DOI: https://doi.org/10.1038/nri3813
Sun L, Zhu YU, Fang M, Shi Y, Peng X, Liao Q, et al. Evaluation of Xpert MTB/RIF ultra assay for diagnosis of childhood tuberculosis: a multicenter accuracy study. J Clin Microbiol. 2020;58(9):10-128. DOI: https://doi.org/10.1128/JCM.00702-20
Kogan F, Broski SM, Yoon D, Gold GE. Applications of PET‐MRI in musculoskeletal disease. J Magnet Resonance Imaging. 2018;48(1):27-47. DOI: https://doi.org/10.1002/jmri.26183
Sharma SK, Mohan A. Extrapulmonary tuberculosis. Indian J Med Res. 2004;120(4):316.
Gain A, Jain AK, Bhalla M, Aggarwal AN, Dhammi IK, Arora VK. Drug resistance in osteoarticular tuberculosis: A study from an endemic zone. Cureus. 2023;15(8):1. DOI: https://doi.org/10.7759/cureus.44173
Rasouli MR, Mirkoohi M, Vaccaro AR, Yarandi KK, Rahimi-Movaghar V. Spinal tuberculosis: diagnosis and management. Asian Spine J. 2012;6(4):294. DOI: https://doi.org/10.4184/asj.2012.6.4.294
Jain AK, Dhammi IK. Tuberculosis of the spine: a review. Clin Orthopaed Rel Res. 2007;460:39-49. DOI: https://doi.org/10.1097/BLO.0b013e318065b7c3
Babhulkar S, Pande S. Tuberculosis of the hip. Clin Orthopaed Relat Res. 2002;398:93-9. DOI: https://doi.org/10.1097/00003086-200205000-00013
Eddabra R, Ait Benhassou H. Rapid molecular assays for detection of tuberculosis. Pneumonia. 2018;10(1):4. DOI: https://doi.org/10.1186/s41479-018-0049-2
WHO. Molecular line probe assays for rapid screening of patients at risk of multidrug-resistant tuberculosis (MDR-TB). Policy statement, 2008. Available at: https://iris.who.int/bitstream/handle/10665/354240/9789240046665-eng.pdf. Accessed on 10 June 2025.
Zignol M, Cabibbe AM, Dean AS, Glaziou P, Alikhanova N, Ama C, et. al. Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study. Lancet Infect Dis. 2018;18(6):675-83. DOI: https://doi.org/10.1016/S1473-3099(18)30073-2
Sharma SK, Mohan A. Tuberculosis: From an incurable scourge to a curable disease-journey over a millennium. Indian J Med Res. 2013;137(3):455-93.
Lalvani A. Diagnosing tuberculosis infection in the 21st century: new tools to tackle an old enemy. Chest. 2007;131(6):1898-906. DOI: https://doi.org/10.1378/chest.06-2471
Teles RM, Graeber TG, Krutzik SR, Montoya D, Schenk M, Lee DJ, et al. Type I interferon suppresses type II interferon–triggered human anti-mycobacterial responses. Science. 2013;339(6126):1448-53. DOI: https://doi.org/10.1126/science.1233665
Conradie F, Diacon AH, Ngubane N, Howell P, Everitt D, Crook AM, et al. Treatment of highly drug-resistant pulmonary tuberculosis. N Eng J Med. 2020;382(10):893-902. DOI: https://doi.org/10.1056/NEJMoa1901814
Häcker B, Schönfeld N, Krieger D, Otto-Knapp R, Hittel N, Pflugmacher P, et al. Long-term safety and tolerability of delamanid-containing regimens in MDR-and XDR-TB patients in a specialised tuberculosis treatment center in Berlin, Germany. Europ Respirat J. 2020;56(6):2000009. DOI: https://doi.org/10.1183/13993003.00009-2020
Sotgiu G, D’Ambrosio L, Centis R, Mura I, Castiglia P, Spanevello A, Migliori GB. The multidrug-resistant tuberculosis threat: old problems and new solutions. J Thoracic Dis. 2015;7(9):E354.
Putra ON, Purnamasari T. BPaL/BpaLM regimen: a bright future for drug–resistant tuberculosis. Asian Pacific J Trop Med. 2024;17(8):335-7. DOI: https://doi.org/10.4103/apjtm.apjtm_244_24
WHO. WHO operational handbook on tuberculosis. Module 4: treatment-drug-resistant tuberculosis treatment, 2022. Available at: https://www.who.int/publications/i/item/9789240065116. Accessed on 10 June 2025.
Tuli SM. Results of treatment of spinal tuberculosis by" middle-path" regime. J Bone Joint Surg Brit Volume. 1975;57(1):13-23. DOI: https://doi.org/10.1302/0301-620X.57B1.13
Aryal A, Garg B, Mehta N, Shekhar S, Gupta V. Is 6 months of antitubercular chemotherapy as effective as more than 6 months regimen in spinal tuberculosis? A systematic review and meta-analysis. Asian Spine J. 2021;16(5):749. DOI: https://doi.org/10.31616/asj.2021.0104
Ryan H, Yoo J, Darsini P. Corticosteroids for tuberculous pleurisy. Cochrane Database Syst Rev. 2017;(3):1. DOI: https://doi.org/10.1002/14651858.CD001876.pub3
Nahid P, Mase SR, Migliori GB, Sotgiu G, Bothamley GH, Brozek JL, et al. Treatment of drug-resistant tuberculosis. An official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respirat and Crit Care Med. 2019;200(10):e93-142. DOI: https://doi.org/10.1164/rccm.201909-1874ST
Singh R, Gogna P, Parshad S, Karwasra RK, Karwasra PK, Kaur K. Video‐Assisted Thoracic Surgery for Tubercular Spondylitis. Minimay Invas Surg. 2014;2014(1):963497. DOI: https://doi.org/10.1155/2014/963497
Fan W, Yang G, Zhou T, Chen Y, Gao Z, Zhou W, et al. One-stage freehand minimally invasive pedicle screw fixation combined with mini-access surgery through OLIF approach for the treatment of lumbar tuberculosis. J Orthop Surg Res. 2022;17(1):242. DOI: https://doi.org/10.1186/s13018-022-03130-4
Guo L, Yang L, Duan XJ, Chen GX, Zhang Y, Dai G. Arthroscopically assisted treatment of adolescent knee joint tuberculosis. Orthop Surg. 2010;2(1):58-63. DOI: https://doi.org/10.1111/j.1757-7861.2009.00059.x
Mahajan NP, Pande KP, Dadhaniya RR, Talukder P, Bagimani PK. Surgical Management of Aggressive Knee Tuberculosis with Open Subtotal Synovectomy-A Case Report and Review of Literature. J Orthop Case Rep. 2022;12(3):48. DOI: https://doi.org/10.13107/jocr.2022.v12.i03.2712
Gautam D, Jain VK, Iyengar KP, Vaishya R, Malhotra R. Total hip arthroplasty in tubercular arthritis of the hip–Surgical challenges and choice of implants. J Clin Orthopaed Trauma. 2021;17:214-7. DOI: https://doi.org/10.1016/j.jcot.2021.03.018
Zheng S, Li M, Chen H, Qin Y. Total hip arthroplasty in hip tuberculosis: a systematic review. BMC Musculosk Disord. 2025;26(1):46. DOI: https://doi.org/10.1186/s12891-024-08053-1
Garg RK, Somvanshi DS. Spinal tuberculosis: a review. J Spinal Cord Med. 2011;34(5):440-54. DOI: https://doi.org/10.1179/2045772311Y.0000000023
Faisal S, Vats D, Panda S, Sharma V, Luthra K, Mohan A, et al. Synergistic role of Mycobacterium indicus pranii and human beta defensin-2 as adjunctive therapy against Mycobacterium tuberculosis. Tuberculosis. 2024;149:102571. DOI: https://doi.org/10.1016/j.tube.2024.102571
Ndlovu H, Marakalala MJ. Granulomas and inflammation: host-directed therapies for tuberculosis. Front Immunol. 2016;7:434. DOI: https://doi.org/10.3389/fimmu.2016.00434
Ganmaa D, Munkhzul B, Fawzi W, Spiegelman D, Willett WC, Bayasgalan P, et. al. High-dose vitamin D3 during tuberculosis treatment in Mongolia. A randomized controlled trial. Am J Respirat Crit Care Med. 2017;196(5):628-37. DOI: https://doi.org/10.1164/rccm.201705-0936OC
Jain AK, Dhammi IK, Prashad B, Sinha S, Mishra P. Simultaneous anterior decompression and posterior instrumentation of the tuberculous spine using an anterolateral extrapleural approach. J Bone Joint Surg Brit Vol. 2008;90(11):1477-81. DOI: https://doi.org/10.1302/0301-620X.90B11.20972
Plantz MA, Gerlach EB, Hsu WK. Synthetic bone graft materials in spine fusion: current evidence and future trends. Int J Spine Surg. 2021;15(1):104-2. DOI: https://doi.org/10.14444/8058
Halloran D, Durbano HW, Nohe A. Bone morphogenetic protein-2 in development and bone homeostasis. J Develop Biol. 2020;8(3):19. DOI: https://doi.org/10.3390/jdb8030019
Jorgensen C, Noël D. Mesenchymal stem cells in osteoarticular diseases. Regenerat Med. 2011;6(6):44-51. DOI: https://doi.org/10.2217/rme.11.80
Xue N, Ding X, Huang R, Jiang R, Huang H, Pan X, et al. Bone tissue engineering in the treatment of bone defects. Pharmaceuticals. 2022;15(7):879. DOI: https://doi.org/10.3390/ph15070879
Bao Z, Chen R, Zhang P, Lu S, Chen X, Yao Y, et al. A potential target gene for the host-directed therapy of mycobacterial infection in murine macrophages. Int J Mole Med. 2016;38(3):823-33. DOI: https://doi.org/10.3892/ijmm.2016.2675
Kohli M, Schiller I, Dendukuri N, Dheda K, Denkinger CM, Schumacher SG, et al. Xpert® MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resistance. Cochrane Database Systematic Rev. 2018;(8):1. DOI: https://doi.org/10.1002/14651858.CD012768.pub2
Nunn AJ, Phillips PP, Meredith SK, Chiang CY, Conradie F, Dalai D, et al. A trial of a shorter regimen for rifampin-resistant tuberculosis. N Eng J Med. 2019;380(13):1201-13. DOI: https://doi.org/10.1056/NEJMoa1811867
Lange C. Management of drug-resistant tuberculosis. Deutsche Medizinische Wochenschrift. 2023;148(19):1236-41. DOI: https://doi.org/10.1055/a-1939-0000
Ghimire S, Van't Boveneind-Vrubleuskaya N, Akkerman OW, de Lange WC, van Soolingen D, Kosterink JG, et al. Pharmacokinetic/pharmacodynamic-based optimization of levofloxacin administration in the treatment of MDR-TB. J Antimicro Chemoth. 2016;71(10):2691-703. DOI: https://doi.org/10.1093/jac/dkw164
Wallis RS, Peppard T, Hermann D. Month 2 culture status and treatment duration as predictors of recurrence in pulmonary tuberculosis: model validation and update. PloS one. 2015;10(4):e0125403. DOI: https://doi.org/10.1371/journal.pone.0125403
Rajpurkar P, Irvin J, Zhu K, Yang B, Mehta H, Duan T, et. al. Radiologist-level pneumonia detection on chest x-rays with deep learning. arXiv. 2017.
Mangtani P, Abubakar I, Ariti C, Beynon R, Pimpin L, Fine PE, et al. Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis. 2014;58(4):470-80. DOI: https://doi.org/10.1093/cid/cit790
Tait DR, Hatherill M, Van Der Meeren O, Ginsberg AM, Van Brakel E, Salaun B, et al. Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis. N Eng J Med. 2019;381(25):2429-39. DOI: https://doi.org/10.1056/NEJMoa1909953
Andersen P, Scriba TJ. Moving tuberculosis vaccines from theory to practice. Nature Rev Immunol. 2019;19(9):550-62. DOI: https://doi.org/10.1038/s41577-019-0174-z
Downloads
Published
How to Cite
Issue
Section
