title: [HISTOLOGICAL ANALYSIS OF BONE DESTRUCTION IN SPINAL TUBERCULOSIS].
abstract: OBJECTIVE
  To investigate the mechanism of bone destruction in spinal tuberculosis (TB) by immunohistochemical analysis of the pathway that includes receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and osteocalcin (OCN) in affected tissues.
  
  
  METHODS
  TB bone specimens were obtained from 30 surgically treated spinal TB patients (13 males and 17 females; average age, 67 years). Normal bone specimens were also obtained from 30 osteoarthritis patients (12 males and 18 females; average age, 70 years) who had undergone knee arthroplasty, wherein a piece of the non-weight-bearing part of the femur was obtained as a part of the resected bone for surgery. The two groups of specimens were examined for the expression of RANK, RANKL, OPG, and OCN by immunohistochemistry.
  
  
  RESULTS
  Spinal TB specimens were significantly infiltrated by inflammatory cells, and bone resorption by multinucleated osteoclasts was observed. RANKL was predominantly expressed in lymphocytes and osteoblasts, whereas RANK was expressed in mononucleated osteoclast precursors among the inflammatory cells. In contrast, there was no infiltration of the inflammatory cells, and the expression of RANKL/RANK was poor in the control specimens. OCN, a bone formation marker, was expressed in the osteoblasts and in part of the bone matrix in normal tissues; however, it was poorly expressed in the tissues of the spinal TB patients. OPG, a neutralizer of the RANK-RANKL pathway, was expressed in the osteoblasts and stromal cells, and there was no significant difference in the expression between the two groups.
  
  
  CONCLUSIONS
  In the tissues from spinal TB patients, the RANK-RANKL pathway was strongly activated, whereas the expression of its neutralizer OPG was not sufficiently induced. In addition, the bone formation marker OCN was poorly expressed, indicating a paucity of reactive bone formation. These findings are consistent with bone-resorption-predominant destruction, which is commonly observed in osteoarticular TB. Activation of the RANK-RANKL pathway has been considered to be caused by cytokines such as tumor necrosis factor-α and interleukin-6, which also play important roles in the immune response against TB. In severe pulmonary TB, an intense and prolonged immune reaction sometimes leads to tissue destruction and the formation of cavity lesions. Therefore, such an immune reaction against spinal TB may also cause activation of the RANK-RANKL pathway, thereby leading to bone destruction.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Izawa
mesh_terms: D000368:Aged; D005269:Femur / Q000473:pathology; D006801:Humans; D008297:Male; D053245:RANK Ligand / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000032:analysis; D014399:Tuberculosis, Spinal / Q000473:pathology*
chemical_list: D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B