Histological changes in bone marrow after treatment of infliximab for rheumatoid arthritis.
To investigate histological evidence of bone remodeling in response to infliximab for rheumatoid arthritis (RA), bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty after treatment of infliximab for an average of 16 months (range, 8-24 months). The patients had a mean age of 65.3 years (range, 57-76 years) with 4.8 mg/week of methotrexate (MTX; 4-6 mg) and 3.8 mg/day of prednisolone (2-5 mg). Control samples were obtained from ten RA patients who did not undergo infliximab therapy. These patients had an average age of 67.6 years (range, 59-78 years) and received 5.2 mg/week of MTX (4-6 mg) and 4.0 mg/day of prednisolone (2-5 mg). Histological examination of structural differences between the infliximab and control groups in bone marrow was performed using hematoxylin and eosin (H & E) to evaluate differences. In immunohistochemical examination, the expressions of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), receptor activator of nuclear (kappa) B ligand (RANKL), osteoprotegerin (OPG), and osteopontin (OPN) were compared between both groups. H & E staining revealed that the bone marrow tissues of the RA patients who underwent infliximab therapy demonstrated newly formed thickness of interstitial septum among the trabeculae as compared with the control group. Moreover, immunohistochemical examinations revealed that TNF-alpha, IL-6, RANKL, OPG, and OPN were expressed in this newly formed bone after infliximab therapy. Therefore, treatment with infliximab improved the histological changes with respect to bone metabolism in the newly formed bone marrow tissues.
Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, Arakawa, Tokyo, Japan. kanbeor@dnh.twmu.ac.jp
Katsuaki
K
Kanbe
Kazuhiko
K
Inoue
Yasuo
Y
Inoue
Yutaka
Y
Suzuki
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000069285:Infliximab; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015850:Interleukin-6; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D053495:Osteopontin; D000069285:Infliximab