Circulating Osteoblasts and Osteoclasts in Peripheral Blood Respond to anit TNF a therapy despite inadequate response of inflammatory markers in seropositive RA patients

초록

Objectives We investigated peripheral bone turnover before, 6 and 12 months after rituximab therapy in seropositive RA patients. Materials and Methods Ten seropositive RA patients were enrolled. They had been refractory to antirheumatic drugs and anti TNF-α therapy, thus they were preparing for rituximab, monoclonal anti-CD 20 antibody, treatment. Peripheral blood mononuclear cells were collected before, 6 and 12 months after rituximab treatment. They were cultured and histochemical staining for tartrate resistant acid phosphatase (TRAP) was carried out. TRAP positive giant cells with more than 3 nuclei were regarded as osteoclasts. In addition, CD 19 cells along with ESR, CRP and RA disease activity such as DAS28 were compared before, 6 and 12 months after anti rituximab therapy. Bone turnover markers including c-terminal telopeptide (CTX), osteocalcin, bone specific alkaline phosphatase (BSALP) were also measured using enzyme linked immunosorbent assay. Results After 6 months of rituximab therapy, number of cultured osteoclasts from peripheral blood and serum level of CTX were both decreased (Table 1) while RA disease activity was improving in accordance with depletion of B-cells (Table 2). BSALP increased after the treatment as well. Conclustion Peripheral bone resorption is suppressed when systemic inflammation is improved in RA patients 6 months after B cell depletion treatment. This was accompanied by an increase in bone formation marker reflected by BSALP. However, one year after rituximab treatment, ESR and CRP began to increase along with peripheral B cell counts, resulting in worsened RA disease activity. The area of bone resorption pit by cultured osteoclasts from peripheral blood increased as well. Therefore, rituximab therapy decreases bone resorption and increases bone formation in RA patients when B cells were depleted and RA activity was improved.