Background/Purpose: We investigated change of bone turnover markers in peripheral blood before, 6 and 12 months after rituximab therapy in seropositive RA patients.

Methods: Ten seropositive RA patients were enrolled. They had been refractory to antirheumatic drugs and anti TNF-¥á therapy, thus received rituximab, monoclonal anti-CD 20 antibody treatment.  Rituximab 1000mg were infused on days 1 and 15. Peripheral blood mononuclear cells were collected before, 6 and 12 months after rituximab treatment. They were cultured and number of osteoclasts was counted. In addition, CD 19 cells and complete blood count (CBC) along with ESR, CRP and RA disease activity such as DAS28 were assessed. Bone turnover markers including c-terminal telopeptide (CTX), osteocalcin, bone specific alkaline phosphatase (BSALP) were also measured using enzyme linked immunosorbent assay.

Results: The number of cultured osteoclasts from peripheral blood and serum level of CTX were lowered, six months after rituximab therapy (Table 1). BSALP which is bone formation marker also increased after the treatment. The acute phase reactants and RA disease activity, measured 6 months after rituximab therapy markedly responded to the treatment as CD 19 cells were depleted (Table 2). On the other hand, twelve months after rituximab therapy, the serum level of acute phase reactants began to rise and CD 19 cells increased in numbers. RA disease activity also got worse. Bone resorption pits by osteoclasts cultured from peripheral blood at 12 months after rituximab treatment significantly increased than bone resorption pits by osteoclasts from peripheral blood at 6 months after the treatment.  

Conclusion: Peripheral osteoclastogenesis decreased when systemic inflammation is improved in RA patients 6 months after B cell depletion treatment. However, one year after rituximab treatment, systemic inflammation increased as peripheral B cell counts began to normalize. The area of bone resorption pit by cultured osteoclasts from peripheral blood increased as well. Therefore, we think peripheral osteoclastogenesis is coming back along with the inflammation, 12 months after rituximab treatment and rituximab therapy should be resumed within a year.