Favorable Effects of anti TNF Therapy on Bone Turnover in Peripheral Blood Despite Inadequate Response of Inflammatory Markers in Seropositive RA Patients

초록

Objectives We investigated the circulating osteoclasts and osteoblast activity in peripheral blood before and 6 months after anti TNF-a therapy in seropositive RA patients. Materials and Methods Thirteen seropositive RA patients were enrolled. They had been refractory to disease modifying antirheumatic drugs (DMARDs) and were preparing for anti TNFa Therapy including infliximab, adalimumab and etanercept. Peripheral blood mononuclear cells (PBMCs) were collected before and 6 months after anti TNF-a Therapy. PBMCs (1 x 106 cells/well) were placed in a 96-well tissue culture plate and cultured for 14 days. Histochemical staining for tartrate resistant acid phosphatase (TRAP) was carried out using an acid phosphatase kit (Sigma 386-A, St.Louis, MO). TRAP positive giant cells with more than 3 nuclei were regarded as osteoclasts. To assess resorption potential of osteoclasts, PBMCs were also cultured on bone slices for 3 weeks under the same condition as described above. Osteoclasts were then removed and the pits were visualized with 0.1% toluidine blue. The areas of pits were quantified using a computerized image analysis program. PBMCs were also cultured, fixed and stained with alizarin S stain to detect any calcified nodules. The optic density measurement of total alizarin S solute was performed for quantitative analysis. Results After 6 months of anti TNF- a therapy, number of ex vivo cultured osteoclasts was reduced and the area of resorption pit decreased as shown in Table 1. The optic density of calcified nodules increased significantly. On the other hand, systemic inflammatory markers including erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) failed to show significant response after anti TNF therapy. Anti-TNF therapy reduced swollen and tender joint counts, resulting in improvement of RA disease activity. Conclusion The number of peripheral osteoclasts and osteoblast activity decreased after 6 months of anti TNF- a tr