1,25-Dihydroxyvitamin D3 prevents bone loss of the secondary spongiosa in arthritic rats by an increase of bone formation and mineralization and inhibition of bone resorption

摘要

Background Active vitamin D metabolites have been shown to have protective effects in experimental arthritis especially when used as preventive treatment. However, because the direct effects of 1,25-dihydroxyvitamin D3 (1,25(OH) ₂D₃) on bone formation and resorption are very complex, the net effect of 1,25(OH)₂D₃ on histomorphometric parameters of bone turnover and mineralisation should be investigated. Therefore, we examined the influence of 1,25(OH)₂D₃ therapy on arthritis-induced alterations of periarticular and axial bone as well as disease activity, inflammation and joint destruction in antigen-induced arthritis (AIA) of the rat. Methods AIA was induced in 20 eight-week-old female Wistar rats. 10 rats without arthritis were used as healthy controls. AIA rats received 1,25(OH)₂D₃ (0.2?μg/kg/day, i.p., n?=?10) or vehicle (n?=?10) at regular intervals for 28 consecutive days beginning 3?days before arthritis induction. Bone structure of the secondary spongiosa of the periarticular and axial bone was analyzed using histomorphometry. Parameters of mineralization were investigated using tetracycline labelling. Clinical disease activity, inflammation and joint destruction were measured by joint swelling and histological investigation, respectively. Results AIA led to significant periarticular bone loss. 1,25(OH)₂D₃ treatment resulted in a highly significant increase in trabecular bone volume and bone formation rate in comparison to both vehicle-treated AIA and healthy controls at periarticular (p?2D₃ at the axial bone (p?2D₃. Conclusions The results of the study indicate a marked osteoanabolic effect of 1,25(OH)₂D₃ presumably due to a substantial increase in mineralization. Thus, 1,25(OH)₂D₃ may be an effective osteoanabolic treatment principle to antagonize the inflammation-associated suppression of bone formation in rheumatoid arthritis.