ADMINISTRATION OF SYSTEMIC MATRIX METALLOPROTEINASE INHIBITORS MAINTAINS BONE MECHANICAL INTEGRITY IN ADJUVANT ARTHRITIS

Objective. To evaluate the influence of systemic tetracycline derived antimetalloproteinase compounds on bone morphology and mechanical inte grity. Methods. Male Lewis rats (n = 78) were randomly assigned to one of 10 groups, comprising controls, adjuvant arthritis (AA), and adjuv ant arthritis with various combinations of 2 chemically modified. non- antimicrobial tetracycline derivatives (CMT3 or CMT8) with either of 2 nonsteroidal antiinflammatory agents (flurbiprofen or tenidap). After AA induction (23 days), pharmacological efficacy was assessed by infl ammatory indices, body mass changes, joint radiological destruction sc ores, and pyridinoline collagen derived crosslinks. The structural and material properties of the rat femoral neck were assessed biomechanic ally. Results. Neither CMT had an antiinflammatory effect, but flurbip rofen and tenidap (alone or together with either CMT) significantly re duced joint inflammation. Pyridinoline excretion increased markedly in untreated AA, but was substantially normalized by either CMT3 alone o r by CMT8 with flurbiprofen. AA produced significant deleterious effec ts on femoral neck structure and mechanical properties. Administration of either CMT, however. had positive effects on the amount of bone an d the biomechanical properties of rat femoral neck, but not the minera lization of the bone in the rat femoral neck. Conclusion. These data s uggest that tetracycline derived antimetalloproteinase compounds can s ignificantly and positively influence bone mechanical integrity associ ated with inhibition of collagen breakdown.