The bisphosphonate zoledronate decreases type II collagen breakdown in patients with Paget's disease of bone

Bisphosphonates have been suggested to be partially chondroprotective in an imal models of arthritis, The aim of this study was to assess the short-ter m effect of the bisphosphonate zoledronate on type II collagen degradation in patients with Paget's disease of bone. Twenty-six patients with active P aget's disease who were a part of a double-blind, placebo-controlled, rando mized study comparing the effects of several doses of a single injection of zoledronate, a potent bisphosphonate, were studied, Type II collagen destr uction was assessed by urinary levels of type II collagen C-telopeptide (CT X-II) using a new immunoassay, Bone resorption was assessed by measuring th e urinary excretion of nonisomerized type I collagen C-telopeptide (alpha C TX-I). Biochemical markers were measured at baseline and 5, 10, 30, and 60 days after injection, At baseline, no significant increase of CTX-II was ob served in patients with Paget's disease compared with a group of 27 gender- and age-matched controls, in contrast to the ninefold (p < 0.0001) increase of urinary ru CTX-I, After a single intravenous injection of zoledronate ( 200 or 400 mug), urinary CTX-II transiently decreased by a median of 25% 5 days after the injection of zotedronate (p = 0.0023 vs, placebo), then incr eased to pretreatment levels after 10 days. In contrast, urinary or CTX-I d ecreased within 5 days with a maximal decrease of 51% at day 10 (p < 0.001 vs, baseline and placebo), and levels remained suppressed during the 2 mont hs of the study, Zoledronate not only reduces bone turnover but also direct ly decreases type II collagen degradation in patients with Paget's disease, suggesting that bisphosphonates may have chondroprotective effects in huma ns. Measurement of type II collagen breakdown by a new urinary biochemical marker may be useful for in vivo assessment of the effects of drugs that po tentially inhibit cartilage destruction, (C) 2001 by Elsevier Science Inc, All rights reserved.