DECREASED BETA-ISOMERIZATION OF THE C-TERMINAL TELOPEPTIDE OF TYPE-I COLLAGEN ALPHA-1 CHAIN IN PAGETS-DISEASE OF BONE

In Paget's disease of bone, the normal lamellar bone is replaced by a woven structure with an irregular arrangement of collagen fibers, In t his study, we investigated whether the degree of beta-isomerization wi thin C-telopeptide of al chain of type I collagen was altered in Paget 's disease compared with other bone diseases with no alteration of bon e structure. In Pagers disease (n = 26), but not in patients with prim ary hyperparathyroidism (n = 6) or hyperthyroidism (n = 17), the urina ry excretion of nonisomerized (alpha) fragments derived from degradati on of type I collagen C-telopeptide (CTX) was markedly increased compa red with beta-isomerized CTX (+ 13-fold vs. + 3.5-fold over controls) resulting in an urinary alpha CTX/beta CTX ratio 3-fold higher than in controls (2.6 +/- 1.0 vs, 0.8 +/- 0.3, p < 0.001). In five pagetic pa tients in complete remission, as demonstrated by normal total alkaline phosphatase activity, the alpha CTX/beta CTX ratio was normal, The im munohistochemistry of normal and pagetic human bone sections showed a preferential distribution of alpha CTX within woven structure, while l amellar bone was intensely stained with an anti-beta CTX antibody, sug gesting a lower degree of beta-isomerization of type I collagen in the woven pagetic bone, In collagenase digest of human bone specimens, we found a lower proportion of beta-isomerized type I collagen molecules in pagetic bone (40% of beta CTX) than in normal bone taken from trab ecular (68%) and cortical compartments (71%), In conclusion, we found that in Paget's disease the alpha CTx/beta CTX ratio in bone and in ur ine is markedly increased, This altered beta isomerization can be accu rately detected in vivo by measuring urinary degradation products aris ing from bone resorption.