Decreased β-Isomerization of the C-Terminal Telopeptide of Type I Collagen α1 Chain in Paget's Disease of Bone

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In Paget's disease of bone, the normal lamellar bone is replaced by a woven structure with an irregular arrangement of collagen fibers. In this study, we investigated whether the degree of β-isomerization within C-telopeptide of α1 chain of type I collagen was altered in Paget's disease compared with other bone diseases with no alteration of bone structure. In Paget's disease (n = 26), but not in patients with primary hyperparathyroidism (n = 6) or hyperthyroidism (n = 17), the urinary excretion of nonisomerized (α) fragments derived from degradation of type I collagen C-telopeptide (CTX) was markedly increased compared with β-isomerized CTX (+ 13-fold vs. + 3.5-fold over controls) resulting in an urinary α CTX/β CTX ratio 3-fold higher than in controls (2.6 ± 1.0 vs. 0.8 ± 0.3, p < 0.001). In five pagetic patients in complete remission, as demonstrated by normal total alkaline phosphatase activity, the α CTX/β CTX ratio was normal. The immunohistochemistry of normal and pagetic human bone sections showed a preferential distribution of α CTX within woven structure, while lamellar bone was intensely stained with an anti-β CTX antibody, suggesting a lower degree of β-isomerization of type I collagen in the woven pagetic bone. In collagenase digest of human bone specimens, we found a lower proportion of β-isomerized type I collagen molecules in pagetic bone (40% of β CTX) than in normal bone taken from trabecular (68%) and cortical compartments (71%). In conclusion, we found that in Paget's disease the α CTX/β CTX ratio in bone and in urine is markedly increased. This altered β isomerization can be accurately detected in vivo by measuring urinary degradation products arising from bone resorption.

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