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Decreased β‐Isomerization of the C‐Terminal Telopeptide of Type I Collagen α1 Chain in Paget's Disease of Bone
Author(s) -
Garnero Patrick,
Fledelius Christian,
Gineyts Evelyne,
Serre ClaireMarie,
Vignot Emanuelle,
Delmas Pierre D.
Publication year - 1997
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1997.12.9.1407
Subject(s) - n terminal telopeptide , paget's disease of bone , type i collagen , chemistry , endocrinology , bone resorption , medicine , bone disease , collagen, type i, alpha 1 , cortical bone , alkaline phosphatase , pathology , osteoporosis , osteocalcin , biochemistry , disease , enzyme , extracellular matrix
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.