RESEARCH SUPPORT, NON-U.S. GOV'T
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Impaired pyridinoline cross-link formation in patients with osteogenesis imperfecta.

Patients with osteogenesis imperfecta (OI) show various degrees of bone fragility. Nevertheless, details of the mechanisms causing bone fragility remain unclear. We hypothesized that differences in pyridinoline cross-link formation at the N-and C-termini in type I collagen molecules partly contribute to bone fragility of OI. To verify this hypothesis, urinary N and C terminal telopeptides of type I collagen (uNTx and ubetaCTx, respectively) and urinary hydroxyproline (uHyp) were measured using second morning void urine samples obtained from OI patients and healthy control children. Ratios of uNTx and ubetaTx to uHyp (uNTx/uHyp and ubetaCTx/uHyp, respectively) of OI patients and healthy normal control children were analyzed. Ratios of uNTx to ubetaCTx (uNTx/ubetaCTx) were also analyzed. In OI patients, uNTx and ubetaCTx were lower than in healthy control children. Also, uNTx/uHyp and ubetaCTx/uHyp were significantly lower than in healthy children. Among OI patients, uNTx/uHyp and uNTx/ubetaCTx of type III OI were significantly lower than of either type I or type IV OI. These results show that pyridinoline cross-link formation is lower than in healthy control children and that pyridinoline cross-link formation at the N-and C-termini in type I collagen molecules might be differently disrupted in OI patients according to the severity of OI.

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