Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bone

Abstract

A new resorption assay measuring non-isomerized collagen type I C-telopeptide fragments (α-α CTX) was evaluated in a cohort comprising 32 Pagetic patients and 48 healthy controls. α-α CTX was found to be a sensitive marker for assessing disease activity and monitoring treatment efficacy in Paget's disease of bone compared with isomerized CTX (β-β CTX) and a number of other established bone turnover markers. Introduction: Collagen type I fragments are generated by resorbing osteoclasts, and some of them can be measured using a C-telopeptide (CTX) immunoassay. The C-telopeptide of collagen type I comprises a DG-motif susceptible to isomerization. In newly synthesized collagen, this motif is in the native form denoted a, but spontaneously converts to an isomerized form (β) during aging of bone. CTX fragments composed of at least two α CTX chains (α-α CTX) originating from degradation of newly formed bone can be determined in the urine using a newly developed sandwich ELISA. The aim of this study was to assess the ability of this marker to monitor disease activity and treatment efficacy in patients with Paget's disease compared with established bone turnover markers. Materials and Methods: A total of 32 patients diagnosed with Paget's disease of bone was included in the study. All received 400 mg/day of oral tiludronate for 3 months. Urinary α-α CTX (U α-α CTX) was measured at baseline and at 1 and 6 months after discontinuation of therapy and in 48 untreated age-matched and healthy controls. Other markers of bone turnover, including urinary β-β CTX, N-terminal cross-linking telopeptide of type I collagen, and deoxypyridinoline, were also measured for comparison. Results and Conclusions: The U α-α CTX marker showed a marked reduction (-82% and -77% at 1 and 6 months of treatment, respectively) in response to antiresorptive therapy in patients with Paget's disease. The response to treatment in this marker exceeded that of the other markers (p < 0.01). The α-α CTX marker also provided a high correlation (r = 0.89) to disease activity as assessed by scintigraphic activity index. In conclusion, α-α CTX seems to be a sensitive marker for assessing disease activity and monitoring treatment efficacy in Paget's disease. © 2005 American Society for Bone and Mineral Research.