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

TY - JOUR

T1 - Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bone.

AU - Alexandersen, Peter

AU - Peris, Pilar

AU - Guañabens, Nuria

AU - Byrjalsen, Inger

AU - Alvarez, Luisa

AU - Solberg, Helene

AU - Cloos, Paul Ac

N1 - Keywords: Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Collagen; Collagen Type I; Diphosphonates; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Molecular Sequence Data; Molecular Structure; Osteitis Deformans; Peptides; Prognosis; Treatment Outcome

PY - 2004

Y1 - 2004

N2 - A new resorption assay measuring non-isomerized collagen type I C-telopeptide fragments (alpha-alpha CTX) was evaluated in a cohort comprising 32 Pagetic patients and 48 healthy controls. alpha-alpha 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 (beta-beta 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 alpha, but spontaneously converts to an isomerized form (beta) during aging of bone. CTX fragments composed of at least two alpha CTX chains (alpha-alpha 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 alpha-alpha CTX (U alpha-alpha 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 beta-beta CTX, N-terminal cross-linking telopeptide of type I collagen, and deoxypyridinoline, were also measured for comparison. RESULTS AND CONCLUSIONS: The U alpha-alpha 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 alpha-alpha CTX marker also provided a high correlation (r = 0.89) to disease activity as assessed by scintigraphic activity index. In conclusion, alpha-alpha CTX seems to be a sensitive marker for assessing disease activity and monitoring treatment efficacy in Paget's disease.

AB - A new resorption assay measuring non-isomerized collagen type I C-telopeptide fragments (alpha-alpha CTX) was evaluated in a cohort comprising 32 Pagetic patients and 48 healthy controls. alpha-alpha 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 (beta-beta 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 alpha, but spontaneously converts to an isomerized form (beta) during aging of bone. CTX fragments composed of at least two alpha CTX chains (alpha-alpha 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 alpha-alpha CTX (U alpha-alpha 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 beta-beta CTX, N-terminal cross-linking telopeptide of type I collagen, and deoxypyridinoline, were also measured for comparison. RESULTS AND CONCLUSIONS: The U alpha-alpha 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 alpha-alpha CTX marker also provided a high correlation (r = 0.89) to disease activity as assessed by scintigraphic activity index. In conclusion, alpha-alpha CTX seems to be a sensitive marker for assessing disease activity and monitoring treatment efficacy in Paget's disease.

U2 - 10.1359/JBMR.041212

DO - 10.1359/JBMR.041212

M3 - Journal article

C2 - 15765177

SN - 0884-0431

VL - 20

SP - 588

EP - 595

JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

IS - 4

ER -