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


BACKGROUND
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.


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.


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.
Alexandersen
Peter
P
Centre for Clinical and Basic Research, Ballerup, Denmark. pa@ccbr.dk
Peris
Pilar
P
Guañabens
Nuria
N
Byrjalsen
Inger
I
Alvarez
Luisa
L
Solberg
Helene
H
Cloos
Paul Ac
PA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D003094:Collagen / Q000652:urine*; D024042:Collagen Type I; D004164:Diphosphonates / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010001:Osteitis Deformans / Q000175:diagnosis* / Q000188:drug therapy*; D010455:Peptides / Q000652:urine*; D011379:Prognosis; D016896:Treatment Outcome
D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; C058651:tiludronic acid; D003094:Collagen