An immunoassay for type I collagen alpha 1 helicoidal peptide 620-633, a new marker of bone resorption in osteoporosis.
Type I collagen fragments are the most sensitive markers of bone resorption in osteoporosis. Currently, all available type I collagen-related bone resorption markers detect in serum and/or urine fragments arising from the telopeptide region of the molecule. Our aim was to evaluate the technical and clinical performances of a new assay detecting in urine a degradation fragment originating from the helical part of type I collagen and consisting of the 620-633 sequence of the alpha1 chain. Urinary helical peptide was measured with a new ELISA (Metra Helical peptide, Quidel Corporation). Results were compared with those of urinary C-terminal cross-linking type I collagen of type I collagen (CTX), an established bone resorption marker. We measured urinary helical peptide levels in 89 healthy women (age 31-89 years) and in 59 postmenopausal women involved in two randomized studies of the efficacy of alendronate (10 mg/day; n = 20) and transdermal 17beta estradiol (50 microg/day; n = 39). The within-run and between-run CVs were < or = 7.3 and 8.7%, respectively. In 59 healthy women, urinary helical peptide levels highly correlated with those of urinary CTX (r = 0.78, P < 0.0001). The long-term intraindividual variability assessed over 6 months in 18 untreated postmenopausal women was 24%. Compared to 24 premenopausal women, urinary helical peptide was 42% (P < 0.0001) higher in 65 postmenopausal women (mean age, 60 years), an increase comparable to that of urinary CTX (+ 47%, P < 0.0001). Urinary helical peptide levels decreased by 72% (P < 0.0001) after 3 months of alendronate treatment and by 59% (P < 0.0001) after 6 months of transdermal estrogen therapy. These changes were of similar magnitude to those of urinary CTX (-69 and -62%, respectively; NS compared with changes in helical peptide). In women treated with transdermal 17beta estradiol, the percentage of change of urinary helical peptide and urinary CTX at 6 months significantly correlated with the change in spinal bone mineral density after 2 years (r = -0.58, P = 0.002, and r = -0.52, P = 0.006, for urinary helical peptide and CTX, respectively). This new assay for type I collagen helical peptide has demonstrated adequate analytical performance and was highly correlated with urinary CTX, an established type I collagen C-telopeptide bone resorption marker. The test was a sensitive indicator of the antiresorptive effects of bisphosphonate and estrogens in postmenopausal women. This new bone resorption marker should be useful for the clinical investigation of patients with osteoporosis.
Garnero
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INSERM Research Unit 403, Hôpital E. Herriot. Pavillon F, 69437 Lyon Cedex 03, France. patrick.garnero@synarc.com
Delmas
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000188:drug therapy / Q000652:urine*; D024042:Collagen Type I / Q000652:urine*; D000090602:Collagen Type I, alpha 1 Chain; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000652:urine*; D010446:Peptide Fragments / Q000652:urine*; D017433:Protein Structure, Secondary; D018709:Statistics, Nonparametric
D015415:Biomarkers; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D010446:Peptide Fragments; D004958:Estradiol