An immunoassay for type I collagen α1 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 α1 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 17β estradiol (50 μg/day; n = 39). The within-run and between-run CVs were ≤ 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 17β 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.