Monitoring bone resorption in early postmenopausal women by an immunoassay for cross-linked collagen peptides in urine

Abstract

A new immunoassay using an ELISA approach for measuring urinary excretion of cross‐linked N‐telopeptides of type 1 collagen was evaluated as a specific measure of bone resorption. The assay was applied to 65 early postmenopausal women who participated in a placebo‐controlled trial of the aminobisphosphonate, alendronate sodium. Eight blood and urine samples were collected over a 9 month interval. Baseline cross‐linked peptide excretion varied from 26 to 216 pmol BCE (bone collagen equivalents)/μmol Cr. Within‐subject variability (CV) for cross‐linked peptide excretion was 20.2% over the 9 months in placebo‐treated subjects, substantially less than that observed for other biochemical markers of bone resorption: 45, 53, and 63% for fasting urinary calcium and hydroxyproline and 24 h urinary lysylpyridinoline (HPLC assay), respectively. Baseline cross‐linked peptide excretion correlated significantly (p < 0.001) with baseline total urine lysylpyridinoline and serum osteocalcin, but not with the other biochemical markers. Initial peptide excretion also correlated inversely with lumbar spine bone mineral density at entry (r = −0.26, p < 0.05). Treatment for 6 weeks with alendronate produced a dose‐dependent suppression of cross‐linked peptide excretion (0 ± 8, 29 ± 6, 56 ± 5, and 64 ± 3% for 0, 5, 20, and 40 mg, respectively, p < 0.01 versus placebo for treatment effect), with a return toward pretreatment values during follow‐up. Measurement of the urinary cross‐linked N‐telopeptides of type I collagen by this new ELISA approach appears promising as a simple and reliable method to assess overall bone resorption. It may prove especially useful in monitoring the treatment of osteoporotic women with antiresorptive therapy. Its utility in identifying those women in the high resorption range at menopause who may be at greater risk for osteoporosis should also be assessed in future studies.