MONITORING BONE-RESORPTION IN EARLY POSTMENOPAUSAL WOMEN BY AN IMMUNOASSAY FOR CROSS-LINKED COLLAGEN PEPTIDES IN URINE

A new immunoassay using an ELISA approach for measuring urinary excret ion of cross-linked N-telopeptides of type 1 collagen was evaluated as a specific measure of bone resorption. The assay was applied to 65 ea rly postmenopausal women who participated in a placebo-controlled tria l of the aminobisphosphonate, alendronate sodium. Eight blood and urin e samples were collected over a 9 month interval. Baseline crosslinked peptide excretion varied from 26 to 216 pmol BCE (bone collagen equiv alents)/mu mol Cr. Within-subject variability (CV) for cross-linked pe ptide excretion was 20.2% over the 9 months in placebo-treated subject s, substantially less than that observed for other biochemical markers of bone resorption: 45, 53, and 63% for fasting urinary calcium and h ydroxyproline and 24 h urinary lysylpyridinoline (HPLC assay), respect ively. Baseline cross-linked peptide excretion correlated significantl y (p < 0.001) with baseline total urine lysylpyridinoline and serum os teocalcin, but not with the other biochemical markers. Initial peptide excretion also correlated inversely with lumbar spine bone mineral de nsity at entry (r = -0.26, p < 0.05). Treatment for 6 weeks with alend ronate produced a dose-dependent suppression of cross-linked peptide e xcretion (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), w ith 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 t o assess overall bone resorption. It may prove especially useful in mo nitoring the treatment of osteoporotic women with antiresorptive thera py. Its utility in identifying those women in the high resorption rang e at menopause who may be at greater risk for osteoporosis should also be assessed in future studies.