Clinical usefulness of urinary CrossLaps as a sensitive marker of bone metabolism

CrossLaps peptide [Glu-Lys-Ala-His-Asp-Gly-Gly-Arg], a part of the C-telopeptide of the alpha 1-chain of type I collagen of bone, is a recently developed biochemical marker of bone turnover. In this study, the clinical utility of measurement of urinary CrossLaps was investigated in eleven premenopausal women who received a gonadotropin-releasing hormone (GnRH) agonist for 6 months for treatment of adenomyosis (n = 1) or leiomyomas (n = 10). Along with urinary CrossLaps, the levels of various biochemical markers, and serum estradiol, calcitonin and intact parathyroid hormone (i-PTH) were measured, and lumbar spine bone mineral density (BMD) was also monitored before, during, and at the end of the course of GnRH agonist therapy. Apart from CrossLaps, markers of bone resorption tested were urinary pyridinoline, deoxypyridinoline and hydroxyproline. Markers of bone formation tested were serum osteocalcin and bone-specific alkaline phosphatase (B-ALP). Serum estradiol levels decreased to undetectable levels at 2 months of GnRH agonist therapy. The values for all biochemical markers increased significantly throughout the therapy. The degree of an increase in CrossLaps levels was greater than that in all other markers. Mean lumbar spine (L2-L4) BMD was decreased by 7.2% at 6 months of treatment. The percent change in BMD at 6 months of treatment correlated inversely with the percent change in CrossLaps levels from the baseline to 1, 2, and 5 months of treatment. These results indicate that measurement of urinary CrossLaps might be a useful tool to predict the risk of bone loss caused by hypoestrogenism including GnRH agonist therapy.