Comparative evaluation of markers of bone resorption in patients with breast cancer-induced osteolysis before and after bisphosphonate therapy

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Abstract
The understanding of the pathophysiology and the monitoring of metastatic bone disease remains unsatisfactory. We compared several new markers of bone turnover in normocalcaemic patients with breast cancer-induced osteolysis before and after a single infusion of the bisphosphonate pamidronate. We studied 19 ambulatory patients with advanced breast cancer and extensive bone metastases who did not receive any systemic antineoplastic therapy. Pamidronate was administered at doses of 30, 60, 90 or 120 mg and the patients were followed weekly during a mean of 8 (range 4-10) weeks. Compared with healthy premenopausal women, the percentage of elevated values at baseline was 47% for fasting urinary calcium (uCa), 74% for hydroxyproline, 83% for CrossLaps (a new marker of type I collagen degradation) and 100% for the collagen cross-links (measured by high performance liquid chromatography), namely pyridinoline (Pyr) and deoxyPyr (D-Pyr). Pretreatment levels of uCa did not correlate significantly with any of the four markers of bone matrix resorption, whereas the correlations between these four markers were generally significant (r(s)=0.43-0.71). Alkaline phosphatase correlated significantly with markers of bone matrix resorption (r(s)=0.54-0.74). All parameters, except phosphaturia (uPi) and the bone formation markers (osteocalcin and alkaline phosphatase), fell significantly after pamidronate therapy, up to day 42 for hydroxyproline, D-Pyr and CrossLaps and day 56 for uCa. This longer lasting effect was probably due to the parathyroid hormone (PTH) surge following the decrease in serum calcium, implying that the decrease in uCa can overestimate the effects of bisphophonates on bone resorption. The decrease in bone turnover parameters was most marked for CrossLaps, indicating the potential of this new marker for monitoring therapy. Sequential determinations of markers of bone matrix resorption should be useful in delineating the optimal therapeutic schemes of bisphosphonates and for evaluating treatment effects on bone in cancer patients.