Markers of bone resorption in patients treated with pamidronate

Pyridinoline (PYD), deoxypyridinoline (DPD), and N-telopeptide (NTX) are markers of bone resorption. In cancer patients with bone metastases, NTX is more often elevated than either of the pyridinolines. Bisphosphonates inhibit osteoclasts and their treatment decreases skeletal complications of malignancy. The aim of this study was to correlate urinary PYD, DPD, and NTX levels with clinical events in patients receiving pamidronate. 25 cancer patients with lytic bone disease were treated with monthly pamidronate combined with endocrine or chemotherapy; 27 others were on placebo. Twenty-four hour urines were collected at baseline, 1, 3 and 6 months. NTX values were determined by enzyme-linked immunosorbent assay (ELISA); PYD and DPD values were determined by reverse phase high performance liquid chromatography (HPLC). Two hour urines were also collected weekly for 21 patients. The greatest difference as a result of pamidronate treatment was observed in NTX values. Maximum suppression was achieved 2 weeks after treatment. Of the 25 patients who received pamidronate, 21 had initially elevated NTX values. 12 of the 21 finished with normal NTX values, whilst 9/21 had NTX values which remained abnormally elevated. The proportions of patients with fractures between these two subgroups approached statistical significance (P = 0.07) while the proportions with bony disease progression were significant (P = 0.03, Fisher's exact test). Measuring NTX levels appears useful in monitoring bisphosphonate therapy of bone metastases. The goal of treatment should be to normalise NTX excretion.