Relationships between biochemical and symptomatic response in a double-blind randomised trial of pamidronate for metastatic bone disease

Abstract

Purpose: The aim of this study was to evaluate pamidronate for bone pain in a randomised double-blind trial and to evaluate the contribution of new markers of bone resorption in patients with bone metastases.

Patients and methods: Fifty-two patients with painful bone metastases were randomised to receive a two-hour infusion of pamidronate 120 mg or an identical infusion of saline. Four weeks later, all patients received pamidronate 120 mg. Bone resorption markers measured included urinary calcium (uCa), hydroxyproline (Hyp), and the collagen breakdown products: NTx, Crosslaps and Free Dpd.

Results: Symptomatic response during the first four weeks was seen after pamidronate, but not with placebo (P < 0.05). Quality of life was maintained with pamidronate and deteriorated after placebo (P < 0.05). Resorption markers did not decrease after placebo, but NTx and Crosslaps both decreased by 70% after pamidronate (P = 0.001). A second infusion of pamidronate did not decrease resorption further, but maintained the suppression of resorption at similar levels for a further four weeks. Symptomatic response to pamidronate correlated closely with the rate of bone resorption; it was more frequent in those patients with an initial NTx value of < 2 times the upper limit of normal (17 of 27, 62%) and in those where the level of Ntx returned to normal (19 of 32, 59%), than in the patients with either high baseline values of NTx (> 2 times the upper limit of normal) or Ntx levels which failed to normalise for whom the response frequencies were 2 of 16 (13%) and 0 of 11 (0%), respectively.

Conclusions: Subjective benefit after intravenous pamidronate is confirmed in this placebo-controlled study. The new bone resorption markers of collagen breakdown were able to predict clinical response to pamidronate.