Levels of parathyroid hormone-related protein (PTHrP) in hypercalcemia of malignancy are not lowered by treatment with the bisphosphonate BM 21.0955.

Parathyroid hormone-related protein (PTHrP) is a major cause of hypercalcemia in malignancy and serum levels are elevated in many patients suffering from this syndrome. In 10 patients with hypercalcemia of malignancy the levels of the midregional fragment of PTHrP in serum were determined by radioimmunoassay over 7 days during a calcium-lowering treatment with a single dose of the bisphosphonate BM 21.0955. PTHrP concentrations remained unchanged 6 days after administration of the drug as compared with pretherapeutic values, thus apparently excluding an effect of either the drug itself or the rapid fall in serum calcium on the release of PTHrP by the tumors or on its clearance from the circulation. In the patients with elevated midregional PTHrP levels (n = 6), the calcium-lowering effect of the drug was significantly less pronounced than in patients with normal PTHrP (n = 4) (mean serum calcium of 2.89 vs. 2.51 mmol/l at day 6), despite similar pretherapeutic concentrations. Of the six patients with elevated PTHrP, five were still hypercalcemic, whereas in the group with normal PTHrP one out of four patients remained hypercalcemic. In conclusion, PTHrP levels in hypercalcemia of malignancy remained unchanged after calcium-lowering therapy with bisphosphonates. High serum PTHrP levels were, however, predictive of a lesser effectiveness of the drug in lowering serum calcium.