Effects of treatment of malignancy-associated hypercalcemia on serum parathyroid hormone-related protein

Parathyroid hormone-related protein (PTHrP) is the primary mediator of hypercalcemia in patients with malignancy-associated hypercalcemia. We conducted this study to examine the effects of treatment with a bisphosphonate on serum PTHrP. We analyzed 41 episodes of hypercalcemia occurring in 38 patients: 22 patients received alendronate, and 16 were treated with pamidronate. At baseline, 29 patients had an increased serum PTHrP (group I) and 9 had low or undetectable levels (group II). The two groups did not differ significantly in baseline hypercalcemia (3.26 versus 3.41 mM) or the response of serum calcium to therapy. Serum calcium was normalized in 88% of group I and 70% of group II patients. Lowering of the mean calcium level was not associated with a change in the level of PTHrP in group I patients (40.2 versus 36.7 pgEq/ml) or group II patients. We also analyzed data on serum PTH and 1,25-(OH)2D in 20 of the patients. Serum PTH rose with treatment in group I patients (9.7-40.2 pg/ml, p < 0.05), as did the serum 1,25-(OH)2D (19.1-32.4 pg/ml, p < 0.001). Similarly, treatment of group II patients was associated with an increase in serum PTH (9.8-37.2 pg/ml) and serum 1,25-(OH)2D (22.9-40.2 pg/ml). The individual increases in 1,25-(OH)2D levels associated with therapy could not be predicted from the level of PTHrP or the changes in levels of serum calcium or PTH. Our data show that effective treatment of malignancy-associated hypercalcemia is not associated with a consistent change in serum levels of PTHrP. Therapy is associated with a variable increase in the serum levels of PTH and 1,25-(OH)2D.