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.