Circulating PTHrP concentrations in tumor-induced hypercalcemia: influence on the response to bisphosphonate and changes after therapy.

We studied the influence of circulating parathyroid hormone-related protein (PTHrP) concentrations on the response of hypercalcemic cancer patients to bisphosphonate therapy. We also examined the changes in circulating PTHrP levels during the normalization of serum Ca to determine if part of the increase in PTHrP concentrations is not secondary to hypercalcemia itself, as suggested by some in vitro data. We sequentially measured in 45 hypercalcemic cancer patients treated by pamidronate the circulating concentrations of PTHrP (by an amino-terminal RIA; normal values < 9 pmol/liter), Ca, Ca2+, Pi, intact PTH, and the fasting urinary excretion of Ca (Ca/Cr) and cyclic AMP (cAMP). Mean +/- SEM baseline PTHrP levels were 9.5 +/- 1.3, with a median (range) value of 6.0 (< 3.4-43) pmol/liter. PTHrP levels were elevated in 18 of 45 patients, more often in epidermoid than in glandular carcinomas (P < 0.05), and they were significantly (P < 0.05) correlated with the concentrations of Pi (r = -0.46), Ca/Cr (r = -0.31), and urinary cAMP (r = 0.47). Mean pretreatment Ca levels were not significantly different between patients with elevated and patients with normal PTHrP levels, 13.3 +/- 0.4 versus 12.9 +/- 0.4 mg/dl, but the concentrations became significantly different (P < 0.005) 4 days after therapy, 10.2 +/- 0.3 versus 9.2 +/- 0.1 mg/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)