Intravenous pamidronate in patients with tumor-induced osteolysis: a biochemical dose-response study

Bisphosphonates are used increasingly in normocalcemic patients for treating tumor-induced osteolysis (TIO) but little is known about the metabolic effects and the most appropriate therapeutic regimen. In 21 patients with breast cancer and TIO, we determined the biochemical effects of a single infusion of pamidronate given at 30 mg (n = 5), 60 mg (n = 5), 90 mg (n = 5), or 120 mg (n = 6). Patients received no other systemic antineoplastic therapy during the trial. We selected patients with baseline fasting urinary Ca/Creat (creatinine) > 0.105 mg/mg (median value of our normal range) and they were followed weekly for up to 14 weeks. The biochemical effects were maximal at day 7. For the whole group, mean (+/- SEM) Ca/Creat levels fell from 0.208 +/- 0.018 to 0.048 +/- 0.008 mg/mg on day 7 and remained significantly ( p < 0.01) lower than baseline up to day 56. Hydroxyproline excretion fell to a lesser degree, from 7.0 +/- 1.2 to 4.0 +/- 0.6 mg x 100/mg of Creat. The falls in Ca/Creat and hydroxyproline excretion were dose-related (ANCOVA, p < 0.05). Changes in serum parameters of calcium metabolism were, however, not significantly dose-related. Serum Ca levels fell from 9.3 +/- 0.1 to 8.7 +/- 0.1 mg/dl on day 7, but not patients developed symptomatic hypocalcemia, and the decrease within each dose group was significant only at 120 mg. Ca2+ levels followed a similar pattern. There was a slight increase in Mg levels and a pronounced fall in Pi levels, from 3.6 +/- 0.2 to 2.8 +/- 0.1 mg/dl. Intact PTH levels increased from 29 +/- 4 to 91 +/- 13 pg/ml and remained significantly (p < 0.05) elevated up to day 28.(ABSTRACT TRUNCATED AT 250 WORDS)