Neoplastic hypercalcemia: Physiologic response to intravenous etidronate disodium

Following a four-day control period during which an elevated serum calcium level either stabilized or continued to rise despite maximally tolerated saline diuresis, 12 patients with neoplastic hypercalcemia were treated with intravenous etidronate disodium (etidronate) 7.5 mg/kg/day for up to seven days. Serum calcium reverted to normal levels in all patients, with the mean pretreatment serum calcium level of 12.5 ± 0.4 mg/dl dropping to 9.2 ± 0.2 mg/dl (p < 0.01) by Day 7. Elevated urinary calcium (1,107 ± 134 mg/g creatinine) and hydroxyproline levels (154 ± 16 mg/g creatinine) declined to 245 ± 52 mg/g creatinine and 75 ± 14 mg/g creatinine, respectively, suggesting a marked reduction in bone resorption following treatment. Serum phosphorus levels were unchanged, but urinary phosphorus levels dropped rapidly from 1,181 ± 125 mg/g creatinine before treatment to 723 ± 94 mg/g creatinine after two days. Serum parathyroid hormone levels (mid-molecule assay) were suppressed before treatment (64 ± 16 pg/ml), but rose rapidly to 223 ± 68 pg/ml by Day 7 of treatment. The value of serum 1,25-dihydroxyvitamin D was initially below normal (16 ± 3 pg/ml), but rose rapidly with treatment to 42 ± 12 pg/ml by Day 7. Symptoms of hypercalcemia and bone pain improved with treatment, and no serious adverse reactions to treatment were encountered. Intravenous etidronate is apparently an effective and safe treatment for neoplastic hypercalcemia.