Efficacy of amino-hydroxypropylidene bisphosphonate in hypercalcemia: Observations on regulation of serum calcium

Abstract

For 2 weeks 27 patients with hypercalcemia received a standard oral treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) as the sole agent. Results were grouped according to causes of hypercalcemia and compared with effects of APD in 13 normocalcemic patients with Paget's disease of bone and 7 with osteoporosis. In 12 hypercalcemic patients with osteolytic bone lesions and in the 20 normocalcemic patients, the mean serum calcium decreased to final levels that were subnormal and significantly lower than those obtained after treatment of 8 patients with primary hyperparathyroidism. In 3 patients with myeloma and in 4 tumor patients without bone lesions, serum calcium did not always decrease to the normal range. Implications of these observations for the mechanism of hypercalcemia are discussed.

Bisphosphonates: Mechanisms of Action

“…The oral administration of bisphosphonates, especially those with a primary amine, can be accompanied by esophageal and gastrointestinal side effects such as nausea, dyspepsia, vomiting, gastric pain, and diarrhea, and sometimes even ulceration (129,130,274). These adverse events have decreased since patients began ingesting the drug with adequate water and without reclining after its intake to minimize esophageal reflux.…”

Medical management of hypercalcaemia.

“…It has been successfully used in the treatment of a wide variety of hypercalcaemic disorders including cancer-associated hypercalcaemia (Body et al, 1986;Cantwell & Harris, 1987;Coleman & Rubens, 1987;Davis & Heath, 1989;Harinck et al, 1987b;Ralston et al, 1989;Sleeboom et al, 1983), thyrotoxicosis (Tan et al, 1988), immobilisation (McIntyre et al, 1989), sarcoidosis (Gibbs & Peacock, 1986), hypercalcaemia following renal transplantation (Leunissen et al, 1986) and primary hyperparathyroidism (Evans, 1987;van Breukelen et al, 1982). In common with the other bisphosphonates, the onset of action is relatively slow, and 1-2 days may elapse before serum calcium values start to fall after intravenous administration (Ralston et al, 1988;Sleeboom et al, 1983;Yates et al, 1987).…”

“…Oral pamidronate has been used successfully in the primary treatment of hypercalcaemia (Thiebaud et al, 1986b;van Breukelen et al, 1982), but at the time of writing, the oral preparation is not yet available for clinical use in the UK.…”

Role of bone and kidney in tumor-induced hypercalcemia and its treatment with bisphosphonate and sodium chloride

“…There is also evidence of a renal contribution to the maintenance of hypercalcemia in many tumor patients. Their excretion of calcium is often diminished by a reduction in the glomerular filtration rate [ 13,141; however, even when this is taken into account, they excrete a smaller fraction of the filtered calcium load than healthy persons after hypercalcemia of the same degree has been induced by short-term intravenous calcium infusion [3,4,15,16]. It has been suggested that this increase in renal tubular resorption of calcium is mediated by a primary action on the kidney of humoral factors elaborated by the tumors [ 16-181.…”

“…It has been suggested that this increase in renal tubular resorption of calcium is mediated by a primary action on the kidney of humoral factors elaborated by the tumors [ 16-181. On the other hand, this increase in calcium resorption may reflect an adaptive increase of calcium-associated sodium resorption in the renal tubules, required for sodium homeostasis, since calcium infusion causes renal sodium loss [ 19,201 and sodium infusion causes calcium loss [3,4,10,17,2 11.…”