Medical management of hypercalcaemia.

Abstract

1. Hypercalcaemia is a common disorder, which frequently requires specific treatment either to control symptoms, or to prevent the development of irreversible organ damage or death. Although the best and most effective way of controlling hypercalcaemia in the long‐term is to treat the underlying cause, medical antihypercalcaemic therapy is often required in clinical practice, either as a holding measure, or because the primary disease cannot itself be treated. 2. The mainstays of medical antihypercalcaemic therapy are firstly, to promote calcium excretion by the kidney by restoring extracellular volume with intravenous saline and secondly, to administer pharmacological agents which inhibit bone resorption. Measures which seek to reduce intestinal calcium absorption are seldom effective. 3. Intravenous bisphosphonates are the treatment of first choice for the initial management of hypercalcaemia, followed by continued oral, or repeated intravenous bisphosphonates to prevent relapse. These drugs have a relatively slow onset of action (1‐3 days) but have potent and sustained inhibitory effects on bone resorption, resulting in a long duration of action (12‐ 30 days). 4. Of the other agents available, calcitonin has an important place in the management of severe hypercalcaemia where a rapid effect is desirable; calcitonin is best used in conjunction with a bisphosphonate however, because of its short duration of action. Intravenous phosphate also has a place in the emergency management of severe hypercalcaemia, but is probably best reserved for patients in whom other less toxic therapies have failed. Corticosteroids are generally ineffective except in certain specific instances and are best avoided in the routine treatment of undiagnosed hypercalcaemia.

Dose-response study of ibandronate in the treatment of cancer-associated hypercalcaemia

“…Alternatively, hypercalcaemia may arise as the result of tumour metastases in bone, which stimulate osteoclastic bone resorption on a multifocal basis, with release of calcium at a rate in excess of that which can be excreted by the kidney. In both situations, increased osteoclastic bone resorption plays an important pathogenic role, providing the rationale for treatment of cancer-associated hypercalcaemia with inhibitors of osteoclast activity (Ralston, 1992). Although several inhibitors of osteoclastic bone resorption have been used in the treatment of cancer-associated hypercalcaemia (Mundy et al, 1983;Warrell et al, 1990), bisphosphonates have emerged in recent years as a highly effective therapy, and in the view of many workers are now the treatment of first choice (Fleisch, 1991;Body, 1992;Ralston, 1992).…”

“…In both situations, increased osteoclastic bone resorption plays an important pathogenic role, providing the rationale for treatment of cancer-associated hypercalcaemia with inhibitors of osteoclast activity (Ralston, 1992). Although several inhibitors of osteoclastic bone resorption have been used in the treatment of cancer-associated hypercalcaemia (Mundy et al, 1983;Warrell et al, 1990), bisphosphonates have emerged in recent years as a highly effective therapy, and in the view of many workers are now the treatment of first choice (Fleisch, 1991;Body, 1992;Ralston, 1992). Ibandronate (1-hydroxy-3-(methylpentyl amine) propylidene-bisphosphonate) is a new bisphosphonate that is approximately 50 times more potent than pamidronate and 500 times more potent than clodronate in inhibiting osteoclastic bone resorption in animal models (Muihlbauer et al, 1991;Fleisch, 1993).…”

Lebensbedrohliche Hyperkalzämie bei einem jungen Mann mit ALL

“…Die Wirkung tritt innerhalb von 48 h ein und hält meist 3-4 Wochen an (12,17). Auch durch Calcitonin werden die Osteoklasten gehemmt (100-500 IE über 24h i.v.).…”

“…Mit einer Kalziumsenkung ist schon nach 2 h zu rechnen, allerdings tritt nach 2-3 Tagen eine Down-Regulation der Calcitoninrezeptoren der Osteoklasten ein. Möglicher-weise können Kortikosteroide diese Down-Regulation verhindern (12). Durch die Gabe von Kortikosteroiden wird die intestinale Kalziumabsorption gehemmt, die renale Kalziumexkretion gesteigert, osteoklastenstimulierende Zytokine gehemmt und bei malignen Erkrankungen ein antitumoröser Effekt erzielt (40-100 mg Prednison i.v.…”

Managing primary hyperparathyroidism in primary care

“… Patients with calcium concentrations above 3mmol/L typically start to develop symptoms of hypercalcaemia, which can include nausea, vomiting, thirst and polyuria, malaise, confusion, lowered pain threshold and coma 1. Milder hypercalcaemia (calcium concentrations <3mmol/L) is often asymptomatic, and the problem is therefore usually discovered as an incidental finding on routine biochemical screening.…”