Bisphosphonates hypercalcaemia

The treatment of Mrs CR s hypercalcaemia is urgent and requires immediate administration of bisphosphonate therapy, the first choice therapy in cases of severe hypercalcaemia. Currently four bisphosphonates are available in the UK for the treatment of malignant hypercalcaemia - sodium clodronate, disodium pamidronate, zoledronic acid and ibandronic acid. The choice of which bisphosphonate to recommend will depend on which one is on the local hospital formulary. 

Continued treatment with bisphosphonate may also be appropriate to not only reduce the likelihood of recurrent hypercalcaemia but also to manage Mrs CR s bone metastases. Many guidelines (including the NICE Improving outcomes guidance for breast cancer, 2002a) recommend the use of bisphos-phonates to reduce the onset of skeletal complications such as skeletal fractures. An appropriate suggestion would be to continue one of the bisphosphonates previously outlined at three-weekly intervals (to coincide with chemotherapy administration). 

Q9 The hypercalcaemia which occurs in hyperparathyroidism may be reduced by administration of a loop diuretic such as furosemide, which helps calcium excretion. Bisphosphonates, which prevent bone resorption and so reduce calcium release from bone, can be used to treat hypercalcaemia associated with malignancies. Calcitonin may also be useful in treating the hypercalcaemia associated with cancer, as it reduces calcium levels both by attenuating its renal reabsorption and by increasing calcium deposition in bone. 

Bisphosphonates (see later). Pamidronate is infused according to the schedule in Table 38.1 it is active in a wide variety of hypercalcaemic disorders. Fall in serum calcium begins in 1-2 d, reaches a nadir in 5-6 d and lasts 20-30 d. Etidronate may be given i.v. in hypercalcaemia of malignant disease. It acts in 1-2 d and a dose lasts 3 weeks it may also provide benefit for neoplastic metastatic disease in bone. Clodronate (oral or i.v.) or zoledonic acid (i.v) are alternatives. 

Uses. Three bisphosphonates (alendronate, etidronate, risedronate) are currently licensed in the UK for the treatment of osteoporosis (zoledronate is also effective), and the others are used in Paget s disease of bone, and hypercalcaemia due to cancer (pamidronate, clodronate, zoledronate). Bisphosphonates may also provide benefit for neoplastic disease that has spread to bone evidence indicates that clodronate by mouth and pamidronate i.v. are effective in the secondary prevention of bone metastases due to multiple myeloma and breast cancer. 

Bisphosphonates are widely used for the prevention and treatment of osteopenia and osteoporosis and for the reduction of skeletal complications in patients with malignant bone disease. Several oral bisphosphonates, including alendronate, risedronate, and ibandronate, are approved worldwide for the treatment of osteoporosis in postmenopausal women, as are intravenous (i.v.) formulations of ibandronate (3 mg quarterly) and zoledronic acid (5 mg annually). Several i.v. bisphosphonates are available for the treatment of the skeletal complications that frequently occur in malignant disease, such as hypercalcaemia of malignancy (HCM), multiple myeloma, and bone metastases associated with solid tumours. Pamidronate is approved worldwide for the treatment of HCM, multiple myeloma, and breast cancer bone metastases. Although not registered for oncology indications in the United States, i.v. ibandronate is widely available elsewhere for HCM and breast cancer bone metastases. 

Zoledronic acid [(l-hydroxy-2-imidazol-l-yl-phosphonoethyl) phosphonic acid] is a bisphosphonate of the third generation that is in clinical use for the treatment of tumor-induced hypercalcaemia. 

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