Bisphosphonates include zoledronic acid, etidronate disodium and pamidronate disodium. Bisphosphonates are toxic to osteoclasts and inhibit osteoclast precursors, thereby decreasing osteoclast function. Currently, etidronate is commercially available in both oral and intravenous dosage forms and pamidronate is only available in the intravenous dosage form. Pamidronate can be given in day case units and community hospital settings quite easily.

Bisphosphonates have replaced older methods used to treat hypercalcaemia. They are the best studied, safest and most effective agents for use in hypercalcaemia associated with malignancy. They take up to 3 days to start working and 5-7 days to exert maximum effect. Approximately 60-90% of patients have normal serum calcium levels within 4-7 days, and responses last for 1-3 weeks. RCTs of pamidronate have shown it to be effective in reduction of hypercalcaemia associated with malignancy [13,17] (Level 1C). Although a direct comparison of the two drugs in a randomised clinical trial showed a statistically significant increase in the efficacy of zoledronate, the difference in control of calcium was small [17].

In a 2005 Cochrane database systematic review of the use of bisphosphonates in multiple myeloma, there was no effect on hypercalcaemia associated with multiple myeloma [15] (Level 1A). However, with the rarity of this complication in myeloma and the large confidence intervals seen in the trials, they commented that such an effect is still possible. As compared with pamidronate, zoledronate has the advantage of rapid and simpler administration (15 min vs. 2 h for infusion), whereas pamidronate is less expensive [16] (Level 1B).

Pamidronate and zoledronate have been reported to cause or exacerbate renal failure, but this effect has generally occurred in patients receiving multiple doses.

Other bisphosphonates include clodronate, etidronate and ibandronate, which are first generation Bisphosphonates and are weak inhibitors of bone resorption.

Learning bite

The mainstay of treatment in addition to rehydration has become bisphosphonates.