Bisphosphonates

Bisphosphonates include zoledronic acid, etidronate disodium and pamidronate disodium. Older first-generation bisphosphonates include clodronate, etidronate and ibandronate.

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 as an intravenous infusion. Pamidronate can be given in day case units and community hospital settings quite easily.

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 [7] (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.

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 [8,9] (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. [9]

Learning bite

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