Pamidronate. A review of its pharmacological properties and therapeutic efficacy in resorptive bone disease

Abstract

Pamidronate [aminohydroxypropylidene diphosphonate disodium (APD), disodium pamidronate] is an orally and intravenously active amino-substituted bisphosphonate which produces potent and specific inhibition of bone resorption at doses devoid of any significant detrimental effect on bone growth and mineralisation. Clinical trials indicate that pamidronate is effective in a variety of conditions characterised by pathologically enhanced bone turnover, including Paget's disease, hypercalcaemia of malignancy, osteolytic bone metastasis, steroid-induced osteoporosis and idiopathic osteoporosis. Pamidronate is highly effective in restoring normocalcaemia in patients with hypercalcaemia of malignancy associated with bone metastases but, in common with other bisphosphonates, is marginally less effective against humoral hypercalcaemia of malignancy. Comparative studies in this area have suggested that, at therapeutic doses, pamidronate has a more pronounced calcium-lowering action than etidronate (etidronic acid) and clodronate (clodronic acid) and provides a longer period of normocalcaemic remission. In Paget's disease arrest and, in some patients, reversal of the progression of osteolytic lesions by pamidronate is associated with a sustained reduction in bone pain, improved mobility and a possible reduced risk of bone fracture. In patients with osteolytic bone metastasis pamidronate reduces skeletal morbidity and slows the progression of metastatic bone destruction. Long term use of low-dose pamidronate in conjunction with conventional antiosteoporotic therapy may halt bone loss in steroid-induced and idiopathic osteoporosis. Pamidronate appears to represent a valuable addition to the drugs currently available for the treatment of symptomatic Paget's disease and cancer-associated hypercalcaemia, and shows promise in the treatment of osteolytic bone metastasis and osteoporosis.