Collapsing glomerulopathy induced by long-term treatment with standard-dose pamidronate in a myeloma patient

Abstract

Bisphosphonates currently are important antiresorptive agents used in the treatment of metabolic bone diseases, including tumour-associated osteolysis and hypercalcaemia, Paget's disease and osteoporosis. These drugs cause a loss of the osteoclast ruffled border, disruption of the osteoclast cytoskeleton and inhibition of actin ring formation, sufficient to prevent bone resorption [1]. Several studies have demonstrated that high concentrations of bisphosphonates can cause apoptotic cell death of mouse, rat and rabbit osteoclasts in vitro and in vivo by inhibiting the mevalonate pathway and protein prenylation [2]. Bisphosphonates are excreted unchanged via the kidneys. The high drug levels attained in the kidney may cause renal toxicity through a mechanism similar to that described in osteoclasts.