Zoledronic acid(ZOMETA): a significant improvement in the bone metastases.

Abstract

Bone metastases are frequent complications of breast, lung and prostate cancers, multiplex myeloma, and less frequently of other neoplasms, causing pain, pathological fractures, hypercalcemia, spinal cord compressions. These symptoms have a major impact on the quality of life and should be controlled by appropriate therapy. Bisphosphonates became an essential element in the treatment of bone metastases. These pyrophosphate analogues target and inhibit osteoclast activity, and in the past 15 years were included in many clinical trials. Newer N-containing bisphosphonates (e.g. zoledronate, pamidronate, ibandronate) inhibit the mevalonate pathway of cholesterol biosynthesis in vitro, and interfere with protein prenylation in osteoclasts in vivo by inhibiting farnesyl diphosphate synthase. Prenylation is an important posttranslational modification of small guanosine triphosphate-binding proteins (as Ras, Rho, Rac) which have many important regulatory functions. It was proved that members of bisphosphonate family (as clodronate, pamidronate) could reduce the incidence and severity of skeletal complications (skeletal-related events, SREs). Further improvement has been achieved by zoledronic acid which in comparative studies with other bisphosphonates was more convenient to use and was also more effective, further decreasing the skeletalrelated events. Recently, the effect of zoledronic acid (4 mg, 15 min infusion, every 4 weeks for 1 year) has been studied in 227 Japanese women with bone metastases (mainly osteolytic lesions) from breast cancer. Besides decreasing the pain (median pain score), the study showed a significant 39% reduction in the rate of SREs in patients treated with zoledronic acid compared with placebo. There are increasing evidences that newer aminobisphosphonates, especially zoledronic acid, have direct anti-