CONSEQUENCES OF NEOPLASIA INDUCED BONE-RESORPTION AND THE USE OF CLODRONATE (REVIEW)

There are several mechanisms whereby the skeleton loses bone tissue in patients with malignant diseases. They include an increase in skeletal turnover, imbalances between bone formation and resorption, and uncoupled bone resorption. Additionally, bone loss may be focal and confined to sites of metastatic disease or generalised due to endocrine consequences of malignancy. Irrespective of the mechanism and pattern of bone loss, this is largely if not exclusively mediated by activation of the bone resorbing cells (osteoclasts) rather than due to direct effects of tumour tissue or their products on bone. The bisphosphonates are potent and specific inhibitors of osteoclast mediated bone resorption. They accumulate at skeletal sites, particularly at sites of disease activity and are not metabolised in vivo. Of the several bisphosphonates tested in man, clodronate is of particular interest since it can be given both intravenously and by mouth, and unlike etidronate does not impair the mineralisation of bone. It has been shown to be highly effective in the management of hypercalcaemia of malignancy, and in some patients, for the acute management of bone pain. Well designed long-term studies indicate that its long-term use decreases the development of skeletal complications of malignancy including the incidence of hypercalcaemia, severe bone pain, fractures and retards the development or extension of osteolytic foci. For these reasons clodronate affords a useful adjunctive role in the management of osteolytic bone disease.