Bisphosphonates in multiple myeloma

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Abstract
Myelomatosis is associated with considerable skeletal morbidity, particularly bone pain and fractures. Hypercalcaemia is a common presenting feature but less common after adequate chemotherapy. These complications are caused by progressive focal and generalized osteolysis due, in turn, to increased activation of osteoclasts by osteoclast activating factors. These include tumor neorosis factor-β, interleukin-1, and interleukin-6. The knowledge that disturbed bone remodeling is due to the activation of authentic osteoclasts provides the rationale for the use of bisphosphonates in myelomatosis. This article reviews the place of bisphosphonates in the management of myeloma. There is good evidence that hypercalcaemia can be corrected with intravenous or oral bisphosphonates, and they are now the specific treatment of choice. Several studies have shown that their intravenous administration is beneficial in the acute management of bone pain due to malignancy, but studies in myelomatosis are lacking. In contrast, a number of well designed controlled studies have shown significant effects of long term treatment with clodronate and pamidronate to decrease the incidence of skeletal complications in myelomatosis. Benefits reported are a decreased incidence of bone pain, hypercalcaemia, vertebral and long-bone fractures, and the extension of osteolytic lesions. There may be a beneficial effect on survival, but this is much less certain. These agents provide a valuable adjunct to the management of myelomatosis. Cancer 2000;88:3022–32. © 2000 American Cancer Society.