ABSTRACT
Bone destruction and its clinical sequelae are a significant cause of morbidity in patients with multiple myeloma. Furthermore, despite progress in antitumor therapy and the use of more aggressive regimens, the incidence of skeletal disease remains high. Bone pain, pathological fracture, and hypercalcemia are all direct consequences of osteolysis, with compelling evidence that this bone destruction is mediated by normal osteoclasts (bone-resorbing cells) stimulated by factors produced by the tumor or by stromal cells in response to the presence of tumor (see also Chapter 6).1,2
The bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption (for reviews see Fleisch3,4). At least ten bisphosphonates are currently available or in development. The newer bisphosphonates have markedly higher potency than earlier agents but current clinical data suggest that they may not differ in their ultimate therapeutic effect. The greatest experience in malignancy-associated bone disease has been gained with the bisphosphonates etidronate, clodronate, ibandronate, and pamidronate. These agents are now the treatment of choice for the management of hypercalcemia due to malignancy.5-9 Their efficacy in this setting has prompted placebo-controlled studies to examine their ability to decrease the incidence of skeletal complications in malignancies, particularly breast cancer and myeloma.10-21
This chapter focuses on studies addressing the long-term efficacy of bisphosphonates in multiple myeloma, but it also addresses the potential of new drugs for treating
bone disease and the treatment of fractures, including novel orthopedic/radiological interventions.
