INTRODUCTION

Multiple myeloma (MM) is the most common cancer to metastasize to bone, with up to 90% of patients developing bone lesions. The bone lesions are purely osteolytic in nature and do not heal in the vast majority of patients. Up to 60% of patients develop pathological fractures over the course of their disease. Bone disease is a hallmark of MM, and myeloma bone disease differs from bone metastasis caused by other tumors. Although myeloma and other osteolytic metastases induce increased osteoclastic bone destruction, in contrast to other tumors, once myeloma tumor burden exceeds 50% in a local area, osteoblast activity is either severely depressed or absent. The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation has been the topic of intensive investigation over the past several years. These studies have helped to identify novel targets for treating myeloma bone disease and are discussed subsequently in this chapter.

The clinical and economic impact of myeloma bone disease in patients with myeloma can be catastrophic. Saad and coworkers retrospectively evaluated data from patients on the control arms of randomized trials of zoledronic acid to assess the impact of pathological fractures on survival of patients with malignant disease. A total of 3049 patients with metastatic bone disease were included in this study, of which 513 had myeloma. Patients with myeloma had the highest incidence of fracture (43%) over the 21 months of the study compared to patients with breast cancer, prostate cancer, and lung cancer.