Treatment for myeloma bone disease.

Multiple myeloma (MM) is a B cell malignancy characterized by enhanced bone loss commonly associated with diffuse osteopenia, focal lytic lesions, pathologic fractures, hypercalcemia, and bony pain. Bone destruction in MM results from asynchronous bone turnover wherein increased osteoclastic bone resorption is not accompanied by a comparable increase in bone formation. Consequently, patients with MM frequently require radiation therapy, surgery, and analgesic medications. The recent development of minimally invasive surgical procedures such as kyphoplasty allows patients with myeloma with vertebral compression fractures to have immediate improvement in their quality of life with shorter hospital stays. Bisphosphonates are specific inhibitors of osteoclastic activity, and these agents have been evaluated in patients with MM with bone disease during the past 15 years. Monthly i.v. infusions of either pamidronate or zoledronic acid have reduced the skeletal complications among patients with MM and are now a mainstay of myeloma therapy. Orally administered bisphosphonates, in contrast, have shown little ability to slow the development of skeletal complications in these patients. Although preclinical studies suggest that nitrogen-containing bisphosphonates have potent antitumor effects, clinical trials will be necessary, probably at higher doses given more slowly, to establish their possible antitumor effects clinically. Moreover, recent advances in the use of bone-seeking radiopharmaceuticals make these attractive therapeutic candidates to combine with bisphosphonates or radiosensitizing drugs (e.g., bortezomib) to achieve a synergistic effect. As our understanding of the pathophysiology of myeloma bone disease continues to grow, new target therapies will continue to emerge, offering new and more advanced options for the management of myeloma bone disease.