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.