Multiple myeloma (MM) is a B-cell
malignancy characterized by enhanced bone loss commonly associated with a 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. Recent characterization of osteoclast-activating factors (OAFs),
receptor activator of nuclear factor-kappaB (
RANK) ligand (RANKL)-
osteoprotegerin-RANK system, and inhibitors of Wnt signaling have provided a better understanding of myeloma
bone disease in molecular level. The development of
minimally invasive surgical procedures such as
kyphoplasty and
vertebroplasty allows myeloma patients with vertebral
compression fractures to have immediate improvement in quality of life and shorter
hospital stays. Monthly
intravenous infusion of either
pamidronate or
zoledronic acid have reduced the skeletal complications among MM patients 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 pre-clinical studies suggest
nitrogen-containing
bisphosphonates have potent anti-
tumor effects, clinical trials will be necessary, probably at higher doses given more slowly, to establish their possible anti-
tumor effects clinically. As our understanding of the pathophysiology of myeloma
bone disease continues to increase, new target
therapies will continue to emerge offering new and more advanced options for the management of myeloma
bone disease.