Myeloma Bone Disease

Found in >80% of newly diagnosed patients, osteolytic bone disease is one of the most debilitating manifestations of myeloma. It dramatically impacts patient quality of life through severe pain, fractures, and spinal cord compression, with resulting neurological pathologies. The severity of myeloma bone disease is reflected in the fact that 40–60% of patients suffer from a bone fracture during the course of their disease, higher than that of other major cancers that metastasize to bone (e.g., breast and prostate cancer). Bone destruction also releases factors that drive tumor growth, further stimulating disease progression. Thus, it is not surprising that high levels of tumor-induced bone resorption is a strong indicator of poor overall survival of myeloma patients. Although advances in the understanding of myeloma bone disease have led to promising new therapies, important questions linger. Bone loss in myeloma results from the uncoupling of the mechanisms that control normal bone degradation and bone formation. Overall, myelomarelated bone disease results from the systemic acceleration of bone turnover together with local suppression of osteoblast activity. Early in myeloma progression, there is an elevation of both bone-degrading (osteoclast) and boneforming (osteoblast) activity. However, as the disease progresses, osteoblast activity is suppressed, shifting the balance to a net increase in bone loss. Although widespread systemic bone loss in myeloma patients occurs, the most dramatic manifestation is the focal lesions that appear as ‘‘holes’’ on X-rays. This results from local suppression of osteoblasts by myeloma cells leaving only osteoclasts, which, in the absence of osteoblast activity, damage bone beyond repair. In contrast, in the small minority of patients that do not exhibit lytic bone disease, the osteoblasts adjacent to myeloma tumor cells remain active. This review focuses on the mechanisms that are responsible for bone loss in myeloma with emphasis on stimulation of osteoclastogenesis and inhibition of osteoblastogenesis. Also included is a brief description of how myeloma bone disease is diagnosed and a summary of current treatments for preserving bone in patients with this cancer.