Therapeutic options in the management of myeloma bone disease.

Advanced multiple myeloma is typically accompanied by osteolytic bone lesions resulting from heightened osteolytic activity of osteoclasts and decreased rates of osteogenesis by osteoblasts. Therefore, patients with myeloma bone disease are at increased risk for skeletal-related events (SREs) such as pathologic fracture, the need for radiotherapy or surgery to bone, spinal cord compression, and hypercalcemia of malignancy. Each of these can reduce patients' functional independence, quality of life, and survival. Radiotherapy and surgery are often used to palliate bone pain and to stabilize, repair, or prevent bone fractures. Bisphosphonates (BPs) may reduce the risk of SREs. In particular, clodronate, pamidronate, and zoledronic acid (ZOL) have demonstrated efficacy for delaying the onset of potentially life-threatening SREs. Overall, BPs have a well established tolerability profile. The introduction of BPs for multiple myeloma was practice-changing, and patients now experience far fewer serious fractures and hypercalcemia of malignancy. Ongoing studies will help further refine and optimize the timing and duration of BP therapy in patients with myeloma bone disease.