Potential Role of IMiDs and Other Agents as Therapy for Myeloma Bone Disease

Abstract

Multiple myeloma (MM) is a plasma cell malignancy characterized by the frequent development of bone lesions (Lentzsch et al. Hematol Oncol Clin North Am 21:1035–1049, 2007). The development of osteolytic lesions is attributable to increased bone resorption caused by stimulation of osteoclast formation and activity (Barille-Nion and Bataille Leuk Lymphoma 44:1463–1467, 2003), (Giuliani et al. Exp Hematol 32:685–691, 2004), and (Roodman Blood Cells Mol Dis 32:290–292, 2004). The increased osteoclast activity is accompanied by decreased osteoblast function resulting in imbalanced bone remodeling, which increases bone resorption and decreases bone formation (Bataille et al. J Clin Oncol 7:1909–1914, 1989) and (Bataille et al. Br J Haematol 76:484–487, 1990). Bisphosphonate therapy targets the inhibition of osteoclast activity. But unfortunately bisphosphonates are associated with side effects such as renal toxicity and osteonecrosis of the jaw. Therefore new drugs capable of targeting activated osteoclasts without completely arresting bone resorption and remodeling are needed. In this chapter, the author discusses potential new drugs which target osteoclast formation and activity and which also lack severe side effects and provide a potential effective treatment for bone disease in MM.