More than 80% of multiple myeloma (MM) patients present with bone involvement
frequently develop serious complications that negatively affect both quality of life and overall survival.
Bone disease in MM is a consequence of unbalanced remodeling resulting in the development of
osteolytic lesions. Generalized osteoclast (OC) activation is the underlying mechanism coupled with
osteoblast (OB) inhibition. The molecular events leading to this imbalance of the OC/OB axis is a result
of the interaction of MM cells with bone cells within the bone marrow milieu and consequent cytokine
deregulation. Here we will discuss the pathogenesis, clinical sequelae and therapeutic strategies for the
treatment of MM bone disease. We will focus on novel therapeutic strategies under investigation to
restore bone homeostasis. Such approaches are being studied not only with the goal of alleviating
morbidity from bone disease but also for their resultant anti-MM activity.
Keywords: Osteoclasts (OCs), osteoblasts (OBs), receptor activator of NF-kB ligand (RANKL),
osteoprotegerin (OPG), OC activating factors (OAFs), dickkopf (DKK) 1, bisphosphonates, denosumab,
osteonecrosis of the jaw (ONJ), activin A, B-cell activating factor (BAFF)
