Role of the microenvironment in multiple myeloma bone disease.

Multiple myeloma bone disease occurs in over 70-80% of patients with myeloma and represents a significant source of morbidity and mortality. Early in multiple myeloma bone disease there is a balance between osteoclast activation and osteoblast suppression. However, this balance appears to be lost in advanced disease, resulting in the development of lytic lesions and bone destruction. Osteoclast activation occurs through a variety of factors, including receptor activator of nuclear factor-kappaB ligand, macrophage inflammatory protein-1alpha, interleukin-3 and interleukin-6, resulting in osteoclast stimulation and bone resorption. There is also significant osteoblast suppression through the inhibitory actions of interleukin-3, dickkopf 1, secreted frizzled-related protein-2 and interleukin-7. Understanding the mechanisms behind myeloma bone disease will help to identify potential future therapeutic interventions to help ameliorate or prevent osteoblast suppression and decrease osteoclast activation, with the goal of improving the overall quality of life for patients with multiple myeloma.