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Multiple myeloma is an incurable plasma-cell malignancy characterized by osteolytic bone disease and immunosuppression. Murine models of multiple myeloma and myeloma bone disease are critical tools for an improved understanding of the pathogenesis of the disease and the development of novel therapeutic strategies. This review will cover commonly used immunocompetent and xenograft models of myeloma, describing the advantages and disadvantages of each model system. In addition, this review provides detailed protocols for establishing systemic and local models of myeloma using both murine and human myeloma cell lines.

The bone is a frequent site for tumor metastasis, and cancer in the bone results in marked disturbances of bone remodeling that can be lytic, blastic or a combination of the two. Patients with advanced malignancies that have metastasized to the bone frequently suffer from debilitating skeletal-related events, including pathologic fractures, spinal cord compression syndromes, disorders of calcium and phosphate homeostasis and severe cancer-related pain. This review will discuss recent studies on the mechanisms responsible for osteolytic and osteoblastic metastasis and how their identification has resulted in the development of new agents for patients with metastatic bone disease.

Multiple myeloma is the second most common hematological malignancy and the most frequent cancer to involve the skeleton. Multiple myeloma bone disease (MMBD) is characterized by abnormal bone remodeling with dysfunction of both bone resorption and bone formation, and thus can be used as a paradigm for other inflammatory bone diseases, and the regulation of osteoclasts and osteoblasts in malignancy. Studies of MMBD have identified novel regulators that increase osteoclastogenesis and osteoclast function, repress osteoblast differentiation, increase angiogenesis, or permanently alter stromal cells. This review will discuss the current understanding of mechanisms of osteoclast and osteoblast regulation in MMBD, and therapeutic approaches currently in use and under development that target mediators of bone destruction and blockade of bone formation for myeloma patients, including new anabolic therapies.