The pathogenesis of the bone disease of multiple myeloma

Abstract

Multiple myeloma is a fatal hematologic malignancy associated with clonal expansion of malignant plasma cells within the bone marrow and the development of a destructive osteolytic bone disease. The principal cellular mechanisms involved in the development of myeloma bone disease are an increase in osteoclastic bone resorption, and a reduction in bone formation. Myeloma cells are found in close association with sites of active bone resorption, and the interactions between myeloma cells and other cells within the specialized bone marrow microenvironment are essential, both for tumor growth and the development of myeloma bone disease. This review discusses the many different factors which have been implicated in myeloma bone disease, including the evidence for their role in myeloma and subsequent therapeutic implications.

Figure 1. Factors implicated in myeloma bone disease

Myeloma bone disease is associated with an increase in osteoclastic bone resorption and a reduction in osteoblastic bone formation. A number of key factors have been identified which play a role in either bone resorption or bone formation.

Figure 2. Cell-cell interactions in myeloma bone disease

Direct Interactions between myeloma cells and bone marrow stromal cells or osteoclasts play a critical role in the development of myeloma bone disease.

Figure 3. Therapeutic approaches in myeloma bone disease

The osteoclast and osteoblast are potential therapeutic targets in the treatment of myeloma bone disease. Proteasome inhibitors and inhibitors of Dkk1 increase osteoblastic bone formation, whereas bisphosphonates and anti-RANKL inhibit osteoclastic bone resorption.