Bone marrow, the spongy tissue inside bones, is a dynamic environment that normally maintains healthy bone structure through a remodeling process that carefully balances destruction of old bone with growth of new bone. Multiple myeloma cells make their home in the bone marrow where they adhere to bone marrow cells and disrupt the remodeling process by inhibiting activity of osteoblasts (cells that build bone) and stimulating activity of osteoclasts (cells that destroy bone). Adhesion of the multiple myeloma cells to bone marrow cells stimulates production of interleukin-6, a growth factor which myeloma cells need to survive and which also stimulates activity of osteoclasts. This establishes a vicious cycle of feeding myeloma cells and eroding bones.
The combination of increased osteoclast activity and inhibited osteoblast activity results in bone lesions (called osteolytic lesions or lytic lesions), osteoporosis, and hypercalcemia (too much calcium in the bloodstream). These harmful effects on bone impair patient quality of life, while simultaneously cultivating an environment in which myeloma cells thrive. Therefore, myeloma therapies aim to reestablish normal bone remodeling, which