Multiple myeloma is a generally incurable bone marrow cancer of unknown
cause characterized by uncontrolled growth of plasma cells. One of its most
prominent clinical features is severe bone destruction caused by
overproduction of osteoclasts --the cells that resorb bone during bone
remodeling. The interaction between the tumor cells and the marrow stroma
is important during osteoclast production, but the underlying molecular
mechanism has been unclear.

Pearse et al. show that multiple myeloma deregulates osteoclast production
by disrupting the balance between TRANCE, a tumor necrosis factor-related
cytokine responsible for osteoclast generation, and its inhibitor,
osteoprotegerin (OPG), in the marrow stroma. In mice, TRANCE antagonists
reduced myeloma-induced bone destruction and, unexpectedly, also inhibited
tumor progression. Thus, bone destruction and tumor cell survival seem to
be interdependent processes in multiple myeloma. Therapies that target the
TRANCE-OPG cytokine axis are already being developed for treatment of
osteoporosis and other bone disorders, and these findings may open up new
possibilities for the treatment of multiple myeloma. -- PAK

Proceedings of the National Academy of Science U.S.A. 98, 11581 (2001).