Bone building with bortezomib
J. Clin. Invest. G. David Roodman, et al. 118:462 doi:10.1172/JCI34734 [Go to this article.]

Figure 1
Combination treatment of myeloma bone disease. Myeloma cells produce or induce OAFs, which increase osteoclast formation as well as produce osteoblast-inhibiting factors, which block bone formation. In this issue of the JCI, Mukherjee et al. (1) show that the proteasome inhibitor Bzb can induce bone formation by increasing BMP-2 production by osteoblasts, which in turn increases Runx-2 levels, which induces MSCs to differentiate into osteoblasts and enhance bone regeneration in mice. In addition, other studies have shown that Bzb and lenalidomide can inhibit osteoclast (OCL) formation in addition to blocking the growth of myeloma cells (10, 16). These results suggest that combination therapy that includes Bzb with lenalidomide or thalidomide may both enhance the antineoplastic effects of either agent and increase bone formation by stimulating osteoblast activity and inhibiting osteoclastic bone destruction, respectively.