Our goal is to develop interventions to simultaneously control myeloma and the accompanying painful bone disease. We showed that bone-forming cells (osteoblasts) inhibit myeloma growth. Osteoblasts produce high levels of small leucine-rich proteoglycans (SLRPs), some of which suppress tumor growth. We propose the following studies: (Aim 1) Determine the involvement of SLRPs in osteoblast-induced myeloma growth inhibition and test their anti-myeloma efficacy in our animal model; (Aim 2) Determine the effects of potent osteoblast-activating agents on bone formation and myeloma development and progression in our animal model. This study will develop alternative, safe approaches for controlling myeloma progression.