This study was to explore the effect of local, matrix-bound bisphosphonates to monocytedifferentiation and osteoclast function in vitro. Experiments were designed using osteoassay plates. Cell-viability, differentiation, resorption pits and gene expression were analyzed to see the effect of matrix-bound BPs on monocyte differentiation and osteoclast function. EDTA was used as a chelating agent to remove the bound BPs. There was a dose dependent response in the differentiation and resorption pits. With chelation, there was increase in differentiation, resorption pits and increase in the calcium and PYD in the supernatant. Thus, matrix-bound Bisphosphonatesare biologically active and they inhibit monocyte differentiation and osteoclast function. Thereby removal of this matrix-bound drug can rescue osteoclast differentiation and function.