Bisphosphonates incorporated in a poly(D,L-lactide) implant coating inhibit osteoclast like cells in vitro

Nitrogen containing bisphosphonates such as zoledronic acid (ZOL) are clinically used to prevent osteoclast induced bone loss. Previous studies indicated that bisphosphonates prevent osteoclast formation, decreases their resorption activity and lead to osteoclast apoptosis. Aim of the study was to investigate the effect of ZOL on fusion and resorption activity of osteoclast like cells (OLC) derived from human peripheral blood mononuclear cells (PBMNC) in vitro. For application of ZOL a local drug delivery system based on a coating for medical devices was used. ZOL was incorporated in the coating based on Poly(D,L-Lactide) (PDLLA) in different concentrations (10-50 microM). Control groups were treated without ZOL or ZOL pure substance in corresponding concentrations. Human PBMNCs were isolated and stimulated to form OLCs. After an experimental period of 144 h, TRAP staining of polynucleated cells was performed and TRAP positive cells were counted. A pit formation assay was performed and resorption lacunas on dentin chips were counted. Results showed a significant dose dependent decrease in the number of TRAP positive cells after exposure to ZOL incorporated in the drug delivery system or applied as pure substance. The amount of resorption lacunas was also dose dependent decreased using both application methods. In conclusion, exposure to specific concentrations of ZOL incorporated in a drug delivery system showed a significant decrease in OLC formation and activity comparable to the effect of pure substance. The effect on osteoclasts might be of clinical benefit to reduce orthopedic implant loosening and to support fracture healing.