Local application of zoledronic acid incorporated in a poly(D,L-lactide)-coated implant accelerates fracture healing in rats.

BACKGROUND AND PURPOSE Zoledronic acid (ZOL) has been shown in vitro and in vivo to inhibit osteoclastic activity and to regulate osteoblasts. Its antiresorptive effect is used clinically in the treatment of bone-consuming pathologies to prevent skeletal complications. Because of its effect on bone cells, there might be a possible benefit in treatment of fractures by local application from a biodegradable poly(D,L-lactide) (PDLLA) coating of osteosynthetic implants. We analyzed the effect of locally applied ZOL from a PDLLA coating of intramedullary implants on fracture healing. MATERIAL AND METHODS Standardized midshaft fractures of the right tibia of 5-month-old rats were stabilized either with uncoated, PDLLA-coated, or ZOL-coated implants. Animals were killed 42 or 84 days after fracture. Tibiae were dissected and mechanically tested. Results Radiographs taken 42 days after fracture showed at least unilateral bridging in all groups. Maximum load and torsional stiffness were highest in the group treated with ZOL. 84 days after fracture, the torsional stiffness of the ZOL-treated group remained higher than that of the uncoated group whereas the maximum load for the control groups reached the results for the ZOL-coated group. INTERPRETATION Local application of ZOL from PDLLA coating appears to accelerate the achievement of mechanical stability in fractures.