Osteogenic effects in a rat osteoporosis model and femur defect model by simvastatin microcrystals

Simvastatin is a translational drug that may be used to induce local bone formation. In this study, simvastatin microcrystals were made by a wet media milling method, and then we verified the osteogenic effect of the microcrystals in rat ovariectomy (OVX)-induced osteoporosis and femur defect models. For the osteoporosis model, we delivered simvastatin microcrystals to the tibia with poloxamer hydrogels via an intraosseous injection. Bone mineral density and the ultimate force of the treated tibia were significantly improved after injection of simvastatin microcrystals at 0.5 and 1 mg compared with the OVX or 0-mg control groups. For the femur defect model, simvastatin microcrystals were incorporated in clinically used calcium phosphate cements (CPCs) as an implant. Quantitative analysis of bone regeneration by microcomputed tomography (μCT) showed improved bone morphology with simvastatin microcrystals at 50 and 100 μg, compared with the CPC vehicle. A semiquantitative scale for histology assessment further demonstrated a higher bone regeneration score in the drug-loaded groups. Our study shows that simvastatin microcrystals can promote bone formation by local delivery using a poloxamer hydrogel or CPC, which may be translationally useful.