In vivo performance of absorbable collagen sponges with rosuvastatin in critical-size cortical bone defects

Rosuvastatin (RSV) is a synthetic statin with favourable pharmacologic properties, but its local effect in bone has yet to be investigated. The aim of this study was to evaluate the potential of absorbable collagen sponge (ACS) as a carrier for RSV to enhance bone formation in critical-size cortical bone defects adjacent to titanium implants. ACS, treated with different concentrations of RSV (R1 = 8.7 + or - 1.8 microg; R2 = 52.0 + or - 4.4 microg; R3 = 259.1 + or - 8.8 microg) or phosphate-buffered saline alone, were placed into the bone marrow through a defect made in the proximal tibial cortical bone of New Zealand White rabbits. One empty defect (SHAM) served as an internal control in each animal. After a healing time of 4 weeks, a concentration-dependent increase of alkaline phosphatase activity in ACS treated with RSV was detected in the bone fluid after removing the implants. In addition, a significant concentration-dependent increase in BMP-2 mRNA levels was found in the cortical bone tissue adjacent to the RSV-treated ACS. The cortical architecture of bone defects analysed by micro-computed tomography showed a trend towards higher bone volume in the ACS+R1 group compared with SHAM, which was accompanied by an increase in the bone mineral density. Evaluation of histological sections showed new bone formation in ACS treated with RSV but not in untreated ACS. These results indicate that RSV, when administered locally in bone, may have a potential effect in stimulating bone formation.