Bone regeneration by statin and low-intensity pulsed ultrasound (LIPUS) in rabbit nasal bone

To compare bone regeneration between local implantation of statin and low-intensity pulsed ultrasound (LIPUS), and the combination of statin with LIPUS in rabbit nasal bone using histological and immunohistochemical methods.

Thirty-two adult male Japanese white rabbits (age: 12-16 weeks, weight: 2.5-3.0 kg) were used in this study. Two bone circular defects (5 mm in diameter) per rabbit were created in the nasal bone while preserving the nasal membrane. The two defects in each rabbit were filled with 2.5 mg/ml simvastatin in 0.2 ml water with an atelocollagen sponge (ACS) and ACS alone respectively. Sixteen rabbits (32 sides) received the LIPUS application; the remaining 16 rabbits (32 sides) did not. Therefore, the subjects composed of 4 groups, namely, (1) LIPUS + ACS + simvastatin (the LAS group), (2) LIPUS + ACS (the LA group), (3) ACS + simvastatin (the AS group) and (4) ACS alone (the A group). Four animals were killed in each period, at 1, 2, 4 and 8 weeks postoperative. The parts that had been operated on were removed and prepared for histological assessment. The expression of BMP-2 and the bone area ratio were evaluated using histological and immunohistochemical methods.

Bone square in the LAS group was significantly larger than that in the AS group after 1 (P < 0.0001) and 2 week (P = 0.0113). The bone square in the LA group was significantly larger than that in the A group after 1 (P < 0.0001) and 2 weeks (P = 0.0090). However, there was no significant difference between the LAS and LA groups. In the number of cells that stained positive for BMP-2, the LAS group was significantly larger than that in the AS group after 1 (P < 0.0001) and 2 weeks (P = 0.0113).

This study suggests that bone regeneration can be promoted by LIPUS alone and statin alone, respectively. However the combination use of LIPUS with statin does not differ from LIPUS alone or statin alone.