title: Locally administrated perindopril improves healing in an ovariectomized rat tibial osteotomy model.
abstract: Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX), tibial fractures were produced in Sprague-Dawley rats and subsequently stabilized with intramedullary wires. Perindopril (0.4 mg/kg/day) was injected locally at the fractured site for a treatment period of 7 days. Vehicle reagent was used as a control. Callus quality was evaluated at 2 and 4 weeks post-fracture. Compared with the vehicle group, perindopril treatment significantly increased bone formation, increased biomechanical strength, and improved microstructural parameters of the callus. Newly woven bone was arranged more tightly and regularly at 4 weeks post-fracture. The ultimate load increased by 66.1 and 76.9% (p<0.01), and the bone volume over total volume (BV/TV) increased by 29.9% and 24.3% (p<0.01) at 2 and 4 weeks post-fracture, respectively. These findings suggest that local treatment with perindopril could promote fracture healing in ovariectomized rats.
authors.affiliation: Department of Orthopeadics, Xijing Hospital, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Zhao
authors.forename: Zi-xiang
authors.initials: ZX
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming-xuan
authors.initials: MX
authors.lastname: Gao
authors.forename: Ya-bo
authors.initials: YB
authors.lastname: Yan
authors.forename: Peng-chong
authors.initials: PC
authors.lastname: Cao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zang
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001696:Biomechanical Phenomena; D002146:Bony Callus / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D010012:Osteogenesis / Q000187:drug effects*; D010027:Osteotomy; D010052:Ovariectomy; D020913:Perindopril / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia; D016474:Weight-Bearing; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D020913:Perindopril