title: Effect of combined local treatment with zoledronic acid and basic fibroblast growth factor on implant fixation in ovariectomized rats.
abstract: Osteoporosis is a skeletal disorder characterized by low bone mass and deterioration of bone microarchitecture resulting in bone fragility, which impairs fixation of the implants. Zoledronic acid (ZOL) is a potential inhibitor of osteoclast-mediated bone resorption and basic fibroblast growth factor (bFGF) is a growth factor that stimulates osteoblast-mediated bone formation, and these drugs could enhance fixation of implants under osteoporotic conditions. In this study, 40 ovariectomized (OVX) rats were randomly divided into 4 groups (n=10 for each group) and underwent bilateral tibiae implantation using hydroxyapatite (HA)-coated titanium implant: Control group (distilled water immersing before implantation), ZOL group (1 mg/ml of ZOL immersing), bFGF group (20 microg/ml of bFGF immersing), and ZOL+bFGF group (1 mg/ml of ZOL and 20 microg/ml of bFGF immersing). At 3 months after implantation, all animal were sacrificed and the tibiae were harvested for histology, micro-CT examinations and biomechanical testing. Bone area and contact, determined by histomorphometric analysis, were 2.7-fold and 1.8-fold in the ZOL-treated implants, 1.9-fold and 1.8-fold in the bFGF-treated implants, 3.6-fold and 2.3-fold in the both-treated implants compared with controls (p<0.01). Such significant effects were further confirmed by microstructure parameters, the bone volume ratio and the percentage osteointegration were significantly increased by ZOL treatment (3.0-fold and 1.8-fold), bFGF treatment (1.2-fold and 1.9-fold) and ZOL+bFGF treatment (3.3-fold and 2.7-fold) (p<0.001). In addition, push-out test showed that the maximum force and the corresponding interfacial shear strength of the implants treated by ZOL, bFGF and ZOL+bFGF was 8.4-fold and 8.6-fold, 3.8-fold and 3.7-fold, 10.8-fold and 10.7-fold of the control levels, respectively (p<0.05). The combined treatment was better than either treatment alone for force, but was not different from ZOL alone for interfacial strength. The significant correlation between biomechanical and micro-CT parameters demonstrates the role of microstructure assessments in predicting mechanical fixation of implants (p<0.01). Our study suggests that locally applied ZOL or bFGF may improve implant fixation in the ovariectomized rats, and that combined treatment has more beneficial effects on osseointegration, peri-implant bone formation and maximum force than either intervention alone.
authors.affiliation: State Key Laboratory of Oral Diseases and Department of Oral and Maxillofacial Surgery, Sichuan University West China College of Stomatology, Chengdu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Gao
authors.forename: En
authors.initials: E
authors.lastname: Luo
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.forename: Songsong
authors.initials: S
authors.lastname: Zhu
authors.forename: Jihua
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D004357:Drug Synergism; D017886:Durapatite / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D021621:Imaging, Three-Dimensional; D007093:Imidazoles / Q000494:pharmacology*; D010052:Ovariectomy; D019919:Prosthesis Implantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties / Q000187:drug effects; D013977:Tibia / Q000166:cytology / Q000000981:diagnostic imaging / Q000648:ultrastructure; D014025:Titanium; D055114:X-Ray Microtomography; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D016222:Fibroblast Growth Factor 2; D000077211:Zoledronic Acid; D017886:Durapatite; D014025:Titanium