The Study Of Peri-implant Ossteointegration With Topical Application Of Alendronate During Unloading Period

Objective:The aim of this study was to observe peri-implant ossteointegration with topical application of alendronate during unloading period, and offer a theoretical basis for shortening the time for the integrated.Methods:6adult healthy male Beagle dogs were fed in1week of acclimation. The mandibular second and fourth premolars of all the dogs were randomly divided into two groups:experimental group and control group, each comprised of12teeth, numbered A1-A12and B1-B12. Time point were divided into three groups:2weeks,4weeks and8weeks group. Each time point in group A and B implants were inserted in four tooth spaces and in the order made by the random number table. Respectively, in the1st day (8weeks),29th day (4weeks) and43rd day (2weeks) of the experiment teeth were extracted, then inserted implants immediately. In the experimental group topically injected500μmol/L alendronate50μL in implant sites, in the control group equivalent physiological saline was injected in the implant sites, with2times a week, until the end of the experiment. All animals were sacrificed after8weeks and then mandibular were taken out. The receptor activator of nuclear factor κB factor ligand (RANKL) and osteoprotegerin (OPG) expression were detected by real-time quantitative PCR. The mandibular were observed as the followings:(1) Implant-bone interface healing and peri-implant bone mineral density were observed by X-ray;(2) The peri-implant morphology changes were observed by HE staining;(3) Non-decalcified bone tissue sections were observed by hard tissue slice. The Osseointergration Index (01) and bone ingrowth fraction (BIF) were calculated. The experimental data were statistically analyzed by statistical software SPSS13.0. Take P <0.05as significantly different.Results: 1. General observation:all animals were healthy, no loosen, no inflammation and no failed.2. X-ray performance:There was no significant gap between implant and bone tissue. The peri-implant bone mineral density increased with time. The experimental group was significantly better than the control group in osseointegration.3. Real time quantitative PCR:The mRNA expression of RANKL and OPG in the experimental group were increased during4weeks after implants were inserted, and then decreased. But the two expressions were increased during2weeks in the control group after implants were inserted, and then decreased. The experimental group was higher than the control group in the gens expression, and there was significant difference between them.4. HE staining:In2week group, large resorption lacunae could be observed in the experimental group, there were more lacunae of osteoclasts could be seen in the control group. In4week group, thread visible new bone tissue and a large number of mature but irregular bone cells were observed in the experimental group. In the control group, the number of mature bone cells was less than the experimental group. In8week group, there were dense mature bone cells in the bone tissue of the experimental group, regularly arranged, the number of mature bone cells in the bone tissue of the control group was significantly increased, but arranged irregularly.5. Hard tissue slice observation:In2week group, the implant-bone interface of the experimental group and control group all had no fibrous tissue ingrowth, and there was no significant new bone formation, no significant difference between the two groups. In4week group, obvious new bone formation were observed in the experimental group, and there was a clear structure of trabecular bone. In the control group a small amount of new bone formation can also be found in the interface. In8week group, good implants osseointegration was observed in the experimental group, and in the control group new bone tissue density was lower than the original bone tissue. Quantitative histological analysis of the experimental group and control group at2weeks of01and BIF are low, the difference was not statistically significant (P>0.05); In4week and8week group,01and BIF were significantly increased, and the experimental group was significantly high than the control group, the difference was statistically significant (P<0.05).Conclusions:1. The topical application of alendronate can increase the OPG/RANKL mRNA expression of peri-implant during unloading period and could extend the bone remodeling active time;2. The topical application of alendronate can promote new bone formation around implant during unloading period and shorten the time of osseointegration.