Effects Of The Third Generation Of Bisphosphonate(Ibandronate) On Orthodontic Root Resorption

Malocclusion is a kind of common disease in Department of Stomatology, just like dental caries and periodontal diseases, its incidence is very high. It affects not only chewing, language, and other functions, but also affects appearance, interferes with sociality and individual physical and mental growth. With the development of society, the improvement of people’s living standard, and the popularization of oral medicine knowledge, people’s pursuit of beauty is getting higher and higher, the demand for correction of malocclusion becomes bigger and bigger. Orthodontic can correct most malocclusions, improve patients’face type by applying orthodontic force on dislocated teeth and jaws, so, more and more people prefer orthodontics. But orthodontic force can inevitably cause different degrees of root resoiption at the same time of tooth movement, it directly affects the treatment outcome and the health of tooth itself.In recent years, BPs(bisphosphonates, BPs) cause the attention of Stomatology area for its impact on oral medicine especially on orthodontics. BPs are the isoreagent of pyrophosphate(pyrophosphate, PPi), they have been used to treat various metabolic bone diseases caused by excessive bone resorption because they selectively inhibit osteoclasts, such as Paget’s disease, myeloma and osteoporosis, etc. The reconstruction of periodontal tissues is also related to osteoclasts, so many scholars both at home and abroad did lots of researches about the application of BPs on orthodontics, but most of which concentrated upon the effect of BPs on orthodontic tooth movement. Ibandronate, a potent blocker of bone resorption, is the representative drug of the third generation of BPs. Because of the extremely similarity of cementoclasts and osteoclasts in morphology and function, is there an inhibitory effect of Ibandronate on orthodontic root resorption? In this study, we established the animal model for orthodontic tooth movement in order to examine the effect of local administration of a BP, Ibandronate, on the orthodontic root resorption and to provide references for the prevention of orthodontic root resorption consequently, combined with tooth movement distances, the amount of cementoclasts, the expression of ODF(osteoclast differentiation factor, ODF) and root resorption degree.Purpose:To investigate the influence of Ibandronate on orthodontic tooth resorption in rats through observing tooth movement distances, the number of cementoclasts, the expression of ODF and root resorption degree.Methods:A total of48SPF female Wistar rats were chosen in this study. Then the animal model for orthodontic tooth movement of rats was established.50μl Ibandronate solution(500μmol/l) was injected into the sub-periosteum area adjacent to the left upper first molar(the experimental side) every three days during the experiment, the right maxillary first molar was served as a control(the control side) with an injection of50μl0.9%NaCl solution into the corresponding area at the same time interval. The administration of Ibandronate solution was started three days before the set of appliances. Then the nickel-titanium(Ni-Ti) closed coil springs initially generating an average force of60g were inserted in each rat’s mouth between the bilateral upper first molar and incisor. After applying orthodontic force3days,7days and14days, all rats were killed in batches(16animals in each period),8animals among them were chosen for histology observation of periodontal tissues, the remaining8animals were used for SEM observation of root resorption. The former8animals were killed, and then their upper jaws were dissected, the amount of upper first molar movement were measured with vernier caliper(with the accuracy of0.02mm), in addition, the slices of upper first molar and adjacent periodontal tissues were prepared and were used for observing bilateral periodontal tissue morphological changes, the amount of cementoclasts after staining with HE, the slices were also used for detecting the expression of ODF in the periodontal tissues by the immunohistochemical techniques, the root resorption indexes on both sides were analyzed with the image processing software; the latter8animals were anesthetized, and then their intact bilateral upper first molars were extracted for SEM sample preparation, root resorption lacunaes were observed by SEM, at last, the animals were executed.Results:1. The animal model for orthodontic tooth movement in rats was established successfully.2. The distances of tooth movement increased gradually as the continuation of experiment, the tooth movement on both sides all presented a trend of rise first and stable later, that is, tooth moved rapidly at0-3days stage, but then remained stable until day7, then moved fast until day14, in addition, the range of increase of tooth movement on experimental side was less than that on the control side. On day3, tooth movement on the experimental side was less than that on the control side, but with no statistically value(P>0.05); on day7and day14, tooth movement on the experimental side was significantly less than that on the control side, with statistically value(P<0.05).3. From the sections stained with HE, we can see that the space of periodontal membrane on the pressure side of rats’bilateral upper first molar decreased, periodontal membrane fibers arranged disorderly, osteoclast and alveolar bone resorption appeared. On day3, cementoclasts appeared in resorption lacunae at the surface of root, with no differences between the experimental side and the control side(.P>0.05); on day7and day14, the number of cementoclasts on the experimental side was significantly less than on the control side(P<0.05). In addition, some cementoclasts on the experimental side had features that were morphologically different from those of normal cementoclasts, such as an increased number of nuclei.4. The expression of ODF on the pressure side of periodontium on rats’ experimental upper first molar was lower than that on the control side on day3,7and14, but with significant differences between two sides on day7and14(P<0.05). The positive expression of ODF on both sides was all positioned mainly in osteoclasts, with positive expression in both cytoplasm and cell membranes.5. On day3,7and14, the root resorption index were all smaller on the experimental side than that on the control side, with significant differences between two sides on day7and14(P<0.05). On day3, the root resorption were mild on both sides, the difference was not significant (P>0.05)6. The SEM results showed smooth root surfaces, homogeneous texture and few root resorption lacunae on both sides on day3; irregular-shaped root resorption lacunaes were found on both sides on day7, there were more, widespread lacunaes on the control side, but fewer and smaller resorption lacunaes on the experimental side; compared with day7, the amount of resorption lacunaes on both sides increased on day14, there were fewer and smaller resorption lacunaes on the experimental side than that on the control side.Conclusion:1. The local administration of Ibandronate caused a significant reduction in tooth movement in rats.2. The local administration of Ibandronate resuced the amount of cementoclasts on the pressure side of periodontium, and weaken the expression of ODF.3. The local administration of Ibandronate also inhibited root resorption incident to orthodontic tooth movement.The administration of Ibandronate provided new ideas for preventing orthodontic root resorption in orthodontics.