| Osteoporosis(OP) is a metabolic bone disease with the characteristic of a lot of bone loss and bone tiny changes in the structure .It related to many facts, such as Sex hormones, cytokines, genetic, environmental , nutritional factors and so on. Maxillary and mandibular bones is part of systemic bone system, so they will certainly lead to the loss of bone mass. OP has a close relationship with heath of the jaw. Observations show that a large number of systemic osteoporosis at the same time often associated with the mass bone reduction of the jaw and bone. Patients with Systemic osteoporosis has a high degree of decreased on the height of alveolar bone. Jonasson's research shows that the mandible bone mineral density can be used to speculate systemic OP state. Under osteoporosis whether implants can achieve stable osseointegration has been a controversial topic. Some scholars believed that the OP will affect the bone healing so that lead to the failure of the implant, however, others thinked that even if the OP patients, implants can create a good integration, and only the time of bone heal is formed longer. Bisphosphonates is the high polar compounds with poor oral absorption and utilization rate of less than 2%.Bisphosphonates distribute to the the non-calcified organizations temporarily,which stay a very short time in the plasma. Almost all of the absorption will be distributed to all of bone or excluded from urine. After the drug administration, about 50-60% of the absorbed dose is distribution to the bone.This kind of drugs generally are excluded by the kidneys, with the short period of staying in the blood cycle. But they can still maintain in the bone tissue in a few days to several years. Academics firstly thinked that it could combine to hydroxyapatite crystal, inhibiting their growth and dissolution.But this explanation hardly interpret the variety of roles. The mechanism of bisphosphonates on the osteoclasts is still not clear.Perhaps the osteoclasts is to shift bisphosphonates within the cells to interference osteoclast differentiation reproduction, resulting in apoptosis through certain biochemical processes. It has been confirmed that TNF-αand IL-1 under-mediated by osteoblasts and stromal cells may lead to osteoclast activity increased. Therefore TNF-αand IL-1 involve in osteoporosis and bone absorption process.So bisphosphonates may be not only direct role in osteoclast cells, but also in the role of cytokines (IL-1, TNF-α)-producing cells, inhibition of cytokine production, thereby reducing osteoclast activation, blocking bone resorption process .The third generation of bisphosphonates represented by alendronate has a strong inhibition of bone resorption, decreased bone transformation,and to prevent bone loss and increase bone mass and reduce the incidence of such fractures.It can inhibit various drug-induced bone resorption, and calcium metabolism in the body of a prominent role. Bisphosphonates as a new type of drug has been used in the treatment of metabolic bone diseases for many years, but very few reports focused on the impact of the osseointegration surrounding the implant under the condition of osteoporosis. Through the establishment of the experimental rabbit model of osteoporosis,this experiment will approach the impact of the implant-bone osseointegration by alendroante intraperitoneal injection. In this experiment 24 Japanese white rabbits were removed bilateral ovaries under general anesthesia and strict disinfection with 3-day-anti-inflammatory therapy with 400,000 units of penicillin per day after the operation.Low calcium diet was given after the operation.1 day,2,4,6,8,10,12 weeks after the operation,in order to observe the change of ALP,Ca2+,P in the blood.12 weeks after the operation , we impanted one Ti-6Al-4V implant which has a 1.2mm diameter and 6mm length in both bilateral distal end of the femur and the proximal tibia,and suture by lamination. Meanwhile, the experimental group(EG) was given alendroante 0.5mg/kg, once 3 days till the end of the experiment .The control group (CG) was given the sanme dose of normal saline . Two groups was abstracted the blood from ear vein to do biochemical tests 4,8,12 weeks after the implant operation. Rabbits in EG and CG in 4, 8,12 weeks were killed (For example ,we killed 4 EG rabbits and also 4 CG rabbits in the same time.) .The tissues were fixed by means of perfusion with 4% PFM. Torque removal values were determined using a Tohinichi BTG60CN torque wrench for half implants. The femur, tibia specimens with implants which were devided into equal piece and specimens of the mandible were get for histological observation, Bone mineral density(BMD) tests and observation by SEM.The state of osseointegration should be evaluated by these means.Experiments show that, the animals'blood biochemical markers corresponding changes in the 12 weeks,as well as the decreasing in bone mineral density significantly,which manifested the success of osteoporosis model.Torque removal values show that, torque removal values areno obvious difference 4 weeks after the implant imbedding,but 8 weeks after the values in EG are greater than that in CG,even significantly difference at the end of 12 weeks after the implant operation.BMD tests suggest that the mandibular bone mineral density in EG and CG begin to show a significant difference from the 8 weeks after the alendronate administration., BMD tests which tested the area of 1 mm outside the implant-bone interface baseline show that BMD were significantly different in the EG and the CG,8,12 weeks after the alendronate administration.SEM observation: There was diversity degrees of difference between the combination rate of the bone in 4 weeks, 8 weeks and 12 weeks group. The biggest bone-implant gap in the experimental group was less than in the control group.The cancellous bone in the experimental group and the control group was almost invisible under general observation. The screws groove in the cortical bone was obvious and there was no significant difference between the experimental group and the control group under the observation of naked eye. With histological observation, the thread structure was obvious and circumvolutio only by the osseouscells. The fat cells were observed in marrow cavity and there was no significant difference between the experimental group and the control group.The results showed that at eight weeks after the use of Alendronate bone mineral density begin to show significant differences. Torque removal values at the moment also show a difference. A combination rate of bone and implant in the two groups is different .It infers that the osseointegration state is closely related to the BMD, furthermore, the use of Alendronate in osteoporosis patients does a inhibition of bone resorption to control the bone mineral density , so as to achieve stability in the bone implant interface,which certify that to improve the success of the implant by using Alendronate is feasible.All in all, Alendronate systemic application in osteoporosis rabbits model affect the bone-implant osseointegration with a marked improvement.It provide an experimental basis on increase the implant success rate in the clinical application in patients with osteoporosis. But in this experiment, there are still some deficiencies, such as the dose of systemic administration,as well as the difference between bone metabolism and maxilla or mandible metabolism. Therefore, in future studies, this problems are to be further addressed.
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