| Objective: With the developing of the technology of artificial joint replacement and updating of the concept of bone diseases therapy,the cementless artificial joint replacement has become the standard operation method young patients choose.Such prothesises can obtain stability promptly through bone compaction technique and can obtain permanent stability through bone grow into the surface of the prothesises. But many studies showthat the bone loss still exsit around the cementless prothesises at the earlier period after operation and the most obvious place is the proximal region of the prothesis,and then the bone loss affects the initial stability of the prothesis.The reason may be that cutting bone marrow and installing prothesis destroy the local microcirculation and the normal bone,activating osteoclasts, inducing osteoblasts apoptosis,finally leading to the bone resorption around the prothesis. Researches show that the initial micro-motion more than 150μm between bone and prosthesis interface can restrain the bone growth.At this time ,bone formation replaces by fibrous tissue formation, so it is very difficult to develop the osseointegration.The micro-motion of interface makes the synovial fluid pump out and in between the bone-prosthesis interface, which produces liquid phase pressure that cut bone- prosthesis interface,wear debris produced from slip joint and inflammatory mediators from interface membrane have also been transferred to the surface of the interface membrane.If the bone mass around prothesis decreases largely,the prothesis micro-motion will occur. Wear debris can induce peri-prosthesis histiocyte to produce a series of biological reaction that stimulate macrophages, osteoblasts,fibroblasts to produce many osteolytic factors, these factors will induce bone absorption and affect the differentiation and function of osteoblasts, and then inhibit bone formation. Therefore,how to inhibit bone loss around prothesis and promote the early new bone formation and accelerate the new bone growing into the surface of prothesis as soon as possible is the most important part of preventing the prothesis from loosening. Bisphosphonates can specifically combine with hydroxyapatite in bone and inhibit the activity of osteoclasts and stimulate bone tissue restitution. In recent years, researches have found that bisphosphonates not only inhibit osteoclast activity,but also inhibit bone cell apoptosis and promote the ability of the proliferation and differentiation of bone marrow stem cells. Ibandronate is the third-generation bisphosphonates(BPS) that inhibits bone resorption more strongly and has smaller adverse reaction and is used more conveniently. The purpose of this experiment is to confirm that if local application of ibandronate can inhibit bone resorption, increase new bone mass at the same time, and improve early implant fixation.Methods:The 44 Zelanian rabbits, 12~18 weeks old,2.5±0.6kg. The experimental group(A):The proximal end of all the rabbits'left tibia was embeded with metal screw, ibandronate(1mg/ml) was sprinkled locally surround the screw hole. The control group (B):The proximal end of all the rabbits'right tibia was embeded with same screw, saline solution was sprinkled locally surround the screw hole .After operration, each animal was injected Gentamicin 40,000u for three days avoiding being infected. 2 thweek afer operation: the specimens of group A and group B were stained with hematoxylin and eosin(HE) and the composition and width of the fibre membrane were observated. 4th week,8th week after operation: the specimens of group A and group B were stained with HE and Masson and were made a histomorphometry study,the new bone mass of the two groups was calculated by using bone tissue image analysis system; The biomechanical pull-out test of the two groups was done to observe the bonding force of bone and screw.All animals did X-ray before they were executed.The data were denoted as mean±standard deviation,all of the data were satistically analyzed by the SPSS 13.0 software.Results: 2th week X-ray showed: There was an obvious light-gap around the screw of the control group,but there was less light-gap in experimental group,no bone trabecula and new bone were observed in both groups. Histomorphology showed: The fibre membrane was existed in both groups,the width of the fibre membrane in control group(B) was 0.660±0.077mm and 0.497±0.056mm in experiment group(A) , there was significant difference(P< 0.001).Moreover, a small quantity of new bone tissue could be seen in group A, no new bone trabecula could be seen around the fibre membrane .4th week and 8th week X-ray showed: The light-gap in groupB was smaller than before and a small quantity of new bone tissue can observed around the interface, there was some new bone formation between screw threads,but they had not contacted with the screw tightly; No light-gap had been found aroud the screws in groupA, the new bone generated around the screws was obviously,and become dense.Histomorphology showed: The new bone formation could be seen in both groups,the volume and the number of trabecula in group A were higher than that in group B,Masson staining showed that the maturity of new bone trabecula of group A was stronger than that of group B.The new bone mass at the 4th week and8th week showed: group A 69.024±5.190%, 86.099±4.962% ,group B 43.741±3.408%, 55.920±5.411%, the new bone mass of group A was obviously higher than that of group B, there was significant difference (P<0.001). The result the biomechanical strike-out test (Pm) : group A 19.683±1.853Kpa, 26.873±1.824Kpa, groupB14.333±0.949Kpa, 23.523±1.836Kpa, the Pm of groupA was higher than that of groupB, there was significant difference (P<0.01).Conclusion:Local application of ibandronate solution(1mg/ml)can obviously inhibit bone resorption,increase new bone formation at the same time , improve the implant fixation and decrease the incidence of aseptic loosening of prothesis.The mechanism of action is mightly related with inhibiting osteoclast activity, inhibiting bone cell apoptosis and promoting the ability of the proliferation and differentiation of bone marrow stem cells. |