Observations On The Effect Of Alendronate On Fracture Healing

ForewordWith the living condition improving, life prolonging and the amount of old people adding, the problem of osteoporosis in old people is becoming more and more important. Osteoporosis is characterized by decreased bone mass, increased bone fragility induced by demolition of bone microstructure and increased susceptibility to fracture. The bisphosphonate is the first choice of oral drugs treating osteoporosis currently. Continuously taking bisphosphonate can increase bone mass and mechanical properties, decrease the incidence of fracture in hip and spine area of osteoporotic people. It takes good result in clinical using.Fracture healing is a complex cascade of cellular events and how itis regulated remains poorly understood. The healing process of fracture can be classified into three phases, ie, inflammation phase, reparative phase and remodeling phase. In the inflammation phase, a hematoma is formed and inflammation occurs. In the three phases, osteoblasts and osteoclasts interacts each other, and calcite deposit, etc, the bone recover to normal structure and function at the end. Both osteoblastes and osteoclasts play very important roles in fracture healing. Osteoclasts clean the dead bone and osteoblasts repair it.The mechanism of bisphosphonate in treating osteoporosis is that it selected combined with osteoclast and depress its activity, and decrease bone absorption. So, it is possible that bisphosphonate will depress and prolong the fracture healing process theoretically.This experiment is to find out if bisphosphonate will influent fracture healing through observing appearance of X-ray and histomorphology and BMD in callus.ObjectTo evaluate the effects of bisphosphonates on fracture healing.Method48 mature female Japan white big ear rabbits were randomly divided into normal control group (n=24) and study group (n=24). A midshaftfracture model was established in radium and ulna. Fractures of forearm were stabilized with splints. Alendronate was made into 0.05% solution. The study group took alendronate 0.5mg·kg^-1·d^-1, while the normal control group fed the same volume of distilled water. After 2 weeks , 3 weeks , 4 weeks and 6 weeks, both groups were observed by X-ray , bone mineral density and pathological examination.Results1. X-rayThere was no significant difference between each group after 2 and 3 weeks. At the end of 4^th week, callus can be seen in both groups apparently, but which in study group was bigger. At the end of 6^th week, fracture in both group healed, but the callus in study group is bigger and the gap of fracture disappeared later.2. Bone Mineral Density (BMD)The callus bone mineral density of study group is lower than that of normal control group (P<0.05)3. PathologyAt the end of 2^nd week, there was no difference between each other. At the end of 3^rd week, the appearances are almost the same, but the shape of the outer callus is a bit larger in study group. There were more cartilagecells and less osteoclast cells in callus of study group at the end of 4^th week, and the process of changing into bony tissue was delayed. Compared with 4 week, at 6 week, fracture in control group healed while that in study group remained bony tissue and the fracture gap still could be seen.ConclusionAlendronate had inhibitory effects on callus formation, leading to large quantity of woven bone and the fracture gap could be seen during a long period, laminar bone decreased, fracture healing delayed.