Pharmacological Inhibition Of Cysteinyl Leukotriene Receptor In The Effect Of Fracture-healing

Objectives:In the present study, we use the rat tibial fracture model in order to determine potential mechanisms by which systemic oral inhibition of cysLTl receptor alters the fracture repair response.Methods:42 adult male SD rats were randomized divided into group A and B,21 rats each group. In each group,three subgroups were established separately according to the observation spots(10,20,30 day)after operation.group A: Montelukast sodium was delivered at 1.5mg/kg/day in a single dose, group group B:saline was administered at 10ml/kg/day in a single dose. At 10,20 and 30 days after fracture for all animals, each time took out 7 rats of each group, undergone a venous blood sampling for alkaline phosphatase and osteocalcin, after that, X-rays were taken to verify the position and quality of each fracture. the degree of healing was evaluated use a radiographic scoring system. Fracture specimens were harvested at various times (10,20 and 30 days) for bone tissue histology examination and bone tissue morphometry quantitative analysis.Results:(1) At each observation spots after fracture, through x-ray observation, fracture healing in group A is faster than group B; With use of a scoring system,the radiographs of the healing tibia made at 10,20,30 days after fracture were scored:Difference is significant at the 0.05 level between group A and B at 10、20 days after fracture; (2) The serum ALP and osteocalcin content are higher in group A than group B at 10 days after fracture, difference is significant at the 0.05 level; (3) At 10 days after operation, group B exhibit an intramembranous ossification during fracture healing, group A exhibit an accumulation of endochondral bone during fracture healing, a higher proportion of cartilage was found; intramembranous ossification and endochondral bone are both accelerated in group A; (4) At each observation spots after fracture, the trabecular bone was more mature、dense and order in group A; At 10、20 days after operation, The trabecula surface index of osteoblast、trabecular volume, and the trabecular width are higher in group A than those of group B difference is significant at the 0.05 level.Conclusion:Our study shows that montelukast sodium group exhibited increased callous size and earlier bone formation when compared with controls. Treatment with montelukast sodium directly targeted the cysteinyl leukotriene leading to increased chondrocyte proliferation at early time points.