Effect Of Aspirin Administration For The Treatment Of Osteoporosis In Ovariectomized Rat Model

BackgroundWith life expectancy increasing, more and more people go into the agingstate and the incidence of osteoporosis has increased year by year. Osteoporosis isa systemic metabolic disease. It is one of the diseases with higher morbidity,mortality and health care costs in the world. Although there are many types ofdrugs have been used in the treatment of osteoporosis, yet a lot of problemsremaining, such as the side effects, high cost and low effectiveness. In recentyears, epidemiological survey found that small doses of aspirin can increase bonemineral density of aged people. The experimental study found that treatment withlow-dose aspirin in ovariectomized mice can significantly improve theirtrabecular and cortical bone density. Aspirin is a century-old drug. It is a commonused drug for the elderly people because its little side effects, cheap cost, and itsbroad indication for many diseases. Therefore it is significant to investigatewhether aspirin can prevent or cure osteoporosis. System experimental study ofaspirin in the treatment of osteoporosis in animals has not been reported currently, and the action mechanism is not clear yet. In this study, aspirineffervescent tablets were dissolved in saline and intragastrically administered tothe osteoporotic SD rats for 3 months. And then the BMD and micro-architecturewere measured by DXA and MicroCT. Alkaline phosphatase and osteocalcinwere measured in peripheral blood, and the trabecular architecture was observedthrough histomorphology. The therapeutic effects of aspirin on post menopausalosteoporosis and the possible mechanism were investigated.Objective1. To evaluate the validity of osteoporotic rat model by the way ofovariectomy.2. To evaluate the ability of aspirin effects in improving bone mineraldensity, trabecular bone microstructure and mechanical strength in osteoporosisrats, and to explore the possible mechanism of aspirin's effects of anti-osteoporosis.Material and MethodsPart 1 Establishment and evaluation of the rat osteoporosis modelSixteen female SD rats were divided into 2 groups randomly with 8 rats ineach: Sham group and OVX group. All rats underwent BMD scan at the time ofOVX. Three months later, body weight of rats and the wet weight of uterus werecompared between Sham group and OVX group. The femoral condylar changeswere observed through histomorphology. BMD of vertebrae and femoral condylewere measured by dual-energy X-ray absorptiometry. Micro-architecture of L4vertebrae were examed by MicroCT. The bio-mechanical properties wereevaluated by axial compression tests of vertebral specimens and three-pointbending tests for femur shaft. Part 2 Effect of Aspirin Administration for the treatment ofOsteoporosis in Ovariectomized Rat Model.Forty female SD rats were divided into 5 experimental groups randomlywith 8 rats in each: sham operated group (Sham), ovariectomized group (OVX),low-dose aspirin group (A1), medium dose aspirin group (A2), high-dose aspiringroup (A3). OVX group and Aspirin groups were ovariectomized (OVX) forthree months in advance. All rats underwent BMD scan at the time of OVX andthree months after OVX. After osteoporosis animal model was established,Aspirin groups was intragastrically administered at a daily dose of 8.93mg/kg(A1), 26.79mg/kg(A2) and 80.36mg/kg (A3) in OVX rats. After threemonths, the BMD of vertebrae was measured by dual-energy X-rayabsorptiometry. Alkaline phosphatase and osteocalcin were measured inperipheral blood. The femoral condylar trabecular were examed throughhistomorphology. Micro-architecture of L4 were surveyed by MicroCT. Axialcompression tests were used to evaluate the mechanical properties of vertebralspecimens and three-point bending tests were used for femur shaft.Results;Part 1: Three months after ovariectomy, the body weight was significantlyincreased in OVX rats (P<0.05), but wet weight of uterus in OVX rats wassignificantly lighter than that in Sham group (P<0.05). DXA analysis showed thatthe BMD in OVX group was significantly lower than Sham group (P<0.05), withthe BMD of vertebral body and femoral condyle in OVX group decreased 18.34%and 21.76% respectively compare to that before OVX. Histological sections foundthat the structural of trabecular bone was integrity and trabecular bone was roundor oval arch in Sham group, while in the OVX group, the trabecular bone wassparse, thinning and there were fracture and bone defect occured locally. MicroCTanalysis showed that the trabecular thickness, trabecular number, the connection rate and BMD of vertebral body in OVX group were significantly lower than thosein the Sham group (P<0.05). Biomechanical studies have shown that vertebralcompression load and three-point bending of femoral shaft in OVX group weresignificantly lower than thagt in the Sham group (P<0.05).Part 2: Three months after intragastrically administered, DXA showed theBMD in Aspirin groups were higher than Sham group (P<0.05), and there was nosignificant difference between A3 group and Sham group. Alkaline phosphatasein peripheral blood in Aspirin groups was decreased significantly than those inOVX (P<0.05), but osteocalcin was no difference in Aspirin groups and OVXgroup(P>0.05). Histopathology indicated that trabecular connectivity andthickness in Aspirin groups were better than the OVX group. The MicroCTshowed the trabecular thickness, trabecular number and BMD in Aspirin groupsincreased significantly than those in OVX group(P<0.05), and there was nosignificant difference between A3 group and Sham group(P>0.05).Biomechanical test showed the maximum compression load of lumbar spine andthree-point bending load of femur shaf in Aspirin groups were significantlyhigher than OVX group(P <0.05).Conclusions:1. Osteoporosis model of rat is effectively established by ovariectomy,.Themethod is simple and reproducible.2. Aspirin can promote postmenopausal osteoporosis rat's trabecular boneremodeling, improve three-dimensional structure of trabecular bone and increasebone density of cancellous in OP rats .It may stimulate bone formation and maybecome a novel drug for anti-osteoporosis.