| Objective:Osteoporosis is characterized by a decrease in bone mass as well as a deterioration of the bone architecture resulting in an increased risk of fracture.With the increasing life expectancy in society,osteoporosis is a major and growing health problem worldwide.Now data suggests that drugs to treat osteoporosis mainly include bone resorption inhibitors (estrogen,selective estrogen receptor modulators,calcitonin, bisphosphonates,calcium,vitamin D and its analogues,etc)and bone anabolic agents(fluoride,PTH,etc).The former mainly inhibit bone resorption,and they can't stimulate bone formation markedly to make osteopic tissue restore normal one.While the latter for example fluoride can stimulate the formation of new bone,but also can reduce the strength of bone,others remain on the stage of study.So it is important to discover safe and effective drug to treat osteoporosis in the future.Recently data suggests that statins lipid-lowering drugs can stimulate bone formation,which becomes focus of medicine treatment of osteoporosis.This study observes the effect of simvastatin on bone metabolism in ovariectomized rats.Methods:45 three-month-old Wistar rats,weighed(200±30)g,were randomly divided into five groups(A,B,C,D,E).Each group had 9 rats.Group A was made pesudo-ovariectomized surgery and others were made ovariectomized surgery.Group A and Group B, were given 0.9% sodium chloride solution 1.5ml·d-1; Group C,given simvastatin 5mg·kg-1·d-1;Group D, given Nylestriol 0.01mg·kg-1·d-1;Group E,given simvastatin 3mg·kg-1·d-1 and Nylestriol 0.005mg·kg-1·d-1.All of the animals were given the agents through gastric tube for ten weeks.When the study finished,we observed markers:Firstly,at the day before surgery and the 70th day after surgery measured the weight of all the rats.Secondly,some urinary and serum biochemical markers of bone turnover were investigated.We collected twenty-four hours urine of rats by metabolic cage to measure urinary calcium by colorimetric analysis,urinary creatinine by the method of picric acid and urinary hydroxyproline by the method of digestion.Then all the rats were sacrified for the measurement of serum BGP and alkaline phosphatase level.Thirdly,to get left femur and tibia of all the animals for the measurement of bone mineral density(BMD) by the dual energy X-ray absorptiometry.Then to observe the cancellous microstructure of distal femur by light microscope and scanning electron microscope.The association between the weight,biochemical markers of bone turnover and bone mineral density of all groups was demon stated in x±s deviation.The analysis of variance was used to the significance test by SPSS 10.0 FOR WINDOWS software,α=0.05.Results:There was no obvious difference in weight of all the animals before surgery.Weight of Group B rats increased significantly compared with that of Group A,when the study finished(P<0.01);Among biochemical markers of bone turnover which reflected bone formation serum BGP:Group B were lower than Group A,Group C,Group D and Group E and the difference was significant(P<0.05);While serum ALP:Group B were higher than other groups(P<0.05).Bone resorption markers the urinary calcium/creatinine ratio and the urinaryhydroxyproline/creatinine ratio:Group B were increased than others,but the difference was not significant(P>0.05).Femoral bone mineral density:Group B were decreased than other groups and the difference was significant(P<0.05).Tibial bone mineral density:Group B,Group C,Group D and Group E were lower than Group A,but the difference was not significant (P>0.05).There was no significant difference among Group C,Group D and Group E of all the results above (P>0.05).Under light microscope and scanning electron microscope,we could see that the bone mass decreased, trabecula lessened and microdamage increased significantly in Group B than other groups.Conclusions:The ovariectomized Wistar rats showed active bone metabolism.Bone formation and bone resorption were all increased,and the latter was shorter than the former,which ca... |
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