| [Objective]Proton pump inhibitors(PPIs)are widely utilized for the treatment of acid-related disorders.All PPIs interfere the final step of acid secretion by blocking the gastric acid pump,H+/K+-adenosine triphosphatase(ATPase),to suppress gastric acid secretion.Recent studies have demonstrated an association between PPI use and increased risks of hip fractures.In this study,we have examined the effects of esomeprazole use on the bone mass and microstructure of male rats.[Methods]AnimalTwenty four 3-month-old male rats were divided into the control group,the low-dose esomeprazole group and the high-dose esomeprazole group by weight randomly.All the rats were treated by oral garage.The low-dose esomeprazole group was treated with esomeprazole of 10 mg/kg·d,the high-dose esomeprazole group was treated with esomeprazole of 50 mg/kg·d and the control group received the vehicle only.Our research lasted 14 weeks and the weights of rats were recorded twice a week.The dose of esomeprazole was adjusted by weight.Bone mineral densities and micro-computed tomography analysisDual-energy X-ray absorptiometry was taken to assess total bone mineral densities(BMDs)at week 0,8,14.Micro-computed tomography was also carried out in vivo in order to evaluate the microstructure of femur.The images were reconstructed and analyzed after scanned and the parameters including bone volume fraction(BV/TV),trabecular number(Tb.N,),thickness(Tb.Th),separation(Tb.Sp)and cortical wall thickness(CWT)were automatically determined.Calcium and bone metabolism markers measurementWe conducted biochemical analysis and enzyme-linked immunosorbent assay(ELISA)to measure the serum concentration of calcium,bone alkaline phosphatase(B-ALP)and tartate resistant acid phosphatase 5b(TRACP 5b)at week 0,8,14.Bone histomorphometric analysisWe dissected out the left proximal femur of rats,and then fixed,embedded,cut into sections and stained with hematoxylin-eosin before sacrifice.At last,we observed the sections under a light microscope and calculated the empty bone lacuna rate(ER).[Results]Weight gainAt week 14,the body weight of the control group increased significantly(P<0.05)and weight gain of the high-dose group was inhibited significantly.A reduced body weight gain was observed already 4 weeks after starting treatment.BMDs and micro-CTThe BMDs of high-dose group decreased significantly while that of the control and low-dose group increased and the differences were significant at week 14(P<0.05).The bone microstructural parameters showed that the cortical wall thickness of high-dose group was smaller than the other groups and the trabecular bone volume fraction,trabecular number and trabecular thickness decreased while the trabecular separation increased.Calcium and bone metabolism markersThe serum concentration of calcium,B-ALP and TRACP 5b of the high-dose group increased at week 14,which was not significant at week 8.There was no significant difference in the control and low-dose group at week 8 and 14.Bone histomorphometric analysisThere were significant differences among three groups.The femoral cortical bone was thin and empty bone lacunae were seen regularly at low power in high-dose group.The bone trabeculae of left proximal femur of the high-dose group were sparse,arranging intricately and partially ruptured;the vessels in the medullary cavity were sparse at high power.ER of the high-dose group was high dramatically(P<0.05).[Conclusion]High-dose esomeprazole use leads to osteopenia and degenerates the bone microstructure of male rats in a time-dependent manner.The possible mechanism is that the reduced gastric acid as a result of using PPIs leads to calcium malabsorption and inhibits the bone mineralization.And increased bone resorption due to osteoclast activation caused by hormonal regulation will eventually lead to osteopenia and degeneration of the bone microstructure of male rats. |
PDF Full Text Request