81COMPARISON OF THE EFFECTS OF SITAGLIPTIN AND ESTROGEN ON OVARIECTOMY INDUCED OSTEOPOROSIS IN RATSOsteoporosis is one of the most prevalent bone diseases, especially among postmenopausal women. Diabetes mellitus may be associated with the development osteoporosis. Hence, the purpose of the current study was to investigate the effect of Sitagliptin (dipeptidyl peptidase-4 inhibitor) on induced osteoporosis in rats. The study was conducted on 40 female rats that were divided into four equal groups: Group 1 served as sham operated group. Osteoporosis was induced by bilateral ovariectomy in group 2 model group, group 3 estrogen replacement therapy (ERT) and group 4 sitagliptin treated for eight weeks. Blood samples were collected at the end of experiment for measurement of serum alkaline phosphate (ALP), calcium (Ca), phosphorus, osteocalcin and malondialdehyde (MDA). Urine samples were collected for measurement of urinary deoxypyridoline/creatinine (DPY)/Cr). Tibias were removed for histopathological assessment. The current study showed a significant increase in bone turnover in model group (increase urinary DPY/Cr, serum osteocalcin and serum ALP) when compared to sham control group. Serum Ca was significantly decreased in model group when compared to sham control group. There was a significant increase in oxidative stress marker (serum MDA) in model group when compared to sham control group. Histopathological examination of tibial bones in model group showed significant osteopenic changes .Such biochemical findings and tibial bones histopathological alterations induced by ovariectomy were significantly ameliorated by administration of ERT and sitagliptin. Sitagliptin was found to be effective in reducing ovariectomy induced osteoporotic changes. Thus, its use as an anti-diabetic agent in postmenauposal women should be encouraged.aaaunis@yahoo.comResearch512015Sitagliptin,Ovariectomy,Osteoporosis,Estrogen,OsteocalcinAmina Unis,Manal Hamza,Eman AbdelzaherDepartment of Pharmacology, Faculty of Medicine, University of Tabuk, Saudi Arabia,Department of Pharmacology, Faculty of Medicine, University of Tabuk, Saudi Arabia,Department of Pathology, Faculty of Medicine, Alexandria University, Egypt