January - March 2014, Volume 10, Issue 1

Baraka A, Korayem H. , Baraka M

Metformin as a Potential Therapeutic Agent for Osteoporosis in Ovariectomized Rats

Acta Endo (Buc) 2014, 10 (1): 31-40
doi: 10.4183/aeb.2014.31

Introduction. There is increasing evidence that 5’ adenosine monophosphateactivated protein kinase (AMPK) signaling pathway plays a role in bone physiology. The aim of the present study was to investigate the effect of a drug activating AMPK, namely metformin, on ovariectomy-induced osteoporosis in the rat. Methods. The present study was conducted on 40 female Wistar albino rats that were divided into 4 groups of 10 rats each, Group I: sham operated, Group II: non-treated ovarictomized (OVX) rats, while groups III and IV were OVX rats treated with metformin and metformin plus a substance that inhibits AMPK, namely compound C, respectively. At the end of the experimental period, urine and blood samples were collected and used for determination of urinary deoxypyridinoline (DPD) serum: osteocalcin, calcium and phosphorus concentrations and serum alkaline phosphatase activity. Biochemical assessment of AMPK activity in isolated fourth lumbar vertebrae (LV4) was carried out. The tibia, left femur and third lumbar vertebrae (LV3) were weighed and biomechanical study on LV3 was carried out. Immune histochemical studies of right femur and the forth-lumbar vertebrae (LV4) were carried out using anti-Fas antibodies to detect apoptotic osteoclastic and osteoblastic cells. Evaluation of cortical bone morphometric indices was done by CT-Scanning technique. Results. The results of the present study demonstrated that metfromin protected against biochemical, histological, biomechanical and histomorphometric osteoporotic changes. Compound C, an inhibitor of AMPK, blocked metformininduced changes in assessed parameters suggesting that the effect of metformin was mediated mainly through activation of AMPK. Conclusions. Drugs modulating AMPK could be effective in ameliorating OVX-induced osteoporotic changes.

Keywords: Osteoporosis, AMPK, Metformin, Ovariectomy.

Correspondence: Azza Baraka PhD, Faculty of Medicine, Clinical Phamacology, Faculty of Medicine, Alexandria University, Alexandria, 00203, Egypt, E-mail: mnhbaraka@yahoo.com