+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Exendin-4, a glucagon-like peptide-1 receptor agonist, prevents osteopenia by promoting bone formation and suppressing bone resorption in aged ovariectomized rats.

      Journal of Bone and Mineral Research

      Alkaline Phosphatase, blood, Amino Acids, urine, Animals, Collagen Type I, Core Binding Factor Alpha 1 Subunit, biosynthesis, Creatinine, Female, Humans, Hypoglycemic Agents, pharmacology, Male, Osteocalcin, Osteoporosis, drug therapy, Ovariectomy, Peptides, Rats, Rats, Sprague-Dawley, Receptors, Glucagon, agonists, Time Factors, Venoms

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Osteoporosis mainly affects postmenopausal women and older men. Gastrointestinal hormones released after meal ingestion, such as glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP)-2, have been shown to regulate bone turnover. However, whether GLP-1, another important gastrointestinal hormone, and its analogues also have antiosteoporotic effects, especially in aged postmenopausal situation, has not been confirmed. In the present study, we evaluated the effects of the GLP-1 receptor agonist exendin-4 on ovariectomy (OVX)-induced osteoporosis in old rats. Twelve-month-old female Sprague-Dawley rats were subjected to OVX, and exendin-4 was administrated 4 weeks after the surgery and lasted for 16 weeks. Bone characters and related serum and gene biomarkers were analyzed. Sixteen weeks of treatment with exendin-4 slowed down body weight gain by decreasing fat mass and prevented the loss of bone mass in old OVX rats. Exendin-4 also enhanced bone strength and prevented the deterioration of trabecular microarchitecture. Moreover, exendin-4 decreased the urinary deoxypyridinoline (DPD)/creatinine ratio and serum C-terminal cross-linked telopeptides of type I collagen (CTX-I) and increased serum alkaline phosphatase (ALP), osteocalcin (OC), and N-terminal propeptide of type 1 procollagen (P1NP) levels, key biochemical markers of bone turnover. Interestingly, gene expression results further showed that exendin-4 not only inhibited bone resorption by increasing the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio, but also promoted bone formation by increasing the expression of OC, Col1, Runx2, and ALP, which exhibited dual regulatory effects on bone turnover as compared with previous antiosteoporotic agents. In conclusion, these findings demonstrated for the first time the antiosteoporotic effects of exendin-4 in old OVX rats and that it might be a potential candidate for treatment of aged postmenopausal osteoporosis. Copyright © 2013 American Society for Bone and Mineral Research.

          Related collections

          Author and article information



          Comment on this article