exenatide and Bone-Diseases--Metabolic

The present brief review looks at the evidence on the role of GLP-1 and its agonists in osteopenia and osteoporosis in type 2 diabetes (T2DM). There is accumulating data to suggest a favourable effect of GLP-1 on bone metabolism. However, most data is from experimental studies, while clinical confirmation is still inadequate. Moreover, little is known on the precise mechanisms underlying these effects. Therefore, we need randomised clinical trials in T2DM patients to learn more on the action of GLP-1 on bone metabolism and its potential clinical implications.

Topics: Bone and Bones; Bone Diseases, Metabolic; Calcitonin; Diabetes Mellitus, Type 2; Exenatide; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Male; Osteoporosis; Peptides; Receptors, Glucagon; Treatment Outcome; Venoms

Increased fat mass contributes to bone deterioration. Glucagon-like peptide 1 (GLP-1) and its related peptide exendin 1-39 amide (Ex-4), two lipid-lowering peptides, exert osteogenic effects in diabetic states. We examined the actions of 3-day administration of GLP-1 or Ex-4 on bone remodeling markers and on bone mass and structure in hyperlipidic (HL) and hypercaloric rats. Wistar rats on a hyperlipidemic diet for 35 days were subcutaneously administered GLP-1 (0.86  nmol/kg per h), Ex-4 (0.1  nmol/kg per h), or saline (control) by continuous infusion for 3 days. After killing, tibiae were removed for total RNA and protein isolation, as well as femurs and L1-L4 vertebrae for bone mass and quality assessment. Body weight and plasma insulin were unaltered in HL rats, which showed osteopenia (by dual-energy X-ray absorptiometry), associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. GLP-1 or Ex-4 administration decreased the levels of glucose, triglycerides, and total cholesterol in plasma but increased osteocalcin (OC) gene expression and the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio - at the expense of an augmented OPG - above corresponding control values in the tibia. Each tested peptide similarly reversed the decreased femoral and vertebral bone mass in these rats, whereas the deteriorated trabecular structure in the vertebrae improved associated with normalization of bone remodeling. These findings demonstrate that GLP-1 and Ex-4 are similarly efficient in reversing the bone alterations in this HL rat model, which has proven to be useful for studying the fat-bone relationships.

Topics: Animals; Biomarkers; Bone Density; Bone Diseases, Metabolic; Dietary Fats; Drug Evaluation, Preclinical; Exenatide; Glucagon-Like Peptide 1; Humans; Hyperlipidemias; Hypoglycemic Agents; Incretins; Lumbar Vertebrae; Osteogenesis; Peptides; Rats; Rats, Wistar; Venoms