TY - JOUR
T1 - Effects of gastric inhibitory polypeptide, glucagon-like peptide-1 and glucagon-like peptide-1 receptor agonists on Bone Cell Metabolism
AU - Hansen, Morten S S
AU - Tencerova, Michaela
AU - Frølich, Jacob
AU - Kassem, Moustapha
AU - Frost, Morten
N1 - © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).
PY - 2018/1
Y1 - 2018/1
N2 - The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.
AB - The relationship between gut and skeleton is increasingly recognized as part of the integrated physiology of the whole organism. The incretin hormones gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are secreted from the intestine in response to nutrient intake and exhibit several physiological functions including regulation of islet hormone secretion and glucose levels. A number of GLP-1 receptor agonists (GLP-1RAs) are currently used in treatment of type 2 diabetes and obesity. However, GIP and GLP-1 cognate receptors are widely expressed suggesting that incretin hormones mediate effects beyond control of glucose homeostasis, and reports on associations between incretin hormones and bone metabolism have emerged. The aim of this MiniReview was to provide an overview of current knowledge regarding the in vivo and in vitro effects of GIP and GLP-1 on bone metabolism. We identified a total of 30 pre-clinical and clinical investigations of the effects of GIP, GLP-1 and GLP-1RAs on bone turnover markers, bone mineral density (BMD), bone microarchitecture and fracture risk. Studies conducted in cell cultures and rodents demonstrated that GIP and GLP-1 play a role in regulating skeletal homeostasis, with pre-clinical data suggesting that GIP inhibits bone resorption whereas GLP-1 may promote bone formation and enhance bone material properties. These effects are not corroborated by clinical studies. While there is evidence of effects of GIP and GLP-1 on bone metabolism in pre-clinical investigations, clinical trials are needed to clarify whether similar effects are present and clinically relevant in humans.
KW - Animals
KW - Bone Density/drug effects
KW - Bone Resorption/chemically induced
KW - Bone and Bones/cytology
KW - Diabetes Mellitus, Type 2/drug therapy
KW - Disease Models, Animal
KW - Fractures, Bone/chemically induced
KW - Gastric Inhibitory Polypeptide/metabolism
KW - Glucagon-Like Peptide 1/metabolism
KW - Glucagon-Like Peptide-1 Receptor/agonists
KW - Humans
KW - Incretins/pharmacology
KW - Insulin/metabolism
KW - Obesity/drug therapy
KW - Osteoblasts/drug effects
KW - Osteocalcin/metabolism
KW - Osteoclasts/drug effects
U2 - 10.1111/bcpt.12850
DO - 10.1111/bcpt.12850
M3 - Journal article
C2 - 28722834
SN - 1742-7835
VL - 122
SP - 25
EP - 37
JO - Basic & Clinical Pharmacology & Toxicology
JF - Basic & Clinical Pharmacology & Toxicology
IS - 1
ER -