incretins and Osteoporosis

Patients with diabetes mellitus are at an increased risk of bone fractures. Several groups of effective antidiabetic drugs are available, which are very often given in combination. The effects of these medications on bone metabolism and fracture risk must not be neglected. Commonly used antidiabetic drugs might have a positive, neutral or negative impact on skeletal health. Increased risk of fracture has been identified with use of thiazolidinediones, most definitively in women. Also treatment with sulfonylureas can have adverse effects on bone. One consequence of these findings has been greater attention to fracture outcomes in trails of new diabetes medication (incretins and SGLT-2 inhibitors). The effect of insulin on bone is discussed and the risk of fractures in patients using insulin seems to be unrelated to insulin as itself. The aim of the review is to summarize effects of antidiabetic treatment on bone - bone mineral density, fractures and bone turnover markers. The authors also try to recommend a strategy how to treat patients with diabetes mellitus regarding the risk of osteoporotic fractures. In this review the problem of how to treat osteoporosis in patient with diabetes is also discussed.

Topics: Animals; Bone and Bones; Bone Density Conservation Agents; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Incretins; Insulin; Metformin; Osteoporosis; Sulfonylurea Compounds; Thiazolidinediones

Type 2 Diabetes Mellitus (T2D) and osteoporosis have been found recently to be tightly correlated. In fact, T2D can result in bone loss through different mechanisms resulting in alteration of bone matrix and inhibition of bone formation. Fracture risk also increases significantly. New antidiabetic agents, dipeptidyl peptidase-4 inhibitors and glucagon like peptide -1 agonists have shown promise in many fields beyond glycemic control. Benefits on the skeletal system are multiple through direct stimulation of osteoblasts, inhibition of advanced glycation end products and inhibition of bone resorption. However, clinical evidence in humans is still not enough to allow definitive conclusions.

Topics: Animals; Blood Glucose; Bone Density; Bone Density Conservation Agents; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Osteoporosis

Patients with diabetes are at greater risk of fractures mostly due to not only to extraskeletal factors, such as propensity to fall, but also to bone quality alteration, which reduces bone strength. In people with diabetes, insulin deficiency and hyperglycaemia seem to play a role in determining bone formation alteration by advanced glycation end product (AGE) accumulation or AGE/RAGE (receptors for AGE) axis imbalance, which directly influence osteoblast activity. Moreover, hyperglycaemia and oxidative stress are able to negatively influence osteocalcin production and the Wnt signalling pathways with an imbalance of osteoblast/osteoclast activity leading to bone quality reduction as global effect. In addition, other factors such as insulin growth factors and peroxisome proliferator-activated receptor-γ pathways seem to have an important role in the pathophysiology of osteoporosis in diabetes. Although there are conflicting data in literature, adequate glycaemic control with hypoglycaemic treatment may be an important element in preventing bone tissue alterations in both type 1 and type 2 diabetes. Attention should be paid to the use of thiazolidinediones, especially in older women, because the direct negative effect on bone could exceed the positive effect of glycaemic control. Finally, preliminary data on animals and in humans suggest the hypothesis that incretins and dipeptidyl peptidase-4 inhibitors could have a positive effect on bone metabolism by a direct effect on bone cells; however, such issue needs further investigations.

Topics: Aging; Animals; Bone Density; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Fractures, Bone; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Incretins; Male; Metformin; Osteocalcin; Osteoporosis; PPAR gamma; Risk Factors; Signal Transduction; Thiazolidinediones; Wnt Proteins

GLP-1 and GIP play an important role as incretin to stimulate insulin secretion from pancreatic β-cells and to maintain the homeostasis of glucose metabolism. As GLP-1 receptors are expressed in thyroid C cells and GIP receptors are expressed in osteoblasts, incretin contributes to bone metabolism. GIP maintains the homeostasis of bone metabolism through transiently activating osteoblasts.

Topics: Animals; Bone and Bones; Diabetes Complications; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Osteoporosis

Type 2 diabetes is closely associated with fragility fracture risk. Metabolic control of diabetes may improve bone status, but several anti-diabetic medicines could directly affect bone metabolism. Thiazolidinediones (TZD) may have a negative effect by switching mesenchymal progenitor cells to adipose rather than bone tissue. Clinical trials and meta-analyses showed that elderly women taking TZD could be at increased risk of fractures. On the contrary, in vitro studies suggest that incretin mimetics and incretin enhancers could positively regulate bone metabolism. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which enhance serum incretin concentration, have been reported to reduce clinical fractures. However, further studies would be required for their long term-efficacy and safety on bone metabolism.

Topics: Animals; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Incretins; Osteoporosis; Osteoporotic Fractures; Thiazolidinediones

Energy deprivation leads to a decrease in white adipose tissue and bone mineral density (BMD), while simultaneously inducing the expansion of marrow adipose tissue (MAT). In short bowel syndrome (SBS), parenteral nutrition mitigates the deterioration of nutritional status, including decreases in MAT. Osteoporosis is, however, a frequent complication of SBS. The objective of our study here was to evaluate the association of fat deposit sites (subcutaneous and visceral adipose tissues: intrahepatic lipid (IHL) and MAT) and the incretin glucagon-like peptide 1 (GLP1) with BMD in individuals with SBS. MAT was negatively correlated with lumbar spine BMD in normal individuals, but not in those in the SBS group, who otherwise showed a positive correlation between MAT and GLP1. In addition, in individuals with SBS, IHL was negatively associated with lumbar spine BMD and positively associated with C-terminal telopeptide of type 1 collagen (a serum biomarker of bone turnover). Caloric maintenance in individuals with SBS, therefore, seems to positively affect the relationship between MAT and BMD, which may be modulated, at least in part, by GLP1.

Topics: Adipose Tissue; Adult; Bone Density; Bone Marrow; Bone Remodeling; Case-Control Studies; Cross-Sectional Studies; Female; Glucagon-Like Peptide 1; Humans; Incretins; Male; Middle Aged; Osteoporosis; Parenteral Nutrition; Short Bowel Syndrome