The impact of diabetes and diabetes medications on bone health.
Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures despite increased body weight and normal or higher bone mineral density. The mechanisms by which T2DM increases skeletal fragility are unclear. It is likely that a combination of factors, including a greater risk of falling, regional osteopenia, and impaired bone quality, contributes to the increased fracture risk. Drugs for the treatment of T2DM may also impact on the risk for fractures. For example, thiazolidinediones accelerate bone loss and increase the risk of fractures, particularly in older women. In contrast, metformin and sulfonylureas do not appear to have a negative effect on bone health and may, in fact, protect against fragility fracture. Animal models indicate a potential role for incretin hormones in bone metabolism, but there are only limited data on the impact of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 agonists on bone health in humans. Animal models also have demonstrated a role for amylin in bone metabolism, but clinical trials in patients with type 1 diabetes with an amylin analog (pramlintide) have not shown a significant impact on bone metabolism. The effects of insulin treatment on fracture risk are inconsistent with some studies showing an increased risk and others showing no effect. Finally, although there is limited information on the latest class of medications for the treatment of T2DM, the sodium-glucose co-transporter-2 inhibitors, these drugs do not seem to increase fracture risk. Because diabetes is an increasingly common chronic condition that can affect patients for many decades, further research into the effects of agents for the treatment of T2DM on bone metabolism is warranted. In this review, the physiological mechanisms and clinical impact of diabetes treatments on bone health and fracture risk in patients with T2DM are described.
Division of Endocrinology and Diabetes (M.P.G.), The University of Vermont College of Medicine, Burlington, Vermont 05405; and Florida Hospital Diabetes and Translational Research Institutes and Sanford-Burnham Medical Research Institute, Orlando, Florida 32827.
Matthew P
MP
Gilbert
Richard E
RE
Pratley
D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D050723:Fractures, Bone / Q000453:epidemiology / Q000378:metabolism; D006620:Hip Fractures / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D058228:Islet Amyloid Polypeptide / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin; C105254:pramlintide