Diabetes, bone and glucose-lowering agents: basic biology

Diabetologia. 2017 Jul;60(7):1163-1169. doi: 10.1007/s00125-017-4269-4. Epub 2017 Apr 22.

Abstract

Skeletal fragility often accompanies diabetes and does not appear to correlate with low bone mass or trauma severity in individuals with diabetes. Instead (and in contrast to those with osteoporotic bone disease), bone remodelling and bone turnover are compromised in both type 1 and type 2 diabetes, contributing to defective bone material quality. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Ann Schwartz (DOI: 10.1007/s00125-017-4283-6 ). This review presents basic science evidence that, alongside other organs, bone is affected in diabetes via impairments in glucose metabolism, toxic effects of glucose oxidative derivatives (advance glycation end-products [AGEs]), and via impairments in bone microvascular function and muscle endocrine function. The cellular and molecular basis for the effects of diabetes on bone are discussed, as is the impact of diabetes on the stem cell niche and fracture healing. Furthermore, the safety of clinically approved glucose-lowering therapies and the possibility of developing a single therapy that would be beneficial for both insulin sensitisation and diabetes bone syndrome are outlined.

Keywords: AGEs; Bone quality; Bone remodelling; Bone vasculature; Glucose; Glucose-lowering therapies; Muscle; Osteoblast; Osteoclast; Review; Stem cells.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Blood Flow Velocity
  • Blood Glucose / analysis
  • Bone Density
  • Bone and Bones / drug effects*
  • Bone and Bones / physiology
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Fractures, Bone / drug therapy
  • Fractures, Bone / metabolism
  • Glycation End Products, Advanced / metabolism
  • Homeostasis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / chemistry
  • Metformin / therapeutic use
  • Mice
  • Microcirculation
  • Muscles / metabolism
  • Osteoporosis / drug therapy
  • Stem Cell Niche / drug effects
  • Sulfonylurea Compounds / therapeutic use

Substances

  • Biomarkers
  • Blood Glucose
  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Metformin