Endocrinol Metab.  2018 Sep;33(3):339-351. 10.3803/EnM.2018.33.3.339.

Skeletal Fragility in Type 2 Diabetes Mellitus

• Starup-Linde J
• Hygum K
• Langdahl B

• KMID: 2447023
• DOI: http://doi.org/10.3803/EnM.2018.33.3.339

Abstract

Type 2 diabetes (T2D) is associated with an increased risk of fracture, which has been reported in several epidemiological studies. However, bone mineral density in T2D is increased and underestimates the fracture risk. Common risk factors for fracture do not fully explain the increased fracture risk observed in patients with T2D. We propose that the pathogenesis of increased fracture risk in T2D is due to low bone turnover caused by osteocyte dysfunction resulting in bone microcracks and fractures. Increased levels of sclerostin may mediate the low bone turnover and may be a novel marker of increased fracture risk, although further research is needed. An impaired incretin response in T2D may also affect bone turnover. Accumulation of advanced glycosylation endproducts may also impair bone strength. Concerning antidiabetic medication, the glitazones are detrimental to bone health and associated with increased fracture risk, and the sulphonylureas may increase fracture risk by causing hypoglycemia. So far, the results on the effect of other antidiabetics are ambiguous. No specific guideline for the management of bone disease in T2D is available and current evidence on the effects of antiosteoporotic medication in T2D is sparse. The aim of this review is to collate current evidence of the pathogenesis, detection and treatment of diabetic bone disease.

Keyword

Diabetes mellitus, type 2; Fracture; Bone remodeling; Antidiabetics; Sclerostin

MeSH Terms

Bone Density
Bone Diseases
Bone Remodeling
Diabetes Mellitus, Type 2*
Epidemiologic Studies
Glycosylation
Humans
Hypoglycemia
Hypoglycemic Agents
Incretins
Osteocytes
Risk Factors
Thiazolidinediones
Hypoglycemic Agents
Incretins
Thiazolidinediones

Figure

• 

  Fig. 1 The hypothesis of osteocyte dysfunction and hypermineralization. Hyperglycemia decreases bone resorption by inhibiting the osteoclast and decreases bone formation directly by inhibiting the osteoblast and indirectly by increasing sclerostin production by the osteocytes. The reduced bone turnover leads to microcracks and bone fractures. Furthermore, the hyperglycemia triggers hypermineralization in the bone causing high bone mineral density (BMD).

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