Diabetes, diabetic medications, and risk of fracture

Patients affected with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) present high risk of fragility fractures. While lack of insulin or Insulin-like growth factor 1 may compromise peak of bone mass in T1D, pathophysiology of T2D is more complex and still not fully determined. Both forms of diabetes present lower bone turnover, altered bone material properties and microstructure. Possible mechanisms include impaired collagen properties caused by deposition of advanced glycation end products, oxidative stress, chronic hyperglycemia, inflammation, microvascular damage, and increased SOST activity. Fracture risk is increased in patients with higher HBA1c, with cardiovascular complications or longer duration. Diagnosis and fracture prediction is challenging, considering that bone mineral density is usually decreased in T1DM, but often normal or increased in T2DM (mostly at the trabecular level) compared with an age-matched control population. Other factors should be taken in consideration in clinical practice, from medications that may induce hypoglycemic events (insulin or sulphanylureas) or compromise bone quality (such as thiazolidinediones), sarcopenia, sudden weight loss. Antiosteoporotic medications have not been specifically tested in diabetic patients but data from post hoc analyses or observational studies confirm efficacy and safety for most bisphosphonates, denosumab or teriparatide.