Bone health in diabetes: considerations for clinical management

Background: The metabolic and endocrine alterations of diabetes adversely affect bone quantity and/or quality and may increase fracture risk. Scope: A survey of the scientific literature on diabetes and bone cited on PubMed/MEDLINE and published in English from January 1970 to November 2008. Findings: Subjects with type 1 diabetes have reduced bone mass and increased risk of fragility fracture, while those with type 2 diabetes, despite having normal or above-normal bone mineral density (BMD), are susceptible to low-trauma fractures, especially hip fractures. A recent meta-analysis, involving 836 000 subjects and 139 000 incident cases of fracture, found that type 2 diabetes was associated with significantly increased risks of non-vertebral (relative risk 1.2), hip (relative risk 1.7) and foot (relative risk 1.3) fracture. The association with hip fracture persisted after adjustment for age, physical activity and body weight, and was more pronounced in men and in those with long-standing diabetes. Insulin has an anabolic effect on bone, and the qualitatively different effects of type 1 and type 2 diabetes on bone mass are consistent with the opposing insulin-secretory states (hypoinsulinaemia vs. hyperinsulinaemia). However, the existence of an elevated fracture risk in type 2 diabetes, despite the underlying hyperinsulinaemia, suggests the involvement of other potential pathogenic influences (e.g., hyperglycaemia, diabetic complications and lifestyle factors) on bone. Animal studies suggest that diabetic bone may be more fragile than non-diabetic bone. Falls arising from diabetes-related comorbidities are another possible cause of low-trauma fracture. Clinical trial findings, supported by bone marker and bone density data, suggest that the oral antidiabetic agents metformin and glibenclamide significantly lower fracture risk, whereas the thiazolidinediones slightly increase fracture risk in postmenopausal women, but not in men, with type 2 diabetes. Recent preclinical studies have helped elucidate the mechanisms underlying the dynamics of bone remodelling, but more research is needed to improve outcomes for patients. Conclusions: Bone health is an important consideration in diabetes, and caution should be exercised in prescribing thiazolidinediones to postmenopausal women with low BMD and patients with prior fracture.