Fracture risk and brittle bones in type 2 diabetes

The authors aimed to analyze data available on type 2 diabetes and osteoporosis (condition that causes bone fragility) and determine the best treatment course to avoid osteoporosis development. The authors concluded that type 2 diabetes moderately increases the risk of fracture, and that new treatments that have a neutral or positive effect on bone health are needed.

Type 2 diabetes is a chronic disease associated with many complications. These include kidney problems, eye disease, nerve damage and heart disease. Bone fragility is a complication often overlooked as it is not life-threatening. Bone fragility results in an increased risk of breaks and fractures. This can impact patient quality of life and can lead to prolonged disability. Body mass index and bone mineral density play a large role in determining the risk of osteoporosis in patients with type 2 diabetes. Body mass index (BMI) measures height and weight to determine overall body mass. Bone mineral density (BMD) is a measure of the amount of minerals (such as calcium) in the bones. This indicates the risk of fracture or broken bones.

The aim of this study was to review data on bone fragility in type 2 diabetes and its management.

In a study examining bone fractures in type 2 diabetes, there was a 64% increased risk of fracture. This was at any body site in patients with diabetes compared to non-diabetic participants. In another study, women with type 2 diabetes experienced a 20% increased risk of fracture.

A separate review noted that patients with type 2 diabetes had two to three times the risk of hip fracture. However, this increased risk was not explained by BMD. In an analysis of 35 studies, patients with type 2 diabetes had a BMD 4-5% higher than patients without diabetes. When an increased BMI and BMD were analyzed together, an increased BMI protected against hip fractures. However, individuals who were overweight or obese were at an increased risk of ankle and upper arm fractures. 

Treatments for type 2 diabetes have also been associated with bone fragility. Results from trials assessing metformin (Glucophage) suggested that this treatment might have either a beneficial or neutral effect on bone. An analysis of 22 trials looking at the effect of thiazolidinediones reported a two times increased risk of fracture when rosiglitazone (Avandia) and pioglitazone (Actos) were used in women. 

An analysis of glucagon-like peptide 1 (GLP-1) agonists reported that they seemed to be neutral with respect to fracture risk. Liraglutide (Victoza) was associated with a 62% reduction in the risk of fractures. However, another GLP-1 agonist, exenatide (Byetta), was associated with double the risk of developing fractures. Further trials are needed to confirm whether GLP-1 agonists can be used in patients at high risk of fracture. 

In one meta-analysis of adverse events, DPP-4 inhibitors (such as Januvia) were associated with 40% decrease in the number of fractures. However, more research is needed.

Sodium-glucose co-transporter type 2 (SGLT2) inhibitors (such as Farxiga) have been associated with an increase in the risk of fracture. Canagliflozin (Invokana), for example, was associated with a 35% increased risk of fracture.

Recommendations for improving bone health include optimum calcium and vitamin D intake, as well as exercise and home modifications to reduce the risk of falling. An HbA1c level (a measurement of average blood glucose levels over the past 3 months) of between 7 to 7.5% is recommended, as higher HbA1c levels have been associated with increased fracture risk. However, the needs of the individual patient must be considered.

The authors concluded that type 2 diabetes leads to a moderately increased risk of bone fracture. New treatments that have a neutral or positive effect on bone health are needed in diabetes to reduce to risk of fracture in those at risk.