Diabetes Drugs and Bone Fractures

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Bone fractures and hypoglycaemia treatment in type 2 diabetic patients: a case-control study, by M. Monami and colleagues. Diabetes Care. Published online ahead of print on 16 November 2007

What is the problem and what is known about it so far?

People with type 2 diabetes have more bone fractures than those without diabetes. Insulin and the diabetes drugs called thiazolidinediones (rosiglitazone [Avandia, GlaxoSmithKline] and pioglitizone [Actos, Takeda]) have been linked to higher rates of bone fracture.   

Why did researchers do this particular study?

The researchers wanted to determine the effects of insulin and different type of diabetes medicines on the rate of bone fractures.

Who was studied?

Eighty-three patients with bone fractures and 249 patients without bone fractures, all with type 2 diabetes.

How was the study done?

Patients were identified from a larger group of people who had been treated for about 4 years at a diabetes clinic in Florence, Italy. The researchers looked at what types of medicines the patients were taking and for how long. Each fracture patient was compared to three similar patients who did not have fractures.

What did the researchers find?

Long-term treatment with either insulin secretagogues (which improve insulin release from the pancreas); the insulin sensitizer metformin (Glucophage, Bristol Myers-Squibb); or insulin did not affect the rate of bone fractures. However, when looking at the type of treatment at the time fractures occurred, insulin use was associated with more fractures for men, but not for women.

What were the limitations of the study?

The study identified bone fractures from hospital records and so may have missed fractures that did not result in hospital care. The researchers did not collect information about patients’ bone density and frequency of falls and so could only speculate about why some medicines are associated with bone fractures. Finally, researchers relied on patient reports, which could be lower than, and prescription records, which could be higher than patients’ actual use of diabetes medicines.

What are the implications of the study?

Because the insulin sensitizer metformin did not increase bone fractures, it is likely that rosiglitazone and pioglitazone, also insulin sensitizers, increase fracture rates not because of their insulin-sensitizing effects, but instead because of how they affect bone metabolism. Because long-term insulin use does not affect bone frailty, higher fracture rates with insulin may be caused by falls during hypoglycemic events (“lows”) or diabetes complications, which are more common among those who have longstanding diabetes, who are more likely to use insulin. The risk of bone fractures should be considered when choosing diabetes medicines.

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