Could a Bisphosphonate Prevent Type 2 Diabetes?

Treatment with a common osteoporosis drug might help to stave off diabetes, according to new research.

In a nationwide case-control study, adults treated with the bisphosphonate alendronate (Fosamax) at any time in their life had a 36% lower odds for developing type 2 diabetes compared with individuals who had never used alendronate (adjusted OR 0.64, 95% CI 0.62-0.66), reported Rikke Viggers, MD, of Aalborg University Hospital in Denmark.

In addition, the longer a person was on alendronate appeared to increase the protection even further, as there was a significant dose-response relationship between longer use of the osteoporosis drug and reduced diabetes risk, Viggers noted during the virtual European Association for the Study of Diabetes meeting.

Specifically, those who were treated with the drug for more than 8 years -- the longest level of use included in the analysis -- saw a 53% reduced chance of developing diabetes (OR 0.47, 95% CI 0.40-0.56), she said. "These data suggest that alendronate may have the possibility to prevent or protect against later development of type 2 diabetes in a dose-dependent manner."

In addition, higher rates of drug compliance, which were estimated by dividing the cumulative dose of the drug by the duration of treatment, were also tied to a lower diabetes risk. This was quantified into a medication possession ratio, she said. "Though not significant, it seems that higher compliance could be related to decreased odds of type 2 diabetes."

Viggers noted that the findings are not especially surprising, since two previous population-based studies had reported a similar relationship.

"It seems that glucose and bone metabolism affect each other," Viggers said. "People with diabetes have a decreased bone turnover, and a high number of these patients have osteoporosis and increased fracture risk, even though the bone density measures via DXA scan are normal."

For the analysis, Viggers and her co-researcher drew upon data from the National Danish Patient Registry. A total of 163,588 adults with type 2 diabetes were included, who were diagnosed with diabetes between 2008 and 2018; those with type 1 diabetes were excluded from the analysis. Diabetes status was identified using ICD-10 code and redeemed drug prescriptions with an ATC code of a glucose-lowering drug in the Health Service Prescription Registry.

The type 2 diabetes patients were then matched in a 3:1 ratio based on age and sex, totaling 490,764 matched control subjects. About 55% of the cohort were male, and average age was 67.

Compared with matched controls, adults with type 2 diabetes were more likely to be heavy smokers; abuse alcohol; have obesity, pancreatitis, hyperthyroidism, or hypothyroidism; use glucocorticoids; and have a higher average Charlson Comorbidity Index score.

Viggers said that while the findings are promising, there are still questions about the exact mechanism of action that would explain the relationship, although there are suggestions that inflammation and oxidative stress could be involved.

Next steps for her research, she said, include further assessment of the intersection between insulin sensitivity, bone indices, and glycemic control, comparing measures in healthy people, those with prediabetes, and those with type 2 diabetes. She also hopes to investigate whether alendronate is the optimal anti-osteoporotic therapy for type 2 diabetes patients.

Study limitations, Viggers noted, included a lack of data on physical activity levels, body mass index, and vitamin D use -- any of which could potentially modify the findings.

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