A nationwide, retrospective, case-control study of older adults in Denmark suggests that the bisphosphonate alendronate that is widely used to treat osteoporosis may protect against new-onset type 2 diabetes. But these preliminary findings need to be confirmed in a randomized controlled trial, experts said.
The registry study showed that from 2008 to 2018, among individuals in Denmark age 50 and older (with a mean age of 67), those who were taking alendronate were 36% less likely to have new-onset type 2 diabetes than age- and sex-matched individuals who were not taking the drug, after controlling for multiple risk factors.
The results also suggest that longer alendronate use and higher compliance might be more protective.
Rikke Viggers, MD, a PhD student in the Department of Clinical Medicine, Aalborg University, Denmark, presented the findings during an oral session at the European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.
“Excitingly, our research suggests that alendronate, an inexpensive medicine widely used to treat osteoporosis, may also protect against type 2 diabetes,” Viggers summarized in a press release issued by the EASD.
“Type 2 diabetes is a serious lifelong condition that can lead to other serious health issues such as stroke, heart disease, blindness, and limb amputation,” she noted, “and anything that prevents or even delays it will also reduce a person’s risk of all these other conditions.”
“We believe that doctors should consider this when prescribing osteoporosis drugs to those with prediabetes or at high risk of type 2 diabetes,” she added.
Preliminary Results, Need for RCT
However, importantly, these are preliminary results, Viggers cautioned during the oral presentation and in an email to Medscape Medical News. “This is a registry-based study,” she stressed, “and we cannot conclude causality.”
“We do not know if this effect [of decreased risk of developing diabetes among people taking alendronate] is ‘real’ and what the mechanisms are.”
“It could be a direct effect on peripheral tissues, for example, muscle and adipose tissue,” Viggers speculated, “or an indirect effect through bone metabolites that may impact glucose metabolism.”
The group is now conducting a randomized controlled trial in patients with diabetes and osteopenia or osteoporosis to examine the relationship between alendronate and insulin sensitivity, bone indices, and glycemic control.
They also aim to investigate whether alendronate is the optimal anti-osteoporotic therapy for patients with type 2 diabetes. Preliminary results suggest that other bisphosphonates have similar effects.
“Alendronate decreases bone turnover and may not be beneficial in healthy bones,” Viggers noted. “However, as far as I know, potential other side effects have not been tested in healthy bones,” so further research is needed.
Invited to comment, Charles P. Vega, MD, who presented a case and a crowd-sourced opinion for Medscape about deprescribing bisphosphonates, noted that type 2 diabetes is most often diagnosed between age 40 and 60, although a few cases are diagnosed after age 65, and the study by Viggers and colleagues suggests that alendronate might help lower the risk of diabetes onset in these older adults.
“This is an interesting retrospective analysis,” said Vega, health sciences clinical professor, family medicine, University of California, Irvine, but like the study authors, he cautioned that “it should be verified with other data.”
“A meta-analysis from clinical trials of bisphosphonates which followed blood glucose levels would be helpful,” he said.
Current Registry Study Findings
Glucose homeostasis has been linked to bone metabolism, Viggers said, and bisphosphonates were associated with increased insulin sensitivity and decreased risk of diabetes risk in two registry studies from Denmark and Taiwan.
The researchers aimed to investigate if the risk of developing type 2 diabetes was altered by previous use of alendronate.
Using data from the national Danish Patient Registry, they identified 163,588 individuals age 50 and older newly diagnosed with type 2 diabetes in 2008-2018.
They matched each patient with three individuals of the same gender and age range who did not have diabetes, for a total of 490,764 controls.
Roughly two thirds of participants were in their 50s or 60s, a quarter were in their 70s, and 10% were 80 or older. About half of participants were women (45%).
Compared to the patients with new-onset type 2 diabetes, the control participants were healthier: they were less likely to have obesity (6% vs 17%) and had a lower mean Charlson Comorbidity Index (0.38 vs 0.88).
Using data from the national Danish Health Service Prescription Registry, the researchers identified individuals who filled prescriptions for alendronate in 2008-2018.
After controlling for heavy smoking, alcohol abuse, obesity, pancreatitis, hyperthyroidism, hypothyroidism, glucocorticoid use, marital status, household income, and Charlson Comorbidity Index, people taking alendronate were less likely to have new-onset diabetes than those not taking this drug (odds ratio [OR], 0.64; 95% CI, 0.62 – 0.66).
The odds of developing type 2 diabetes were even lower among those who took alendronate for 8 years or more versus never-users (OR, 0.47; 95% CI, 0.40 – 0.56), after controlling for the same variables.
Session Chair Zhila Semnani-Azad, a PhD student in nutritional science, University of Toronto, Ontario, Canada, wanted to know if the researchers accounted for physical activity and vitamin D use. Viggers replied that the registries did not have this information.
The study was funded by a Steno Collaborative Project grant from the Novo Nordisk Foundation, Denmark. Viggers has disclosed receiving a grant from the foundation. Vega has disclosed serving as a consultant for Johnson & Johnson.
EASD 2021 Annual Meeting. Presented September 28, 2021. Abstract 71.
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