- Researchers investigated how a common anti-osteoporosis drug, alendronate, affects patients’ risk of developing diabetes.
- The study found that patients who took alendronate were 36% less likely to develop type 2 diabetes than those who did not take the drug.
- The researchers say that further studies and clinical trials are needed to understand why anti-osteoporosis drugs may reduce the risk of type 2 diabetes, and if it could one day be used as a preventive measure for the condition.
Diabetes is a chronic disease involving the body’s production and response to insulin, a hormone that regulates blood sugar.
Over time, unmanaged blood sugar damages nerves and blood vessels, as well as many of the body’s systems. Complications from diabetes include cardiovascular disease, kidney disease, neuropathy, blindness, and lower extremity amputation.
Type 1 diabetes typically occurs during childhood. It happens when the body does not produce enough insulin and thus requires daily insulin injections.
Type 1 diabetes is much rarer than type 2 diabetes, which happens when the body does not use insulin effectively. This condition is linked to lifestyle factors, including excess body weight and physical inactivity.
Globally, the number of people living with diabetes has risen, from an estimated 108 million people in the 1980s to 476 million in 2017. The World Health Organization (WHO) says that in 2019, 1.5 million deaths worldwide were directly linked to the condition. The underlying causes and mechanisms of diabetes, however, are still being explored.
Previous research has found that the balancing of blood sugar levels, known as glucose homeostasis, affects the formation of bones, known as bone homeostasis, and vice versa.
Studies have also reported that some antidiabetes drugs may affect the skeleton and that anti-osteoporosis drugs may influence glucose metabolism. Osteoporosis is a condition in which bones become weak, fragile, and more likely to break.
Understanding the effects of anti-osteoporosis medications on diabetes could help treat and prevent the condition.
In a recent study, researchers from Aalborg University Hospital, Aalborg, Denmark, conducted an observational study on how first-line osteoporosis medication, alendronate, affects type 2 diabetes risk.
“It has been known for decades that people with diabetes are in greater risk of fractures, compared to people without diabetes,” Rikke Viggers, MD, one of the authors of the study, told Medical News Today. “In addition, a few studies during the last 10 years have suggested that treatments against osteoporosis may as well impact on glucose metabolism.”
“These results suggest that alendronate may protect against type 2 diabetes in a dose-dependent manner with a possible effect of higher compliance, but we question the mechanism of action,” she added.
The study was presented at the annual meeting of the European Association for the Study of Diabetes. Once peer-reviewed, the research may appear in the journal Diabetologia.
Data analysis
The researchers examined hospital records between 2008–2018 from the Danish National Patient Registry to identify patients 50 years and older who developed diabetes after 2008.
They then matched each of these individuals with three randomly selected people without diabetes. Altogether, the researchers examined records from 163,588 people with type 2 diabetes and 490,764 matched controls. Their mean age was 67 years old, and 45% were female.
The researchers also examined redeemed prescription records from the Danish National Health Service Prescription Database to calculate whether participants used alendronate and how this influenced diabetes onset.
The researchers found that patients who had taken alendronate were 36% less likely to be diagnosed with type 2 diabetes than those who did not take the drug.
They also found a dose-dependent effect of taking the drug: The longer patients took alendronate, the lower their risk of being diagnosed with type 2 diabetes.
Those taking alendronate for more than 8 years were 53% less likely to develop type 2 diabetes than those who did not use the drug.
Unknown mechanisms
“We do not know the mechanism of action and if this even exists — we need more clinical trials,” Dr. Viggers told MNT. “However, it is possible that alendronate impacts directly in peripheral cells, e.g., a direct action on adipose and muscle tissue.”
“It is also likely, that the effect is driven indirectly by the known alteration of bone cells by alendronate. This will change secretion and release of bone metabolites that are potential actors on insulin sensitivity and glucose metabolism,” Dr. Viggers added.
“Since this is an observational study, the major concern is that people who are prescribed alendronate were a group that is less likely to get diabetes,” Grenye O’Malley, MD, assistant professor of diabetes and bone disease at the Icahn School of Medicine at Mount Sinai, who was not involved in the study, told MNT.
“Though the authors report controlling for current BMI, women who have been low weight throughout their lives are more likely to have osteoporosis and less likely to have diabetes. This association could be what is being picked up in this study,” she continued.
“There are some hypotheses also related to vitamin D also having an effect on diabetes. If those studies were to also confirm this, it would give weight to there being a closer link between bone metabolism and diabetes,” she added.
“Another concern is that the difference in diabetes rates was seen in people who took alendronate for over 8 years — since we now often start drug holidays when using alendronate to treat osteoporosis after 5 years, this population may have had more severe osteoporosis,” she explained.
The researchers conclude that their results suggest a possible protective effect of alendronate against type 2 diabetes. However, they say that future clinical research is needed to see if the drug regulates blood sugar levels.
“This is a register-based study that is merely ‘just’ generating hypotheses, so, these results need to be confirmed in one and more clinical trials before we can talk about a possible causality and potential to impact on current guidelines,” said Dr. Viggers.
“We are currently performing a clinical trial to investigate if alendronate may actually improve glucose metabolism and insulin sensitivity among people with diabetes.”
“It could be beneficial to include high quality analyses, e.g., insulin clamp, tissue biopsies, and bone markers before and after alendronate treatment to investigate if and where the effect of alendronate is located. If this is the case, alendronate could be beneficial as treatment in patients with osteoporosis and high risk of developing type 2 diabetes,” she added.
Study strengths and limitations
“It’s promising that long-term use of alendronate — a cheap and readily available drug that is commonly used to treat osteoporosis — is linked to reduced risk of developing type 2 diabetes,” Esther Walden, senior clinical advisor at Diabetes UK, who was not involved in the study, told MNT.
“In the meantime, this research may help inform clinicians’ decisions, with alendronate potentially offering an added advantage when treating people with bone density issues who may also be at risk of type 2 diabetes,” she added.
“At this point, I would not change management based on this study since it was observational, but it should prompt a lot more research,” said Dr. O’Malley, “Use of alendronate for long term is likely not the answer to preventing diabetes, but this finding could prompt other research to learn more about bone and diabetes metabolism.”
“This study is an interesting one,” Robert Gabbay, MD, Ph.D., chief scientific and medical officer for the American Diabetes Association, told MNT. “Since it represents looking back at data previously collected (retrospective analysis), one can only create a hypothesis around the possibility that alendronate may be beneficial. We, of course, always like to see the full paper for better analysis and it is difficult to judge based on an abstract.”
“If these results hold true, I suspect there are many other data sets that could be interrogated to see if there is some association between alendronate use and diabetes. The limitation of the study is that it is retrospective. And of course, the full studies have not been published yet, to my knowledge,” he added.
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