John “Gabby” Horneff, an orthopedic surgeon at Pennsylvania Hospital, had noticed a distinct trend: Some patients taking GLP-1s would come away with significant respiratory injuries from a relatively minor physical excursion.
For example, some suffer from rotator cuff tears in the shoulder area while Doing simple housework like vacuuming or raking leaves.
“They didn’t necessarily have to go down the stairs,” he said.
This anecdotal pattern of muscle injuries prompted him to conduct an investigation into whether the use of popular weight loss and diabetes medications increases a person’s risk of osteoporosis and gout.
His team looked at data from nearly 150,000 adults from the National Diabetes and Obesity Database. Half had taken GLP-1 for five years, and half had not. Their results were compared by looking at their medical records and accounting for factors including age, sex, race, BMI, tobacco use, and other health issues.
The rate of osteoporosis, a disease in which bones become fragile and break, was 3.2% in the group not taking the drug, compared to 4.1% in the GLP-1 group.
While significant, the difference is not cause for alarm, Horneff said. The findings, which have not yet been peer-reviewed, were presented earlier this month at the annual meeting of the American Society of Orthopedic Surgeons in New Orleans.
“It’s obviously helping patients a lot, but what are we supposed to be looking at?” Horniff said.
The study also found that the incidence of gout, a painful form of arthritis, was 6.6% in the group that did not take the drug and 7.4% in the GLP-1 group. This condition is caused by a build-up of uric acid, which can trigger rapid weight loss, he said.
The study was observational, meaning it could only find associations. The gold standard for establishing cause and effect relationships is a randomized controlled trial.
The GLP-1 drugs in the study — which include semaglutide (sold as Vigovi and Ozempic), liraglutide, dolaglutide, and exenatide — have skyrocketed in popularity in recent years for weight loss and blood sugar control.
They work by mimicking a hormone that the body naturally has, called GLP-1.
GLP-1 normally stimulates the pancreas to release Insulin, a hormone that acts like a key, opens the “door” to the cells to allow sugar to enter. Without it, sugar builds up in the blood. This has made GLP-1 drugs popular for use in diabetes.
Medicines can also reduce appetite by reducing the rate at which the stomach empties, and possibly through effects on the brain.
Attention is focused on the side effects of these drugs Gastrointestinal symptoms, but bone health is an area where research is still early — and conflicting.
For obesity medicine experts, the study’s findings are “nothing new,” said Carolyn Upwin, a professor at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital.
Patients are usually counseled about the potential bone damage that comes with weight loss and are asked to take preventative measures such as resistance training and the use of vitamin D and calcium supplements.
“When you lose weight, you’re at risk of losing bone,” said Upwin, who was not involved in the study.
An open question
Any form of weight loss—whether it’s due to medication, surgery, or lifestyle changes—usually leads to bone loss, experts say. said A person’s skeleton will not need as much weight, so it may adapt to the loss of bone density.
“Bones are constantly breaking and rebuilding themselves,” Horneff explained.
If a person does not engage in physical activity and does not exert force on their bones, bone density can be “wasted.”
Astrologers experience an extreme example of this when they Go to the International Space Station for a long time. When they come back to earth, their muscles are a little weaker, and they often have less bone density.
“They’re not used to the pull of gravity,” Horneff said. “There is no strength in their bones.”
Horneff theorizes that taking GLP-1 drugs without exercise can exacerbate this effect.
It’s possible that the associated loss of bone density is due to patients eating less, he said. GLP-1 drugs suppress appetite, which can lead to decreased vitamin D and calcium, important for bone health.
“I don’t want my patients to think, ‘I can just take this medicine, and I never have to work,'” Horneff said.
He thinks doctors should monitor patients’ bone health and nutrition labs to check for loss of density and risk of fractures.
Further research is needed
Studies have also looked at osteomalacia, a condition in which the bones become soft and weak. The rate was 0.2% in the group taking GLP-1s, compared to 0.1% in the group not taking the drug.
Elaine Yu, who directs the Bone Density Center at Massachusetts General Hospital in Boston, did not find this particular difference to be “very clinically significant,” arguing that the condition is often miscoded and likely underdiagnosed in both groups. She was not involved in the study.
However, she called the finding of osteoporosis “an early signal” and noted that “I don’t think it’s definitive.”
Future research on GLP-1 drugs should focus on the incidence of fractures, which loss of bone density can increase risk, she said.
Researchers should also study patients taking GLP-1s for obesity without diabetes. One said that the doses used for obesity are usually much higher than the doses used for diabetes.
The benefits still outweigh the potential risks.
One compared it to bariatric surgery, a weight-loss procedure that can cause significant bone loss and increase the risk of fractures.
Still, she said, she would not tell patients to avoid surgery, which in some cases can be life-saving.
He advises doctors to be proactive in monitoring risk in patients on GLP-1, particularly postmenopausal women and men over 50 who are already at high risk of bone loss due to their age. (The average age in Horniff’s study was 59.8 years, with half over 61.)
“While that may be a signal that we need to pay more attention to bone [health]I don’t think that should dissuade people from considering this treatment,” Yu said.
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