GLP-1 drugs — including Ozempic and Vegovi — may be linked to a slightly higher risk of osteoporosis and gout, according to research presented Monday at the American Academy of Orthopedic Surgeons annual meeting.
Dr. John Horneff, assistant professor of orthopedic surgery at the University of Pennsylvania and lead author of the study, said he began looking into the problem after some patients developed serious tendon tears after relatively minor injuries. This led us to examine whether GLP-1s could affect bone and other connective tissues more widely.
“People are taking these drugs, and obviously there’s a tremendous amount of upside,” Horneff said. “But with that, they start to reduce their food and nutrient intake.”
Osteoporosis is a disease that weakens bones and makes them prone to breaking or fracturing, often from minor falls. This is a common concern for many older adults and people who lose significant amounts of weight in a short period of time. Gout, meanwhile, is a painful form of arthritis that occurs when the body has too much uric acid, which can come from a diet high in red meat and alcohol — as well as rapid weight loss.
In the new study, not yet published in a peer-reviewed journal, researchers analyzed five years of medical records from more than 146,000 adults diagnosed with obesity and type 2 diabetes.
The study compared patients taking GLP-1 medications to patients not taking them.
The records did not include detailed information about which GLP-1 drug each patient was taking, although the drugs documented included semaglutide, Ozempic, and Vegovi, and liraglutide, marketed as Victoza and Saxenda.
About 4% of GLP-1 users developed osteoporosis, compared to slightly more than 3% of non-users — an increased risk of about 30%. A related condition, osteomalacia, which involves softening of the bones, was rare but twice as common in people on GLP-1s.
Gout rates were also slightly higher – 7.4% for GLP-1 users and 6.6% for non-users – with the risk increased by about 12%.
“It’s not that big,” Horneff said. “But in the data that was put out there, you saw a doubling of the risk of having some type of bone mineral density problem within five years.”
“Weight loss causes bone loss,” Dr. Clifford Rosen, professor of medicine at Tufts University, has studied the potential effect of GLP-1s on bone health. He is not involved in new research.
“The question we’re studying is, is this a normal repair of the skeleton, is it remodeling itself, or is it really a risk of losing bone, much faster than expected,” Rosen said.
Because the new research is observational, it cannot prove either drug caused the condition. Horneff said the team didn’t know about the patients’ diet or exercise habits, or whether they were taking vitamin D supplements or other nutrients important for bone health. But the results echo other findings, including a study published in February in the Journal of Clinical Endocrinology & Metabolism that linked GLP-1 medications to an increased risk of osteoporosis-related fractures in older adults with type 2 diabetes.
The Food and Drug Administration suggests semaglutide on its label may increase fracture risk in older adults and women, Rosen said.
Endocrinologist and senior medical director of the Office of Population Health Management at Duke Health in North Carolina Susan Spratt questioned whether the increased risk was due to rapid weight loss or some other mechanism of the drug.
Some studies have suggested musculoskeletal benefits with GLP-1 drugs, and they often see improvements in joint pain in patients who lose weight on the drugs, he said. But he emphasized that joint health and bone density are not the same thing.
More research is needed to understand why GLP-1 drugs may affect bone health, Horneff said.
One theory is that because the drugs suppress appetite, some patients don’t get enough of important nutrients, such as vitamin D and calcium, which are important for maintaining bone health.
Another possibility is that rapid weight loss changes how the body builds and breaks down bone.
“We always hear about astronauts going into space and they stay in a zero-gravity environment for a long time,” Horneff said. “There’s nothing forcing their bones to hold their weight anymore. And most of those astronauts come back with low bone density. So the thinking is, these patients, their skeleton was used to maintain a kind of framework and then all of a sudden it’s decreasing.”
For gout, Horneff said, rapid weight loss can cause a temporary spike in uric acid, increasing the risk of gout.
A gastroenterologist who runs a weight loss clinic in Cary, North Carolina. Christopher McGowan, Although GLP-1 drugs increase the risk, this does not mean that patients are powerless. Other data, he said, show that when GLP-1s are combined with structured exercise, bone density loss is often reduced.
“This tells us that lifestyle factors play an important role,” he said.
The research, McGowan said, should not change the prescription of GLP-1 drugs. He added that obesity treatment requires guidance on protein intake, exercise and bone health monitoring.
“The takeaway is not fear. It’s refinement,” he said.
