GLP-1 drugs — including Ozempic and Wegovy — may be tied to a slightly higher risk of osteoporosis and gout, according to research presented Monday at the American Academy of Orthopaedic Surgeons’ annual meeting.
Dr. John Horneff, an associate professor of orthopedic surgery at the University of Pennsylvania and the lead author of the study, said he began looking into the issue after some patients appeared to develop serious tendon tears after relatively minor injuries. That led them to examine whether GLP-1s might affect bone and other connective tissue more broadly.
“People are taking these medications, and obviously there’s a tremendous amount of upside,” Horneff said. “But with that, they start to decrease their intake of food and nutrients.”
Osteoporosis is a disease that weakens the bones and makes them likelier to break or fracture, often from minor falls. It’s a common concern for many older adults and for people who lose a significant amount of weight over a short period of time. Gout, meanwhile, is a painful form of arthritis that can occur 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, which has not yet been published in a peer-reviewed journal, researchers analyzed five years of medical records from more than 146,000 adults with a diagnosis of both obesity and Type 2 diabetes.
The study compared patients taking GLP-1 drugs to patients not taking them.
The records didn’t include detailed information about which GLP-1 drug each patient was taking, though medications documented included semaglutide, sold as Ozempic and Wegovy, and liraglutide, sold as Victoza and Saxenda.
About 4% of GLP-1 users developed osteoporosis, compared with a little over 3% of nonusers — an increased risk of about 30%. A related condition, osteomalacia, which involves the softening of the bones, was rare but also occurred about twice as often among people on GLP-1s.
Rates of gout were also slightly higher — 7.4% for GLP-1 users versus 6.6% for nonusers — an increased risk about 12%.
“It’s not huge,” Horneff said. “But within that data that was put in there, you even saw nearly a doubling of the risk of having some sort of bone mineral density issue at five years.”
“Weight loss does cause bone loss,” Dr. Clifford Rosen, a professor of medicine at Tufts University who has been studying the potential impact of GLP-1s on bone health. He wasn’t involved with the new research.
“The question we’ve been studying is whether this is a normal compensation of the skeleton, it’s just reshaping itself, or whether this is truly a risk for losing bone that’s more rapid than what would be expected,” Rosen said.
Because the new research was observational, it can’t prove the medications caused either condition. Horneff said the team didn’t know about 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 research, including a study published in February in the Journal of Clinical Endocrinology & Metabolism that linked GLP-1 drugs to a higher risk of osteoporosis-related fractures in older adults with Type 2 diabetes.
The Food and Drug Administration notes in its label for semaglutide that it might increase the risk of bone fractures in older adults and women, Rosen said.
Dr. Susan Spratt, an endocrinologist and the senior medical director for the Population Health Management Office at Duke Health in North Carolina, questioned whether the increased risk was due to the rapid weight loss or some other mechanism of the drug.
She said some studies have suggested musculoskeletal benefits with GLP-1 drugs and that she often sees improvements in joint pain among patients who lose weight on the medications. But she emphasized that joint health and bone density are not the same.
Horneff said more research is needed to understand why GLP-1 drugs might affect bone health.
One theory, he said, is that because the medications suppress appetite, some patients may not get enough key nutrients, such as vitamin D and calcium, which are important for maintaining bone health.
Another possibility is that the rapid weight loss itself changes how the body builds and breaks down bone.
“It’s the same idea like when we always hear about astronauts going up into space and they’re in a gravity-zero environment for too long,” Horneff said. “There’s nothing forcing their bones to kind of hold their weight anymore. And a lot of those astronauts come back with low bone density. So the thought is, these patients, their skeleton was used to kind of maintaining one frame, and then all of a sudden, that’s being decreased.”
For gout, Horneff said, rapid weight loss can lead to a temporary spike in uric acid, increasing the risk of gout.
Dr. Christopher McGowan, a gastroenterologist who runs a weight loss clinic in Cary, North Carolina, said that even if GLP-1 drugs do increase the risk, it doesn’t mean patients are powerless. Other data, he said, suggest that when GLP-1s are combined with structured exercise, bone density loss is largely mitigated.
“That tells us lifestyle factors play a major role,” he said.
The research, McGowan said, shouldn’t alter the prescribing of GLP-1 medications. He said it’s a reminder that obesity treatment also requires guidance on protein intake, exercise and bone health monitoring.
“The takeaway isn’t fear. It’s refinement,” he said.
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