GLP-1 drugs – including Ozempic and Wegovy – may be tied to a slightly higher risk of osteoporosis and gout, according to a study presented Monday at the annual meeting of the American Academy of Orthopedic Surgeons.
Dr. John Horneff, a professor of orthopedic surgery at the University of Pennsylvania and lead author of the study, said he began looking into the issue after some patients appeared to develop serious tendon tears after minor injuries. That led them to explore whether GLP-1 might affect bones and other connective tissues more broadly.
“People are taking these drugs, and obviously there’s a lot of upside,” Horneff said. “But with that, they start reducing their food intake and nutrients.”
Osteoporosis is a disease that weakens the bones and makes them more prone to fractures or breaks, usually from minor falls. It is a common problem for many adults and people who lose significant weight in a short period of time. Gout is a painful form of arthritis that can occur when the body has too much uric acid, which can come from eating too much red meat and alcohol – and rapid weight loss.
In the new study, which has yet to be 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 with patients not taking them.
The records did not include detailed information on which GLP-1 drug each patient was taking, although the drugs listed included semaglutide, sold as Ozempic and Wegovy, and liraglutide, sold as Victoza and Saxenda.
About 4% of GLP-1 users develop osteoporosis, compared to just over 3% of non-users – an increased risk of about 30%. A related condition, osteomalacia, which involves softening of the bones, was rare but also occurred about twice as often among people taking GLP-1s.
Rates of gout were also slightly higher – 7.4% in GLP-1 users compared to 6.6% in non-users – an increased risk of about 12%.
“It’s not a big deal,” Horneff said. “But in that data that was put in there, you even saw a doubling of the risk of having some kind of bone mineral density problem at five years.”
“Weight loss causes 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 was not involved in the new research.
“The question we’ve been studying is whether this is normal skeletal compensation, remodeling, or whether this is really a risk of faster-than-expected bone loss,” Rosen said.
Because the new study was observational, it cannot prove that the medication caused any condition. Horneff said the team did not know about the patients’ diet or exercise, or whether they were taking vitamin D or other nutrients important for bone health. But the results are consistent with 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 on its semaglutide label that it may increase the risk of bone fractures in older adults and women, Rosen said.
Dr. Susan Spratt, an endocrinologist and senior medical director of the Population Health Management Office at Duke Health in North Carolina, asked whether the increased risk was due to rapid weight loss or other medication.
He said other studies have suggested musculoskeletal benefits with GLP-1 drugs and that he often sees improvement in joint pain among patients who lose weight with the drugs. But he emphasized that joint health and bone strength are not the same.
Horneff said more research is needed to understand why GLP-1 drugs may affect bone health.
He said another theory is that because the medication suppresses appetite, some patients may not be getting important nutrients, such as vitamin D and calcium, which are important for maintaining healthy bones.
Another possibility is that rapid weight loss changes the way the body builds and breaks bones.
“It’s the same idea as we hear about astronauts going up into space and being in zero-gravity for a long time,” Horneff said. “There’s nothing to force their bones to hold their weight. And many of those astronauts come back with thin bones. So the thought is, these patients, their skeleton was used to support one skeleton, and then all of a sudden that shrinks.”
With gout, Horneff said, rapid weight loss can lead to a temporary increase in uric acid, which increases 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 increase the risk, it doesn’t mean that patients are powerless. Some data, he said, suggest that when GLP-1 is combined with structured exercise, the reduction in bone density is significantly reduced.
“That tells us that lifestyle factors play a big role,” he said.
The research, says McGowan, should not change the prescribing of GLP-1 drugs. He said it is a reminder that treating obesity also requires guidance on protein intake, exercise and monitoring bone health.
“The takeaway is not fear. It’s better,” he said.
