Popular weight-loss and diabetes drugs known as glucagon-like peptide-1 receptor agonists (GLP-1s) may raise the risk of osteoporosis and gout, according to new research presented Monday (March 2) at the annual meeting of the American Academy of Orthopaedic Surgeons (AAOS) in New Orleans, Louisiana.

The study, which has not yet been published in a peer-reviewed journal, analyzed five years of medical records from more than 146,000 adults diagnosed with both obesity and Type 2 diabetes. Researchers compared patients taking GLP-1 drugs — including semaglutide, sold under the brand names Ozempic and Wegovy, and liraglutide, sold as Victoza and Saxenda — to patients not taking them.

The study found that about 4% of GLP-1 users developed osteoporosis, compared with just over 3% of nonusers — a roughly 30% increased risk. Osteomalacia, a condition that causes the bones to soften, was rare overall but occurred about twice as often in GLP-1 users. Gout rates were also slightly higher — 7.4% for GLP-1 users versus 6.6% for nonusers — representing about a 12% increased risk.

Dr. John Horneff, an associate professor of orthopedic surgery at the University of Pennsylvania and the lead author of the study, said he began investigating after noticing some patients developed serious tendon tears from minor injuries. "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 weakens bones, making them more likely to break — even from a small fall. It's a common concern for older adults and people who lose a large amount of weight quickly. Gout is a painful form of arthritis caused by too much uric acid in the body, which can spike during rapid weight loss.

Horneff compared the bone changes to what happens to astronauts in space. "There's nothing forcing their bones to kind of hold their weight anymore," he said. "And a lot of those astronauts come back with low bone density."

Muaaz Wajahath, a fourth-year medical student at Michigan State University College of Human Medicine and the study's primary investigator, said clinicians should act now. According to the AAOS press release, Wajahath said, "Whenever you have a patient who is prone to osteoporosis, gout or osteomalacia, clinicians should consider bone health surveillance and monitor for delayed-onset complications in at-risk populations."

Because the study was observational, it cannot prove the drugs directly caused these conditions. Researchers also lacked data on patients' diets, exercise habits, or whether they were taking vitamins like calcium or vitamin D — both of which are key to bone health.

The new results echo 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.

Murphy, Sam & Jodi

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