New research presented to orthopaedic surgeons in the United States has raised significant questions about the potential impact of popular weight-loss medications on musculoskeletal health, suggesting a notable increase in the risk of bone and joint conditions.
The study, presented at the American Academy of Orthopaedic Surgeons (AAOS) annual meeting in New Orleans, analysed five years of medical records from tens of thousands of adults with obesity and Type 2 diabetes. It found “statistically significant increases” in the diagnoses of osteoporosis, gout, and osteomalacia among those using GLP-1 receptor agonist drugs, such as semaglutide (found in Ozempic and Wegovy), compared to non-users.
According to the AAOS statement, the risk of the degenerative bone disease osteoporosis was approximately 30% higher for GLP-1 users. The bone-softening condition osteomalacia occurred about twice as often, while diagnoses of gout, a painful form of arthritis, were 12% more frequent.
Understanding the potential links
The research is observational and cannot prove the medications caused these conditions. However, the researchers outlined several biological mechanisms that could explain the associations, emphasizing that the rapid, widespread adoption of these drugs warrants close scrutiny of their long-term effects on bone and joint health.
A primary concern is that GLP-1 drugs suppress appetite and slow gastric emptying, which can lead to reduced intake and impaired absorption of essential nutrients. Nutritional deficiencies are common among users, with vitamin D deficiency—critical for calcium absorption and bone strength—being the most frequently diagnosed. Deficiencies in iron, B vitamins (including thiamine and B12), calcium, protein, and minerals like zinc and selenium have also been observed.
“Any medication that sees this rapid adoption warrants close examination, particularly in orthopedics where obesity and surgical intervention often overlap, and when the long-term effects of GLP-1 RA exposure on bone and joint health remain poorly understood,” said Muaaz Wajahahth, a fourth-year medical student at Michigan State University College of Human Medicine, who was involved in the research.
Rapid weight loss itself presents multiple risks. It can decrease the mechanical load on bones, akin to astronauts in zero gravity, signaling the body to reduce bone production. It also frequently leads to muscle loss (sarcopenia), which is linked to osteoporosis. In women, rapid weight loss can cause a decrease in bone-protecting estrogen levels. Furthermore, shedding pounds quickly can trigger a temporary spike in uric acid—a waste product created when the body breaks down chemicals called purines—thereby raising the risk of gout.
“It may also be possible that the weight loss changes how the body builds and breaks down bone,” Dr. John Horneff, an associate professor of orthopedic surgery at the University of Pennsylvania and the study’s lead author, told NBC News.
Context and existing warnings
The findings align with some previous research, including studies linking the drugs to a higher risk of osteoporosis-related fractures in older adults with Type 2 diabetes. The U.S. Food and Drug Administration label for semaglutide already notes it may increase the risk of bone fractures in older adults and women.
Women are more susceptible to fractures due to having smaller, thinner bones and a sharp decline in protective estrogen during menopause, according to the Bone Health & Osteoporosis Foundation. However, some research presents a nuanced picture, suggesting GLP-1 drugs might have neutral or even beneficial effects on bone health in certain contexts, particularly for patients with Type 2 diabetes.
The conditions highlighted by the study are major public health concerns. Osteoporosis, the most common bone disease, affects some 10 million Americans. Tied to genetics, age, gender, and chronic health conditions, it increases fracture risk and can lead to loss of height and changes in posture. Gout already afflicts more than nine million Americans, being more common in older people and men, and can also be influenced by genetics, obesity, and kidney disease. Osteomalacia, caused by severe deficiencies in vitamin D, calcium, or phosphate, is rarer, affecting approximately one in 1,000 people in the U.S. since milk fortification in the 1930s.
Clinical recommendations and ongoing research
The researchers stress that their findings indicate patients on these medications need their bone health monitored closely. They recommend clinicians consider bone health surveillance and targeted nutritional assessments for those at risk. Mitigation strategies could include ensuring adequate protein consumption, weight-bearing exercise, and correcting vitamin deficiencies—osteomalacia, for instance, is often treatable by addressing vitamin D and calcium shortfalls.
Separate research presented at the same conference suggested that stopping GLP-1 drugs 14 days before total joint replacement surgery could minimise anaesthesia-related complications, such as aspiration. Meanwhile, the scientific quest to understand the full impact continues. A clinical trial is underway to assess semaglutide’s effects on bone metabolism in adolescents with obesity, and a drug called bimagrumab is being investigated for its potential to counteract the muscle and bone loss associated with rapid weight loss.
The study from the AAOS meeting remains preliminary, awaiting publication in a peer-reviewed journal. A significant limitation is the lack of data on whether patients maintained healthy diets, exercise regimens, or took bone-supporting supplements, all factors that could mitigate the observed risks.
