Fracture risk may be higher after bariatric surgery than after treatment with weight-loss drugs, propensity-score matched data suggested.
Among 2,887 matched pairs, adults with obesity who received the GLP-1 receptor agonist semaglutide (Ozempic, Wegovy) had a 26% lower risk of fracture than those who underwent sleeve gastrectomy (HR 0.74, 95% CI 0.56-0.98), reported Jairo Noreña, MD, of Stanford University in California.
Over the roughly 3-year follow-up period, 86 patients (2.98%) treated with semaglutide and 128 patients (4.43%) who underwent a sleeve gastrectomy experienced a fracture.
The findings underscore a possible bone benefit with GLP-1 receptor agonists, Noreña said at the annual meeting of the American Association of Clinical Endocrinology. He referenced preclinical data, mostly about first-generation drugs, that indicated GLP-1 agonists may promote bone formation by increasing osteoblast differentiation and survival while reducing osteoclast differentiation and resorption.
Timothy Garvey, MD, of the University of Alabama at Birmingham, questioned the interpretation of the study results. "I think one way to look at it is semaglutide-associated weight loss could produce more fractures [than no treatment], and bariatric surgery, even more than that," he commented during a Q&A session.
Garvey, who wasn't involved with the research, brought up two prior landmark studies, the first being the SELECT study. While there was an overall low fracture rate in 17,600 participants over 3 years of follow-up, there was a somewhat higher fracture rate in the semaglutide group than the placebo group, an imbalance that emerged only in postmenopausal female patients.
"In the Look AHEAD study -- lifestyle intervention and diabetes -- some analyses with longer follow-up showed increased fractures in the intensively treated group, who lost more weight than the control group," Garvey added. "I just think fractures with especially pharmaceutically-induced weight loss is a longer-term adverse event that we haven't thought as much about."
While his study didn't have a comparator group who lost no weight, Noreña said this is an area for future research.
For their retrospective cohort analysis, Noreña's group scanned the Eversana Life Sciences electronic health record dataset, which represented over 130 million patients from community hospitals and large practices in the U.S. They looked for adults with a diagnosis of obesity at least 90 days prior with no history of fracture from January 2016 to December 2023. Most (72%) started treatment or underwent surgery since 2020.
All patients started semaglutide or had sleeve gastrectomy -- currently the most common bariatric surgery in the U.S. -- within 1 year of their obesity diagnosis. Using propensity-score matching, the researchers paired 2,887 patients based on sociodemographic and clinical factors.
Even after matching, more patients on semaglutide had diabetes (40.15% vs 30.14%) and diabetes with complications (12.37% vs 7.59%) compared with the surgery group. This was likely because some data were collected prior to semaglutide's approval for chronic weight management in June 2021, Noreña pointed out.
Fewer patients on semaglutide had chronic pulmonary disease and mild liver disease. About half of the study sample was white, 78% were female, and the average age was 45 years -- younger than the average age at menopause. One audience member highlighted this as a limitation, saying he was most concerned about bone outcomes in his postmenopausal patients.
The analysis didn't adjust for weight lost, which presumably was higher in the bariatric surgery group. Noreña said his group has examined this and will soon share findings.
Disclosures
Noreña reported no disclosures.
Primary Source
American Association of Clinical Endocrinology
Source Reference: Noreña J, et al "Fracture risk following semaglutide treatment vs. sleeve gastrectomy" AACE 2025.
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