At a Glance

• Fracture risk with GLP-1s appears to vary by patient population.
• Some studies suggest fracture protection in patients with diabetes.
• Older adults and patients with severe obesity may face higher risk.

Estimated read time: 4 minutes

The widespread use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has facilitated large population studies examining associations between these medications and a range of health outcomes, including fracture risk. This class of medication impacts both the metabolic and mechanical environments of the skeletal system, a complex interplay that likely influences the net skeletal impact. Consideration of specific medications and underlying patient factors can help surgeons anticipate fracture risk for patients. AAOS Now interviewed two experts to clarify the topic.

Fracture protection
Overall, GLP-1 RA use appears to offer modest fracture protection in patients with diabetes. Several meta-analyses have been published, including one covering 44 randomized controlled trials, that demonstrated a pooled relative risk for fractures of 0.77 for patients using GLP-1 RAs compared to placebo or other diabetic medications. Another study in patients with diabetes found a lower risk of vertebral compression fractures with GLP-1 RA use.

In the wake of the GLP-1 RA explosion, Sun H. Kim, MD, MS, associate professor in the Stanford Endocrinology division, had concerns about the impact of weight loss on bone and muscle loss. Dr. Kim shared her preliminary study findings, recently presented at a national endocrine meeting, in an interview with AAOS Now. With her team, Dr. Kim performed a matched analysis of more than 35,000 patients with type 2 diabetes, which demonstrated a 15% fracture reduction in patients using semaglutide compared to dulaglutide and other FDA-approved weight loss medications. Sharing details of her study and discussing possible mechanisms for the results, Dr. Kim noted that in populations with diabetes, fracture risk factors are stacked: glycosylation and chronic inflammation impact bone quality; hypoglycemia is a fall risk.

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Controlling diabetes with GLP-1 RAs can mitigate these risks. But weight loss itself is associated with bone loss, hence increased fracture risk. To tease out drug effects from the weight loss effect, both her most recent study and prior work comparing semaglutide to sleeve gastrectomy used comparators who were undergoing weight loss.

Earlier studies have assessed the impact of GLP-1 RAs on bone mineral density (BMD). A meta-analysis found a statistically significant improvement in lumbar spine, femoral neck, and total BMD as well as bone turnover markers. While these findings are encouraging, Dr. Kim’s work assesses the clinically meaningful end point that orthopaedic surgeons encounter every day: fracture. Further subgroup analysis is pending as the work approaches publication.

Variable by medication
Not all GLP-1 RAs appear equivalent in their impact on fracture risk. Dr. Kim’s study demonstrated that semaglutide had an advantage over dulaglutide. A prior meta-analysis showed a neutral effect on fracture risk for these common medications. Liraglutide had demonstrated the most consistent fracture risk reduction. As Dr. Kim noted, it may take more time to determine individual drug effects versus class effects on bone.

Additionally, the duration of treatment may also be a relevant variable, based on findings that demonstrated a protective effect of GLP-1 RA after 52 weeks of treatment in one meta-analysis and more than 78 weeks in another.

Increased fracture risk in other populations
In contrast to the relative protection observed in other studies, two recent articles demonstrated increased vulnerability in different subgroups. Alexander Lauder, MD, the senior author of a study published in June 2026 in the Journal of the AAOS¨, provided his perspectives in an interview with AAOS Now. Dr. Lauder is associate chair of orthopaedics at Denver Health and associate professor at the University of Colorado School of Medicine. His team conducted a retrospective propensity-matched case-control study of adults who were overweight or obese but without diabetes or other major risk factors for fragility fractures. Of more than 600,000 eligible patients identified in the TriNetX database, 33,210 patients treated with a GLP-1 RA were propensity matched to 33,210 controls. Within one year, the GLP-1 RA group had a higher fracture incidence than controls (3.05% vs. 2.61%) corresponding to a 9% relative increase in risk (risk ratio 1.09; odds ratio 1.19). The analysis included all fracture patterns regardless of mechanism and did not differentiate fragility fractures from other fracture types.

Dr. Lauder noted, “The increased risk was primarily observed in two populations.” The first was in patients with a BMI of 40 kg/m² or greater. Among patients with a BMI ³40 kg/m², the odds ratio for fracture was 1.26, whereas patients aged 78 to 88 years had nearly a fivefold increase in odds of fracture (odds ratio 4.99).

Dr. Lauder emphasized that this retrospective database study demonstrates an association rather than causation. Unlike much of the existing literature, which has focused on patients with diabetes, this study evaluated overweight or obese patients without diabetes, allowing assessment of GLP-1 RA use independent of the known effects of diabetes on bone health. He noted the observed increase in fracture risk may reflect multiple factors associated with rapid weight loss, including sarcopenia, reduced mechanical loading of bone, nutritional deficiencies, and subsequent declines in bone mineral density Ñ variables that were not available for propensity matching or analysis within the database. Another recent database study in the endocrine literature, with similar limitations, supported these findings, identifying an 11% increase in fracture risk over 35 months in a group older than age 65.

Conclusion
The impact of GLP-1 RAs on fracture risk is complex and multifactorial. Understanding the effects of the medications on bone helps surgeons anticipate bone quality for surgical planning, as well as counsel patients on musculoskeletal impacts. From his findings, Dr. Lauder recommends that for older patients or those with obesity on the medication, “consider a broader assessment of bone health, review prior fragility fractures, and ensure patients have adequate diet, calcium, vitamin D, and protein intake.”

Dr. Kim summarized, “While benefits of GLP-1 medications on fractures need to be clarified, these medications are likely less harmful to bone compared to other antihyperglycemic medications (e.g., pioglitazone).” She notes, “I emphasize strength training [to patients] to preserve muscle and bone mass.” That is an easy message for orthopaedic surgeons to share.

Alexandra E. Page, MD, FAAOS, is a foot and ankle specialist in private practice in San Diego, California, and the editor-in-chief of AAOS Now.

References

1. Kasher Meron M, Hornik-Lurie T, Twig G, Rotman-Pikielny P. GLP-1 receptor agonists and the risk of fragility fractures in older adults with type 2 diabetes. J Clin Endocrinol Metab. 2026;111(7):1949-1958. doi:10.1210/clinem/dgag056. PMID: 41665888.
2. Constantine E, Enthoven L, Kahan R, Pflug E, Lauder A. The impact of glucagon-like peptide-1 receptor agonists on fracture risk in overweight or obese, nondiabetic patients. J Am Acad Orthop Surg. 2026;34(12):p e1610-e1619. DOI: 10.5435/JAAOS-D-24-01505
3. Cheng L, Hu Y, Li YY, et al. Glucagon-like peptide-1 receptor agonists and risk of bone fracture in patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetes Metab Res Rev. 2019;35:e3168. doi:10.1002/dmrr.3168
4. Tan Y, Liu S, Tang Q. Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis. Acta Diabetol. 2025;62(5):589-606. doi:10.1007/s00592-025-02468-5. PMID: 39985672.
5. Zhang Y, Chen G, Wang W, Yang D, Zhu D, Jing Y. Association of glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: a meta-analysis of randomized controlled trials. Bone. 2025;192:117338. doi:10.1016/j.bone.2024.117338. PMID: 39603373.