Authors
Westin Keime, OMS-II¹, Derek McClune, OMS-III¹, Noah Johnson, OMS-II¹, Connor Parry, PGY1²

Affiliations
¹Rocky Vista University College of Osteopathic Medicine – Southern Utah
² Valley Health Systems – Department of Orthopedic Surgery

Conflict of Interest
The authors declare there is no conflict of interest.

Introduction
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for glycemic control and weight management, but their effects on bone metabolism remain uncertain. Weight loss is often associated with decreased bone mineral density (BMD), yet some studies suggest that GLP-1RAs may exert protective effects through modulation of bone turnover markers and fracture risk [1–4]. However, findings across the literature are inconsistent. Some research indicates that GLP-1RAs, such as liraglutide and dulaglutide, may help preserve BMD despite weight loss, while exenatide has been associated with increased osteoprotegerin levels, potentially promoting bone formation [2,5,7]. In contrast, semaglutide has been linked to increased bone resorption and reductions in BMD, suggesting that its skeletal effects may differ from other GLP-1RAs [15]. Large population-based studies have found no significant reduction in fracture risk with GLP-1RA use compared to other antihyperglycemic medications [10,12,13]. Given the conflicting findings, further investigation is needed to clarify the impact of GLP-1RAs on skeletal health.

Methods
Sixteen peer-reviewed studies were analyzed, including randomized controlled trials, observational studies, and population-based research evaluating the relationship between GLP-1RAs and bone health. Only human studies were included. Articles were selected based on relevance to BMD, bone turnover markers, and fracture risk, with data extracted from PubMed, Google Scholar, and other scientific databases covering research conducted between 2011 and 2025 [1–16].

Results
GLP-1RAs demonstrated varied effects on bone health. Some studies reported that liraglutide preserved BMD at clinically relevant sites despite weight loss, while others suggested neutral or minimal effects [2,5,7]. Exenatide was associated with decreased bone resorption and increased osteoprotegerin levels, potentially influencing bone remodeling [3,7]. However, semaglutide was linked to increased bone resorption and reductions in BMD, raising concerns about its impact on skeletal integrity [15]. Additionally, population-based analyses showed no significant reduction in fracture risk with GLP-1RA use compared to placebo or other antihyperglycemic drugs [10,12,13]. In schizophrenia patients, exenatide showed potential beneficial effects on bone turnover markers, but findings were limited [14].

Discussion
GLP-1RAs may have complex and drug-specific effects on bone metabolism, with some agents showing promise in mitigating bone loss while others may increase resorption. Current evidence does not support a consistent reduction in fracture risk with GLP-1RAs. Future studies should focus on long-term skeletal outcomes, dose-dependent effects, and subgroup analyses to refine therapeutic recommendations for individuals at risk of osteoporosis and fractures.

References

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