GLP-1 Receptor Agonists Use Linked to Reduced Vertebral Fracture Risk: JAMA
Taiwan: A cohort study of individuals with type 2 diabetes (T2D) revealed that glucagon-like peptide 1 (GLP-1) receptor agonists were associated with a modest long-term reduction in vertebral fractures.
While the study, published in JAMA Surgery, cannot prove causation due to its observational design, the findings suggest that beyond their well-known cardiometabolic benefits, these agents may also confer advantages for bone health, warranting further investigation.
Type 2 diabetes is a recognized risk factor for vertebral fractures, which can lead to long-term disability and increased mortality. Although GLP-1 receptor agonists have demonstrated benefits in glycemic control, their role in skeletal health has remained unclear, with prior evidence on fracture risk yielding mixed results.
To explore this, researchers from National Cheng Kung University Hospital in Taiwan analyzed electronic health records to examine the relationship between GLP-1 receptor agonist use and vertebral fractures.
The team utilized TriNetX, a global database aggregating deidentified records from 151 healthcare organizations, harmonized with standard diagnostic and procedural codes. Adults diagnosed with T2D between 2015 and 2022 were included. GLP-1 receptor agonist users had records of semaglutide, liraglutide, or dulaglutide within six months of diagnosis, while nonusers had no recorded use.
Patients with prior vertebral fractures, inflammatory spinal disorders, cancers of the vertebral column, or previous vertebral procedures were excluded. Propensity score matching created two well-balanced cohorts of 193,563 patients each.
The results were as follows:
- GLP-1 receptor agonist use was associated with a 17% lower risk of vertebral compression fractures compared with nonuse (1.5% vs 1.8%; OR 0.83).
- Users of GLP-1 receptor agonists had a 20% lower likelihood of needing surgical procedures such as vertebroplasty or kyphoplasty (0.08% vs 0.10%; OR 0.80).
- The results suggest a possible bone-protective effect of GLP-1 receptor agonists in individuals with type 2 diabetes, despite the overall low frequency of these surgical interventions.
The benefit is likely driven by multiple mechanisms. GLP-1 receptor agonists may boost bone formation and limit resorption by modulating osteoblasts and osteoclasts through the RANKL/OPG pathway. They may also improve bone microarchitecture by influencing calcium–phosphate balance and bone-related hormones via the hypothalamic-pituitary-parathyroid axis. Additionally, by reducing chronic inflammation and insulin resistance, these drugs help preserve osteoblast function and overall bone quality, potentially lowering fracture risk.
Despite these promising results, the study’s observational nature prevents definitive conclusions about causality. Limitations include the inability to assess dose-response relationships, treatment duration, or capture unmeasured confounding factors. Nonetheless, the research underscores a potential ancillary benefit of GLP-1 receptor agonists in maintaining skeletal health, providing a foundation for prospective studies to confirm these effects and clarify underlying mechanisms.
"As GLP-1 receptor agonists continue to gain attention for their dual impact on obesity and diabetes, their possible role in bone protection represents an intriguing avenue for future investigation," the authors concluded.
Reference:
Khor W, Chi K, Lin H, Chang Y. Glucagon-Like Peptide 1 Receptor Agonist Use and Vertebral Fracture Risk in Type 2 Diabetes. JAMA Surg. Published online December 10, 2025. doi:10.1001/jamasurg.2025.5372
Next Story