Exogenous testosterone use was associated with increased 2-year incidence of vertebral fractures, with TRT patients showing higher rates than matched controls (0.31% vs 0.04%), though a causal relationship could not be established.
Key Findings
Results
TRT patients had significantly higher 2-year vertebral fracture rates compared to matched controls.
Vertebral fracture rate was 0.31% in TRT patients versus 0.04% in controls (P < 0.001).
A total of 77,491 matched patients were analyzed using 1:1 matching by demographic variables.
Mean age of the cohort was 54.7 ± 10.4 years, 74.3% were male, and mean Charlson Comorbidity Index was 0.17 ± 0.54.
The PearlDiver database was used to identify patients with and without history of TRT.
Vertebral fracture incidence rates were observed to increase with age in TRT patients.
Results
Both men and women on TRT separately showed significantly higher vertebral fracture rates than their respective controls.
Men on TRT had a vertebral fracture rate of 0.36% versus 0.04% in male controls (P < 0.001).
Women on TRT had a vertebral fracture rate of 0.16% versus 0.03% in female controls (P < 0.001).
The sex-stratified analyses confirm the association is not limited to one sex.
Results
Multivariate logistic regression identified TRT as the strongest independent predictor of vertebral fractures among the variables examined.
TRT was associated with an odds ratio of 7.7 (95% CI = 5.1–11.7, P < 0.001) for vertebral fractures.
Alcohol abuse was also an independent predictor (OR = 2.5, 95% CI = 1.8–3.5, P < 0.001).
Diphosphonate use was an independent predictor (OR = 2.2, 95% CI = 1.4–3.5, P < 0.001).
Chronic kidney disease was an independent predictor (OR = 1.4, 95% CI = 1.1–2.0, P = 0.026).
Methods
The study design used matched retrospective cohort analysis from a large administrative database.
The PearlDiver database was queried to identify patients with and without history of TRT.
Groups were matched 1:1 by demographic variables.
The primary outcome was 2-year vertebral fracture incidence rate.
Multivariate logistic regression was performed to identify independent predictors of vertebral fractures.
A causal relationship between TRT and vertebral fractures could not be established given the retrospective observational design.
Conclusions
The authors recommend using screening measures such as DEXA scans to identify TRT patients at risk of vertebral fractures.
Dual-energy X-ray absorptiometry (DEXA) scan was highlighted as a recommended screening tool.
The findings highlight the need for screening measures given the association between TRT and increased vertebral fracture incidence.
The study could not establish a causal relationship, but the association warrants clinical attention.
Singh M, Daher M, Diebo B, Daniels A, Arcand M. (2025). Testosterone Replacement Therapy Is Associated With Increased Incidence Rate of Vertebral Fractures: A Matched Retrospective Analysis.. Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews. https://doi.org/10.5435/JAAOSGlobal-D-24-00248