JOT - 2026-05-05 - Journal Article
Non-tobacco nicotine dependence is associated with increased fracture risk in adolescents and young adults.
Zhang J, Meydan Y, Chen B, Barsi J
Topics
Key Takeaway
Non-tobacco nicotine dependence in adolescents and young adults is associated with a two-fold increased fracture risk at 5 years (RR 2.1, 95% CI 1.5–2.9) compared to propensity-matched controls.
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Summary
This retrospective cohort study queried the TriNetX network to determine whether non-tobacco nicotine dependence (NTND) in patients ≤21 years increases incident fracture risk. After 1:1 propensity score matching excluding prior tobacco use, pre-existing bone pathology, and prior fracture, NTND patients had a fracture incidence of 1.1% vs. 0.5% in controls at 5 years (RR 2.1) and 2.0% vs. 1.0% over extended follow-up (RR 1.9; HR 1.9, 95% CI 1.5–2.4).
Key Limitation
The absolute fracture incidence is low (1.1% vs. 0.5% at 5 years), and the database design precludes determination of nicotine product type, dose, or duration, making it impossible to establish a dose-response relationship or identify which NTND products confer the greatest risk.
Original Abstract
OBJECTIVES
To evaluate whether non-tobacco nicotine dependence (NTND) in adolescents and young adults is associated with an increased risk of new-onset fractures over a medium and long term follow up.
METHODS
Design: retrospective cohort query of TriNetX network.
SETTING
Multi-center study conducted using de-identified electronic health records from the TriNetX network of participating healthcare organizations.
PATIENT SELECTION CRITERIA
Adolescents and young adults (≤21 years) were included if they had a diagnosis of NTND between June 1, 2005, and June 1, 2020. Exclusions: any prior tobacco use, environmental tobacco exposure, tobacco use disorder, pre-existing bone/joint pathology (e.g., osteoporosis, osteoarthritis, osteogenesis imperfecta, malignant neoplasms of bone/cartilage), or prior fracture. NTND patients were propensity score matched 1:1 with controls without any documented nicotine or tobacco use.
OUTCOME MEASURES AND COMPARISONS
The primary outcome was incident fracture after the most recent eligible clinical encounter documented between June 1, 2005, and June 1, 2020. Fracture risk was assessed over a fixed 5-year period following the index date and across the longest available follow-up in TriNetX. Risk ratios (RR) and 95% confidence intervals (CI) were calculated. Kaplan-Meier survival analysis was used to estimate hazard ratios (HR) for time-to-event comparison.
RESULTS
The matched cohort was comprised of 10,576 patients per group with an average age at index of 19.4 + 1.7 years. The NTND group was comprised of 44.9% males and 54.7% females while the control group was comprised of 44.7% males and 55.0% females. At 5 years, fracture incidence was 1.1% in the NTND group and 0.5% in controls (RR, 2.1; 95% CI, 1.5 - 2.9; p < 0.001). Over the extended follow-up, fracture incidence was observed to be 2.0% in NTND group and 1.0% in the control group (RR, 1.9; 95% CI, 1.5-2.4; p < 0.001). Over the extended follow-up, the elevated fracture risk in NTND group when compared to controls was confirmed time-to-event analysis (HR, 1.9; 95% CI, 1.5-2.4).
CONCLUSIONS
Non-tobacco nicotine dependence was associated with a two-fold increased risk of fracture among adolescents and young adults (RR, 2.1; 95% CI, 1.5-2.9 at 5 years; RR, 1.9; 1.5-2.4 over an extended follow up period). It is suggested by these findings that skeletal health consequences should be considered when evaluating the long-term impact of nicotine use in youth.
LEVEL OF EVIDENCE
Level III.