Non-tobacco nicotine dependence is associated with increased fracture risk in adolescents and young adults.
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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.