NonTobacco Nicotine Dependence Is Associated With Increased Fracture Risk in Adolescents and Young Adults

The aim of this study was to evaluate whether nontobacco nicotine dependence (NTND) in adolescents and young adults is associated with an increased risk of new-onset fractures over a medium-term and long-term follow-up.

retrospective cohort query of TriNetX network.

Multicenter study conducted using deidentified electronic health records from the TriNetX network of participating health care organizations.

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 previous tobacco use, environmental tobacco exposure, tobacco use disorder, preexisting bone/joint pathology (eg, osteoporosis, osteoarthritis, osteogenesis imperfecta, and malignant neoplasms of bone/cartilage), or previous fracture. Patients with NTND were propensity score matched 1:1 with controls without any documented nicotine or tobacco use.

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 after 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.

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, whereas 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 with controls was confirmed time-to-event analysis (HR, 1.9; 95% CI, 1.5-2.4).

Nontobacco 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 effect of nicotine use in youth.

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.