Abstract
BACKGROUND: Periodontitis is a common chronic disease characterized by the destruction of periodontal tissues and the resorption of alveolar bone, which severely impacts the quality of life of patients. Alkaline phosphatase (ALP), as a crucial marker of bone metabolism, is involved in the bone formation process. However, the mechanisms linking ALP to periodontitis remain unclear. Bone mineral density (BMD) of the skull is an important indicator reflecting bone mineral content and bone strength, yet its mediating role in the relationship between ALP and periodontitis has not been thoroughly investigated. OBJECTIVE: This study aimed to explore the association between serum ALP and the risk of periodontitis and to evaluate the potential mediating role of cranial BMD in this relationship, with the goal of providing new insights into the etiology of periodontitis and informing treatment strategies. METHODS: Data from periodontitis patients from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 were utilized with ALP as the independent variable, periodontitis as the dependent variable, and cranial BMD as the mediating variable. A logistic regression model was used to analyse the relationship between ALP and periodontitis, and subgroup analyses were conducted to explore the association between ALP and periodontitis in different subgroups. Restricted cubic splines (RCS) were used to explore the nonlinear relationship between the two. Additionally, mediation analysis was employed to study the potential mediating role of cranial BMD on the association between ALP and periodontitis. RESULTS: After adjusting for confounding variables, ALP showed a significant positive association with periodontitis (OR: 1.006, 95% CI: 1.002-1.011, P < .05). Subgroup analyses showed that this association was particularly pronounced in males, drinkers, and individuals lacking physical activities. RCS analysis revealed a nonlinear relationship between ALP and periodontitis (P-non-linear = 0.0006), with a threshold level of 68 U/L. The mediation analysis revealed that cranial BMD played a mediating role of 2.71% in the relationship between ALP and periodontitis (P = .006). Furthermore, ALP was significantly negatively correlated with cranial BMD (β = -0.0016, 95% CI: -0.0024 to -0.0007, P < .001). CONCLUSION: Elevated serum ALP levels were positively associated with an increased risk of periodontitis, and cranial BMD partially mediated this association. Monitoring ALP levels may contribute to the early diagnosis and intervention of periodontitis, while targeting bone metabolism regulation could offer a novel direction for the treatment of periodontitis.