Abstract
Periodontitis is a chronic inflammatory disease and a leading cause of tooth loss among adults. Beyond their lipid-lowering effects, statins exhibit anti-inflammatory and bone-regenerative properties that may influence periodontal health; however, the existing evidence remains inconsistent. This study aimed to examine the association between statin use and periodontitis in a nationally representative US cohort. Data were obtained from 10,714 adults aged ≥30 years who participated in the 2009 to 2014 National Health and Nutrition Examination Survey. Statin use and duration were determined from prescription medication records, and periodontitis was defined according to the Centers for Disease Control and Prevention and the American Academy of Periodontology criteria. Weighted logistic regression models were applied to assess the association between statin use and periodontitis while adjusting for demographic, socioeconomic, lifestyle, and metabolic factors. Subgroup analyses were performed based on statin type and duration of use. After the application of survey weights, the findings were representative of 144.1 million US adults, with an overall periodontitis prevalence of 37.96%. In the fully adjusted model, statin use was significantly associated with a reduced risk of periodontitis (adjusted odds ratio [OR] = 0.83, 95% confidence interval [CI]: 0.69–0.98, P = .038). This inverse association was more pronounced among overweight individuals (OR = 0.73, 95% CI: 0.56–0.95, P = .031), long-term statin users (>5 years; OR = 0.77, 95% CI: 0.61–0.98, P = .039), and users of atorvastatin (OR = 0.68, 95% CI: 0.48–0.97, P = .037). Statin use was independently associated with a lower risk of periodontitis among US adults. This protective association was particularly evident in long-term users and individuals taking atorvastatin, supporting the hypothesis that the pleiotropic anti-inflammatory effects of statins may provide periodontal benefits. These findings suggest a potential role for statins in host-modulation therapy; however, prospective studies are required to establish causality.
Keywords: cross-sectional study, inflammation, NHANES, oral health, periodontitis, statins
1. Introduction
Periodontitis is a chronic, multifactorial inflammatory disease associated with dental plaque accumulation and is characterized by progressive destruction of the tooth-supporting structures, including the periodontal ligament and alveolar bone.[1–3] Globally, periodontitis is the leading cause of tooth loss,[4,5] and the number of affected individuals is projected to continue increasing.[6] In the United States, 42.2% of adults are affected by periodontitis, with 7.8% experiencing severe disease.[7]
Conventionally, the therapeutic gold standard for periodontitis is mechanical debridement aimed at disrupting the bacterial biofilm. However, mechanical therapy alone may be insufficient in deep periodontal pockets or anatomically inaccessible areas, prompting the exploration of adjunctive pharmacotherapies. Accordingly, the ongoing development of chemotherapeutic agents and an improved understanding of the social and environmental determinants of disease remain critical for optimizing overall medical treatment strategies.[8–10] In periodontology, although traditional antimicrobial chemotherapy focuses on reducing bacterial burden, concerns about antibiotic resistance and its limited capacity to reverse tissue destruction have shifted attention toward host-modulation therapies. This shift underscores the need to investigate agents capable of both modulating inflammation and promoting tissue regeneration.
Statins, inhibitors of 3-hydroxy-3-methylglutaryl–coenzyme A reductase, are the most widely prescribed lipid-lowering medications in clinical practice. They are well established to significantly reduce blood cholesterol levels and effectively prevent cardiovascular events.[11] In addition to their lipid-lowering properties, statins exert multiple pleiotropic effects, including anti-inflammatory, immunomodulatory, antioxidant actions, and modulation of bone metabolism.[12]
Emerging evidence suggests that statins may influence periodontal health. Experimental studies have demonstrated that statins promote osteogenesis by upregulating bone morphogenetic protein-2, inhibiting osteoclastic bone resorption, and suppressing the release of pro-inflammatory cytokines and matrix metalloproteinases, thereby facilitating periodontal tissue repair and regeneration.[13,14] Furthermore, clinical studies and systematic reviews indicate that adjunctive statin therapy, administered either systemically or locally, can enhance the outcomes of nonsurgical periodontal treatment, as reflected by greater clinical attachment gain, reduced probing depth, and improved alveolar bone fill.[15,16]
However, statins have yielded inconsistent findings across multiple preclinical and clinical studies.[17,18] These discrepancies highlight the need for large-scale, nationally representative investigations to clarify the association between statin use and periodontitis.
The National Health and Nutrition Examination Survey (NHANES) provides a valuable platform to address this gap. NHANES employs a multistage probability sampling design to produce nationally representative estimates of the US civilian, noninstitutionalized population. Between 2009 and 2014, NHANES conducted comprehensive periodontal examinations at 6 sites per tooth, allowing for detailed assessment of periodontitis prevalence and severity.[19] Concurrently, NHANES collected extensive data on prescription medication use.
Therefore, this study aims to leverage data from NHANES 2009 to 2014 to examine the association between statin use and periodontitis among US adults, providing more robust, population-based evidence on this relationship.
2. Methods
2.1. Study design and population
The NHANES, conducted from 2009 to 2014, served as the foundation for this cross-sectional study. The NHANES program aims to assess the nutritional status of adults and children in the United States and its relationship to health outcomes. The survey includes both physical examinations and structured interviews, covering demographics, socioeconomic status, dietary habits, and health-related information. All participants provided written informed consent, and the study protocol was approved by the Research Ethics Review Committee of the National Centers for Disease Control and Prevention (CDC) and the National Center for Health Statistics. Detailed information is available on the CDC website (https://www.cdc.gov/nchs/nhanes/index.html).
The NHANES database includes periodontal disease assessment data from 2009 to 2014. The Full Mouth Periodontal Examination (FMPE) protocol was implemented in NHANES from 2009 to 2010 and remained consistent through 2011 to 2014. Notably, eligibility for FMPE required participants to be aged 30 years or older. Figure 1 illustrates a flowchart outlining the participant selection and inclusion process. After applying the inclusion and exclusion criteria, 10,714 participants were included in the final analysis, representing an estimated 144.1 million noninstitutionalized US adults after applying survey weights. This study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for reporting observational studies.[20] As NHANES data are publicly available and fully deidentified, no additional institutional ethical approval was required.
Figure 1.
Flowchart of participant selection in the NHANES 2009 to 2014 study. aOR = adjusted odds ratio, BMI = body mass index, CKD = chronic kidney disease, NHANES = National Health and Nutrition Examination Survey.
2.2. Definition of statin users
Participants who reported using any type of statin, either alone or in combination with other lipid-lowering medications, were classified as statin users. Medication use was determined from the NHANES prescription medication questionnaire, which records all prescription drugs taken by participants in the past 30 days. Statin use duration was further categorized as <1 year (<365 days), 1 to 5 years (≥365 and <1825 days), and >5 years (≥1825 days) based on self-reported days of use.
2.3. Outcome variable
The primary outcome of this study was the presence of moderate or severe periodontitis. Periodontal assessments were conducted using the FMPE protocol, which evaluated 6 sites per tooth (mesiobuccal, midbuccal, distobuccal, mesiolingual, midlingual, and distolingual) for all teeth except third molars, resulting in up to 168 sites across 28 teeth per participant. Clinical attachment loss (CAL) and probing pocket depth (PPD) were measured at each site to determine periodontal status. Periodontitis was defined according to the criteria established by the CDC and the American Academy of Periodontology.[7,21] Severe periodontitis was defined as having ≥2 interproximal sites with CAL ≥ 6 mm (on different teeth) and ≥1 interproximal site with PPD ≥ 5 mm. Moderate periodontitis was defined as having ≥2 interproximal sites with CAL ≥ 4 mm (on different teeth) or ≥2 interproximal sites with PPD ≥ 5 mm (on different teeth). For this analysis, participants with moderate or severe periodontitis were classified as cases, while those with no or mild periodontitis were assigned to the reference group. This categorization approach has been widely used in previous studies examining the relationship between periodontitis and systemic health.[22–24]
2.4. Covariates
Based on previous studies,[25–28] covariates included age, gender, race/ethnicity, education level, marital status, annual household income, smoking status, alcohol consumption, obesity, diabetes, hypertension (HTN), hyperlipidemia, and chronic kidney disease (CKD). Race/ethnicity was classified as non-Hispanic White, non-Hispanic Black, Hispanic, or Other. Education level was grouped into higher than high school, high school, and less than high school. Marital status was categorized as married or living with a partner, never married, or separated. Annual household income was divided into <US$20,000 and US$20,000 or more. Alcohol consumption was classified as never drinkers, former drinkers, current light/moderate drinkers, or current heavy drinkers.[29] Smoking status was categorized as never smokers, current smokers, or former smokers.[30] Detailed definitions of all covariates are provided in Table S1, Supplemental Digital Content, https://links.lww.com/MD/R650.
Health status characteristics included body mass index (BMI), HTN, and diabetes. BMI was categorized as underweight or normal (<25 kg/m2), overweight (≥25–<30 kg/m2), and obese (≥30 kg/m2). Participants were classified as having HTN if their average systolic blood pressure was ≥130 mm Hg, their average diastolic blood pressure was ≥80 mm Hg, or if they were currently taking antihypertensive medication.[31] Diabetes was defined by any of the following criteria: self-reported diagnosis, use of insulin or oral hypoglycemic medications, hemoglobin A1c > 6.5%, or fasting plasma glucose >126 mg/dL.[32] Hyperlipidemia was defined as a self-reported physician diagnosis or current use of lipid-lowering medication.[33]
The 2021 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline defines CKD as an estimated glomerular filtration rate of ≤60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio of ≥30 mg/g.[34] Table S1, Supplemental Digital Content, https://links.lww.com/MD/R650, presents estimated glomerular filtration rate values calculated using the formula recommended by the National Kidney Foundation and the American Society of Nephrology Task Force, without adjustment for race.[35]
2.5. Subgroup analysis
To assess the robustness of the association between statin use and periodontitis and to explore potential effect modification, subgroup analyses were conducted. Participants were stratified by sex (male or female), age (<60 or ≥60 years), BMI category, diabetes, HTN, hyperlipidemia, and CKD. Within each subgroup, multivariable weighted logistic regression models were applied using the same covariates as in the primary analysis. Multiplicative interaction terms between statin use and each demographic or clinical factor were tested to evaluate potential heterogeneity across subgroups. In addition, stratified analyses examined whether the associations varied by statin type (e.g., atorvastatin, simvastatin, rosuvastatin) and duration of use (<1 year, 1–5 years, >5 years). These analyses were descriptive and exploratory, employing the same covariate adjustment as the main model.
2.6. Statistical analysis
To ensure the reliability and validity of the findings, NHANES employs stratified, multistage sampling, with each cycle spanning 2 years, resulting in 3 cycles over the 2009 to 2014 period. For the main analyses, we used the examination sample weights (The 2-year mobile examination center examination weight) provided by NHANES, as periodontitis data were obtained from the oral health examination, and statin use was collected via questionnaire. Because this study combined 3 2-year survey cycles, the original 2-year weights were divided by 3 to generate appropriate 6-year weights, following NHANES analytic guidelines. This approach enabled valid national estimates while accounting for the complex sampling design. Descriptive statistics were calculated using sample weights, with continuous variables presented as weighted means ± standard errors and categorical variables as weighted percentages. Group comparisons were performed using weighted t tests for continuous variables and Rao–Scott χ2 tests for categorical variables.
Weighted binary logistic regression models were used to assess the association between statin use and periodontitis, reported as odds ratios (ORs) with 95% confidence intervals (CIs). To evaluate the robustness of this association, a series of models was constructed: model 1, unadjusted; model 2, adjusted for age, gender, and race/ethnicity; and model 3, further adjusted for BMI, income, education level, marital status, smoking status, alcohol consumption, HTN, hyperlipidemia, CKD, and diabetes mellitus. Subgroup analyses were performed to explore potential effect modification by demographic and clinical factors. Multicollinearity among covariates was assessed using the generalized variance inflation factor (GVIF), which is suitable for models containing both categorical and continuous variables. The adjusted measure, GVIF1/(2Df), was calculated to allow comparability across variables with different degrees of freedom, with GVIF1/(2Df) > 5 indicating potentially problematic multicollinearity.[36] GVIF results for all covariates are presented in Table S2, Supplemental Digital Content, https://links.lww.com/MD/R650. Statistical analyses were performed using DecisionLinnc version 1.0 (Hangzhou, China).[37] Two-sided P-values < .05 were considered statistically significant.
3. Results
3.1. Baseline characteristics of study samples
A total of 144.06 million weighted US adults were included in the analysis, of whom 54.69 million (38.0%) had periodontitis. The mean age of participants was 50.8 ± 13.6 years, with individuals with periodontitis being significantly older than those without the disease (55.4 vs 48.0 years, P < .001). The mean BMI was 29.2 ± 6.6 kg/m2, and was slightly higher in the periodontitis group (P = .013).
Males represented 48.8% of the total population but were more prevalent among individuals with periodontitis (58.2% vs 41.2%, P < .001). By race/ethnicity, non-Hispanic Whites comprised the majority overall (68.4%) but accounted for a lower proportion of those with periodontitis (59.8% vs 73.6%), whereas non-Hispanic Blacks and Hispanics had higher proportions of periodontitis (14.4% and 17.4%, respectively; P < .001). Participants with periodontitis were more likely to be separated or divorced (25.7% vs 16.9%, P < .001), have lower educational attainment (<high school: 24.5% vs 9.7%, P < .001), and report lower household income (<US$20,000: 17.8% vs 8.5%, P < .001). Lifestyle behaviors also differed significantly between groups. Current smoking was more common among individuals with periodontitis (26.7% vs 11.7%), whereas never smokers were more prevalent in the non-periodontitis group (64.1% vs 44.0%, P < .001). Alcohol consumption patterns also varied, with a higher proportion of former drinkers observed in the periodontitis group (13.0% vs 6.9%, P < .001).
Regarding comorbidities, participants with periodontitis had significantly higher prevalences of HTN (41.4% vs 29.9%), diabetes (17.2% vs 9.1%), and CKD (18.1% vs 10.1%), with all P < .001. Hyperlipidemia was also more prevalent in the periodontitis group (75.3% vs 72.1%, P = .004). Notably, statin use was significantly higher among individuals with periodontitis (23.9% vs 16.5%, P < .001). Baseline characteristics of the study population are summarized in Table 1.
Table 1.
Baseline characteristics of participants stratified by periodontitis status.
| Characteristic | Total | No periodontitis | Periodontitis | P-value |
|---|---|---|---|---|
| 144,064,731 | 89,375,274 | 54,689,457 | ||
| Age | 50.84 (13.55) | 48.04 (12.76) | 55.41 (13.55) | <.001 |
| BMI | 29.17 (6.57) | 29.03 (6.55) | 29.40 (6.61) | .013 |
| Gender, n (%) | <.001 | |||
| Male | 70,350,527 (48.83) | 38,520,865 (41.22) | 31,829,662 (58.20) | |
| Female | 73,714,204 (51.17) | 50,854,409 (56.90) | 22,859,795 (41.80) | |
| Race, n (%) | <.001 | |||
| Non-Hispanic White | 98,528,555 (68.39) | 65,824,983 (73.65) | 32,703,571 (59.80) | |
| Non-Hispanic Black | 15,413,625 (10.70) | 7,542,189 (8.44) | 7,871,436 (14.39) | |
| Hispanic | 19,482,319 (13.52) | 9,969,766 (11.15) | 9,512,553 (17.39) | |
| Other | 10,640,232 (7.39) | 6,038,335 (6.76) | 4,601,897 (8.41) | |
| Marital status, n (%) | <.001 | |||
| Accompanied | 99,948,813 (69.38) | 65,176,048 (72.92) | 34,772,765 (63.58) | |
| Never married | 14,857,725 (10.31) | 9,077,699 (10.16) | 5,780,026 (10.57) | |
| Separated | 29,186,644 (20.26) | 15,110,483 (16.91) | 14,076,161 (25.74) | |
| Missing | 71,549 (0.05) | 11,042 (0.01) | 60,506 (0.11) | |
| Education level, n (%) | <.001 | |||
| <High school | 22,071,656 (15.32) | 8,686,506 (9.72) | 13,385,150 (24.47) | |
| Completed high school | 29,994,442 (20.82) | 15,883,537 (17.77) | 14,110,904 (25.80) | |
| >High school | 91,998,633 (63.86) | 64,805,230 (72.51) | 27,193,404 (49.72) | |
| Income, n (%) | <.001 | |||
| <US$20,000 | 17,341,886 (12.04) | 7,585,778 (8.49) | 9,756,108 (17.84) | |
| >US$20,000 | 122,024,703 (84.70) | 79,316,276 (88.75) | 42,708,427 (78.09) | |
| Missing | 4,698,142 (3.26) | 2,473,219 (2.77) | 2,224,923 (4.07) | |
| Alcohol intake, n (%) | <.001 | |||
| Never | 27,976,008 (19.42) | 16,680,528 (18.66) | 11,295,480 (20.65) | |
| Former | 13,261,121 (9.20) | 6,168,059 (6.90) | 7,093,062 (12.97) | |
| Current light/moderate | 47,690,093 (33.10) | 31,811,222 (35.59) | 15,878,870 (29.03) | |
| Current heavy | 45,995,459 (31.93) | 29,078,277 (32.54) | 16,917,182 (30.93) | |
| Missing | 9,142,050 (6.35) | 5,637,187 (6.31) | 3,504,863 (6.41) | |
| Smoking status, n (%) | <.001 | |||
| Never | 81,291,124 (56.43) | 57,253,389 (64.06) | 24,037,735 (43.95) | |
| Former | 37,691,230 (26.16) | 21,688,061 (24.27) | 16,003,168 (29.26) | |
| Current | 25,046,544 (17.39) | 10,433,823 (11.67) | 14,612,721 (26.72) | |
| Missing | 35,833 (0.02) | 0 (0.00) | 35,833 (0.07) | |
| CKD, n (%) | <.001 | |||
| No | 119,625,007 (83.04) | 77,074,868 (86.24) | 42,550,139 (77.80) | |
| Yes | 18,924,384 (13.14) | 9,041,663 (10.12) | 9,882,721 (18.07) | |
| Missing | 5,515,340 (3.83) | 3,258,742 (3.65) | 2,256,597 (4.13) | |
| Hypertension, n (%) | <.001 | |||
| No | 94,554,847 (65.63) | 62,614,537 (70.06) | 31,940,310 (58.40) | |
| Yes | 49,355,472 (34.26) | 26,721,604 (29.90) | 22,633,868 (41.39) | |
| Missing | 154,412 (0.11) | 39,133 (0.04) | 115,279 (0.21) | |
| Diabetes, n (%) | <.001 | |||
| No | 126,523,300 (87.82) | 81,247,848 (90.91) | 45,275,453 (82.79) | |
| Yes | 17,500,938 (12.15) | 8,101,503 (9.06) | 9,399,434 (17.19) | |
| Missing | 40,493 (0.03) | 25,922 (0.03) | 14,571 (0.03) | |
| Hyperlipidemia, n (%) | .004 | |||
| No | 38,443,396 (26.68) | 24,918,588 (27.88) | 13,524,808 (24.73) | |
| Yes | 105,609,011 (73.31) | 64,450,447 (72.11) | 41,158,565 (75.26) | |
| Missing | 12,324 (0.01) | 6239 (0.01) | 6085 (0.01) | |
| Statins, n (%) | <.001 | |||
| No | 116,274,711 (80.71) | 74,641,571 (83.51) | 41,633,140 (76.13) | |
| Yes | 27,790,020 (19.29) | 14,733,703 (16.49) | 13,056,318 (23.87) | |
BMI = body mass index, CKD = chronic kidney disease, n = number.
Overall, participants with periodontitis were more likely to be older, male, socioeconomically disadvantaged, and have a higher burden of metabolic and cardiovascular comorbidities compared with those without periodontitis.
3.2. Association between statin use and periodontitis
Table 2 presents the weighted logistic regression results examining the association between statin use and periodontitis. In the unadjusted model (model 1), statin users had significantly higher odds of periodontitis compared with nonusers (OR = 1.59, 95% CI: 1.37–1.84, P < .001). After adjusting for age, gender, BMI, and race/ethnicity (model 2), the association was attenuated and no longer statistically significant (OR = 0.86, 95% CI: 0.74–1.01, P = .064). In the fully adjusted model (model 3), which additionally accounted for socioeconomic status, lifestyle factors, and comorbidities (income, education, smoking, alcohol consumption, HTN, diabetes, hyperlipidemia, and CKD), statin use was significantly associated with a lower risk of periodontitis (OR = 0.83, 95% CI: 0.69–0.98, P = .038).
Table 2.
Adjusted association of statin with periodontitis.
| Outcomes | Model 1 | Model 2 | Model 3 | |||
|---|---|---|---|---|---|---|
| OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Statins | ||||||
| No | Reference | Reference | Reference | Reference | ||
| Yes | 1.59 (1.37–1.84) | <.001 | 0.86 (0.74–1.01) | .064 | 0.83 (0.69–0.98) | .038 |
Model 1: unadjusted.
Model 2: adjusted for age, gender, BMI, and race.
Model 3: adjusted for age, gender, BMI, race, income, education, hypertension, diabetes, smoking, alcohol consumption, hyperlipidemia, and CKD.
95% CI = 95% confidence interval, BMI = body mass index, CKD = chronic kidney disease, OR = odds ratio.
These findings suggest that the initial positive association between statin use and periodontitis is largely attributable to confounding factors, including age, metabolic conditions, and socioeconomic disparities. After full adjustment, statin use was independently associated with a modest but statistically significant protective effect against periodontitis.
3.3. Subgroup analyses based on demographic and clinical characteristics
Subgroup analyses were conducted to explore potential effect modification in the association between statin use and periodontitis (Fig. 2). Significant interactions were observed for age (P for interaction < .001) and BMI (P for interaction = .002).
Figure 2.
Subgroup analyses of the association between statin use and periodontitis in US adults. The blue squares represent the OR, and the horizontal error bars indicate the 95% CI. BMI = body mass index, CI = confidence interval, CKD = chronic kidney disease, OR = odds ratio.
Among participants younger than 60 years, statin use was associated with higher odds of periodontitis (OR = 1.31, 95% CI: 1.07–1.62, P = .017), whereas no significant association was observed in participants aged 60 years or older (OR = 0.90, 95% CI: 0.72–1.21, P = .351). In terms of BMI, a significant protective association was detected among overweight individuals (OR = 0.73, 95% CI: 0.56–0.95, P = .031) but not among participants with normal weight or obesity.
No significant interactions were observed for sex, diabetes, HTN, hyperlipidemia, or CKD (all P for interaction > .05). The direction and magnitude of the associations were generally consistent across these subgroups, indicating that the inverse relationship between statin use and periodontitis may be partially influenced by age and BMI.
3.4. Subgroup analyses by statin type
Table 3 presents the results of subgroup analyses by specific statin types. Among all agents, atorvastatin use was significantly associated with a lower risk of periodontitis (OR = 0.68, 95% CI: 0.48–0.97, P = .037). No statistically significant associations were observed for simvastatin, pravastatin, or rosuvastatin (all P > .05). Although lovastatin showed a trend toward increased odds of periodontitis (OR = 1.36, 95% CI: 0.93–1.99), this association was not statistically significant (P = .107). Overall, only atorvastatin demonstrated a significant protective effect, while other statin types showed no consistent relationship with periodontitis.
Table 3.
Association between different statin types and periodontitis (NHANES 2009–2014).
| Variates | P-value | aOR (95% CI) |
|---|---|---|
| Atorvastatin | .037 | 0.68 (0.48–0.97) |
| Simvastatin | .318 | 0.91 (0.75–1.11) |
| Lovastatin | .107 | 1.36 (0.93–1.99) |
| Pravastatin | .543 | 0.87 (0.54–1.40) |
| Rosuvastatin | .576 | 0.89 (0.60–1.37) |
aOR = adjusted odds ratio, CI = confidence interval, NHANES = National Health and Nutrition Examination Survey.
3.5. Subgroup analyses by statin duration
To further examine the temporal relationship between statin use and periodontitis, participants were categorized by duration of statin use: <1 year, 1 to 5 years, and >5 years (Table 4). Short-term use (<1 year) was not significantly associated with periodontitis risk (adjusted OR = 0.98, 95% CI: 0.67–1.43, P = .920), nor was use for 1 to 5 years (adjusted OR = 0.83, 95% CI: 0.62–1.13, P = .238). By contrast, long-term statin use (>5 years) was associated with significantly lower odds of periodontitis (adjusted OR = 0.77, 95% CI: 0.61–0.98, P = .039), indicating a potential duration-dependent protective effect.
Table 4.
Association between duration of statin use and periodontitis (NHANES 2009–2014).
| Variates | P-value | aOR (95% CI) |
|---|---|---|
| <365 d | .920 | 0.98 (0.67–1.43) |
| 365–1825 d | .238 | 0.83 (0.62–1.13) |
| >1825 d | .039 | 0.77 (0.61–0.98) |
aOR = adjusted odds ratio, CI = confidence interval, NHANES = National Health and Nutrition Examination Survey.
4. Discussion
In this large, nationally representative study of US adults, statin use was independently associated with a lower risk of periodontitis after adjusting for demographic, socioeconomic, lifestyle, and metabolic factors. This comprehensive adjustment reversed the crude positive association, which was largely driven by confounders such as age and comorbidities. To our knowledge, this is the first study to move beyond simple binary exposure assessments and provide a detailed analysis of the statin–periodontitisrelationship. Notably, we identified a novel, agent-specific protective effect for atorvastatin. We also observed a duration-dependent benefit of statin use, particularly for use exceeding 5 years, and found that BMI significantly modified this association, offering new insights into the personalized implications of statin therapy for periodontal health.
Our findings support and extend the growing evidence that statins have beneficial effects on periodontal health. While previous systematic reviews have shown that adjunctive statin therapy improves clinical attachment levels and alveolar bone fill during periodontal treatment,[38–40] our study provides population-level confirmation of these clinical trial findings. Importantly, the agent-specific protective effect observed for atorvastatin aligns with a recent meta-analysis, which identified atorvastatin as superior to other statins in promoting bone regeneration.[41] This enhanced potency is further supported by a controlled trial showing that high-dose atorvastatin significantly reduced periodontal inflammation, as measured by fluorodeoxyglucose positron emission tomography/computed tomography imaging (80 mg vs 10 mg; P = .04), providing direct in vivo evidence in humans.[42] Mechanistically, the superior efficacy of atorvastatin may be attributed to its high lipophilicity, which enhances tissue penetration compared with hydrophilic statins.[43] This effect likely acts in concert with the general pleiotropic actions of statins – such as suppressing macrophage-mediated inflammatory responses and upregulating bone morphogenetic protein-2[43,44] – to reduce periodontal tissue destruction.
The heterogeneity in statin duration observed in our study provides an important refinement to the existing literature. We found that protective associations were significant only among long-term users (>5 years), with no benefit observed for short-term use. This contrasts with some short-term clinical trials (3–6 months) reporting rapid improvements[45] but aligns with findings from longitudinal osteoporosis studies, which indicate that meaningful modulation of bone density and reduction in fracture risk require sustained therapy over several years. These results suggest that while statins may confer acute anti-inflammatory benefits, their effect on preventing the cumulative tissue loss characteristic of periodontitis (such as alveolar bone loss and tooth loss) is likely a gradual, chronic process requiring prolonged exposure. Regarding other statin types, the lack of significant associations does not necessarily indicate an absence of biological effect, but may reflect lower prescription rates or pharmacokinetic differences compared with atorvastatin.
From a clinical and public health perspective, our findings support the emerging paradigm of oral–systemic health integration. Given the high prevalence of both hyperlipidemia and periodontitis in many populations, the potential for statins to provide additional periodontal benefits is noteworthy. If confirmed, these results could inform periodontal risk stratification in patients already receiving statin therapy and promote closer interdisciplinary collaboration between dental and medical professionals.
This study has several limitations. First, the cross-sectional design of NHANES precludes causal inference and leaves open the possibility of reverse causation. Second, although multiple confounders were adjusted for, residual confounding from unmeasured factors – such as oral hygiene practices, statin dosage, and medication adherence – cannot be ruled out. Additionally, information on statin use and duration was self-reported, which may have introduced recall bias. Third, because the analysis was based on a US population, the generalizability of these findings to other populations may be limited. Future prospective cohort studies and randomized controlled trials are needed to confirm these associations and elucidate the mechanisms linking statin use with periodontal health.
5. Conclusion
This study provides strong epidemiological evidence that statin use is independently associated with a lower prevalence of periodontitis in US adults. Notably, the protective effect was both duration-dependent – significant only in long-term users (>5 years) – and agent-specific, with atorvastatin demonstrating the most pronounced benefit. These findings support the biological hypothesis that the pleiotropic immunomodulatory and osteogenic properties of statins may help mitigate periodontal inflammation and tissue destruction. Accordingly, statins merit further investigation as potential host-modulation agents in periodontal therapy. Future longitudinal studies and randomized controlled trials are needed to confirm causality and clarify the precise molecular mechanisms underlying this association.
Author contributions
Conceptualization: Jin-feng Liu.
Methodology: Da-jun Lai.
Data curation: Da-jun Lai.
Investigation: Jin-feng Liu.
Software: Wei Wei.
Writing – original draft: Da-jun Lai, Wei Wei.
Writing – review & editing: Da-jun Lai, Jin-feng Liu, Liang Huang, Wei Wei.
Supplementary Material
Abbreviations:
- BMI
- body mass index
- CAL
- clinical attachment loss
- CDC
- Centers for Disease Control and Prevention
- CI
- confidence interval
- CKD
- chronic kidney disease
- FMPE
- Full Mouth Periodontal Examination
- GVIF
- generalized variance inflation factor
- HTN
- hypertension
- NHANES
- National Health and Nutrition Examination Survey
- OR
- odds ratio
- PPD
- probing pocket depth
- STROBE
- Strengthening the Reporting of Observational Studies in Epidemiology
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
The datasets generated and/or analyzed during the current study are publicly available.
Supplemental Digital Content is available for this article.
How to cite this article: Lai D-j, Liu J-f, Huang L, Wei W. Statin use and risk of periodontitis in US adults: A population-based cross-sectional study. Medicine 2026;105:15(e48301).
Contributor Information
Da-jun Lai, Email: 195898458@qq.com.
Jin-feng Liu, Email: 59675270@qq.com.
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