Abstract
Background
Proton pump inhibitors (PPIs), such as omeprazole, esomeprazole, and pantoprazole, are frequently prescribed to treat acid-related gastrointestinal diseases. PPIs inhibit the hydrogen potassium–adenosine triphosphatase proton pump in gastric parietal cells, decreasing acid release. However, PPIs also affect bone metabolism by altering mineralization and resorption rates and inducing changes in the gastrointestinal microbiota. Therefore, the authors assessed whether PPIs also might be associated with periodontal pathogenesis.
Methods
Medical and dental records (N = 1,017) of patients seeking treatment at the School of Dental Medicine at the State University of New York, University at Buffalo Postgraduate Periodontics Clinic (2010-2017) were reviewed to obtain periodontal status, medication history, systemic diseases and conditions, and demographic information. Patients who received a diagnosis of generalized periodontitis stages III through IV, grades B through C were further assessed in this study (n = 518).
Results
A statistically significant inverse relationship was found between the use of PPIs and the percentage of teeth with 6 mm or greater probing depths. That relationship persisted after adjusting for diabetes, smoking, and the presence of systemic factors. The prevalence of pocket depths 6 mm or greater was 13.1% in patients taking PPIs vs 19.9% in patients not taking PPIs (group difference, 6.8%; 34.2% decrease; 95% CI, 2.1% to 11.6%; P = .006). There were no statistically significant differences in oral hygiene efficacy or age in the PPI vs non-PPI groups (P > .05), implying that either potentially confounding factor did not influence the observed results.
Conclusions
The use of PPIs is associated with less severe periodontal disease.
Key Words
Why Is This Important?
Proton pump inhibitors (PPIs) are used to treat acid-related gastrointestinal diseases. However, PPIs also can affect the gastrointestinal microbiome, influence bone metabolism, alter bone resorption rates, and increase bone fracture risk. Because the pathogenesis of periodontitis is influenced by microbiological factors and characterized by progressive bone loss, the authors assessed whether PPIs also might influence the severity of the periodontal disease. This study suggests that PPIs are associated with less severe periodontitis. Further studies are indicated to determine whether the mechanism underlying this potentially beneficial association is causal and, if so, to elucidate how this process might occur.
Introduction
Proton pump inhibitors (PPIs), such as omeprazole, esomeprazole, and pantoprazole, are widely prescribed medications used by an estimated 7% of the US population annually, with costs exceeding $10 billion.
1
PPIs are indicated to treat acid-related gastrointestinal (GI) disorders, including gastroesophageal reflux disease, Helicobacter pylori–related infection, peptic ulcer disease, and secondary gastroesophageal reflux disease symptoms associated with inflammatory bowel diseases.2
PPIs also are used to mitigate gastric ulcer formation in at-risk patients taking nonsteroidal anti-inflammatory drugs.3
,4
PPIs primarily affect the hydrogen potassium–adenosine triphosphatase (H+/K+ ATPase) proton pump in gastric parietal cells by irreversibly binding the H+/K+ ATPase in parietal cells resulting in decreased acid release and, ultimately, an increase in pH.5
, 6
, 7
With PPIs, patients can experience multiple side effects, including reducing the intestinal absorption of vitamins and minerals, leading to a decrease in bone mineral density.
8
Consequently, those patients appear to be at increased risk of bone fracture at sites of potentially greater mechanical stress, such as at the hip or wrist.9
In addition, PPI medications have the potential to induce a dysbiotic gastric microflora indirectly through an increase in GI pH or by directly targeting proton pumps within commensal organisms.10
This allows for a shift in the bacterial taxa to species such as Clostridium difficile and genera Campylobacter, Shigella, and Salmonella, leading to an increased risk of infection.10
, 11
, 12
, 13
In addition, increased numbers of Streptococcaceae have been observed among PPI users throughout the upper GI tract, posing a risk for respiratory infections, including pneumonia.13
, 14
, 15
- Lambert A.A.
- Lam J.O.
- Paik J.J.
- Ugarte-Gil C.
- Drummond M.B.
- Crowell T.A.
Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis.
PLoS One. 2015; 10e0128004https://doi.org/10.1371/journal.pone.0128004
Periodontal disease is an inflammatory condition associated with the development of plaque biofilms and characterized by progressive destruction of tooth-supporting hard and soft tissue.
16
,17
Periodontal disease is widely prevalent among patient populations, with at least 40% of adults 30 years or older in the United States having a diagnosis of periodontitis.18
Clinical manifestations of periodontal disease include periodontal pocketing, clinical attachment loss, alveolar bone loss, and gingival bleeding.16
,17
,19
Since periodontal disease is microbiologically mediated, PPIs can affect the GI microflora, influence bone homeostasis, and decrease mineral absorption; we hypothesized that PPIs might also influence the severity of periodontal disease as assessed by probing depth measurements. In a pilot study, we previously showed that patients from a private periodontics practice concurrently taking PPIs had a smaller percentage of elevated probing depths than patients not taking PPIs.20
However, the degree to which those findings can be generalized to other patient populations has not yet been determined. As a result, we conducted a study to examine an independent population consisting of patients seeking treatment at a university-based advanced education program in periodontics to assess the potential association between PPI use and the severity of probing depths.Methods
Patient population
This study was reviewed and approved by the State University of New York, University at Buffalo Health Sciences Institutional Review Board (00001811), which did not require individual informed consent for this retrospective records analysis. The manuscript was prepared according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Medical and dental records of participants (N = 1,017) seeking treatment at the Postgraduate Periodontics Clinic at the School of Dental Medicine at the State University of New York University at Buffalo from 2010 through 2017 were initially considered. Exclusions included pregnancy and being younger than 35 years at the initial examination. Demographic data included sex, date of birth, and initial examination date. Patient medical histories were reviewed for systemic factors, such as smoking history, diabetes, inflammatory bowel disease, untreated hypothyroidism, and other autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Medication history included PPIs, systemic steroids, hormone replacement therapy (HRT), and the use of immunobiologics. The specific PPIs evaluated in this study are described in Table 1.
Table 1Proton pump inhibitor medications considered for this study.
| Generic Name | Brand Name (Manufacturer) |
|---|---|
| Dexlansoprazole | Dexilant (Takeda Pharmaceuticals USA) |
| Esomeprazole | Nexium (AstraZeneca) |
| Lansoprazole | Prevacid (Takeda Pharmaceuticals USA) |
| Omeprazole | Prilosec (Proctor & Gamble) |
| Pantoprazole | Protonix (Pfizer) |
| Rabeprazole | Aciphex (Eisai) |
Criteria analysis
Probing depths of 6 mm or greater were chosen as a threshold to identify moderate to severe periodontitis within this patient population on the basis of prior studies that used periodontal probing depths as a parameter for classifying periodontal disease severity.
21
, 22
, 23
Records from patients initially diagnosed with chronic, generalized, moderate to severe periodontitis, as determined using the criteria established at the 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, were subsequently reviewed to meet the criteria of generalized periodontitis stages III through IV, grades B through C, as described by the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.16
This preexisting initial periodontal diagnosis was determined by the patient’s provider using the complete dental record, including radiographs and clinical attachment levels. Probing measurements were made using Michigan O probes with standardized Williams markings measuring from the free gingival margin to the base of the pocket at 6 sites per tooth at the mesiobuccal, midbuccal, and distobuccal aspects as well as the corresponding lingual aspects of all teeth excluding third molars. Patient oral hygiene was determined using 1 of 2 different methods. The percentage of plaque-positive surfaces was calculated using either mean whole mouth plaque scores24
or the Ramfjord Periodontal Disease Index sampling technique.25
Both plaque index methods were dichotomous and were used to yield a percentage of plaque-positive surfaces. The whole-mouth plaque score technique yielded a percentage on the basis of the positive surfaces from each tooth present, whereas the sampling method produced a percentage calculated from the Ramfjord teeth only. One author (P.A.H.) was designated to eliminate intraexaminer bias for data collection.Equality of variances (Levene) was assessed with independent sample t tests (using equal or unequal variance as appropriate) for statistical analyses. When equal variances were assumed (P < .05), pooled variances were used. In cases in which equal variances could not be assumed, the unpooled variances and a correction to the df were used. Significance was measured by computing 95% CIs and P values of the group mean differences. We used an exclusion approach to account for potential bias rather than regression analysis because the sample size was relatively large and the number of confounding factors considered was small, and we wished to reduce the computational bias associated with regression analysis.
26
Results with and without adjustment were reported as described in the Results section below. All calculations were performed using SPSS (Version 26; IBM).Results
We found an inverse relationship between the use of PPIs and the percentage of teeth with 6 mm or greater probing depths (Table 2). Among patients who received a diagnosis of generalized periodontitis stage III or IV, grade B or C (n = 518), an inverse relationship between the use of PPIs and the severity of periodontal disease was observed. Specifically, 15.7% of teeth from patients taking PPIs had periodontal pocket depths 6 mm or greater vs 22.6% of teeth in patients not taking PPIs (30.5% decrease; P = .004). This relationship persisted after excluding smokers and people with diabetes. The prevalence of pocket depths 6 mm or greater was 12.7% in patients taking PPIs vs 19.7% in patients not taking PPIs (35.5% decrease; P < .001). Furthermore, after excluding smokers, people with diabetes, use of systemic steroids or immunobiological medications, HRT, hypothyroidism, and other autoimmune diseases from the population, the prevalence of pocket depths 6 mm or greater was 13.1% in patients taking PPIs vs 19.9% in patients not taking PPIs (34.2% decrease; P = .006). There were no statistically significant differences in oral hygiene efficacy, age, or sample variance in any PPI vs non-PPI groups (P > .05; Tables 3 and 4).
Table 2Periodontal disease severity among patients taking vs not taking PPIs.
| Patient Characteristics | All Patients | Excluding Smoking and Diabetes | Excluding Smoking, Diabetes, Systemic Medications and Conditions | Excluding Smoking, Diabetes, Systemic Medications and Conditions, and Treated Hypothyroidism |
|---|---|---|---|---|
| No PPI Teeth with probing depths ≥ 6 mm, % PPI | 22.6 (n = 461) | 19.7 (n = 324) | 19.9 (n = 314) | 19.9 (n = 314) |
| Teeth with probing depths ≥ 6 mm, % No PPI-PPI | 15.7 (n = 57) | 12.7 (n = 42) | 12.6 (n = 40) | 13.1 (n = 33) |
| Teeth with probing depths ≥ 6 mm, % Mean difference, % | 6.9 30.5 decrease | 7.0 35.5 decrease | 7.3 36.7 decrease | 6.8 34.2 decrease |
| 95% CI of mean difference | 0.02 to 0.11 | 0.03 to 0.11 | 0.03 to 0.11 | 0.02 to 0.12 |
| P value | .004 | .001 | .001 | .006 |
∗ PPI: proton pump inhibitor.
† Including systemic steroids, hormone replacement therapy, and immunobiologics.
‡ Patients taking thyroid hormone supplementation medications.
Table 3Mean plaque index for patients using PPIs vs not using PPIs.
| Patient Characteristics | All Patients | Excluding Smoking and Diabetes | Excluding Smoking, Diabetes, Systemic Medications and Conditions | Excluding Smoking, Diabetes, Systemic Medications and Conditions, and Treated Hypothyroidism |
|---|---|---|---|---|
| No PPI Mean plaque index, % | 56.5 (n = 275) | 56.2 (n = 193) | 56.2 (n = 187) | 56.2 (n = 187) |
| PPI Mean plaque index, % No PPI-PPI | 60.8 (n = 35) | 60.1 (n = 27) | 59.9 (n = 26) | 58.8 (n = 22) |
| Mean plaque index, % mean difference | 4.3 | 3.9 | 3.7 | 2.6 |
| 95% CI of mean difference | 0.04 to 0.13 | 0.06 to 0.14 | 0.07 to 0.14 | 0.08 to 0.14 |
| P value | .329 | .44 | .479 | .643 |
∗ PPI: proton pump inhibitor.
† Including systemic steroids, hormone replacement therapy, and immunobiologics.
‡ Patients taking thyroid hormone supplementation medications.
Table 4Mean age of patients using PPIs vs not using PPIs.
| Patient Characteristics | All Patients | Excluding Smoking and Diabetes | Excluding Smoking, Diabetes, Systemic Medications, and Conditions | Excluding Smoking, Diabetes, Systemic Medications and Conditions, and Treated Hypothyroidism |
|---|---|---|---|---|
| No PPI Mean age, y PPI | 64.4 (n = 461) | 65 (n = 324) | 64.8 (n = 323) | 65 (n = 314) |
| Mean age, y No PPI-PPI | 66.6 (n = 57) | 67 (n = 41) | 67 (n = 40) | 66.5 (n = 33) |
| Mean age, y, mean difference | −2.2 | −2.0 | −2.1 | −1.5 |
| 95% CI of mean difference | 0.89 to 5.3 | 1.8 to 5.8 | 1.6 to 5.9 | 2.6 to 5.7 |
| P value | .161 | .299 | .265 | .454 |
∗ PPI: proton pump inhibitor.
† Including systemic steroids, hormone replacement therapy, and immunobiologics.
‡ Patients taking thyroid hormone supplementation medications.
Discussion
The results suggest that, among patients who received a diagnosis of periodontitis stage III or IV, grade B or C, PPIs are associated with a statistically significant decrease in periodontal probing depths compared with participants not taking PPIs. When smokers, those with diabetes, patients using systemic steroids or HRTs, or with a diagnosis of hypothyroidism, rheumatoid arthritis, or systemic lupus erythematosus were excluded, the effect of PPIs in the observed population persisted, suggesting that those potential confounding factors did not influence the observed outcome. In addition, there were no significant differences in patient age or oral hygiene efficacy between the PPI and non-PPI groups, also suggesting that those factors did not influence the results.
A possible explanation of how PPIs could mitigate the development of periodontal disease might be related to their ability to alter bone metabolism. Proposed mechanisms for the PPI omeprazole include inhibition of H+/K+ ATPases within the acid vesicles of osteoclasts, inhibition of calcium release from bone, and a decrease in transcription factor expression in osteoclastic cells leading to a decrease in bone resorption.
27
, 28
, 29
, 30
In addition to a potential decrease in osteoclast metabolism, PPIs also might enhance osteoblast function. Lansoprazole has been reported to inhibit various enzymes, including alkaline phosphatase, thereby favoring bone remineralization.27
,31
Conversely, a study on 3 PPI medications (omeprazole, esomeprazole, lansoprazole) showed a dose-dependent inhibitory effect on osteoclasts and osteoblasts and a decrease in cell density at therapeutic concentrations of PPIs.27
Therefore, it is possible that PPIs could influence bone metabolism by decreasing bone turnover, which in the case of periodontitis might be a protective factor because of slowing the destructive effects of the inflammatory immune response through decreased bone cell activity.Another mechanism through which PPIs might affect periodontal disease is their effect on ATPase function in periodontal pathogens. In a manner similar to their inhibitory effect in gastric parietal cells, PPIs have shown a mechanism of irreversibly binding and inhibiting H+/K+ ATPases in gram-negative asaccharolytic anaerobes.
32
,33
Bacteria such as Porphyromonas gingivalis generate energy by transporting amino acids and oligopeptides across their plasma membrane, using a proton gradient generated through ATPases.32
, 33
, 34
, 35
, 36
, 37
P. gingivalis is a potential etiologic agent for the development of periodontal disease, and studies have shown that known ATPase inhibitor molecules, including resveratrol and stilbenoids, significantly decrease the growth of that organism.33
Because PPIs have been shown to alter the GI microflora and lead to the potential introduction of bacteria, including streptococcal species, the inhibition of a key regulatory system for proton gradients by PPIs could lead to a decrease in the growth of certain gram-negative anaerobes, including P. gingivalis.33
Further research into the mechanisms of action of PPI medications in the presence of asaccharolytic anaerobic bacteria commonly found in the oral cavity and in bone metabolism are indicated to more fully elucidate how PPIs might affect the function of periodontal pathogens.27
A 2020 study by Wang et al
38
(N = 1,121) investigated the potential effect of multiple medications on the severity of the periodontal disease. Probing depths were used to indicate moderate to severe periodontal disease, similar to our methods. However, in contrast to our study, antacid medications were not significantly associated with periodontal disease severity. This discrepancy might exist because PPIs and histamine-2-receptor antagonists were both classified as common antacid medications in the Wang et al38
study; however, these 2 antacid medications have different mechanisms of action, and any potential impact of PPIs on probing depth may have been lost.39
The impact of histamine-2-receptor antagonist antacid medications on periodontal disease severity remains elucidated.Limitations associated with this study are similar to retrospective studies in general and include variability in the duration and dosing of PPI medications. Information describing the onset of periodontal disease and the timing of use of PPIs in the study population was not available. In addition, probing depths at the time of periodontal examination was used as a surrogate for periodontal disease severity, whereas a future prospective clinical trial might also incorporate changes in attachment level or radiographic factors to more precisely characterize periodontal severity over time. Potential sources of bias are related to the use of multiple examiners to obtain periodontal probing values, which might lead to differences in periodontal probing pressure calibrations among examiners. In addition, the effect of race or sex was not assessed. Consequently, studies are planned or underway in our laboratory that include animal trials and prospective human clinical studies to further investigate the effects of PPIs on the oral microbiota and explore mechanisms through which PPIs might influence periodontal disease.
PPIs might serve as an adjunctive therapeutic agent for the treatment of periodontitis. Potential applications could include treating sites with persistent pocketing after nonsurgical therapy or for recurrent probing depths observed at periodontal maintenance visits. Similarly, in adult patients undergoing orthodontic treatment, PPIs might be considered in short-term situations in which appliances limit access for effective plaque control. PPIs might also be considered before, or in conjunction with, periodontal surgical procedures to alter a potentially periodontopathic microbiome to facilitate pocket resolution. If the relationship between PPIs and periodontal disease is further substantiated, supplementation with local or systemic medications, such as PPIs, might be considered adjunctively to enhance periodontal treatment outcomes. Additional research is required to elucidate the mechanism through which PPIs might influence periodontal pathogenesis.
Conclusions
Patients using PPIs have fewer teeth with probing depths of 6 mm or greater, implying less severe periodontal disease. That relationship appears to be independent of smoking, diabetes, or the presence of a variety of systemic conditions. Further studies are indicated to precisely elucidate the potential mechanisms through which PPIs might affect periodontal disease and assess whether PPIs could be useful adjuncts to periodontal therapy.
References
- National trends in prescription proton pump inhibitor use and expenditure in the United States in 2002-2017.J Am Pharm Assoc. 2021; 61: P87-P94https://doi.org/10.1016/j.japh.2020.09.015
- Long-term safety concerns with proton pump inhibitors.Am J Med. 2009; 122: 896-903https://doi.org/10.1016/j.amjmed.2009.04.014
- Guidelines for prevention of NSAID-related ulcer complications.Am J Gastroenterol. 2009; 104: 728-738https://doi.org/10.1038/ajg.2009.115
- Proton pump inhibitors and fracture risk: a review of current evidence and mechanisms involved.Int J Environ Res Public Health. 2019; 16: 728https://doi.org/10.3390/ijerph16091571
- No potassium, no acid: K+ channels and gastric acid secretion.Physiology (Bethesda). 2007; 22: 335-341https://doi.org/10.1152/physiol.00016.2007
- The chemically elegant proton pump inhibitors.Am J Pharm Educ. 2006; 70: 101https://doi.org/10.5688/aj7005101
- Proton pump inhibitors in pediatrics: mechanism of action, pharmacokinetics, pharmacogenetics, and pharmacodynamics.Paediatr Drugs. 2013; 15: 119-131https://doi.org/10.1007/s40272-013-0012-x
- Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency.JAMA. 2013; 310: 2435-2442https://doi.org/10.1001/jama.2013.280490
- Proton pump inhibitors and fracture risk: response to comments.Osteoporos Int. 2016; 27: 1673-1674https://doi.org/10.1007/s00198-015-3434-1
- Effects of proton pump inhibitors on the gastrointestinal microbiota in gastroesophageal reflux disease.Genomics Proteomics Bioinformatics. 2019; 17: 52-63https://doi.org/10.1016/j.gpb.2018.12.004
- Systematic review: the use of proton pump inhibitors and increased susceptibility to enteric infection.Aliment Pharmacol Ther. 2011; 34: 1269-1281https://doi.org/10.1111/j.1365-2036.2011.04874.x
- Proton pump inhibitors affect the gut microbiome.Gut. 2016; 65: 740-748https://doi.org/10.1136/gutjnl-2015-310376
- Proton pump inhibitors: risks of long-term use.J Gastroenterol Hepatol. 2017; 32: 1295-1302https://doi.org/10.1111/jgh.13737
- Risk of community-acquired pneumonia and use of gastric acid-suppressive drugs.JAMA. 2004; 292: 1955-1960https://doi.org/10.1001/jama.292.16.1955
- Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis.PLoS One. 2015; 10e0128004https://doi.org/10.1371/journal.pone.0128004
- Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions.J Periodontol. 2018; 89: S173-S182https://doi.org/10.1002/JPER.17-0721
- Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.Am J Epidemiol. 2000; 151: 273-282https://doi.org/10.1093/oxfordjournals.aje.a010203
- Recent epidemiologic trends in periodontitis in the USA.Periodontol 2000. 2020; 82: 257-267https://doi.org/10.1111/prd.12323
- Tobacco smoking and risk for periodontal disease.J Clin Periodontol. 2003; 30: 107-113https://doi.org/10.1034/j.1600-051x.2003.00272.x
- Association between proton pump inhibitors and periodontal disease severity.Clin Exp Dent Res. 2022; 8: 395-401https://doi.org/10.1002/cre2.495
- A clinical survey of periodontal conditions in Greece.J Clin Periodontol. 1996; 23: 758-763https://doi.org/10.1111/j.1600-051x.1996.tb00606.x
- Periodontal diseases in the U.S. in 1981: prevalence, severity, extent, and role in tooth mortality.J Periodontol. 1989; 60: 363-370https://doi.org/10.1902/jop.1989.60.7.363
- A systematic review of definitions of periodontitis and methods that have been used to identify this disease.J Clin Periodontol. 2009; 36: 458-467https://doi.org/10.1111/j.1600-051X.2009.01408.x
- The plaque control record.J Periodontol. 1972; 43: 38https://doi.org/10.1902/jop.1972.43.1.38
- Representativeness of the “Ramfjord teeth” for epidemiologic studies of gingivitis and periodontitis.Commun Dent Oral Epidemiol. 1987; 15: 221-224https://doi.org/10.1111/j.1600-0528.1987.tb00525.x
- Comparing effects of treatment: controlling for confounding.Neurosurgery. 2020; 86: 325-331https://doi.org/10.1093/neuros/nyz509
- Dose-dependent inhibitory effects of proton pump inhibitors on human osteoclastic and osteoblastic cell activity.FEBS J. 2013; 280: 5052-5064https://doi.org/10.1111/febs.12478
- Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases.Biochim Biophys Acta. 1991; 1065: 261-268https://doi.org/10.1016/0005-2736(91)90238-4
- Omeprazole, a specific inhibitor of H+-K+-ATPase, inhibits bone resorption in vitro.Calcif Tissue Int. 1986; 38: 123-125https://doi.org/10.1007/BF02556841
- Modularity of osteoclast behaviour and “mode-specific” inhibition of osteoclast function.Biosci Rep. 1990; 10: 547-556https://doi.org/10.1007/BF01116615
- Lansoprazole is an uncompetitive inhibitor of tissue-nonspecific alkaline phosphatase.Acta Biochim Pol. 2009; 56: 301-305https://doi.org/10.18388/abp.2009_2462
- Proton pumping ATPases and diverse inside-acidic compartments. Article in Japanese.Yakugaku Zasshi. 2004; 124: 243-260https://doi.org/10.1248/yakushi.124.243
- Porphyromonas gingivalis is highly sensitive to inhibitors of a proton-pumping ATPase.Biochem Biophys Res Commun. 2018; 498: 837-841https://doi.org/10.1016/j.bbrc.2018.03.066
- A resistance-nodulation-cell division family xenobiotic efflux pump in an obligate anaerobe, Porphyromonas gingivalis.Antimicrob Agents Chemother. 2002; 46: 3257-3260https://doi.org/10.1128/AAC.46.10.3257-3260.2002
- Putative respiratory chain of Porphyromonas gingivalis.Future Microbiol. 2010; 5: 717-734https://doi.org/10.2217/fmb.10.32
- Complete genome sequence of the oral pathogenic bacterium Porphyromonas gingivalis strain W83.J Bacteriol. 2003; 185: 5591-5601https://doi.org/10.1128/JB.185.18.5591-5601.2003
- Iron and heme utilization in Porphyromonas gingivalis.FEMS Microbiol Rev. 2005; 29: 119-144https://doi.org/10.1016/j.femsre.2004.09.001
- Association between periodontitis and systemic medication intake: a case-control study.J Periodontol. 2020; 91: 1245-1255https://doi.org/10.1002/JPER.19-0593
- Theoretical studies on the histamine H2 receptor: molecular mechanism of action of antagonists.Mol Pharmacol. 1992; 42: 373-381
Article info
Publication history
Published online: June 09, 2022
Footnotes
Disclosure. None of the authors reported any disclosures.
This study was supported by the William M. Feagans Endowed Chair Research Fund and the Department of Periodontics and Endodontics, School of Dental Medicine, State University of New York, University at Buffalo. The funding agency had no role in the administrative or scientific conduct of the study.
This study was reviewed and approved by the State University of New York, University at Buffalo Health Sciences Institutional Review Board (00001811).
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