Evaluation of Non-surgical Treatment in Chronic Periodontitis Patients on Blood Parameters

Introduction

Periodontitis is a common disease (1) involving supporting tissues of teeth through a chronic infection (2). Previous epidemiological studies suggested the relationship between periodontal diseases and systemic conditions including cardiovascular problems (3), cerebrovascular diseases (3), atherosclerosis (4), preterm birth with low birth weight (5) and Diabetes mellitus (6). Recently few studies have also reported the relationship between anemia and periodontal disease (7,8). Pre-inflammatory cytokines play a significant role in progress of periodontal disease (9). Cytokines bind to receptors on various target cells and cause transmission of intercellular signals. Low levels of these proteins affect different type of cells. Cytokines binding to cell surface receptors initiate intercellular changes that produce a group of materials and cause cell behavior changes. These events eventually cause increase in cytokine secretion. Due to the positive feedback, these continuous changes cause inflammation. Cytokines are produced by various inflammatory cells such as neutrophils, macrophages, lymphocytes and periodontal cells including epithelial cells and fibroblasts. Cytokines are in conjunction with each other and usually do no act alone. Cytokines can induce biological changes or tissue damages such as destruction of connective tissue and alveolar bones. These cytokines may be also effective in creating anemia by preventing proliferation and differentiation of erythrocyte precursors (10) and changing the metabolism of iron (11). In addition, they can suppress release of erythropoietin hormone from kidneys causing anemia (12).

Routine laboratory test for anemia is as follows: Complete blood count (CBC) including Hb, HCT and erythrocyte indices, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC) and Ferritin.

Anemia of chronic disease (ACD) is one of the most common types of anemia observed in patients with inflammation, infection and tumors. Such anemia occurs despite presence of sufficient iron reservoirs and normal function of bone marrow (13). ACD is typically recognized as a normocytic normochromic anemia. Patients with this type of anemia have a certain pattern of iron distribution in which, serum iron (SI) and Total Iron-Binding Capacity (TIBC) are low or normal while the level of Ferritin is high or normal. (14) Such changes occur due to presence of Hepcidin regulating iron level. Hepcidin is a hormone produced by liver in response to inflammatory cytokines such as IL-6 or other inflammatory cytokines that are high in blood circulation in periodontitis (15). Briefly, periodontitis may lead to a systemic chronic inflammation that may reduce RBCs and hemoglobin in patient’s blood.

In a study in 2012, red blood cell count (RBC), hemoglobin and hematocrit were significantly lower among patients with generalized chronic periodontitis. However, no significant difference was observed in MCV, MCH and MCHC (16). In another study in 2016, RBC, hemoglobin and PCV in periodontal patients was significantly lower than the control group (8).

Treatment of anemia is important due to its reducing effect on blood supply of periodontal tissues along with other systemic side effects. There are some controversies about the results of previous studies on the relationship between presence of periodontitis and reduction of blood indices.  On the other hand, there are only few clinical studies about effect of Periodontal treatment on blood indices. The present study designated to determine possible role of periodontal therapy in improvement of blood parameters.

Materials and Methods

The clinical trial entry number of this study was IRCT20151013024509N3 and it was approved by the Ethics Committee of Shahid Sadoughi University of Medical Sciences.

The patients participating in this study completed and signed the consent form. In addition, no fee was taken for laboratory tests or periodontal treatment. In the case of having abnormal blood indices, a consultation was made with our hematologist for probable further interventions.

Because of ethical considerations, selection of patients with certain anemia level and then subsequent delay in their treatment for 8 weeks was not possible. So, we had to choose patients with normal ranges of blood parameters whose indices should have been improved according to the opinion of our hematologist.

Thirty-six 25-50 years old males with moderate to severe chronic periodontitis referred to hematology clinic of Shahid Sadoughi Hospital were selected (except for periodontitis, they were perfectly healthy with no systemic diseases). 18 out of these 36 subjects received non-surgical periodontal treatment immediately (case group) while the treatment began for the remaining 18 patients after eight weeks (control group). It should be mentioned that means of age and periodontal and hematological indices of both case and control groups were matched before beginning of the study by overall matching. Other 18 males without any periodontal disease were selected as periodontally healthy group. To minimize bias of probable random changes in hematological indices during the 8 weeks of study, all efforts were made for matching age and similar blood parameters to between groups even without any specified intervention. The inclusion and exclusion criteria are summarized in Table I.

Table I. Inclusion criteria

First, an informed consent was received from all patients and the questionnaire was completed. After selection of samples, periodontal indices including BOP, PPD, and CAL and PI were recorded by a post-graduate student of periodontology.

All three groups were instructed about appropriate oral hygiene instruction including brushing and flossing using a dental model. The first phase of periodontal treatment (scaling and root planning and polishing by ultrasonic device (Guilin Woodpecker Medical Instrument, China) was performed by the same post-graduate student of periodontology in the case group. It should be noted that patients with severe periodontitis were followed up at the end of the study to evaluate for any further surgical treatment need. Four weeks later, the case group was called for checking the adequacy of periodontal treatment and if necessary, supplementary periodontal treatment was performed. In case of no appropriate oral health, oral hygiene instructions were re-enforced. After eight weeks from the beginning of the study, all periodontal indices were re-measured by another post-graduate student.

Two cc of venous blood was taken from all participants to evaluate blood indices such as hemoglobin, hematocrit, MCV, MCH, MCHC and serum Ferritin after periodontal examinations in the follow up stage (eight weeks later). CBC tests were performed using KX21 cell counter (Sysmex® Automated Hematology Analyzer KX-21) and the Ferritin test was performed by Electrochemiluminescence e411 device.  The results were analyzed using SPSS 23 software by independent and paired t-testand ANOVA test. The level of statistical significance was assigned at 0.05.

 Results

Eighteen patients with healthy periodontium (group A) were selected. Half of the patients with chronic periodontitis) 18 out of 36) went under periodontal treatment (group B) while the other half were treated after the end of the study (group C). The mean age of patients participating in all three groups was not significantly different. (P-value = 0.801)

The mean PPD, CAL, BI and PI in each of three groups at the beginning of the study and eight weeks later is presented in Table II. The mean PPD (P-value = 0.859) and PI (P-value =0.093) in the group A were not statistically significant at the beginning and eight weeks after the study. However, the mean PI (P-value =0.012) indicated a significant difference.

Table II: Comparison of mean periodontal indices of each group at the beginning of the study and eight weeks later

* Significant with more than 95% confidence (P value <0.05) based on Paired T-test

In group B, mean PI, PPD, BI and CAL indices at the end of the study was significantly less than the beginning of the study (P-value <0.001).

The mean BI, PPD and CAL indices in group C at the end of the study was less than the beginning of the study while no statistically significant difference was observed (P-values were 0.407, 0.644, 0.163). Meanwhile, the mean PI decreased and it was statistically significant (P-value = 0.006).

There was a significant difference in terms of BOP, CAL, and probing depth (P-value = 0.001) and PI (P-value= 0.000) between group B and C at the end of study. (Table III)

Table III. Comparison of mean periodontal indices in the case (B) and control (C) groups at the beginning of the study and eight weeks later

* Significant with more than 95% confidence (P- value <0.05) based on ANOVA test

In group B, mean values of hematocrit, hemoglobin, MCH, MCHC, and MCV indicated a statistically significant increase at the beginning of the study and eight weeks later and it was also clinically significant according to the co-hematologist. Furthermore, mean ferritin at the end of the study was slightly lower than the beginning which was not statistically significant. No significant difference in blood parameters was seen in group C. After eight weeks, no significant changes in blood parameters was seen in group A (Table IV)

Changes of mean blood indices in groups B and C were also compared in the present study (Table V).

Table IV: Comparison of mean blood indices of each group at the beginning of the study and eight weeks later

* Significant with more than 95% confidence (P-value <0.05)

Table V. Comparison of mean blood indices in all three groups (comparison between groups) at the beginning of the study and eight weeks later

* Significant with more than 95% confidence (P-value <0.05) based on Paired T-test