Evaluation of the effectiveness of perioceutics as an adjunct to scaling and root planing in the treatment of chronic periodontitis:An interventional study.

Need for Study.

Periodontitis is a group of inflammatory diseases that affect the connective tissue and supporting structures around the teeth. The initiation and the progression of periodontitis are dependent on both the presence of lethal microorganisms and the host responses to the same. The host immune inflammatory response against bacterial plaque can thus be viewed as a “dual-edged sword,†i.e., the response is protective by intent, yet in susceptible patients who exhibited an exaggerated inflammatory response to plaque, is ultimately responsible for perpetuating destruction of the periodontium(1). The disease progresses with the loss of collagen fibers and attachment to the cemental surface, apical migration of the junctional epithelium, formation of deepened periodontal pockets, and resorption of alveolar bone. If left untreated, the disease continues with progressive bone destruction, leading to tooth mobility and subsequent tooth loss.

There is ongoing periodontal research directed toward the reduction and/or elimination of these pathogenic bacteria that are thought to cause periodontitis. Accomplished in large part by the use of mechanical and chemical plaque control measures, the sudden paradigm shift towards the importance of the role of host response in periodontal pathogenesis has helped in exploiting new treatment strategies for periodontitis. This shift in paradigms, with emphasis on host response, has led to the development of host modulatory therapies (HMTs). HMTs can improve therapeutic outcomes by slowing the disease progression, thus allowing for more predictable management of patients. In comparison with other therapeutic modalities employed against infection, host response modulation is noninvasive, is relatively easier to apply and has fewer side effects. “Perioceutics†includes antimicrobial therapy and host modulating agents to produce changes in the microflora and the host response respectively. The term perioceutic (periodontal+therapeutic) was first introduced by Heska Corporation (Fort Collins, CO) (1).  It is an emerging aid in the management of periodontal disease as an adjunct to mechanical therapy.

Glucosamine sulfate (GS) has been proven to have anti -inflammatory action due to its ability to suppress the neutrophil function. Moreover, GS inhibits nuclear factor-kappa B activation and prostaglandin E2 synthesis induced by interleukin 1ß (IL-1ß). Fibrillated cartilage chondrocyte adhesiveness to fibronectin is restored by Glucosamine by the suggested activation of protein kinase C, thereby augmenting the process of repair (2).

Vitamin C or L-ascorbic acid is a compound that belongs to the scavenging (chain breaking) group of antioxidants. It is a potent antioxidant essential for maintaining the integrity of connective tissue, osteoid tissues, and dentine. It also scavenges free radicals and professor’s potent antioxidant and immune modulatory properties which can effectively control excessive ROS generated in chronic inflammatory condition. Vitamin C also considered an important dietary antioxidant in the maintenance of periodontal health. Furthermore, it has been shown to decelerate the rate of progression of periodontitis by stimulating the differentiation of progenitor cells of the periodontal ligament(3).

Collagen is the most abundant protein in mammals, also making it the most important component of the body structurally and functionally. It is the oldest known protein, the most defining feature of which is its structure, which gives it stability, functional ability, strength, and physical characteristics. Collagen plays an important role in development, wound healing, platelet activation, angiogenesis, provides cell occlusiveness, biocompatibility, and resorbability.Additionally, upon breakdown through the resorption process, its byproducts are utilized by the host to form native tissue (4).

GS with the combination of collagen and vitamin C is a unique nutritional preparation which is postulated to counteract the immunoinflammatory effects of periodontitis.

Alkaline phosphatase (ALP), a vital marker associated with bone formation is an enzyme found in many periodontal cells, osteoblasts, fibroblasts, and neutrophils. ALP is released from polymorphonuclear leukocytes during inflammation, osteoblasts during bone formation, and periodontal ligament fibroblasts during periodontal regeneration. Thus, it is involved in the process of both periodontal inflammation and regeneration (5).

Thus, the present study attempts to evaluate the effectiveness of perioceutics as an adjunct to scaling and root planing in the treatment of chronic periodontitis patients.

|Review of Literature

1) F Mahmoodian et al (1996) 6

The study aimed at analyzing the regulation and properties of bone alkaline phosphatase during Vitamin C deficiency in guinea pigs. They found that decreased alkaline phosphatase activity in bone and serum during scurvy was not completely due to the "fasting effect" and that the decrease in serum was due to loss of bone isoenzyme activity. There also was a decrease in immunoreactive enzyme protein and alkaline phosphatase mRNA concentrations in bone of scorbutic animals, indicating that synthesis of the enzyme was inhibited. Sialylation and addition of the glycosylphosphatidylinositol anchor to the enzyme in bone tissue were not affected by scurvy. The decreased expression of collagen, alkaline phosphatase, and osteocalcin could explain the defects in bone caused by scurvy.

2) Renganath et al (2018)7

This study aimed at comparing the quantitative levels of alkaline phosphatase (ALP) in saliva and serum before and after scaling and root planning in patients with chronic generalized periodontitis.A total number of 50 participants (40 with chronic generalized periodontitis and 10 periodontally healthy volunteers) of 30-50 years were included in the study. Clinical parameters such as simplified oral hygiene index (OHI-S), gingival index, probing depth, and clinical attachment loss (CAL) were measured, and then, saliva and blood sample collection was done and analyzed for ALP levels by spectrometry. The clinical parameters along with saliva and serum ALP levels were reevaluated after 30 days following Phase I periodontal therapy. The saliva and serum ALP levels were significantly decreased following Phase I periodontal therapy along with improvement in clinical parameters.

3)Raghavendra et al (2018)8

The aim of the study was to assess the effectiveness of Vitamin C supplementation, a known antioxidant, on periodontal health in patients with chronic periodontitis (CP) and salivary total antioxidant capacity (TAOC) levels. A sample of 50 patients diagnosed with CP and 50 healthy controls were selected. Fifty CP patients were further randomly divided into two groups. CP1 (25 patients received nonsurgical therapy alone) and CP2 (25 patients received Vitamin C supplementation (1500 mg/day) as an adjunct to nonsurgical therapy). Clinical parameters such as plaque index (PI) gingival index (GI), gingival bleeding index (GBI), pocket depth (PD), and clinical attachment level (CAL) were recorded at 1-month and 2-month post therapy. Salivary TAOC levels were measured by Koracevic’s method at baseline and 2 months’ post therapy. Vitamin C supplementation showed significant reduction in GBI score at 1-month and 2-month post therapy.

4)Akio Tada et al (2019) 9

This study aimed to systematically review the studies addressing the relationship between vitamin C and periodontal disease, and the preventive ability of vitamin C against periodontal disease. Electric searches were performed using PubMed, EMBASE, Cochrane Library, and Web of Science. Studies addressing the relationships between periodontal disease and vitamin C in adults aged over 18 years were included. Quality assessment was done using the Critical Appraisal Skills Program guideline and GRADE-CERQual. There were 716 articles that were retrieved and 14 articles (seven cross-sectional studies, two case-control studies, two cohort studies, and three randomized controlled trials (RCT)) were selected after reviewing all of the articles. The vitamin C intake and blood levels were negatively related to periodontal disease in all seven cross-sectional studies. The subjects who suffer from periodontitis presented a lower vitamin C intake and lower blood-vitamin C levels than the subjects without periodontal disease in the two case-control studies. The patients with a lower dietary intake or lower blood level of vitamin C showed a greater progression of periodontal disease than the controls. The present systematic review suggested that vitamin C contributes to a reduced risk of periodontal disease.

5)Penmetsa et al (2020)2

This study evaluated the host modulatory effects of Orthoboon on periodontal status and estimated the C reactive protein (CRP) levels before and after nonsurgical periodontal therapy (NSPT).A total numbers of 40 patients with chronic periodontitis were randomly divided into two groups of 20 patients each. The test group patients (n = 20) received 500 mg Orthoboon three times daily for 45 days. Prior to the initiation of Orthoboon, all patients in both test group and control group were subjected to Phase I periodontal therapy. CRP levels were estimated immediately after phase I therapy and 45 days after therapy. Clinical parameters including plaque index, gingival index, and bleeding index were recorded before and after NSPT for the two groups. Administration of Orthoboon, was proved in this study to be of significant benefit in the test group than in the control group.

  |Aim & Objectives of the study

Aim:

â—       To evaluate the effectiveness of a perioceutic agent as an adjunct to scaling and root planing in chronic periodontitis patients.

Objectives:

â—       To evaluate the effectiveness of a perioceutic agent as an adjunct to scaling and root planing on the periodontal status among chronic periodontitis patients (Test group).

â—       To evaluate the effectiveness of scaling and root planing aloneon the periodontal status among chronic periodontitis patients (Control group).

â—       To assess Serum Alkaline phosphatase levels in the test and control group.

â—       To compare the periodontal status and Serum Alkaline Phosphatase levels between the Test and Control groups.

|MATERIALS AND METHODS

|Data:

The patients will be selected from Out Patient Department of Periodontics, A.J. Institute of Dental Sciences, Mangalore.

|Inclusion criteria:

1. Patients aged between 30 – 60 years.
2. Patients with chronic periodontitis with periodontal pockets measuring≥4mm.
3. Systemically healthy patients.

Exclusion criteria:

1. Patients who have undergone periodontal therapy in the last 6 months.
2. Patients diagnosed with diabetes, peptic ulcers, blood dyscrasias, nutritional deficiencies, infected with immunodeficiency virus, Acquired Immunodeficiency Syndrome.
3. Pregnant & Lactating women.
4. Patients on antibiotics, diuretics, steroids, oral contraceptives.
5. Patients with the habit of smoking, tobacco chewing and alcohol consumption.

  |Methodology:

The study sample will consist of subjects in the age group of 30- 60 years of both genders. They will be selected based on convenience sampling from the Out Patient Department of Periodontics, A.J. Institute of Dental Sciences, Mangalore. Consent form from subjects will be collected prior to the clinical examination which will be done based on the inclusion and exclusion criteria mentioned above.

Intervention

At baseline, the periodontal status will be assessed with the use of clinical parameters namely- Gingival index, Community Periodontal index and probing pocket depth.

1. Gingival index (1963)10

Gingival Index was given by Loe H and Silness P. It was developed for assessing the severity of gingivitis.

   The index teeth are-

16                   12                      24

44            32                                36

A score ranging from 0-3 is given.

SCORES

GINGIVAL STATUS

CRITERIA

|0

Normal Gingiva

Absence of inflammation.

|1

Mild inflammation

Slight change in color, slight edema. No bleeding on probing.

|2

Moderate inflammation

Moderate redness, slight edema and moderate glazing. Bleeding on probing.

|3

Severe inflammation

Marked redness and hypertrophy, ulceration. Tendency to spontaneous bleeding.

 2) Community Periodontal index10

The oral cavity is divided into 6 sextants defined by tooth numbers: 17-14, 13-23, 24-27, 37-34, 33- 43 and 44-47. Index teeth for adults aged 20 years and over, the teeth to be examined are:

17-14

13-23

24-27

|47-44

43-33

34-37

             

Score

Criteria10

|0

Healthy

|1

Bleeding observed directly or by using a mouth mirror, after probing

|2

Calculus detected during probing but all of the black band on the probe visible

|3

Pocket 4-5mm (gingival margin within the black band on the probe)

|4

Pocket 6mm or more (black band on the probe not visible

|X

Excluded sextant (less than 2 teeth present)

|9

Not recorded

Loss of Attachment scoring criteria.

Score

Criteria

|0

Loss of attachment 0-3mm (CEJ not visible and CPI score 0-3)

|1

Loss of attachment is 4-5mm (CEJ within the black band)

|2

Loss of attachment is 6-8mm (CEJ between the upper limit of the black band and 8.5mm)

|3

Loss of attachment 9-12mm (CEJ between the 8.5mm and 11.5mm ring)

|4

Loss of attachment 12mm or more (CEJ beyond 11.5mm ring)

|X

Excluded sextant (less than two teeth present)

|9

Not recorded (CEJ neither visible nor detectable)

 3) Probing pocket depth

It will be measured using William’s periodontal probe. It is measured as the distance from the gingival margin to the base of the sulcus/pocket.

  

P

|8

7

6

5

4

3

2

1

1

2

3

4

5

6

7

8

|P

 Also at baseline, blood will be collected from the medial cubital vein for the estimation of serum alkaline phosphatase, which will be done at the Central Diagnostic Laboratory, AJ Institute of Medical Sciences hospital based on PNP kinetic method11.

Treatment allocation will be randomly done (By using lottery method).

Group A will comprise of 15 patients receiving scaling and root-planing along with 500mg of the perioceutic agent (Once daily) for a period of 45 days.

Group B will comprise of 15 patients receiving only scaling and root- planing.

On the 45th day, the periodontal status and serum alkaline phosphatase levels will be reassessed by the above-mentioned methods.

CTRI registration will be done.

|Statistical Analysis2:

Sample size estimated using G*power-version 3.1.9.6

t tests - Means: Difference between two dependent means (matched pairs)

Analysis: A priori: Compute required sample size

Input: Tail(s) = Two

Effect size dz = 1.2363636

α err prob = 0.05

Power (1-β err prob) =0.95

N=11 with power of 95%

With attrition of 15% the total sample size is estimated to be 13

Students paired t Test /Wilcoxon signed rank test (based on normality) will be used to compare serum alkaline phosphatase level, gingival and periodontal status pre and post treatment. Unpaired t test/ Mann- Whitney test will be used to compare between the groups before and after treatment. Any further test will be used at the time of analysis based on the data obtained.

Level of significance will be set at P<0.05.