Edilbiev Z.V., Malkarukova A.A., Edilbieva L.V., Fedorov A.A., Gusov R.M. Changes in efficiency markers of therapeutic physical agents and rational pharmacotherapy in elderly patients with chronic generalized periodontitis

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Publication date 01.03.2021

UDC 616.314.18-002.4:615.838.7

CHANGES IN EFFICIENCY MARKERS OF THERAPEUTIC PHYSICAL AGENTS AND RATIONAL PHARMACOTHERAPY IN ELDERLY PATIENTS WITH CHRONIC GENERALIZED PERIODONTITIS

Z.V. Edilbiev¹, A.A. Malkarukova^1,2, L.V. Edilbieva¹, A.A. Fedorov^3,4, R.M.Gusov⁵

¹Medical Institute, FSBEI of HE “Kh.M. Berbekov Kabardino-Balkarian State University”, Nalchik, Russia

²LLC “Elifia”, Nalchik, Russia

³FSBEI of HE "Ural State Medical University”, Ministry of Health of Russia, Yekaterinburg, Russia

⁴FBIS "Yekaterinburg Medical Scientific Center for Prevention and Health Protection of Industrial Workers”, Rospotrebnadzor, Yekaterinburg, Russia

⁵Pyatigorsk Medical and Pharmaceutical Institute, the branch of Volgograd State Medical University, Ministry of Health of Russia, Pyatigorsk, Russia

 

Key words: periodontitis, geriatrics, mud therapy, physical therapy, Hypoxenum, AlfaVit50+, immune status.

Annotation. The main purpose of the study is to evaluate the effectiveness of the combination peloid, physiological and rational pharmacotherapy in elderly patients with inflammatory diseases of the periodontium. The study included 120 patients aged 60 to 75 years with chronic generalized periodontitis. Three groups were formed by simple randomization. The control group received standard therapy, the comparison group received additional vitamin-mineral complexes and antihypoxants; the experimenta; group received mud therapy. To monitor the effectiveness of treatment, an assessment of the parameters of the immune and metabolic status was used. The analysis of the effectiveness of therapeutic measures carried out in a comparative aspect showed that in patients of the main group with combination peloid, physiological, and rational pharmacotherapy, restoration of the immune and metabolic status was noted, which was significantly more significant in relation to the use of only standard therapy. The inclusion of vitamin and mineral complexes, antihypoxants and mud therapy in chronic periodontitis in elderly and senile patients is pathogenetically justified, provides a significant increase in the effectiveness of therapeutic measures.

 

Studies in geriatric dentistry indicate certain dissatisfaction with standard methods of treatment of chronic generalized periodontitis (CGP) in older age groups. The relationship between periodontal diseases and somatic diseases is also evidenced by the work of Zh. Rizaev and G.A. Gafurov (2018), in which it is shown that, on the one hand, inflammatory-destructive diseases of periodontal tissues induce reactions in various tissues and organs, on the other hand, decompensated somatic diseases cause the development of a chronic inflammatory process in periodontium [6].  The relevance of the development of new approaches to the therapy of this category of patients is indicated by works on the use of combination medical technologies, including both medications and physical factors (impulse phoresis, photodynamic therapy, bischofite complexes), which, in turn, makes it possible to achieve prolonged anti-inflammatory effect without the use of antibiotics [7, 8].

In favor of the advisability of including natural and preformed factors in treatment complexes, there are weighty scientific arguments proving the presence of a wide spectrum of therapeutic action, and, consequently, sanogenetic processes in various pathologies [9, 10, 11]. At the same time, therapeutic mud (peloids) with their unique chemical composition showed, in addition to anti-inflammatory, analgesic, antispasmodic and resorption effects, a pronounced immunomodulatory effect; and, apparently, the longest preservation of the achieved positive results is associated with these effects [12].

The use of balneological methods in gerodontics is described in the works of O.M. Sadykova (2017), N.A. Sharonova et al. (2019) [13, 14]. It has been shown that their wide use in clinical practice is due, on the one hand, to therapeutic effects (anti-inflammatory, immunomodulatory, bactericidal, etc.), on the other hand, to the absence of side effects, to the simplicity of dosing balneomedications, to the relatively cheap price.

Consequently, the main hypothesis of the study was that a modified standard treatment complex, due to the inclusion of peloids including their ultra-phonophoresis, with elderly patients suffering from CGP will increase the body's immune resistance and, therefore, stabilize the results achieved.

The purpose of the study is to evaluate the effectiveness of the combination peloid, physiological and rational drug therapy with elderly patients suffering from periodontium inflammatory disease in different periods of the study.

Methods and organization. The study included 120 patients with CGP (women – 83 (69.2%), men – 37 (30.8%)) at the age of 60 to 75 years old (average age – 69.3±4.82).

Inclusion criteria were CGP; persons of both genders; involvement of periodontal tissues of most of the teeth on both jaws in the pathological process; 2nd degree pathological mobility of teeth; condition after ultrasonic treatment of periodontal pockets; the duration of the disease – from three to ten years; informed voluntary consent to participate in the study; personal data processing consent.

Exclusion criteria were general contraindications for mud therapy and physiotherapy procedures; severe CGP with the presence of purulent pockets with impaired outflow of purulent contents; decompensated concomitant somatic diseases; intolerance to Actovegin, Hypoxenum and AlfaVit50+.

Three groups were formed by simple randomization. Patients of the control group (CG; 36 people) received treatment in accordance with the approved standards (oral cavity debridement, closed curettage, selective grinding and temporary splinting of movable teeth; Solcoseryl dental adhesive paste (applied with a thin layer on the gums, twice a day); the comparison group (ComG; 41 people), in order to correct vascular, trophic, metabolic disorders, received additional drug therapy (Actovegin, 1 tab. 3 times a day with meals, for 1 month; Hypoxenum/sodium polyhydroxyphenylenethiosulfonate, 2 caps., twice a day, with food, for 3 weeks; AlfaVit50+ vitamin and mineral complex 1 tab., 3 times a day, with food, for 1 month); the experimental group (EG; 43 people), in addition to the ComG complex, received combined sonopeloid therapy (ultraphonophoresis of an oil solution of silt sulfide mud from Lake Tambukan on the upper and lower jaws with an intensity of 0.2 W/cm², duration – 10 minutes, for a course of treatment – 10 procedures, daily) and native mud applications according to the segmental-reflex technique on the projection of the cervical-collar zone, at 38-40^°C, duration 8-10 minutes, 6-8 sessions, every other day.

To monitor the effectiveness of the therapy, the cytokine profile in blood serum and oral fluid was studied. The level of pro-inflammatory and anti-inflammatory interleukins (IL-1β and IL-10), as well as tumor necrosis factor-α (TNF-α) was determined by means of enzyme-linked immunosorbent analysis using “Biohimmak” reagents (St. Petersburg, Russia). To assess the degree of assimilation of vitamins and microelements, the level of homocysteine was also studied using high performance liquid chromatography.

Statistical analysis of materials was carried out using "SPSS 13.0 Mathematica 5.1" (United States of America).

Results and discussion. Analysis of changes in the efficacy markers with elderly patients suffering from CGP showed the best results when using the newly developed therapeutic complex. Thus, EG patients who received combination peloid, physiological and drug therapy, immediately after the treatment, had a decrease in the level of IL-1β in the blood serum by 1.69 times (p<0.01), TNF-α – by 1.82 times (p<0.01) with a simultaneous increase in the level of IL-10 by 1.89 times (p<0.01). The normalization of immune parameters in the oral fluid occurred with the same reliability: the level of IL-1β decreased by 1.92 times (p<0.01), TNF-α – by 2.14 times (p<0.01) with an increase in the level of IL-10 – by 2.97 times (p<0.01) (Table 1).

ComG also showed positive dynamics of immune parameters: in the blood serum, the level of IL-1β decreased by 1.56 times (p<0.01), TNF-α – by 1.54 times (p<0.01) against the background of an increase in the level of IL-10 to 1.53 (p<0.01); in the oral fluid, respectively – by 1.55 (p<0.01), 1.72 (p<0.01), and 2.16 (p<0.01) times.

CG showed statistically significant favorable shifts, which, however, were significantly less pronounced in relation to the data in EG (comparison of the final results). Thus, in the blood serum, the level of IL-1β decreased only by 1.33 times (p<0.05), TNF-α – by 1.31 (p<0.05) against the background of an increase in the level of IL-10 by 1.28 times (p<0.05); in the oral fluid, the improvement was by 1.39 (p<0.01), 1.46 (p<0.01), and 1.63 (p<0.01) times.

We should note that, most of all, the effectiveness of our technique for the rehabilitation treatment of elderly patients with CGP is evidenced by the data of distant observations. The preservation of the achieved positive results in terms of 6 and 12 months was most revealed with the patients of EG: after 6 months the serum level of IL-1β remained 1.5 (p<0.01) times lower than the initial values, after 12 months – 1.32 (p<0.05) times, TNF-α – 1.56 (p<0.05) and 1.36 (p<0.05) times, with an increase in the content of IL-10 by 1.64 (p<0.01) and 1.43 (p<0.05) times, respectively; in the oral fluid after 6 months the level of IL-1β remained 1.59 (p<0.01) times lower than the initial values, after 12 months – 1.42 (p<0.05) times, TNF-α – 1.70 (p<0.01) and 1.45 (p<0.05) times, while the level of IL-10 remained above the initial values by 2.59 (p<0.01) and 2.18 (p< 0.01) times, respectively.

In ComG the serum level of IL-1β after 6 and 12 months significantly reduced level by 1.34 (p <0.05) and 1.19 times, TNF-α – by 1.31 (p <0.05) and 1.17 times, while the content of IL-10 remained 1.40 (p <0.01) and 1.39 (p <0.01) times higher than the initial values; in the oral fluid, respectively – IL-1β – 1.59 (p<0.01) and 1.21 (p<0.05) times, TNF-α - by 1.29 (p<0.05) and 1.10 times, and the level of IL-10 - 1.82 (p<0.01) and 1.39 (p<0.01) times.

In CG in the blood serum during these periods of the study, for most of the indicators, a distinct persistence of the results obtained was not registered. After 6 months, the level of IL-1β was only 1.16 times lower than the initial values, TNF-α – 1.16 times, while the level of IL-10 remained only 1.17 times higher. At the same time, after 12 months, all indicators returned to almost their initial values (the difference was 1.07 times) both in the blood serum and in the oral fluid (Table 1).

When analyzing changes in the content of homocysteine in biological media, a significant decrease was recorded after a course of procedures in all groups of patients in the oral fluid (by 1.23-1.72 times; p <0.05-0.01). In addition, in EG and ComG, a statistically significant decrease in its content in the blood was noted (by 1.54 and 1.24 times; p <0.01 and 0.05).

At the same time, further study of this indicator did not reveal a pronounced stability of the results obtained. If EG had the level of homocysteine after 6 months still significantly lower than the initial level in both studied humoral media – by 1.30 (p<0.05) and 1.37 times, then patients of ComG - only in the oral fluid (1.30; p<0.05).

After 1 year, all groups of patients had their level of homocysteine in biological media close to the initial data (Table 1).

Table 1

 Changes in the indicators of the immune status and metabolism in geriatric patients with chronic generalized periodontitis

Indicators	Groups	Study/treatment period
		before	after treatment	after 6 months	after 12 months
blood serum indicators
IL-1β, pg/ml	EG (n=43)	78.92±3.28	46.72±2.68**″	52.74±2.85**″	59.93±3.41*″
	ComG (n=41)	78.29±3.81	50.26±2.44**	58.61±3.26*	65.39±3.63
	CG (n=36)	77.34±3.52	58.35±2.39*	66.83±3.37	73.28±3.56
TNF-α, pg/ml	EG (n=43)	62.16±3.24	34.11±2.19**″	39.91±2.25**″	45.81±2.35*
	ComG (n=41)	61.21±3.29	39.83±2.12**	46.88±2.63*	52.36±2.73
	CG (n=36)	61.82±3.36	47.02±2.27*	53.41±2.66	58.48±2.76
IL-10, pg/ml	EG (n=43)	10.65±2.24	20.26±1.14**″	17.48±1.14*″	15.26±1.11*
	ComG (n=41)	11.21±2.53	17.17±1.16*	15.71±1.18*	13.35±1.12
	CG (n=36)	11.04±2.30	14.16±1.13*	12.83±1.22	11.68±1.16
Homocysteine, μmol/L	EG (n=43)	15.83±1.07	10.26±0.08**″	12.18±1.10*	13.56±1.10
	ComG (n=41)	14.67±1.14	11.83±1.02*	12.76±1.00	13.38±1.06
	CG (n=36)	14.38±1.16	12.16±1.07	13.20±1.12	13.89±1.07
oral fluid indicators
IL-1β, pg/ml	EG (n=43)	6.12±0.11	3.18±0.09**″	3.86±0.07**″	4.32±0.08**″
	ComG (n=41)	5.98±0.12	3.85±0.12**	4.31±0.19**	4.93±0.07*
	CG (n=36)	5.92±0.09	4.27±0.11**	4.88±0.14*	5.46±0.12
TNF-α, pg/ml	EG (n=43)	3.34±0.06	1.56±0.07**″	1.96±0.05**″	2.29±0.08*″
	ComG (n=41)	3.24±0.07	1.88±0.09**	2.51±0.10*	2.95±0.11
	CG (n=36)	3.29±0.05	2.26±0.08**	2.91±0.08	3.14±0.09
IL-10, pg/ml	EG (n=43)	0.32±0.08	0.95±0.06**″	0.83±0.06**″	0.70±0.05**″
	ComG (n=41)	0.38±0.04	0.82±0.05**	0.69±0.03**	0.53±0.08*
	CG (n=36)	0.41±0.05	0.67±0.04**	0.58±0.04*	0.44±0.02
Homocysteine, μmol/L	EG (n=43)	0.81±0.04	0.47±0.03**″	0.59±0.06**	0.72±0.04
	ComG (n=41)	0.79±0.03	0.53±0.05**	0.61±0.04*	0.68±0.05
	CG (n=36)	0.79±0.05	0.64±0.02*	0.71±0.03	0.76±0.07

Note: * - p<0.05 and ** - p<0.01 – reliability of differences in comparison with the indicators before treatment; ″ - p <0.05 – reliability of differences between the experimental and control groups.

 

Thus, the data obtained indicate a more significant positive dynamics of markers of the immune status and metabolic activity (almost to the reference values) both in the blood serum and in the oral fluid after a course of a new developed medical technique for CGP. At the same time, the stability of the achieved results up to a year was noted for the main markers of treatment efficacy (immune tests), both at the systemic (in the blood) and local (oral fluid) levels. These positive shifts, apparently, can be explained, first of all, by the inclusion in the standard of treatment of peloid therapy and its preformed form in the form of phonophoresis. This statement is supported by works on the beneficial effect of therapeutic mud on the bioregulatory systems of the body, in particular, the correction of metabolic and immune disorders [11, 12]. At the same time, it is the summation and synergy of the therapeutic effects of pharmaceuticals, therapeutic mud and ultrasound that provides high clinical efficiency. The rapid reverse development of pathological immune and metabolic processes in the CG dictates the need to optimize the standard methods of treating CGP of aged patients.

Conclusion. A comparative analysis of monitoring of markers of treatment efficacy (indicators of immunity and metabolism) of elderly patients suffering from CGP indicates the feasibility and pathogenetic justification of the use of the new developed technology, which is confirmed by the following facts:

1. In EG, immediately after the treatment, the level of local and systemic parameters of immunity improved by an average of 2.07 (p<0.01) times versus 1.68 (p<0.01) in ComG and 1.40 times (p<0.01) in CG;
2. The longest duration of preservation of the achieved positive results was also obtained in EG, which indicates the advisability of including mud therapy in a standard therapeutic complex;
3. Metabolic processes (local and systemic), according to the level of sulfur-containing amino acid homocysteine in EG immediately after the treatment, improved on average by 1.63 (p<0.01) times, while the preservation of positive results after 6 months was by 1.34 (p<0.01), and after 12 months – by 1.16 times (p<0.05); in ComG – by 1.37 (p<0.01), 1.23 (p<0.05), and 1.13 times, respectively, in CG – by 1.21 (p<0.05), 1.12, and 1.05 times.

 

Conflict of interest. The authors declare no conflict of interest.

 

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Information about the authors: Edilbiev Zelimkhan Vakhaevich – Dentist, Postgraduate Student of the Medical Institute, FSBEI of HE “Kh.M. Berbekov Kabardino-Balkarian State University”, Nalchik, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.; Malkarukova Aminat Alekseevna – Lecturer of the Medical Institute, FSBEI of HE “Kh.M. Berbekov Kabardino-Balkarian State University”, Nalchik; Dental Therapist of the LLC “Elifia”, Nalchik, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.; Edilbieva Lamara Vakhaevna – Dentist, Postgraduate Student of the Medical Institute, FSBEI of HE “Kh.M. Berbekov Kabardino-Balkarian State University”, Nalchik, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.; Fedorov Andrei Alekseevich – Doctor of Medical Sciences, Professor of the Department of Physical and Rehabilitation Medicine of the Faculty of Advanced Training and Professional Retraining of the FSBEI of HE "Ural State Medical University”, Ministry of Health of Russia; Head of the SPA of Rehabilitation Treatment, Physiotherapy and Balneology of the FBIS "Yekaterinburg Medical Scientific Center for the Prevention and Health Protection of Industrial Workers", Rospotrebnadzor, Yekaterinburg, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.; Gusov Ruslan Mikhailovich – Candidate of Pharmaceutical Sciences, Associate Professor, Department of Disaster Medicine of the PMPI, the branch of the FSBEI of HE "Volgograd State Medical University" of the Ministry of Health of Russia, Pyatigorsk, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.