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International Medical Scientific Journal     Issue-2 

10.5281/zenodo.5080522  

11 

  



Art of Medicine          Volume-1 

International Medical Scientific Journal     Issue-2 

10.5281/zenodo.5080522  

12 

Art of Medicine 
International Medical Scientific journal 

 
Founder and Publisher Pascual Izquierdo-Egea 

Published science may 2021 year. Issued Quarterly. 

Internet address: http://artofmedicineimsj.us 
E-mail: info@artofmedicineimsj.us 

11931 Barlow Pl Philadelphia, PA 19116, USA +1 (929) 266-0862 

 

 
 

 

 

 
  



Art of Medicine          Volume-1 

International Medical Scientific Journal     Issue-2 

10.5281/zenodo.5080522  

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Dynamics of markers of bone metabolism in the oral fluid in patients with diseases 

of the cardiovascular system in preparation for dental implantation 

A.A. Khadjimetov, A.A. Yuldashev. 

 Tashkent State Dental Institute 

 

Abstract. The purpose of this study was to study the dynamics of markers of bone 

metabolism in the oral fluid in patients with diseases of the cardiovascular system 
in preparation for dental implantation. A total of 74 patients with chronic 

generalized periodontitis and concomitant diseases of the cardiovascular system 

and with partial secondary adentia (absence of 1-2 teeth, duration of dentition 

defect up to 1 year) were examined before dental implantation. oral fluid in 
patients with chronic periodontal pathology and combined disease of the 

cardiovascular system during the preparation of dental implantation is statistically 

significant, indicating the state of the alveolar bone and hard tissues of the teeth on 
the contact and cervical surfaces. 

Keywords: alkaline phosphatase, osteocalcin, hydroxyproline, calcium, 

phosphorus, oral fluid, urine 

 

Introduction. As you know, the success of dental implantation is associated 

primarily with the osseointegration of implants, their survival and long-term 

functional constancy. Meanwhile, a very important condition for bone restoration 
and osseointegration of dental implants is the normal functioning of the bone 

tissue, which is ensured by the balance between the interrelated processes of bone 

resorption and its formation. The noticeable influence of osteocytes and immune 

cells has recently been widely discussed as a key regulatory moment in the 
osseointegration of a dental implant. Changes in homeostasis that occur during the 

development of inflammatory and destructive processes in the maxillofacial region 

can affect the biochemical parameters of the oral fluid, which, along with other 
compounds, contains a system of enzymes that activate various osteogenesis 

processes. According to the literature, based on the dynamics of the parameters of 

the oral fluid (OC), one can judge the activity and completeness of the processes of 

bone tissue regeneration, and the analysis of specific components in the OC 
reflects the state of the periodontium around the implant, including the 

development of the inflammatory process in soft tissues. Alkaline and acid 

phosphatase levels are one of the markers that allow assessing the processes of 

bone tissue regeneration. Alkaline phosphatase plays a key role in mineralization 
by breaking down inorganic pyrophosphate and releasing free inorganic phosphate. 

It is believed that this enzyme can also be used as a biochemical marker to 

determine the activity of osteoblasts, since it is present on fragments of their 
plasma membranes. One of the important markers of bone metabolism is 

osteocalcin, which is a non-covalent calcium-ion binding protein, also known as y-



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carboxyglutamic acid protein, produced by both osteoblasts and odontoblasts. 

Osteocalcin binds hydroxyapatite and calcium during the mineralization of the 

organic matrix. It is one of the serological markers in the process of bone 
formation. Found that osteocalcin plays an important role in the formation and 

metabolism of bone tissue. It should be noted that in many studies, blood was the 

material for studying the processes of reparative bone regeneration, and very little 
information is available on the determination of the above parameters in gastric 

cancer. To date, there are limited studies examining bone metabolism around 

dental implants, the consequences and complications of dental implantation, and 

most of these studies are experimental in nature. Most researchers believe that the 
use of alkaline phosphatase and osteocalcin as potential indicators of the activity of 

reparative and destructive inflammatory processes requires more detailed study. 

Based on the foregoing, the purpose of this study was to study the dynamics of 
markers of bone metabolism in the oral fluid in patients with diseases of the 

cardiovascular system in preparation for dental implantation. 

 

                                  Material and research methods 

We examined 109 people aged 40 to 60 years, all patients showed signs of 

chronic generalized periodontitis (CGP). In accordance with the objectives of the 

study, 3 groups were formed: Group I - 50 patients (39 men and 11 women) with 

chronic generalized periodontitis against the background of AH and IHD: 

exertional angina pectoris II-IV functional class (according to the Canadian 

classification), aged 43 to 60 years. Group II - 34 patients (22 men and 12 women) 

with CGP on the background of AH and coronary artery disease combined with 

adentia who are at the stages of treatment for CVD, Group III - 25 patients (15 men 

and 10 women) with periodontal pathology (CGP), without diseases of the 

cardiovascular system (CVS) at the age of 40 to 60 years. It was mandatory for all 

study participants to read and sign an informed consent approved by the local 

ethics committee of the Ministry of Health of the Republic of Uzbekistan. It should 

be noted that all patients included in the groups were examined by a cardiologist. 

To clarify the diagnosis of coronary artery disease, all patients underwent physical 

and instrumental examination: ECG at rest in 12 conventional leads, two-

dimensional echocardiography, coronary angiography, 24-hour blood pressure 

monitoring, 24-hour Holter monitoring and laboratory studies. All patients were 

examined by a dentist. A standard clinical dental examination was carried out: 

assessment of patient complaints, medical history and life, objective status, 

assessment of periodontal indices. The level of individual hygiene and the 

condition of periodontal tissues were assessed in all patients. The hygienic state of 

the oral cavity was determined by the Green-Vermillion (OHI-S) method 

(Simplified Oral Hygiene Index). The depth of the periodontal pocket (PC) and the 



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loss of the periodontal attachment (PZP) were measured. Gingival bleeding was 

assessed using H.R. Muhleman. Tooth mobility was determined using the Miller 

scale (modified by T.J. Fleszar). To identify the developed forms of periodontal 

pathology, the periodontal index was used (PI, Rüssel, 1956); the degree of 

gingival recession according to P.D. Miller (1985). 

Oral fluid (OR), which was collected on an empty stomach, from 8.00 to 9.30 

was used as a biological material. The activity of alkaline phosphatase and the 

content of osteocalcin in the gastric fluid were measured by ELISA using 

diagnostic test kits from Hoffmann-LaRoche (Switzerland). To study calcium-

phosphorus metabolism, the daily excretion of calcium and phosphorus in the urine 

was determined. The calcium content was determined in daily urine by the 

Greenblatt and Hartman method. Determination of inorganic phosphorus in daily 

urine was carried out according to the method of O.A. Bodansky (1978). The 

excretion of free hydroxyproline in daily urine was carried out according to the 

method of Neumann and Logan modified by P.N. Sharaeva (2002). 

Statistical processing of the obtained data was carried out using standard 

software packages Statisticaversion7.0 (USA). Differences in comparison of mean 

values in paired comparisons were considered significant when _p <0.05. 

 

Research results and their discussion 

 

When analyzing the dental status of patients, more pronounced changes in the 

periodontal index were found, which indicates inflammatory processes in the 

periodontium of patients of the first and second observation groups. The average 

value of the PMA index in the observation group was 63% (in the comparison 

group - 34%), the periodontal index Russel-PI = 4.9 ± 0.3 (in the comparison 

group - 1.4 ± 0.1). The PBI bleeding index in the observation group is almost 

three times higher than in the comparison group (3.1 and 1.1, respectively), 

although the mean values of the OHI-S hygiene index in patients of the 

observation group and the comparison group differ insignificantly: 2.5 and 2.3 

... 

The main factor affecting the state of the periodontium in patients without 

concomitant pathology is the hygienic state of the oral cavity. The values of 

hygiene indices in the observation group were statistically significantly higher 

than in the comparison group, which indicated a deterioration in the state of oral 

hygiene. Based on the complaints identified, it should be assumed that the 

majority of patients with coronary heart disease have bleeding gums; they 



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associate this with the intake of antiplatelet agents and anticoagulants, and not 

with unsatisfactory hygienic care. The analysis of the obtained research results 

showed that the majority of patients of group I complained of gum bleeding 

(spontaneous, when eating and brushing teeth) - 57.9%. In group II patients, 

bleeding of the gums was observed only in 68.7%. Pain sensations when 

chewing food and brushing teeth were more often observed in patients of group 

II - 69.4%, in group II - 20%. No less characteristic complaint in generalized 

periodontitis is the mobility of the teeth, so. Group I patients noted this 

symptom in 65.1% of cases, versus 72% of Group II patients.  

                                                                               Table 1 

 
Patient complaints 

 

 Group I patients 

n = 50 

Group II patients 

            n = 34 

Comparison 

group n = 25 

Bleeding gums           31 (61%)            28  (83%)           6  ( 25%) 

Painful sensations (when 

experiencing food, 
brushing teeth) 

 
          26  (52%) 

 
            24  (71%) 

 
          4  (17%) 

Tooth mobility           27  (54%)             23  (67%)            5  (18%) 

  Dry mouth           31  (62%)             27  (78%)           10  (39%) 

   Burning tongue           15  (29%)             12  (34%)             5  (18%) 

   Smell from the mouth           38  (76%)              28  (84%)           11  (42%) 

 
 

     Thus, all patients of groups I and II presented complaints. associated with 

periodontal damage. The study of periodontal pockets revealed that in patients of 

group I, the average value of the pocket depth was 3.7 ± 1.5 mm. in patients of 

group II - 4.1 ± 0.3. To assess the state of the periodontium, the CPITN index was 

calculated. These tables show that more severe periodontal damage is observed in 

the second group than in the first group of patients, this is shown by the high 

values of the CPITN index. Analysis of the OHI-S hygiene index (G&V) shows 

that higher values are noted in both the first and second groups. The PI index, 

which reflects the severity of periodontal lesions, is 3.9 ± 0.5 in the first group, and 

4.1 ± 0.3 in the second group. At the same time, the maximum value of the PI 

index was noted in CGP against the background of coronary artery disease with 



Art of Medicine          Volume-1 

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combined adentia. It is 4.1, which corresponds to a moderate-severe degree of 

chronic generalized periodontitis. 

Alkaline phosphatase levels are one of the indicators that allow assessing the 

processes of bone tissue regeneration. It was found that this enzyme is involved in 

the regulation of phosphorus-calcium metabolism. Alkaline phosphatase plays a 

key role in mineralization by breaking down inorganic pyrophosphate and 

releasing free inorganic phosphate. It is believed that this enzyme can also be used 

as a biochemical marker to determine the activity of osteoblasts, since it is present 

on fragments of their plasma membranes. Alkaline phosphatase is directly involved 

in the implementation of the phagocytic function and its level changes depending 

on the severity of the inflammatory and necrotic process of the tissue. The data we 

obtained, presented in table 2, indicate the inhibition of the enzyme activity in the 

examined persons of groups 1 and 2 relative to the indicators of the comparison 

group. As you know, one of the important markers of bone metabolism is 

osteocalcin, which is a non-covalent calcium-ion binding protein produced by both 

osteoblasts and odontoblasts. Osteocalcin binds hydroxyapatite and calcium during 

the mineralization of the organic matrix. The analysis of the obtained research 

results showed that in patients of the 1st group the content of osteocalcin in the oral 

fluid increased insignificantly, while in the patients of the 2nd group the increase 

in osteocalcin was significantly higher - on average by 26% relative to the 

indicators of the comparison group. The increase in the levels of osteocalcin in the 

oral fluid in the examined persons with concomitant pathology indicated the 

formation and metabolism of bone bone tissue. A comparative analysis of the study 

results regarding the excretion of oxyproline in daily urine revealed an increase in 

this indicator in the main group compared with the comparison group. So the 

indicators of hydroxyproline in urine in patients of group 1 exceeded the initial 

level by 14%, while this indicator in patients of group 2 averaged 81.63 ± 5.33 

μmol / l, which is 38% higher than the indicators of the comparison group.  

                                                                                                    Table 2 

    Indicators of markers of bone metabolism in patients with the disease 

    cardiovascular system in preparation for dental implantation 

 

 
               Indicators 

Group III 
    Comparisons 

n = 25 

The patients 
I-groups 

n = 50 

The patients 
II-groups 

         n = 34 

Alkaline phosphatase in the 

oral fluid U / L 

28,98 ± 1,21 27,17 ± 1,14 25,02 ± 1,03* 



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Osteocalcin in the oral fluid U / 

L 

 0,73 ± 0,05    0,81 ± 0,07 0,92 ± 0,08* 

 Free hydroxyproline in 

urine, μmol / l 

59,17 ± 4,03 67,24 ± 4,89 81,63 ± 5,33* 

Calcium content in urine, 

          μmol / l 

 2,28 ± 0,19 2,59 ± 0,17 3,34 ± 0,21* 

Phosphorus content in urine, 

          μmol / l 

 21,03 ± 1,42 23,58 ± 2,07 27,12 ± 1,62* 

 

Note: *- reliability of differences P <0.05 relative to the group comparisons 

When analyzing the elemental composition of urine in the examined 

individuals, it was found that the average indicators of calcium concentration in the 

urine in patients of group 1 relative to the indicators of the comparison group 

increased by 14% and amounted to 2.59 ± 0.17 μmol / l versus 2.28 ± 0.19 μmol / 

l. In the group of patients with concomitant pathology against the background of 

adentia, the average was 3.34 ± 0.21 μmol / l, which is 46% higher than the initial 

values. 

The average indicator of the level of phosphorus in urine in patients of 

group 1 increases to 23.58 ± 2.07 μmol / l, which is 12% more than in the 

comparison group. In patients with chronic periodontal pathology and combined 

disease of the cardiovascular system against the background of adentia, the studied 

indicator was 27.12 ± 1.62 μmol / l , which is 29% higher than the initial 

indicators. 

Thus, the results of a comprehensive assessment of the metabolic state of 

bone tissue in patients with chronic periodontal disease and combined 

cardiovascular pathology indicate a systemic impairment of the remodeling of the 

alveolar bone of the jaw, depending on the severity of the underlying and 

concomitant pathology. The pathological changes are based on increased 

resorption of bone tissue and suppression of the processes of its formation. At the 

same time, the biochemical parameters of the oral fluid and urine of the examined 

patients allow us to assess the intensity of damage to soft tissues, alveolar bone and 

hard tissues of teeth on the contact and cervical surfaces. 

Conclusions 

1. A decrease in alkaline phosphatase activity and an increase in osteocalcin in the 

oral fluid in patients with chronic periodontal pathology and combined disease of 

the cardiovascular system during the preparation of dental implantation is 

statistically significant, indicating the state of the alveolar bone and hard tissues of 

the teeth on the contact and cervical surfaces. 



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2. The content of hydroxyproline, calcium and phosphorus in urine was increased 

relative to the comparison group. The revealed features of mineral mineral 

metabolism in patients with combined pathology confirm the possibility of the 

development of osteopenic syndrome in the examined individuals. 

  

  



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