the relationship between marginal bone loss and serum zinc levels

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Acta Med Scand 207: 67-70, 1980 The Relationship between Marginal Bone Loss and Serum Zinc Levels L. Frithiof, S. Lavstedt, G. Eklund, U. Soderberg, K. 0. SkArberg, J. Blomqvist, B. Asman and W. Eriksson From the Departments of Oral Surgery, Periodontology, Internal Medicine and Odontological Roentgenology, School of Dentistry, Karolinska Instituter, Stockholm, and the Neurophysiological Laboratory, Ullerdkers sjukhus, Uppsala, Sweden ABSTRACT. Serum was analyzed for zinc in 51 pa- tients of varying age and with varying degrees of alveolar bone loss as recorded on roentgenograms. There was a reversed correlation between marginal alveolar bone loss and serum zinc levels. The obser- vations are discussed in relation to the physiological functions of zinc. Key words: periodontal disease, zinc. Acta Med Scand 207: 67. 1980. In a detailed medical survey of a few patients with advanced periodontal disease, some extremely low serum zinc levels were recorded. The present study was performed in order to find out if any reversed correlation actually existed between the degree of periodontal disease and the serum zinc levels in a larger material. As other laboratory tests on blood samples from patients with periodontal disease usu- ally only reveal levels within the normal range, we presumed that our observations might be of some interest. SUBJECTS AND METHODS The study comprises 21 males and 30 females. Their age and sex distribution is presented in Table I. The subjects were recruited by four different dentists among patients attending general dental and periodontal care in four dif- ferent private dental clinics and among patients from the University Clinic of Periodontology. According to the routine interview, the participants were presumably healthy. Evaluation of marginal bone loss Intraoral roentgenograms were used for determining an index of marginal bone loss (MBL) (7, 14). For each tooth, excluding the wisdom teeth, the mesial and the distal alveolar bone loss was evaluated on roentgenograms. The distance from the alveolar crest to the apex of the tooth was determined in per cent of the distance from the cementoenameljunction to the apex. A modifcation of a ruler described by Schei et al. (20) was used for the meas- urements (Fig. I). Eleven equispaced radii are drawn on a translucent plastic ruler. The radii are given numbers 0- 10. A number of lines, indicating the inclination of the ruler at the measurement, are drawn perpendicular to the middle radius. The ruler was applied over the roentgeno- gram with the radius 0 covering the cementoenamel junc- tion, approximally projected, and moved until radius 10 covered the apex. MBL value 1 was noted when the alveo- lar crest was visible between radii 0 and 1, MBL value 2 when the alveolar crest was visible between radii 1 and 2, and so on. In cases where the alveolar crest could be seen under a radius line, the higher score was chosen. The point of the alveolar crest referred to is the junction be- tween the lamina dura dentis and interdental bone. The mean value of all recordings from each patient is called the MBL index. Serum analysis Venous blood, 10 ml, was drawn from each participant and allowed to clot. Blood was centrifuged at about 3 OOO r.p.m. for 5 min to obtain serum. The serum sample was inspected and if the slightest haemolysis was observed, the specimen was discarded. All glass tubes were acid- cleaned and thoroughly rinsed in deionized water. The concentration of zinc in serum was analyzed, mostly with- in 24 hours, in an atomic absoption spectrophotometer type Perkin Elmer 306. Separate tests were made to en- sure that the glass tubes and stoppers used did not contrib- ute any measurable amount of zinc to the specimens. RESULTS The mean serum zinc level of the 51 participants was 0.73 ppm (S.D. 0.099). In Fig. 2 each serum zinc level is plotted against the recorded MBL index. The mean MBL was 2. 92 (S.D. 1 S7). The statisti- Requests for reprints to: K. 0. Skirberg, M.D., Depart- ment of Internal Medicine, School of Dentistry, Karo- linska Institutet, S-10401 Stockholm, Sweden. Actri Med Scund 207

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Page 1: The Relationship between Marginal Bone Loss and Serum Zinc Levels

Acta Med Scand 207: 67-70, 1980

The Relationship between Marginal Bone Loss and Serum Zinc Levels

L. Frithiof, S. Lavstedt, G. Eklund, U. Soderberg, K. 0. SkArberg, J. Blomqvist, B. Asman and W. Eriksson

From the Departments of Oral Surgery, Periodontology, Internal Medicine and Odontological Roentgenology, School of Dentistry, Karolinska Instituter, Stockholm,

and the Neurophysiological Laboratory, Ullerdkers sjukhus, Uppsala, Sweden

ABSTRACT. Serum was analyzed for zinc in 51 pa- tients of varying age and with varying degrees of alveolar bone loss as recorded on roentgenograms. There was a reversed correlation between marginal alveolar bone loss and serum zinc levels. The obser- vations are discussed in relation to the physiological functions of zinc.

Key words: periodontal disease, zinc. Acta Med Scand 207: 67. 1980.

In a detailed medical survey of a few patients with advanced periodontal disease, some extremely low serum zinc levels were recorded. The present study was performed in order to find out if any reversed correlation actually existed between the degree of periodontal disease and the serum zinc levels in a larger material. As other laboratory tests on blood samples from patients with periodontal disease usu- ally only reveal levels within the normal range, we presumed that our observations might be of some interest.

SUBJECTS AND METHODS The study comprises 21 males and 30 females. Their age and sex distribution is presented in Table I. The subjects were recruited by four different dentists among patients attending general dental and periodontal care in four dif- ferent private dental clinics and among patients from the University Clinic of Periodontology. According to the routine interview, the participants were presumably healthy.

Evaluation of marginal bone loss

Intraoral roentgenograms were used for determining an index of marginal bone loss (MBL) (7, 14). For each tooth, excluding the wisdom teeth, the mesial and the distal alveolar bone loss was evaluated on roentgenograms. The distance from the alveolar crest to the apex of the tooth

was determined in per cent of the distance from the cementoenamel junction to the apex. A modifcation of a ruler described by Schei et al. (20) was used for the meas- urements (Fig. I). Eleven equispaced radii are drawn on a translucent plastic ruler. The radii are given numbers 0- 10. A number of lines, indicating the inclination of the ruler at the measurement, are drawn perpendicular to the middle radius. The ruler was applied over the roentgeno- gram with the radius 0 covering the cementoenamel junc- tion, approximally projected, and moved until radius 10 covered the apex. MBL value 1 was noted when the alveo- lar crest was visible between radii 0 and 1, MBL value 2 when the alveolar crest was visible between radii 1 and 2, and so on. In cases where the alveolar crest could be seen under a radius line, the higher score was chosen. The point of the alveolar crest referred to is the junction be- tween the lamina dura dentis and interdental bone. The mean value of all recordings from each patient is called the MBL index.

Serum analysis Venous blood, 10 ml, was drawn from each participant and allowed to clot. Blood was centrifuged at about 3 OOO r.p.m. for 5 min to obtain serum. The serum sample was inspected and if the slightest haemolysis was observed, the specimen was discarded. All glass tubes were acid- cleaned and thoroughly rinsed in deionized water. The concentration of zinc in serum was analyzed, mostly with- in 24 hours, in an atomic absoption spectrophotometer type Perkin Elmer 306. Separate tests were made to en- sure that the glass tubes and stoppers used did not contrib- ute any measurable amount of zinc to the specimens.

RESULTS

The mean serum zinc level of the 51 participants was 0.73 ppm (S.D. 0.099). In Fig. 2 each serum zinc level is plotted against the recorded MBL index. The mean MBL was 2. 92 (S.D. 1 S7). The statisti-

Requests for reprints to: K. 0. Skirberg, M.D., Depart- ment of Internal Medicine, School of Dentistry, Karo- linska Institutet, S-10401 Stockholm, Sweden.

Actri Med Scund 207

Page 2: The Relationship between Marginal Bone Loss and Serum Zinc Levels

68 L . Frithiof et al.

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Table I. Dam on the 51 subjects studied (group means)

Serum No. of subj. zinc MBL with serum Zn

Age group Males Females (ppm) index r 30.80 ppm

20-30 3 7 0.73 1 1.97 -0.33 4 30-40 6 9 0.747 2.38 -0.17 6 40-50 5 7 0.73 1 3.51 -0.55 5 5 0 - 7 7 0.719 3.71 -0.43 1

Total 21 30 0.732 2.92 -0.37 16

cal analysis indicates that the correlation between serum zinc concentration and MBL is -0.37 and is significant on the 1 % level. Correlations were also calculated separately for each age group (Table I). Sixteen participants with a mean serum zinc level of 0.80 ppm or higher had a mean MBL of 1.96. Serum zinc levels below 0.80 ppm in 35 subjects corre- sponded to a mean MBL of 3.37. The normal range of serum zinc with the present method is 0.80- 1.25 ppm.

DISCUSSION

The participants in the present study were selected by four of the authors during a period of about six months with the primary aim of making up the age groups with patients with various degrees of periodontal disease. Periodontal patients were un- treated or in various stages of treatment. Periodon- tal surgery had not been performed within 3 weeks prior to their participation. The study population is markedly selected and is not meant to & represen- tative of the general population.

Periodontitis is an extremely common, chronic disease characterized by a gradual loss of the

U Fig. 1 . Ruler used for measurement of MBL on roentgenograms. Tooth 35 has distally an MBL value of 2.

tooth-supporting tissues, as a result of a more 0 1

less pronounced inflammatory reaction to the bac- terial plaque deposited on the tooth surfaces close to the gingiva. In the general population, periodon- titis results in a significant increase of MBL with advancing age (14), a fact which is also reflected in the present material (Table I).

The human body contains 1.4-2.3 g Zn. the largest amounts being localized in muscle, bone and skin (1). Zinc is also present in the plasma, erythro- cytes, leucocytes and platelets (23). For clinical purposes it is usually analyzed in serum.

The normal serum zinc levels given by different authors vary greatly. Disintegration of platelets dur- ing clotting and haemolysis results in higher serum zinc recordings. There are also geographical differ- ences in the normal zinc levels (1 I), which might be explained by dietary factors. The influence of age and sex on normal plasma and serum zinc levels as

. . .. .. . . . . . . . . .

I I I 1 c

I 2 I 4 5 6 7 UBLind..

Fig. 2. Serum zinc levels plotted against the recorded MBL index for each patient.

Page 3: The Relationship between Marginal Bone Loss and Serum Zinc Levels

Marginal bone loss and serum zinc levels 69

reported by several investigators was reviewed by Chooi et al. (2). They concluded that up to the age of 50, the mean plasma zinc of normal individuals remains relatively constant, while above 50 it de- creases significantly with age.

Our subjects did not show any significant de- crease in serum zinc levels with age (Table I). The reversed correlation between serum zinc and MBL index can therefore not be related to the influence of age. Various degrees of zinc deficiency seem to occur even in presumably "well-nourished" so- cieties (23) as a result of an increased excretion due to decreased absorption and utilization.

A large number of diseases and conditions are associated with a decreased serum zinc level (19). They include infectious diseases (16), surgical trauma (17, 22), and bums (13). To the best of our knowledge, periodontal disease has not previously been discussed in relation to the physiological func- tions of zinc.

Zinc occurs in all types of cells and body fluids and is known to be a vital part of about 20 metal- loenzymes (18). It participates in almost all phys- iological processes. Its functions are frequently related to the presence of other trace elements (8).

The concentration of zinc in serum seems to have several regulating functions. The aggregability of platelets is decreased (4) and the release of his- tamine is inhibited (9, 10) by increasing the content of zinc in serum. Also some functions of mac- rophages (25) and granulocytes (4) are inhibited by zinc administration. Chvapil et al. (5 ) demonstrated in vitro that increased zinc levels, in the presence of magnesium, reversibly inhibited various functions of dog peripheral granulocytes and that this func- tion is closely associated with zinc uptake by the cells. The functions influenced were O2 consump- tion, phagocytosis and bactericidal activity. The depression of serum zinc values which occurs as a result of a redistribution within the body a few hours after infection, coincides with enhancement of some neutrophil functions (24). It has also been suggested (3) that zinc ions have a membrane- stabilizing function; with increasing concentrations of zinc, there is a reduced release of lysosome content and a decreased mobility of the inflam- matory cells.

The chronic inflammatory periodontal lesion as- sociated with progressive destruction of periodontal tissues is an extremely complex reaction. Most of the evidence indicates that the presence of plaque

initiates immunopathologic and other destructive inflammatory mechanisms (15, 21). One main fea- ture is the decreased content of collagen in affected tissue. A part of the collagen destruction is probably due to the release of enzymes from the membrane- coated lysosomes in the inflammatory cells (12). There are also indications that the loss of connec- tive tissue substance may be a consequence of de- pressed collagen production (2 1). Fernandez-Mad- rid et al. (6) showed that in zinc-deficient rats the deposition of collagen in healing wounds is defec- tive.

In view of the regulatory functions of zinc in the inflammatory process and in collagen metabolism, there are reasons to believe that the low serum zinc level in patients with periodontal disease may be a factor of clinical importance that deserves further attention.

REFERENCES 1. Beisel, W. R., Pekarek, R. S. & Wannemacher, R. W.,

Jr: Homeostatic mechanisms affecting plasma zinc levels in acute stress. In: Trace elements in human health and disease, vol. I (ed. A. S. Prasad and D. Oberleas), p. 87. Academic Press, New York 1976.

2. Chooi, M. K. , Todd, J. K. & Boyd, N. D.: Influence of age and sex on plasma levels in normal and diabetic individuals. Nutr Metab 20: 135, 1976.

3. Chvapil, M.: New aspects in the biological role of zinc: A stabilizer of macromolecules and biological membranes. Life Sci 13: 1041, 1973.

4. - Effect of zinc on biomembranes and cells. Med Clin North Am 60: 4, 1976.

5. Chvapil, M., Stankova, L., Zukoski, C., IV & Zukos- ki, C., 111: Inhibition of some functions of polymor- phonuclear leukocytes by in vitro zinc. J Lab Clin Med 89 135, 1977.

6. Fernandez-Madrid, F., Prasad, A. S. & Oberleas, D.: Effect of zinc deficiency on collagen metabolism. J Lab Clin Med 78: 853, 1971.

7. Henrikson, C.-0. & Lavstedt, S.: Precision and accu- racy in intraoral roentgenological determination of proximal marginal bone loss. Acta Odontol Scand (Suppl) 33: 26, 1975.

8. Hill, C. H.: Mineral interrelationships. In: Trace ele- ments in human health and disease, vol. 11 (ed. A. S. Prasad and D. Oberleas), p. 231. Academic Press, New York 1976.

9. Kazimierczak. W. & Maslinski, C.: Histamine release from mast cells by compound 48/80. The membrane action of zinc. Agent Action 4: 320, 1974.

10. - The effect of zinc ions on selective and nonselec- tive histamine release in vitro. Agent Action 4: I , 1974.

1 I . Kubuta, J., Lazar, V. A. & Loose, F.: Copper, zinc, cadmium and lead in human blood from 19 locations

A m M e d Sciirrd 207

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70 L. Frithiof et al.

in the United States. Arch Environ Health 16:788, 1966.

12. Lange, D., Bang, J. & Cimasoni, G.: Cytochemical demonstration of lysosomal enzymes in human cre- vicular fluid. J Dent Res 50: 756, 1971.

13. Larson, D. L., Maxwell, R., Abston, S. & Dobrkovs- ky, M.: Zinc deficiency in burned children. Plast Re- constr Surg 46: 13, 1970.

14. Lavstedt, S. & Eklund, G.: Some factors of signifi- cance for proximal marginal bone loss studied on an epidemiological material. Acta Odontol Scand (Suppl) 33: 50, 1975.

15. Niesengard, R. J.: The role of immunology in periodontal disease. J Periodontol48: 505, 1977.

16. Oon, B. B., Khong, K. Y., Greaves, M. W. & Plum- mer, V. M.: Trophic skin ulceration of leprosy: Skin and serum zinc concentrations. Br Med J 25918, 1974.

17. Pories, W. J., Mansour, E. G., Plecha, F. R., Flynn, A. & Strain, W. H.: Metabolic factors affecting zinc metabolism in the surgical patient. In: Trace elements in human health and disease, vol. I (ed. A. S . Prasad and D. Oberleas), p. 115. Academic Press, New York 1976.

18. Riordan, J. F. & Vallee, B. L.: Structure and function of zinc metalloenzymes. In: Trace elements in human health and disease, vol. I (ed. A. S. Prasad and D.

Oberleas), p. 227. Academic Press, New York 1976. 19. Sandstead, H. H., Vo-Khactu, K. P. & Solomons, N.:

Conditioned zinc deficiencies. In: Trace elements in human health and disease, vol. I (ed. A. S. Prasad and D. Oberleas), p. 33. Academic Press, New York 1976.

20. Schei. O., Waerhaug, J., Lovdal, A. & Arno, A,: Alveolar bone loss as related to oral hygiene and age. J Periodontol 30: 7, 1959.

21. Schluger, S . , Yuodelis, R. A. & Page, R. C.: Periodontal disease, chapter 8. Lea & Febiger, Philadelphia 1977.

22. Sefton, G., Clark, R. G. & Owen, G.: Changes in serum zinc after operation. Br J Surg 61: 329. 1974.

23. Underwood, E. J.: Trace elements in human and ani- mal nutrition, pp. 202, 228. Academic Press, New York 1977.

24. Wannemacher, R., Pekarek, R. S.. Klainer, A., Bar- telloni, P., Dupont, H., Hornick, R. & Beisel, W.: Detection of a leucocytic endogenous mediator-like mediator of serum amino acid and zinc depression during various infectious illnesses. Infect lmmun 11:873, 1975.

25. Zukoski, C. F., Chvapil, M.. Carlson, E., Hattler, B. & Ludwig, J.: Functional immobilization of perito- neal macrophages by zinc. J Reticuloendothel SOC 1 6 6 a, 1974.

Actci Med Scund 207