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METABOLIC STUDIES OF CHILDREN WITH DENTAL CARIES BY JULIAN D. BOYD, CHARLES L. DRAIN, AND GENEVIEVE STEARNS (From the Department of Pediatrics, College of Medicine and the College oJ Dentistry, State University of Iowa, Iowa City) (Received for publication, September 5, 1933) The dependence of human dental caries upon the type of diet employed has been established and confirmed by various inde- pendent investigators (l-7). However, there is no general agree- ment as to the mechanisms involved in safeguarding the tooth against decay. Various hypotheses have been presented, and some of them have been accepted, even though their validity has not been established. These suggested mechanisms have been reviewed elsewhere (8, 9). This report requires consideration only of the so called ‘Lhumoral” theory, since the data presented here bear directly on the validity of its assumptions. According to the proponents of this theory, the susceptibility of the tooth to decay is determined by the concentrations of the inorganic con- stituents of t,he body fluids which come into relation with the tooth; the acid-base equilibrium and the levels of calcium and of phosphorus in the blood serum and saliva have been held most significant. Directly and through implication, it has been as- sumed that the effect of the diet was exerted through its influence on humoral levels of these constituents. If there were any causative relationship between the chemical composition of the body fluids and the resistance or susceptibility of teeth to decay, it. should be possible to demonstrat,e through parallel dental and biochemical studies that certain chemical equilibria are characteristic indices of the status of the tooth. In order to evaluate this hypothesis, a statistical correlation has been made of certain biochemical and dental data obtained in the observation of over 100 children. During the past 7 years, detailed dental examinations have been made of every patient admitted to the pediatric or children’s 327 by guest on April 6, 2020 http://www.jbc.org/ Downloaded from
Transcript

METABOLIC STUDIES OF CHILDREN WITH DENTAL CARIES

BY JULIAN D. BOYD, CHARLES L. DRAIN, AND

GENEVIEVE STEARNS

(From the Department of Pediatrics, College of Medicine and the College oJ Dentistry, State University of Iowa, Iowa City)

(Received for publication, September 5, 1933)

The dependence of human dental caries upon the type of diet employed has been established and confirmed by various inde- pendent investigators (l-7). However, there is no general agree- ment as to the mechanisms involved in safeguarding the tooth against decay. Various hypotheses have been presented, and some of them have been accepted, even though their validity has not been established. These suggested mechanisms have been reviewed elsewhere (8, 9). This report requires consideration only of the so called ‘Lhumoral” theory, since the data presented here bear directly on the validity of its assumptions. According to the proponents of this theory, the susceptibility of the tooth to decay is determined by the concentrations of the inorganic con- stituents of t,he body fluids which come into relation with the tooth; the acid-base equilibrium and the levels of calcium and of phosphorus in the blood serum and saliva have been held most significant. Directly and through implication, it has been as- sumed that the effect of the diet was exerted through its influence on humoral levels of these constituents.

If there were any causative relationship between the chemical composition of the body fluids and the resistance or susceptibility of teeth to decay, it. should be possible to demonstrat,e through parallel dental and biochemical studies that certain chemical equilibria are characteristic indices of the status of the tooth. In order to evaluate this hypothesis, a statistical correlation has been made of certain biochemical and dental data obtained in the observation of over 100 children.

During the past 7 years, detailed dental examinations have been made of every patient admitted to the pediatric or children’s

327

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Metabolism and Dental Caries

orthopedic services of the Children’s Hospital. In many instances, repeated subsequent examinations of the same mout,h were made. The form of record employed distinguished the degree, extent, and activity of dental caries. Simultaneously, metabolic data were obtained concerning a considerable group of these children. This report is based upon a correlation of the nature of the metabolic findings with the dental condition noted at the same time. The biochemical data available included estimations of the level of calcium and of inorganic phosphorus in blood serum and in saliva, and balance studies relative to the retent.ion of calcium, phos- phorus, and nitrogen. In some subjects, only isolated observa- tions were obtained; in many, multiple determinations were avail- able. The subjects ranged in age from 3 to 20 years, averaging about 10 years. The physical condition varied widely; some were children without apparent disease, while others were under treat- ment for various types of chronic ailment. A considerable proportion had disturbances of normal metabolism of clinical sigticance, such as diabetes mellitus, late rickets, hyperparathy- roidism, chronic acidosis, or celiac disease. The only phase to be considered in this report is the correlation of the condition of the teeth with the biochemical data available. From such a corre- lation, it is believed t,hat the data presented permit deductions of significance in determining the factors primarily operative in pro- tecting the tooth from decay.

Methods

The dental examinations were made under the direction of the same personnel throughout; most were made by the same indi- vidual. The degree of activity of caries was determined by the permeability of the exposed dentin to the exploring tine. Histo- logical studies of exfoliated or extracted teeth have confirmed the accuracy of these observations. Standard procedures of bio- chemical analysis were used throughout in the determination of serum, salivary, urinary, and fecal constituents. In the balance studies, fore periods of 3 days or longer were employed; in many instances the diets used were not essentially different from those to which the child had been accustomed. The periods of collec- tion of excreta were of 3 to 5 days duration. Carmine ingested at the beginning and close of each period was used for stool demar-

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Boyd, Drain, and Stearns 329

cation. The composition of the ingested diet was determined by chemical analysis of an aliquot portion of an identical diet. Dis- tilled water only was permitted in addition. Only data from periods of study which seemed mechanically satisfactory were used in these correlations. Saliva was collected before breakfast; the flow was stimulated by the chewing of paraffin (10). Initial portions were discarded to assure uniformity and freedom from debris. Blood samples were obtained several hours after previous ingestion of food; in the great majority of instances the blood was drawn before breakfast.

TABLE I

Serum Calcium and Inorganic Phosphorus Content Correlated with Condition of Teeth

No cavities, no caries

No. of children.. . . . . . . . . . . . 26

mg. per 100 cc.

Serum calcium Average......................... 10.4 Range, . . . . . . . . . . . . . . 7.8-12.6 Standard deviation.. . . . . 1.30 Probableerror.................. ~kO.17

Serum inorganic phosphorus Average. . . . . . . . . . . . . . 4.2 Range.......................... l.l- 5.9 Standard deviation.. . . 1.26 Probable error. . . . . . fO.17

- 1

- -

_-

bctive caries

-

_-

..-

Active caries

32 44

nag. per 100 cc. mg. pm 100 CC.

11.0 10.6 9.2-17.2 9.1-13.6 1.30 1.13

f0.15 320.12

4.7 4.4 2.4~ 6.2 2.6- 6.1 0.96 1.14

f0.12 rto.12

Results

Table I gives the averages of the observed concentrations of serum calcium and inorganic phosphorus of three groups of chil- dren, representing a total of 102 observations. One group is com- posed of children whose teeth were free from any evidences of decay, either past or present,. Anot,her group presented dental cavities, but no active caries. The third group exhibited active decay, in a wide range of extent and degree of activity. The data presented fail to indicate any correlation between the concentra- tion of these two serum constituents and the condition of the teeth. Moreover, :in view of the metabolic data to be presented, it is

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330 Metabolism and Dental Caries

evident that the levels of serum constituents are not dependable gages of the adequacy of metabolic processes.

Table II offers data similarly presented concerning the concen- tration of salivary calcium and phosphorus.1 As in the case of the serum, no parallelism is evident between the chemical compo- sition of the saliva and the susceptibility of the tooth to decay.

Table III represents the average retentions of calcium, phos- phorus, and nitrogen observed in 98 balance studies, correlated with the dental condition. It is apparent that a definite corre- lation exists between the degree of retention of calcium and of phosphorus and the freedom of teeth from decay. Statistical

TABLE II

Salivary Calcium and Phosphorus Content Correlated with Condition of Teeth

No. of children.. . . . . . .

Calcium Average........................ Range. . . . . . . . . . . . . . . . . . . .

Phosphorus Average........................ Range. . . . . . . . . . . . . . . . . . .

. -.

-

No cavities. no caries

1

mg. pm 100 cc.

5.0 4.5- 5.2

10.2 7.2-12.1

-

__

--

-

Inactive caries

5.4 3.8- 7.8

12.4 8.8-17.8

Active caries

13

5.5 2.8- 7.7

12.6 7.1-16.6

analysis indicates that such an-assumption is valid from the data presented. The same conclusion may be drawn from a comparison of the retentions of seven children studied when the caries was active and when it was inactive. These averages are presented in Table IV. Although these data would indicate that a similar relationship existed between the adequacy of nitrogen retention and resistance to caries, this is not borne out in the averages of the whole series, and the number of observations presented in Table IV are too few to be evaluated statistically.

If there is any validity in the premise that dental caries is dependent directly upon the level of the inorganic constituents of the body fluids, one would expect caries to be universally present

1 We are indebted to Dr. Roskin for most of the salivary analyses (10).

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TABL

E III

Daily

Re

tent

ions

of C

alciu

m,

Phos

phor

us,

and

Nitro

gen

Corre

lated

wi

th

Dent

al Co

nditio

n

No.of

childr

en

......

......

......

......

......

......

......

......

Av

etage

sge,y

s 28

...

......

......

......

......

......

......

......

...

Rang

e, wr

s 11

.2 ...

...

Stan

dard

devis

t~dr

;l1;;:

::::::

::::::

::::::

::::::

::::::

::::::

:: 3-l

7

4.4

Calci

um

rete

ntio

n Av

erag

e ...

......

......

......

......

......

....

Rang

e ...

......

......

......

......

......

......

St

anda

rd

devia

tion.

...

......

......

......

.....

Prob

able

erro

r ...

......

......

......

......

....

Phos

phor

us

rete

ntio

n Av

erag

e ...

......

......

......

......

......

....

Rang

e ...

......

......

......

......

......

......

St

anda

rd

devia

tion

......

......

......

......

...

Prob

able

erro

r ...

......

......

......

......

....

Nitro

gen

rete

ntio

n Av

erag

e ...

......

......

......

......

......

....

Rang

e ...

......

......

......

......

......

......

St

anda

rd

devia

tion.

...

......

......

......

....

Prob

able

erro

r ...

......

......

......

......

....

0.01

7 -0

.011

to

+0

.049

0.

0134

10

.001

7

0.01

4 -0

.002

to

+0

.064

0.

0134

zk

o.00

17

0.08

7 $0

.002

to

0.

210

0.09

2 *o

.o1t3

I _.-

Inacti

ve

carie

s Ac

tive

carie

s

32

38

10.7

10.4

3-20

3-17

3.5

2.9

gm.

per

kg.

gm.

per

kg.

0.01

5 0.

010

-0.0

02

to

+0.0

31

-0.0

25

to

+o

031

0.00

76

0.00

57

10.0

0085

&0

.000

63

0.01

1 0.

009

-0.0

10

to

+0.0

32

-0.0

12

to

+0.0

25

0.00

88

0.00

68

10.00

11

f0.0

0075

0.07

1 0.

079

+0.0

19

to

0.31

0 -0

.047

to

+0

.218

0.

0645

0.

0546

*0

.008

3 10

.006

2

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332 Metabolism and Dental Caries

in association with those disturbances of metabolism which are accompanied by marked alterations in the concentrations of these substances. A summary of the dental and chemical findings in

TABLE IV

Mineral Retentions during Periods of Active and Inactive Caries in Same Individual

Averages of values from seven subjects.

Average age of subjects, yrs ....... Range. yrs ........................

Calcium retention Average. . Range, .

Phosphorus retention Average. . . Range..................

Nitrogen retention Average................ Range. .

Active caries

10 3-13

gm. per kg.

0.007 -0.001 to +0.014

0.007 f0 to +0.014

0.051 -0.047 to +0.125

Inactive caries

10 6-14

gm. per kg.

0.015 -0.002 to +0.025

0.013 +0.002 to 0.020

0.087 f0 to +0.195

TABLE V

Correlation of Chemical with Dental Data in Subjects with Profound Chronic Disturbances of Mineral Metabolism

Nature of meta- bolic anomaly

Chronic sci- dosis

Late rickets (idiopathic hypophos- phatemia)

Hyperpara- thyroidism

3

3

2

-

Dental condition

Csties

Slight in 1; none in 2

Inactive in 1; none in 2

None in 1; moderate in 1

Absorption in 2; 1 ap- peared normal

Absorption in 2; 1 ap- peared normal

Absorption in 1; 1 ap- peared normal

hlcium Phos- phorus

--

%i 5: wl. Per 100 cc.

7% 2.1- 12.65 5.7

8.4 l.l- 12.5 3.85

2.5 1.17- 24.5 5.55

co, -

__

-

Pd. per loo cc.

Normal

Normal

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Boyd, Drain, and Stearns

eight such individuals is offered in Table V.2 It will be noted that in spite of the wide variation from normal and the diversity of the chemical anomalies studied, no noteworthy tendency toward any increased incidence of caries is evident. On the other hand, the incidence of destruction of the bony supporting structures of the teeth was striking.

DISCUSSION

The conclusion that no predictable relationship exists between the concentrations of calcium and phosphorus in the serum or the saliva and the existence of active dental caries is in accord with the experimental work reported by others (7, 15-17). The data here presented do not support the opinions offered by t,hose who would attribute caries to a lowering of the level of serum phosphorus, with subsequent alterations of the composition of the saliva. The unusually low incidence of caries in the group of subjects with persistently and markedly abnormal levels of the substances which are considered deciding fact,ors in the deposition of bone (Table V) seems sufficient in itself to establish that dental caries is not caused per se by low levels of serum phosphorus or severe acidosis. It has been claimed by some of t,he proponents of the humoral theory (18-22) that deficiency of dietary phosphorus or improper acid-base relationships of the ash of the diet are significant in the production of dental caries. These views were adduced from animal experiments in which marked alterations in the dietary were imposed, and from a theoretical consideration of the tooth as being strictly analogous to bone in its response to metabolic alterations. It is apparent that these premises cannot be accepted as explanatory of the etiology of human dental caries. It has been shown that children can have severe dental caries without altera- tion of the levels of serum calcium or phosphorus, and that the caries can be arrested without significant shift in the level of the serum values. Children whose serum phosphorus for years has been at levels supposedly incompatible with normal bone forma- tion have shown continuous freedom from dental caries during the corresponding interval. Even though it were demonstrable that dietaries used prevalently in this country are deficient in phos-

2 The records of several of these subjects have been published previously (11-14).

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Metabolism and Dental Caries

phorus, it is difficult to believe t,hat t,he deficit is sufficient, in degree to lower the serum phosphorus to abnormal levels, com- parable to those produced in rats receiving manifestly abnormal diets. Furthermore, from the evidence here presented that long continued hypophosphatemia of marked degree is compatible with sound teeth, it seems most unlikely that dietary deficiency of phosphorus plays as major a role in the production of dental caries as that recently attributed to it. Similarly, the freedom from significant degree of dental caries noted in children with prolonged chronic severe acidosis would discount the significance of any degree of acidosis dependent upon the acid-base relationships of the ash of any ordinary diet. It is probably true that the ideal diet will have an ash with reaction approaching neutrality, as it will have an optimum content of phosphorus and a favorable calcium to phosphorus ratio. Yet this does not justify the assump tion that the beneficial effect of such a diet is to be attributed to any one of these, or to any other isolated group of factors.

An exceptionally high incidence of alveolar rarefaction was noted in the children with persistently abnormal serum values. In all such inst.ances, abnormality of bone was present elsewhere as well, giving rise to evidences of rickets or osteoporosis. The coexistence of rarefaction of bone with apparently intact teeth offers evidence that bone and tooth do not respond similarly, at least in degree, to conditions favoring bone dissolution. Re- ported histopathological observations (23) indicate that profound disturbances of bone may be associated with parallel histological alterations of the tooth. structure. The observations herein recorded demonstrate that such alterations do not become grossly demonstrable during periods of years. The children under discus- sion were able to maintain adequate retentions of calcium and phosphorus, and to obtain partial or apparently complete repair of their bone lesions, in spite of the chemical abnormalities which in their nature were typical of those associated with active rickets or equivalent bone alterations. The findings point to the conclu- sion that the deposition of bone and its integrity, as well as that of the tooth, are dependent more upon the ability to retain suitable amounts of calcium and of phosphorus than upon the actual con- cent,rations of inorganic constituents of the body fluids.

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Boyd, Drain, and Stearns

The strong correlation demonstrated between the degree of reten- tion of calcium and phosphorus and the resist,ance to caries sup ports the view that such resistance is dependent primarily upon forces acting from within the tooth. In a collateral study to be report,ed elsewhere (24), the authors have confirmed and extended the observations of others that Bacillus acidophilus and other acid-forming bacteria are ubiquitous in their occurrence, and that they may be demonstrated in significant quantity in some mouths throughout the process of arrest of caries. It is apparent that any effective alteration in the susceptibility to caries pro- duced by adjusOment of the diet cannot be attributed properly to its effect upon the growth propensities of such organisms.

Histological studies now in progress indicate that resistance to dental caries is dependent upon the ability of the tooth to deposit secondary de&in in an adequate manner and degree. This in turn seems to be determined by the metabolic integrity of the indi- vidual as a whole. No factor contributing to the adequacy of metabolism, whether it, be of exogenous or endogenous origin, can be ignored in evaluating the causes of dental caries. It is evident that considerable individual variation exists in the efficiency of utilization of similar diets. The children observed in this study had been accustomed to various types of diets previous to t,he period of observation. During the balance periods, however, the diets of all were quite similar. On corresponding diets, the average retent,ions of t,hose witChout caries were much better than those wit.h active decay. Subsequent studies of children with caries after long periods of well chosen diet,s showed increased retentions. The degree of retention of the children without caries was higher than that customarily considered as adequate. This may indicate that optimum retention levels are greater t,han those usually accepted as desirable. Two reported studies (25,26) indicate that, the period of complete mineralization of bone is determined by the level of intake of inorganic bone constituents and of related sub- stances during the period of growth. It seems very possible that the degree of mineralization of the toot.h as reflected in the degree of dentinal sclerosis and its subsequent resistance to decay are similarly dependent upon the level of adequacy of the diet.

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336 Metabolism and Dental Caries

SUMMARY AND CONCLUSIONS

A correlation of the dental status with various biochemical studies in a large group of children leads to the conclusion that the levels of serum calcium and phosphorus and the acid-base relation- ships are not primarily of significance in the production or the pre- vention of dental caries. The same is true of the chief inorganic constituents of the saliva. A definite and very significant relation appears to exist between the degree of adequacy of retention of calcium and phosphorus and the resistance of the tooth to decay. The studies here reported offer no evidence that dietary deficiency of phosphorus is an outstanding factor in the incidence of dental caries, or that degrees of acid-base imbalance induced by any ordinary diet can be held responsible. They indicate that a close correlation exists between the metabolic efficiency of the organism as a whole and the resistance of the tooth to decay. They offer evidence that resistance to decay is dependent primarily upon factors operating from within the tooth. Furthermore, the data suggest that optimum retentions of calcium and of phosphorus may be higher than those usually accepted as adequate.

BIBLIOGRAPHY

1. Boyd, J. D., and Drain, C. L., J. Am. Med. Assn., 90,1867 (19%). 2. Boyd, J. D., Drain, C. L., and Nelson, M. V., Am. J. Dis. Child., 36,

721 (1929). 3. Bunting, R. W., Delves, E., and Hard, D. G., Proc. Sot. Exp. Biol. and

Med., 27,426 (1939). 4. Hanke, M. T., J. Nutrition, 3,433 (1931). 5. Mellanby, M., &fed. Research Council, Special Rep. Series, No. 169

(1931). 6. McBeath, E. C., J. Dent. Research, U, ‘723 (1932). 7. Schoenthal, L., and Brodsky, R. H., Am. J. Dis. Child., 48,91 (1933). 8. Kesel, R. G., J. Am. Dent. Assn., 19,903 (1932). 9. Bing, F. C., J. Am. Dent. Assn., 19,1843 (1932).

10. Roskin, M., Proc. Sot. Exp. Biol. and Med., 26,465 (1928). 11. Boyd, J. D., Am. J. Dk. Child., 33,539 (1927). 12. Stearns, G., andBoyd, J. D., J. Clin. Inu., 10,591 (1931). 13. Boyd, J. D., Am. J. Dis. Child., 42,366 (1931). 14. Boyd, J. D., Milgram, J. E., and Stearns, G., J. Am. Med. Assn., 93,

684 (1929). 15. Youngburg, 0. E., J. Dent. Research, 12,454 (1932). 16. Krssnow, F., J. Dent. Research, 12, 530 (1932). 17. Leonard, H. S., J. Dent. Research, 12,473 (1932).

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Boyd, Drain, and Stearns 337

18. Klein, H., and McCollum, E. V., J. Dent. Researck, 12, 524 (1932); Science, 74, 662 (1931).

19. Agnew, M. C., Agnew, R. G., and Tisdall, F. F., J. Pediat., 2, 196 (1933).

20. Forbes, J. C., J. Dent. Research, 11,591 (1931). 21. Lennox, J., Brit. Dent. J., 62,570 (1931). 22. Jones, M. R., Larsen, N. P., and Pritchard, G. P., J. Am. Med. ASsn.,

99, 1849 (1932). 23, Zajewloschin, M. N., and Libin, S. J., Frankf. Z. Path., 43,245 (1932). 24. Boyd, J. D., Zentmire, Z., and Drain, C. L., unpublished data. 25. Sherman, H. C., and Booher, L. E., J. Biol. Chem., 93,93 (1931). 26. Hogan, A. G., Missouri Agric. Exp. Stat., Research Bull. 167 (1932).

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Genevieve StearnsJulian D. Boyd, Charles L. Drain and

WITH DENTAL CARIESMETABOLIC STUDIES OF CHILDREN

1933, 103:327-337.J. Biol. Chem. 

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