TETRACYCLINES AND PERMANENT TEETH: THE RELATION BETWEEN DOSE AND TOOTH COLOR

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(Received February 17, 1970; revision accepted for publication September 28, 1970.) ADDRESS FOR REPRINTS: (E.R.C.) 1650 Walnut Street, Berkeley, California 94709.

TETRACYCLINES

AND

PERMANENT

TEETH:

THE

RELATION

BETWEEN

DOSE

AND

TOOTH

COLOR

Elmer R. Grossman, M.D., Alexander Walchek, D.D.S., and Helen Freedman, Ph.D.

with the technical assistance of Cynthia Flanagan, L.D.H.

From the Department of Pediatrics, University of California-San Francisco it! edical Center, San Francisco, California

ABSTRACT. A quantitative estimation of the

dark-ening effect of tetracychines on permanent incisors

was made b correlating tooth colors with the

re-corded history of tetracycline exposure in 160

children under our care since infancy. The average

darkening caused by one 6-day course of oral

tet-racvcline or demethylchlortetracycline during the

years of permanent incisor formation was 0.3 of a shade on a 14 shade dental scale. Children with

five such courses of tetracycline therapy during the

first 43 to 5 years of life had permanent incisors averaging about two shades darker than children

with no tetracycline exposure, a nearly

impercepti-ble and cosmetically negligible difference; however,

3 of these 14 children had moderately darkened

teeth.

With greater frequency of tetracycline exposure,

the risk increases; four of our six patients with

eight or more courses had noticeably dark teeth.

After age 6 for girls and 7 for boys the risk of

tet-racycline staining can be ignored since the

cosmeti-cally important anterior teeth have all formed. When tetracycline therapy is indicated during the

first 6 to 7 years, the use of oxytetracycline (or

pos-sibly doxycychine) may diminish tooth darkening.

Pediatrics, 47:567, 1971, TETRACYCLINES; TEETH.

I

T has been known for some years that tetracyclines darken teeth if adminis-tered during the time of tooth crown

forma-tion.14 What has not been known, however, is the quantitative relationship between tet-racyclines and tooth color. How much

dark-ening of teeth will result from a given amount of tetracyclines? Is there a safe level of use at which the resultant effect on

tooth color is cosmetically unimportant? We have attempted to answer these ques-tions for the effect of tetracycline and de-methylchlortetracycline

(

Declomycin) on

permanent teeth.

PROCEDURE

We studied 160 children aged 6 to 12

years all of whom had been under the care

of the Berkeley Pediatric Medical Group

since infancy. Any child who had received antibiotic therapy elsewhere was excluded except in those few in whom drug and dose information was obtained from the other physicians. The history of tetracycline ex-posure was tabulated by drug, age of pa-tient, and courses of treatment. Although

there was some variation in dose and

dura-tion of treatment, demethylchlortetracy-dine was usually given at 6 mg/lb/day and tetracycline at 10 mg/lb/day for 6

days.

When

the

treatment record indicated that medicine was ordered 7 or more days after a preceding course, we considered this to be an additional course of treatment.

The dental examination consisted of

cleaning the anterior teeth followed by

in-spection under a standard dental light, un-der light from a north window, and with tl-traviolet

(

Wood’s

)

light. Tooth color was

determined separately by a dental hygienist

(

C. F.

)

and a dentist (A. W. ), using a standard tooth shade guide

(

Bioform

)

. The

Bioform shade guide numbers 59-72 are expressed as - 1 to 13 for ease of

computa-tion and clarity of expression in the statisti-cal evaluation. Permanent incisors tend to be somewhat lighter colored than perma-nent cuspids. If cuspids as well as incisors were erupted and there was a difference in

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13

12

11

GREY 10

HUE

YELLOW

HUE 0

0

I’)

I

I-.

0 0

.

COURSES OF TETRACYCLINES GIVEN DURING FORMATION OF PERMANENT INCISORS

Fic. 1. The relation of tooth color to tetracyclines given during formation of permanent incisor crowns. The central heavy line is the line best fitting the mean incisor colors (95% confidence limits).

568 TETRACYCLINES AND PERMANENT TEETH

#{176}

I-

. . ____________________________ ___________________

MILKY 1 :u..::... .

-..---.-

___________________________________

.________________________

WHITE UI 1 2 3 4 5 6 7 8 9 10 11 12 13

color independently to a recording

secre-tary. Neither knew the other’s judgment of tooth color nor did they have access to the tetracycline exposure history of the

pa-tients.#{176}

Data were analyzed for

(

1

)

the relation between tooth shade and the number of courses of tetracycline and demethylchlor-tetracycline given during the years of crown formation

(

2) the relation of tooth color to medication given after crown for-mation was complete and

(

3

)

the differ-ence between exposure in the first year only and exposure at age 3 and 4 years.

RESULTS

Figure 1 shows a clear linear relationship

between number of courses of tetracyclines and tooth color. The average darkening of tooth color is about 0.3 of a shade per course-an exceedingly small amount, so that a child who had five courses of

tetracy-#{176}Average inter-observer difference was 1.6 on

our 14 point scale; agreement was closest on

lighter teeth. There was most difference in judging

the darkest teeth because variation in hue made a

precise match to the standards difficult.

clime or demethylchlortetracycline during the 43 to 5 years of incisor crown formation

had an average tooth shade which was less than two guide numbers darker than a

child who was never exposed to the tetracy-dines. The difference is nearly impercepti-ble to an untrained eye and of no cosmetic importance.

Variation in the color of permanent teeth at any level of tetracycline exposure is

strik-ing. Our 33 patients with no tetracycline had incisors of average color 0.86 with a

spread of - 1 to + 6.5; the 14 patients with

five exposures to tetracycline had an aver-age of 2.57 with a spread from - 1 to 8.

Our data confirm the fact that staining

occurs only if tetracyclines are given during the period of crown calcification. No corre-lation was found between incisor color and

exposure to tetracyclines after 4% years for girls and 5 years for boys, the ages at which the permanent incisors have completed crown formation (Fig. 2).

Comparison between the 12 children

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0 0 U I 0 0 YELLOW flUE 6 IVORY 7 ---‘ - % ,_ 1 F I OR 4 CREAM WHITE 3-I I I, F I #{149}% I %\ I/

I “I 0 -1 .

--‘1

- ..._--#{149}.. /

1-*-90% of doto MILKY

WHITE 1 1 1 1

1 2 3 4 5 6 7 8 9 10

COURSES OF TETRACYCLINES GIVEN AFTER

FORMATION OF PERMANENT INCISORS

Fm. 2. The relation of tooth color to tetracycines given after formation of permanent incisor crowns.

ARTICLES

569

DISCUSSION

Though these data refer to the color of the permanent incisors, cuspids and first bi-cuspids are also highly visible teeth. The

cuspids complete their crown formation at 5 years in girls and 63 in boys, the first bi-cuspids at 6 in girls and 7 in boys, and the second bicuspids about a year later.5 For dental appearance, then, the period to age

6 years in girls and 7 in boys is most impor-tant. Staining of the less visible second bi-cuspids and molars does not concern us

here.

If we extrapolate our results from incisor color to include the cosmetically important teeth, we can say that tetracycline and

demethylchlortetracycline used sparingly in the first 6 years for girls and 7 years for boys are likely to darken teeth very little.

At our dose level, a child with five courses of tetracyclines had teeth two shades darker than a child without; the risk of mild noticeable darkening was 3/ 14. However,

heavier use carries a more substantial risk;

four of our six patients with eight or more courses had moderate darkening.

None of these children had the enamel

hypoplasia of the permanent teeth associ-ated with high doses of tetracyclines.6 In general, the permanent teeth showed less

tetracycline effect than primary teeth

be-cause the larger, thicker, darker, and more opaque permanent teeth more effectively

hid the bands of tetracycline-complex laid down in the enamel and dentin.T In a recent study8 of extracted deciduous molars, the teeth were sectioned and the bands of tetra-cycline-complex counted, each band

repre-senting the effect of one course of tetracy-dine. Discoloration of the crown was noted in most of the deciduous teeth showing six or more bands, a risk of staining which

ap-pears to be higher than we found for

per-manent incisors.

The variability of staining with similar tetracycline exposure remains a problem. Some of this must be due to differences in administration-variable teaspoon size,

for-gotten doses, early discontinuance of

medi-cation. Part of

the

variability has been as-cribed to the intermittent nature of tooth calcffication; only when tetracycline ad-ministration coincides with active

minerali-zation does a band of staining resuIt. A

third factor is the age of exposure. Brearley and Storey8 found darker staining in

pri-mary teeth when the earliest formed dentin

(

near the dentino-enamel junction

)

showed a band of tetracycline. Our limited data fails to confirm this for permanent teeth.

We have no information on the question

of relative stain-producing properties of the

various tetracyclines. We have used mostly

demethylchlortetracycline during the past

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570 TETRACYCLINES AND PERMANENT TEETH

Numerous authors 2,4,941 have noted less

intense staining with oxytetracycline

(

Ter-ramvcin

)

than with the other commonly used congeners. Furthermore, the creamy

discoloration due to oxytetracycline is sta-ble, unlike other tetracyclines whose stain

may darken with exposure to light.2’10’12’13 Doxvcvcline, a semi-synthetic derivative of oxytetracycline, binds less to calcium than other tetracyclines do. For this reason it might be expected to cause less tooth

stain-ing. One recent report suggests that this may be the case.’4

CONCLUSION

Demethvlchlortetracycline and tetracy-dine used in normal oral doses no more than five times in the first 5 years of life

cause a very mild, cosmetically trivial dark-ening of permanent incisor color in most children. The risk of noticeable discolor-ation with five exposures is about 1/5. With increasing frequency of exposure or with higher doses, darkening of an

objec-tionable nature is increasingly likely. After age 6 for girls and 7 for boys, the danger of tooth discoloration from tetracyclines can

be ignored since the crowns of the incisors, cuspids, and first bicuspids have formed by then. When a tetracycline is indicated dur-ing the first 6 to 7 years, the use of oxytetra-cycline (or possibly doxycycline) may fur-ther diminish the risk of dental staining.

REFERENCES

1. Schwachman, H., and Schuster, A.: The tetra-cychines: Applied pharmacology. Pediat. Clin. N. Amer., 3:295, 1956.

2. \Vallman, I. S., and Hilton, H. C.: Teeth

pig-mented by tetracycline. Lancet, 1 :827, 1962.

3. Weyman, J., and Porteous, J. R. : Tetracycline

discolouration and bands in human teeth.

Brit. Dent. J., 115:499, 1963.

4. Toaff, R., and David, R. :Tooth discolouration

due to tetracycline. In Meyler, L. and Peck,

H. M., ed : Drug Induced Diseases, Vol. 3.

New York: Excerpta Medica Foundation.

1963, pp. 117-133, 1963.

5. Nolla, C. M. : The development of the

perma-nent teeth. Cited in Watson, E. W., and

Lowrey, C. H. :Growth and Development of Children, ed. 2. Chicago: Year Book

Publish-ers, pp. 269-270, 1954.

6. Witkop, C. J., and Wolf, R. 0. : Hypoplasia

and intrinsic staining of enamel following tetracycline therapy. J.A.M.A., 185:1008, 1963.

7. Stewart, D. J.:Tetracychines: Their prevalence

in children’s teeth. Brit. Dent. J., 124:318,

1968.

8. Brearley, L. J., and Storey, E. : Tetracycline

in-duced tooth changes. Med. J. Aust., 2:714,

1968.

9. Annotation: Tetracychines and the teeth. Lan-cet, 2:71, 1965.

10. Weyman, J.: Clinical appearance of

tetracy-dine staining of the teeth. Brit. Dent. J.,

121:118, 1965.

11. Keitel, H. C., and Soentgen, M. L.: Letter to the editor. Canad. Med. Ass. J., 93:129, 1965.

12. Kline, A. H., Blatther, R. J., and Lunin, M.:

Transplacental effects of tetracycline on teeth. J.A.M.A., 188: 178, 1964.

13. Owen, L. N.: Effects of administering tetracy-cline to young dogs with particular

refer-ence to localization of the drugs in the teeth. Arch. Oral Biol., 8:715, 1963.

14. Forti, C., and Benincori, C.: Letter to the edi-tor. Lancet, 1:782, 1969.

Acknowledgment

We are grateful for the helpful organizational

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1971;47;567

Pediatrics

Elmer R. Grossman, Alexander Walchek, Helen Freedman and Cynthia Flanagan

DOSE AND TOOTH COLOR