Experimental Osteo-fluorosis in the Domestic Pig: A Histomorphometric Study of Vertebral Trabecular Bone

Abstract

The experiment aimed at describing effects of fluoride on structure and remodeling of vertebral trabecular bone in pigs. Eight animals receiving a supplement of 2 mg F /kg b. w. per day from age eight to 14 mo were compared with eight controls. Plasma fluoride increased from 0.7 ± 0.1 μM/1 to 12.7 ± 2.0 μM/1 in pigs receiving fluoride. At slaughter, the concentration of fluoride in dry fat-free bone was 149.3 ± 10.5 mM/kg for fluorotic animals and 9.5 ± 0.9 mM/kg for controls. Morphologic changes were assessed in un-decalcified specimens of the fourth lumbar vertebra by quantitative histology using fluorochromes as intra-vital tissue time markers. The volume of trabecular bone tissue (bone + marrow) was unchanged in fluorotic animals, but the volume density of bone was increased by 17%. Surface densities of cancellous bone were almost unchanged, whereas the thickness of trabeculae increased in fluorosis. Fluoride enhanced remodeling of trabecular surfaces: The fraction of surface occupied by resorption lacunae increased 40%, and the formative surface approximately 30%. No changes were demonstrated at surface points undergoing formation: Osteoid thickness, calcification rate, lamellar thickness, and completed wall thickness were normal. It is concluded that the observed findings cannot be explained by fluoride-induced changes in a single cell. Fluoride appears to affect all cells involved in remodeling by direct or indirect mechanisms.

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References

Briancon, D. and Meunier, P.J. (1981): Treatment of Osteoporosis with Fluoride, Calcium, and Vitamin D, Orthop Clin North Am 12:629-648.

Cass, R.M. ; Croft, J.D. ; Perkins, P. ; Nye, W. ; Water-House, C. ; and Terry, R. (1966): New Bone Formation in Osteoporosis Following Treatment with Sodium Fluoride, Arch Intern Med 118:111-116.

Christie, D.P. (1980): The Spectrum of Radiographic Bone Changes in Children with Fluorosis, Radiology 136:85-90.

Faccini, J.M. (1969): Fluoride and Bone, Cadcif Tissue Res 3 :1-16.

Faccini, J.M. and Teotia, S.P.S. (1974): Histopathological Assessment of Endemic Skeletal Fluorosis, Calcif Tissue Res 16:45-57.

Fejerskov, O. ; Richards, A. ; and Josephsen, K. (in press): Pathogenesis and Biochemical Findings of Dental Fluorosis in Various Species. In: Proceedings of International Symposium on Fluoride, Shupe, J.L. , Ed., Logan, Utah: Utah State University Press .

Fejerskov, O. ; Yaeger, J.A. ; and Thylstrup, A. (1979): Microradiography of the Effect of Acute and Chronic Administration of Fluoride on Human and Rat Dentine and Enamel, Arch Oral Biol 24:123-130.

Frost, H.M. (1976): Supracellular Organization of Bone Turnover (Remodelling) in Larger Mammals and its Parameters. In: Proceedings of the First Workshop on Bone Histomorphometry, Jaworski, Z.F.G., Ed., Ottawa, Canada: University of Ottawa Press, pp. 8-15.

Fry, B.W. and Taves, D.R. (1970): Serum Fluoride Analysis with the Fluoride Electrode , J Lab Clin Med 75: 1020-1025.

10.

Guy, W.S. ; Taves, D.R. ; and Brey, W.S., Jr. (1976): Organic Fluorocompounds in Human Plasma: Prevalence and Characterization. In: Biochemistry Involving Carbon-Fluorine Bonds, Filler, R., Ed., Am Chem Soc Symp Ser 28:117-134.

11.

Kragstrup, J. ; Gundersen, H.J.G. ; Melsen, F. ; and Mose-Kilde, L. (1982): Estimation of the Three-Dimensional Wall Thickness of Completed Remodeling Sites in Iliac Trabecular Bone, Metab Bone Dis Rel Res 4:113-119.

12.

McCann, H.G. (1968): Determination of Fluoride in Mineralized Tissues using the Fluoride Ion Electrode, Arch Oral Biol 13: 475-477.

13.

Parfitt, A.M. (1983): The Physiologic and Clinical Significance of Bone Histomorphometric Data. In: Bone Histomorphometry: Techniques and Interpretation, Recker, R.R. , Ed., Boca Raton, FL: CRC Press, pp. 143-223.

14.

Pindborg, J.J. (1970): Pathology of the Dental Hard Tissues, Copenhagen: Munksgaard, pp. 162-166.

15.

Recker, R.R. (1983): Bone Histomorphometry: Techniques and Interpretation , Boca Raton, FL: CRC Press, pp. 1-2.

16.

Richards, A. (1982): The Pig as an Experimental Model for Studying Fluorosis, Ph.D. Dissertation, Royal Dental College, Aarhus, Denmark.

17.

Richards, A. ; Fejerskov, O. ; and Ekstrand, J. (1982): Fluoride Pharmacokinetics in the Domestic Pig , J Dent Res 61: 1099-1102.

18.

Roholm, K. (1937): Fluorine Intoxication. A Clinical-Hygienic Study with a Review of the Literature and some Experimental Investigations, London: H.K. Lewis & Co., pp. 269-291.

19.

Schour, I. and Smith, M.C. (1934): The Histologic Changes in the Enamel and Dentin of the Rat Incisor in Acute and Chronic Experimental Fluorosis, Univ Ariz Tech Bull No. 52:62-91.

20.

Suzuki, H.K. and Mathews, A. (1966): Two-Color Fluorescent Labeling of Mineralizing Tissues with Tetracycline and 2,4-Bis(N,N-Di-(Carbomethyl)Aminomethyl/Fluorescein , Stain Technol 41:57-60.

21.

Teotia, M. ; Teotia, S.P.S. ; and Singh, R.K. (1979): Metabolism of Fluoride in Pregnant Women Residing in Endemic Fluorosis Areas, Fluoride 12:58-64.

22.

Van Kesteren, R.G. ; Duursma, S.A. ; Visser, W.J. ; Van Der Sluys Veer, J. ; and Backer-Dirks, O. (1982): Fluoride in Serum and Bone During Treatment of Osteoporosis with Sodium Fluoride, Calcium and Vitamin D, Metab Bone Dis Rel Res 4:31-37.

23.

Weatherell, J.A. and Weidmann, S.M. (1959): The Skeletal Changes of Chronic Experimental Fluorosis , J Path Bacteriol 78: 233-241.

24.

Weibel, E.R. (1979): Stereological Methods. Practical Methods for Biological Morphometry, London: Academic Press , pp. 101-161.