Abstract
One hundred gram male Sprague-Dawley rats were divided into groups which were injected daily for 10 or 30 days with vehicle (control group), 0.2, 0.4, 2.0, or 10.0 mg ethane-1-hydroxy-1,1-diphosphonate (EHDP)/kg/day. The proximal tibial metaphysis and epiphysis were assayed for changes in percentage of hard tissue and bone formation factors. Knowing these, information about hard tissue resorption was deduced.
After ten or thirty days treatment with 2.0 or 10.0 mg EHDP/kg/day, there was an increase in percentage of hard tissue. This was due to a decrease in bone formation with a greater decrease in hard tissue resorption. Furthermore, after thirty days treatment with 0.2 and 0.4 mg EHDP/kg/day, there was an increase in percentage of hard tissue, which was due to a decrease in resorption with no change in formation.
Ultrastructural studies on osteoclasts from EHDP-treated rats showed a general decrease in their vacuolization and amount of organelles as dosage of EHDP increased. Histologic findings suggest that EHDP is similar to fluoride in the way in which it depresses hard tissue resorption.
Similar content being viewed by others
References
Bliss, C. I.: Statistics in biology, vol. 1, p. 243–247. New York: McGraw-Hill 1967.
Cabanela, M. E., Jowsey, J.: The effects of phosphonates on experimental osteoporosis. Calcif. Tiss. Res.8, 114–120 (1971)
Cameron, D. A.: The ultrastructure of bone. In: The biochemistry and physiology of bone (G. H. Bourne, ed.), vol. 1, p. 191–236. New York: Academic Press 1971
Faccini, J. M.: Fluoride and bone. Calcif. Tiss. Res.3, 1–16 (1969)
Fleisch, H. A., Russell, R. G. G., Francis, M. D.: Diphosphonates inhibit hydroxyapatite dissolutionin vitro and bone resorption in tissue culturein vivo. Science165, 1262–1264 (1969)
Frost, H. M.: Tetracycline-based histological analysis of bone remodeling. Calcif. Tiss. Res.3, 211–237 (1969)
Frost, H. M.: Bone modeling and skeletal modeling errors, p. 73–74. Springfield, Illinois: C. C. Thomas 1973
Gonzales, F., Karnovsky, M. J.: Electron microscopy of osteoclasts in healing fractures of rat bone. J. biophys. biochem. Cytol.9, 229–316 (1961)
Henning, A.: Critical survey of volume and surface measurement in microscopy. Zeiss-Werkzeitschr.30, 78–87 (1958)
Jowsey, J., Holley, K. E., Linman, J. W.: Effect of sodium etidronate in adult cats. J. Lab. clin. Med.76, 126–133 (1970)
Kember, N. F.: Cell division in endochondral ossification. J. Bone Jt Surg.42B, 824–839 (1960)
Kimmel, D. B., Jee, W. S. S.: A rapid plastic embedding technique for preparation of three microns thick sections of decalcified hard tissue. Stain Technol. (in press)
King, W. R., Francis, M. D., Michael, W. R.: Effect of disodium ethane-1-hydroxy-1,1-diphosphonate on bone formation. Clin. Orthop.78, 251–270 (1971)
McManus, J. F. A., Mowry, R. W.: Staining methods histologic and histochemical, p. 201. New York: Paul B. Hoeber, Inc. 1960
McQueen, C. M., Smith, D. A., Monk, I. B., Horton, P. W.: A television scanning system for the measurement of the spatial variation of microdensity in bone sections. Calcif. Tiss. Res.11, 124–132 (1973)
Michael, W. R., King, W. R., Francis, M. D.: Effectiveness of diphosphonates in preventing “osteoporosis” of disuse in the rat. Clin. Orthop.78, 271–276 (1971)
Minkin, C., Rabadjija, L., Goldhaber, P.: Bone remodelingin vitro: the effects of two diphosphonates on osteoid synthesis and bone resorption in mouse calvaria. Calcif. Tiss. Res.14, 161–168 (1974)
Posner, A. S., Eanes, E. D., Harper, R. A.: X-ray diffraction analysis of the effect of fluoride on human bone apatite. Arch. oral. Biol.8, 549–556 (1963)
Russell, R. G. G., Muhlbauer, R. C., Bisaz, S., Williams, D. A., Fleisch, H. A.: The influence of pyrophosphate, condensed phosphates, phosphonates, and other phosphate compounds on the dissolution of hydroxyapatitein vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomized rats. Calcif. Tiss. Res.6, 183–196 (1970)
Russell, R. G. G., Smith, R.: Diphosphonates: experimental and clinical aspects. J. Bone Jt Surg.55B, 66–86 (1973)
Schenk, R.: Principles of stereology in bone studies. In: Proceedings of the First Workshop on Bone Morphometry (Z. F. G. Jaworski, ed.). (In press)
Schenk, R., Merz, W. A., Fleisch, H. A., Muhlbauer, R. C., Russell, R. G. G.: Effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif. Tiss. Res.11, 196–214 (1973)
Scott, B. L., Pease, D. C.: Electron microscopy of the epiphyseal apparatus. Anat. Rec.126, 465–475 (1956)
Talmage, R. V., Doty, S. B.: The effect of sodium fluoride on parathyroid function in the rat as studied by peritoneal lavage. Gen. comp. Endocr.2, 473–479 (1962)
Thorngren, K. G., Hansson, L. I.: Cell kinetics and morphology of the growth plate in the normal and hypophysectomized rat. Calcif. Tiss. Res.13, 113–139 (1973)
Walker, K. V. R., Kember, N. F.: Cell kinetics of growth cartilage in the rat tibia. Cell Tiss. Kinet.5, 409–419 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miller, S.C., Jee, W.S.S. Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) effects on growth and modeling of the rat tibia. Calc. Tis Res. 18, 215–231 (1975). https://doi.org/10.1007/BF02546241
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02546241