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Effect 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

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Abstract

Young male rats (70–90 g) were treated for various periods with several doses of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) or disodium dichloromethylene diphosphonate (Cl2MDP). Effects of treatment on the changes in the thickness, growth and mineralization of proximal growth plate and metaphysis of the tibia were assessed histologically and by micro-radiography. High doses (10 or 30 mg P/kg/day) of EHDP impaired mineralization of the growth cartilage, which became increased in thickness, and of the osteoid in the metaphysis and diaphysis. Matrix formation continued, although at a diminished rate. High doses (10 or 30 mg P/kg/day) of Cl2MDP produced a different effect. There was no inhibition of mineralization, but there was a marked impairment of normal metaphyseal remodelling, with persistence of columns of calcified cartilage. Resorption at the periosteal surface in the metaphysis was also inhibited, so that the metaphysis became club-shaped. Osteoclasts were present in large numbers in the metaphysis, but their appearance was abnormal and similar to that seen in human osteopetrosis.

Résumé

Des jeunes rats mâles (70–90 g) ont été traités pendant des laps de temps variables avec différentes doses d’éthane-1-hydroxy-1,1-diphosphonate disodique (EHDP) ou de dichlorométhylène diphosphonate disodique (Cl2MDP). Les effects de ces traitements sur l’épaisseur, la croissance et la minéralisation du cartilage de conjugaison et de la métaphyse du tibia ont été étudiés par des méthodes histologiques et microradiographiques. Des doses élevées (10 ou 30 mg P/kg/jour) d’EHDP empêchent la minéralisation de l’ostéoide dans la métaphyse et la diaphyse et celle du cartilage épiphysaire dont l’épaisseur augmente. La formation de la matrice osseuse se poursuit, mais à une vitesse réduite. Le Cl2MDP à doses élevées (10 ou 30 mg P/kg/jour) produit un effet différent. On n’observe aucune inhibition de la minéralisation, mais une diminution nette du remodàlement normal de la métaphyse, où des colonnes de cartilage calcifié persistent. Il y a également, pour la métaphyse, une inhibition de la résorption à la surface périostale provoquant une métaphyse en forme de massue. Dans la métaphyse on note la présence de nombreux ostéoclastes d’apparence anormale qui ressemblent à ceux observés dans l’ostéopétrose humaine.

Zusammenfassung

Junge männliche Ratten (70–90 g) wurden während verschiedenen Zeitabschnitten mit unterschiedlichen Dosen von Dinatrium Äthan-1-hydroxy-1,1-Diphosphonat (EHDP) oder Dinatrium Dichloromethylen-Diphosphonat (Cl2MDP) behandelt. Die Wirkung der Behandlung auf die Veränderungen in Dicke, Wachstum und Mineralisation der proximalen Wachstumsplatte und Metaphysis der Tibia wurde histologisch und mikroradiographisch untersucht. Hohe Dosen (10 oder 30 mg P/kg/Tag) von EHDP beeinträchtigten die Mineralisation des Wachstumsknorpels, welcher breiter wurde, und des Osteoids in der Metaphyse und Diaphyse. Die Matrixbildung ging weiter, jedoch weniger schnell. Hohe Dosen (10 oder 30 mg P/kg/Tag) von Cl2MDP hatten eine andere Wirkung. Die Mineralisation wurde nicht gehemmt, aber der normale Metaphysenumbau wurde merklich gestört, wobei Säulen von verkalktem Knorpel bestehen blieben. Die Resorption auf der Periostoberfläche in der Metaphyse wurde ebenfalls gehemmt, so daß die Metaphyse keulenförmig wurde. Osteoclasten traten in großen Mengen in der Metaphyse auf, aber ihr Aussehen war abnormal und glich demjenigen, das bei der menschlichen Osteopetrose beobachtet wird.

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Schenk, R., Merz, W.A., Mühlbauer, R. et al. Effect 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. Calc. Tis Res. 11, 196–214 (1973). https://doi.org/10.1007/BF02547219

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  • DOI: https://doi.org/10.1007/BF02547219

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