Cale. Tiss. Res. 11, 179--195 (1973) 9 by Springer-Verlag 1973 Original Papers Effect of Diphosphonates and Calcitonin on the Chemistry and Quantitative Histology of Rat Bone R. G. G. Russell, Anne-Marie Kislig, P. A. Casey, H. Fleisch Department of Pathophysiology, University of Berne Laboratory for Experimental Surgery, Davos Janet Thornton, R. Schenk Department of Anatomy, University of Berne D. A. Williams Department of Statistics, University of Edinburgh Received March 6, accepted June 14, 1972 Young male rats were treated with one of three diphosphonates, disodium ethane-l-hydr- oxy-l,l-diphosphonate (EHDP), disodium dichloromethylene-diphosphonate (C12MDP), or disodium methane-l-cyelohexyl-l-hydroxy-l,l-diphosphonate (MCHDP), or with porcine calcitonin. Changes in the length, weight, calcium, phosphorus, and ash of the femora and in plasma calcium, phosphate and alkaline phosphatase were measured. Bone formation rate was measured histologically in the tibial diaphysis using tetracycline markers. The lower dose (0.01-1 mg P/kg/day s.c.) of the phosphonates, which block immobilization osteoporosis and reduce bone turnover measured by 45Ca kinetics, did not cause marked changes in the composition of the femora or in plasma values. This suggests that, at these doses in intact animals, the diphosphonates similarly reduce both resorption and mineralization rates. Higher doses of EHDP and MCHDP (10 or 30 mg P/kg/day s.c.) impaired bone growth both in length and width and inhibited mineralization of new cartilage and osteoid. The total calcium content of the bones decreased but the plasma values remained unchanged. CI.zMDP did not impair mineralization at equivalent doses. EHDP, unlike C12MDP, therefore seems to have two effects on bone. At lower doses it reduces bone turnover rate; but at higher doses it also directly prevents the full mineralization of new matrix. This difference between the effects of EHDP and CI~MDP may be important. Key words: Diphosphonates -- Calcitonin -- Calcification -- Histology -- Analysis -- Bone. Des jeunes rats ms (70-90 g) ont 6t6 trait6s pendant dix jours avec 1) l'un des trois diphosphonates suivants: l'6thane-l-hydroxy-l,l-diphosphonate disodique (EHDP), le di- chlorom6thyl6ne diphosphonate disodique (ClzMDP) ou le m6thane-l-cycloh6xyl-l-hydroxy- 1,1-diphosphonate disodique (MCHDP), 2) de la calcitonine porcine. L'influence de ces traitements sur la longueur, le poids, le contenu en calcium, phosphore et cendres des f6murs, ainsi que sur le calcium, le phosphate et la phosphatase alcaline du plasma a 6t6 6valu6e. La vitesse de la formation osseuse a 6t6 mesur6e histologiquement dans la diaphyse du tibia en utilisant le marquage & la tdtracyeline. Des 6tudes pr6c6dentes oat montr6 qu'aux faibles doses (0,01-1 mg P/kg/jour s.c.), les diphosphonates peuvent bloquer l'ost6oporose d'immobili- sation et r6duire le remodellement osseux mesur6 par la cin6tique du Ca as. Daas cette 6rude, For reprints: Prof. H. Fleisch, Department of Pathophysiology, University of Berne, Hiigel- weg 2, Ch-3012 Berne, Switzerland. 13 Calc.Tiss. Res., Vol. 11