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

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.