The effects of long-term administration of ethane-1-hydroxy-1, 1-diphosphonate on osteoarthrosis and heterotopic ossification in the mouse knee joint.

Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered weekly for up to 15 months in either a high (50 mg/kg body weight) or low (5 mg/kg body weight) dose to the males of an inbred strain of mouse (SRT/ORT) which suffers from a high incidence of osteoarthrosis of the knee joint accompanied by extensive periarticular soft-tissue metaplasia forming cartilage and bone. The diphosphonate had two effects. In both doses it caused a reduction in the level of bone resorption. In high doses it caused a partial inhibition of mineralization resulting in the deposition of uncalcified osteoid. The diphosphonate did not influence the incidence or severity of the articular degeneration. The development of periarticular sort-tissue metaplasia was not halted by the EHDP although its form was slightly modified in the high dose. In both treated groups the proximal end of the tibia developed into an abnormal club shape as a result of interference with the normal turnover of bony spicules in the metaphyses. High-dose mice given 85Strontium as a tracer for calcium had much lower radioactivity in their bones than did the low dose and control mice.