[Clinical, biological and histological effects of ethane-1-hydroxy 1, 1-diphosphonate (EDHP) in Paget's disease]

The diphosphonates are analogues of the pyrophosphates that are capable of resisting enzymatic destruction and they become fixed in the bone tissue where they have a powerful inhibitory action on osteoclastic resorption and on osteoid mineralization. Ethane-1-hydroxy-1, 1-diphosphonate (EDHP) was administered by mouth at the dose of 20 mg/kg/day over a period of 3 to 6 months to 11 patients with painful Paget's disease. A marked analgesic effect was noted in 7 of the 11 patients. Spectacular metabolic effects were noted with return to normal of the total hydroxyprolinuria/24 h and of the alkaline phosphatases 3 months after treatment in 6 of the 11 treated subjects and a marked improvement in these parameters in 4 other patients. Histologically, there was almost total disappearance of osteoclasia and of osteoblastosis in the affected areas. Clinically, the secondary effects presented in some cases as diarrhoea, and an early and marked rise in phosphoraemia was recorded. Histologically, hyperosteoidosis was seen, equally in the affected and nonaffected zones. This resulted from an almost complete stoppage in the calcification of the osteoid as indicated by the double labelling by tetracycline. The review of the literature shows that considerable therapeutic effects are obtained even with very small doses of EHDP, e.g., 10 mg/kg/day for 3 months, but that these are often accompanied by more marked secondary effects. The diphosphonates appear to be a promising treatment for Paget's disease.