Effects of ethane-1 hydroxy-1, 1-Diphosphonate (5 mg/kg/day dose) onquantitative bone histology in paget's disease of bone

Abstract

The effects of ethane hydroxy diphosphonate (EHDP) on quantitative bone histology have been studied in 43 pagetic patients treated for 6 months at a dose of 5 mg/kg/day. To determine the therapeutic effects on pagetic bone and to appreciate the side effects in non-pagetic bone, the patients were biopsied either in pagetic or non-pagetic areas of the ilium before the beginning of the treatment and at 3, 6 and 9 months (i.e. 3 months post-therapy) after the inception of treatment. Tetracycline double labelling of bone was performed before biopsies in each patient to measure the calcification rate. The results demonstrate that 5 mg/kg/day EHDP given for 6 months has a marked antiosteoclastic effect which is prolonged after the cessation of treatment. Pagetic osteoclasts appear more sensitive to EHDP than normal osteoclasts. The new bone formed during treatment has a regular lamellar texture. At the same time, the high appositional rate of pagetic bone is reduced to a normal value. Marrow fibrosis is reduced along with the reduction in the osteoclast population. Thus, pagetic bone changes to bone normal in quantity, quality and metabolism. Dynamically, in nonpagetic areas, a transitory decrease of calcification rate Is noted at the end of the treatment, without morphological evidence of osteomalacia, except for 2 out of 43 cases. Histologically, EHDP given at a dose of 5 mg/kg/day for 6 months appears to be an effective and safe treatment for Paget's disease of bone.