Objectives-To study changes in bone mineral density (BMD) in patients with Paget's disease of bone treated with risedronate. Methods-Whole body dual energy x ray absorptiometry (DXA) scans were carried out on 20 patients with Paget's disease treated with oral risedronate. DXA scanning was carried out at baseline and 11 months. Whole body bone mineral content (BMC) was measured. In addition, regions of interest were drawn around the skull, individual lumbar vertebrae, hemipelvis, femora, and tibiae to obtain BMD for these sites. An uncoupling index was also calculated as the area under the curve for serum alkaline phosphatase (ALP) divided by the area under the curve for hydroxyproline excretion (HYPRO) for the period of treatment. Results-Median whole body BMC increased from 3057 g to 3156 g (p < 0.001) resulting from an increase in pagetic and non-pagetic BMD. From the analysis of regions of interest it was found that pagetic trabecular bone showed the largest increase in BMD. The pretreatment HYPRO and the uncoupling index were significantly related to the change in BMD for all pagetic sites for a patient (r = 0.65 , p < 0.01 and r = 0.57, p < 0.05 respectively). Conclusion-Bisphosphonate treatment of Paget's disease results in an increase in BMD of pagetic bone without redistribution of mineral from non-pagetic bone. The remodelling space and extent of uncoupling are significantly related to increases in BMD at pagetic sites. (Ann Rheum Dis 1997;56:405-409) Bisphosphonates are now widely used in the treatment of a variety of bone diseases.1-3 Current evidence suggests a dual mode of action, with a direct inhibitory eVect on osteoclasts 4 5 as well as an indirect inhibitory eVect via osteoblasts.6 7 As a result of inhibition of osteoclastic activity, both the temporal relation between bone resorption and formation, as well as the volume of the remodelling space, are transiently shifted in favour of formation. These eVects would be expected to increase bone mineral density (BMD), the magnitude of the increase in BMD being related to the change in bone turnover. These mechanisms are the basis of the use of bisphosphonates in the treatment of osteoporosis. 8-10Paget's disease of bone is characterised by increased bone turnover, often at multiple skeletal sites. The primary abnormality is believed to be that of increased osteoclastic resorption with a secondary eVect on bone formation.11 Despite this increased rate of remodelling the normal coupling between bone resorption and formation remains intact, 12 13 although the remodelling space is increased. It would be predicted that bisphosphonate treatment of Paget's disease would increase bone mass by decreasing bone resorption and the resorption space, 13 although there is a surprising lack of data. In this paper we report our measurements of bone density using dual energy x ray absorptiometry (DXA), before and after treatment with risedronate, a new cyclic bisphosphonate. Methods PATIENTS AND STUDY DESIGNTwenty patients with Paget's disease of bone (...

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