A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of bone
Introduction
Paget’s disease is a chronic, progressive disorder of bone characterized by focal areas of excessive osteoclastic resorption accompanied by a secondary increase in osteoblastic activity [1]. This results in bone expansion, structural weakness, and deformity. Calcitonin and the first generation bisphosphonate etidronate were widely used to treat the disorder, but have largely been superseded by potent second and third generation bisphosphonates such as pamidronate, alendronate, and risedronate [1], [2], [3]. These drugs are more effective than calcitonin or etidronate [3], [4], [5], [6], [7] and are now regarded as the treatments of choice [1], [2], [3]. There have been no randomized clinical trials comparing two or more second or third generation bisphosphonates in a head to head fashion, and it is not known if these drugs differ in therapeutic efficacy. We conducted a randomized clinical trial comparing intravenous pamidronate and oral alendronate sodium for the treatment of Paget’s disease of bone. Preliminary data from some subjects were published previously in a paper examining resistance to bisphosphonate treatment [8]. In this paper, we report the final results of the study.
Section snippets
Study design, subjects, and treatments
The trial was an investigator-initiated study with a randomized, open-label, parallel design conducted in three centers in Western Australia. Patient eligibility was based on the presence of typical lesions of Paget’s disease on isotope bone scanning and radiographs and plasma total alkaline phosphatase (ALP) concentration above the upper limit of the laboratory reference range (135 U/l). Subjects previously treated for Paget’s disease were eligible only if at least 3 months had elapsed since
Baseline characteristics, patient disposition, and treatments
Recruitment began in May 1997, and the study was completed in October 2001. A flowchart of patient disposition is shown in Fig. 1. Seventy-two subjects were recruited to the study, of whom 36 were randomized to alendronate and 36 to pamidronate. Slow recruitment towards the end of the study led to a decision to halt recruitment at 72 subjects, rather than 80 as originally planned. Fifty-nine patients (82%) completed the 2-year study, comprising 31 in the alendronate group and 28 in the
Discussion
In this study, the first randomized controlled trial of two potent bisphosphonates for the treatment of Paget's disease, oral alendronate had superior efficacy compared with intravenous pamidronate. A significantly greater proportion of subjects assigned to alendronate treatment achieved full biochemical remission compared with pamidronate, and there was a significantly greater reduction in bone turnover in the alendronate group. There was, however, a major difference in treatment response
Acknowledgements
This work was supported by research grants from Merck, Sharp & Dohme (Australia), Novartis Pharmaceuticals Australia, and the Arthritis Foundation of Western Australia.
References (21)
- et al.
Guidelines on the management of Paget's disease of bone
Bone
(2002) - et al.
Biochemical and radiologic improvement in Paget's disease of bone treated with alendronate: a randomized, placebo-controlled trial
Am. J. Med.
(1996) - et al.
Clinical, biochemical, hematologic, and radiographic responses in Paget's disease following intravenous pamidronate disodium: a 2 year study
Bone
(1996) - et al.
A randomized, double-blind comparison of risedronate and etidronate in the treatment of Paget's disease of bone
Am. J. Med.
(1999) - et al.
Prevention of appendicular bone loss in Paget's disease following treatment with intravenous pamidronate disodium
Bone
(1999) Long-term follow-up of therapy with intermittent disodium etidronate in Paget's disease of bone
Am. J. Med.
(1985)- et al.
Alendronate in the treatment of Paget's disease of bone
Bone
(1997) - et al.
The management of Paget's disease of bone
N. Engl. J. Med.
(1997) - et al.
A clinical approach to diagnosis and management of Paget's disease of bone
J. Bone Miner. Res.
(2001) - et al.
Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone
J. Clin. Endocrinol. Metab.
(1996)