Purpose: The purpose of this study is to determine if pamidroante will improve mobility impairments, functional status, pain, and psychosocial performance in patients with Paget's disease of bone. Methods: In order to determine if pamidronate will improve mobility impairments, functional status, pain, and psychosocial performance, we propose to use a randomized, double-blind, placebo-controlled trial in which 66 patients with active Paget's disease of femur, tibia, and/or acetabular portion of the ilium will be treated (pamidronate or placebo) and then followed for 6 months. All patients who enter the trial must have documented impairments in mobility, defined as an abnormal mobility measure (ten foot walk time, 360 degree turn, mobility skills protocol score, or 6 minute walk distance) and bone resorption or formation markers that are at least twice the normal level. When patients who have Paget's disease enter the study, they will have baseline measures performed and then be randomized to receive pamidronate 90mg intravenously over six hours or placebo. Measurements will be made at one, three and six months post therapy. Changes in mobility impairments will be assessed by measuring changes in ten foot walk time, (primary response variable), mobility skills protocol score, steps to make a 360 degree turn, or six minute walk distance. Changes in functional status impairments will be assessed with the Functional Status Questionnaire (FSQ). The primary response variable for functional status will be the instrumental activities of daily living scale of the FSQ. Changes in pain will be assessed by the West Haven Pain Inventory. Changes in impairments in psychosocial performance will be measured with the Rosenberg Self-Esteem Scale, the Beck Depression Scale and the Hopkins Symptom Checklist 90 Revised. Changes in bone remodeling activity will be followed by measuring serum alkaline phosphatase levels and urinary hydroxyproline and N-Telepeptide excretion. Results: Patients continue to be actively recruited and enrolled in this trial. Over the past year on the GCRC twenty-six patients were evaluated who were potential candidates for the study. Of the twenty-six, six were enrolled and two more have been offered a chance to participate in the study but have not yet been consented. We have treated the six patients with pamidronate, a second generation bisphosphonate, and shown improvement in mobility and functional status impairments as well as bone remodeling activity. Significance: Paget's disease of bone is a chronic skeletal disease that affects elderly people and is characterized by areas of increased skeletal remodeling which can lead to pain, deformity, secondary arthritis, fractures and rarely malignant degeneration. Several studies suggest that Paget's disease affects 1.8-5% of people over 60 years of age and 10% of people at 90 years of age. Improved therapy will enhance the ability of these patients to function in normal life activities. Future plans: Since the trial was started, two new bisphosphonates have been approved by the FDA to treat Paget's disease of bone: Alendronate (Fosamax) and Risedronate (Actonel). Both of these drugs are oral preparations and some patients have wished to receive oral medication rather than an intravenous preparation. More importantly, these drugs give many patients sustained biochemical and clinical remissions of their Paget's disease lasting 24 to 36 months. This means that many of the patients referred for evaluation of their Paget's disease do not need treatment of their disease as frequently as we had initially planned for this study.
Showing the most recent 10 out of 128 publications
