A randomized, double blind, placebo-controlled trial of alendronate treatment for fibrous dysplasia of bone

Context: Fibrous dysplasia (FD) is a rare skeletal disorder, resulting in deformity, fracture, functional impairment, and pain. Bisphosphonates have been advocated as a potential treatment. Objective: To determine the efficacy of alendronate for treatment of FD. Design: Two-year randomized, double-blind, placebo-controlled trial. Setting: Clinical research center. Patients: 40 subjects with polyostotic FD (24 adults, 16 children). Subjects were randomized and stratified by age. Interventions: Study drug was administered over a 24 month period in 6 month cycles (6 months on, 6 months off). Alendronate dosing was stratified: 40 mg daily for subjects >50 kg, 20 mg for 30-50 kg, 10 mg for 20-30 kg. Main Outcome Measures: Primary endpoints were bone turnover markers, including serum osteocalcin and NTX-telopeptides. Secondary endpoints included areal bone mineral density (aBMD), pain, skeletal disease burden score, and functional parameters including the 9-minute walk test and manual muscle testing. Results: Clinical data was collected on 35 subjects who completed the study. There was a decline in NTX-telopeptides in the alendronate group (p = 0.006), but no significant difference in osteocalcin between groups. The alendronate group had an increase in areal BMD in normal bone at the lumbar spine (p = 0.006), and in pre-determined regions of FD (p < 0.001). There were no significant differences in pain scores, skeletal disease burden scores, or functional parameters between the groups. Conclusions: Alendronate treatment led to a reduction in the bone resorption marker NTX-telopeptides, and improvement in aBMD, but no significant effect on serum osteocalcin, pain, or functional parameters.