Bone Abstracts

Fibrous dysplasia (FD) is a benign skeletal disease caused by activating mutations of G_sα. These mutations lead to formation of abnormal and mechanically unsound bone and fibrotic tissue. Clinical sequelae include deformity, fracture, and pain. Studies in bisphosphonates have shown improvement in bone pain and inconsistent effects on FD mineralization; however interpretation has been limited by a lack of controlled trials.

Objective: To determine the efficacy of oral alendronate for treatment of FD.

Methods: Forty subjects with FD (15 children, median age 10, range 6–16, and 23 adults, median age 40, range 20–57) were enrolled in a randomized, double-blind placebo-controlled trial of alendronate (one subject in each group withdrew prior to treatment). The co-primary efficacy endpoints were the change from baseline in N-telopeptide and osteocalcin at 18 months. Secondary endpoints included effects on pain, and bone mineral density at FD and non-FD sites. Subjects received drug or placebo for 6 months, followed by 6 months off, 6 months on, and 6 months off. Dosing was stratified as follows: 40 mg/day for subjects >50 kg, 20 mg for 30–50 kg, and 10 mg for 20–30 kg.

Results: Compared to placebo at baseline, at 18 months alendronate use was associated with a decrease in the resorption marker N-telopeptide (P=0.001), with no significant effect on the formation marker osteocalcin (P=0.7). Subjects in the alendronate group did not show significant changes in pain as compared to placebo. At FD sites there was no significant change in bone mineral density at affected femora or humeri. At non-FD sites there was a significant increase in bone mineral density (P=0.003). Three subjects in the placebo and three in the alendronate group sustained fractures during the study period. One alendronate-treated subject with an undisclosed history of reflux developed an esophageal stricture.

Conclusions: Alendronate at four times the osteoporosis dose decreased bone resorption markers, but did not improve FD mineralization or bone pain. These data support findings from previous open-label studies which demonstrated a lack of effect of bisphosphonates on FD mineralization, and suggest that oral bisphosphonates may be ineffective for FD-related bone pain.