IMPE Abstracts

Objectives: Fibrous dysplasia (FD) is a rare disorder resulting in fractures, pain, and skeletal deformities. Abnormal osteoprogenitor cells produce excess FGF23, leading to hyperphosphaturia in most patients and frank hypophosphatemia in a smaller subset. Studies suggest that FGF23-mediated hypophosphatemia is associated with increased FD-related morbidity. However, the relationship between serum phosphorus levels and skeletal complications has not been investigated, and the optimal therapeutic target for serum phosphorus has not been determined. The objectives of this study were to characterize the impact of serum phosphorus on FD-related morbidity and identify threshold levels associated with increased skeletal complications.

Methods: 240 natural history study patients were reviewed. The average age was 25±17 years (range 3-84), with 6.8±7.8 years follow-up (0-40). Intact FGF23 levels were elevated at 83±44 pg/mL (24-223, normal<59). Patients presented along a broad spectrum of FD involvement, with average Skeletal Burden Scores of 29±23 (0.3-75). Patients were categorized by average age-related phosphorus Z-scores: frank hypophosphatemia (Z-score ≤-2) (n=48); low-normophosphatemia (Z-score >-2 to ≤-1) (n=66); mid-normophosphatemia (Z-score >-1 to <0) (n=78); and high-normophosphatemia (Z-score ≥0) (n=48).

Results: Lifetime rates of fractures and orthopedic surgeries were highest in patients with frank hypophosphatemia (0.60±0.87 fractures/year and 0.28±0.31 surgeries/year, P<0.02 compared to normophosphatemic groups). Subjects with low-normophosphatemia also experienced increased fractures (0.19±0.23 fractures/year) and surgeries (0.14±0.26 surgeries/year) compared to those with mid-normophosphatemia (0.11±0.21 fractures/year, 0.18±0.07 surgeries/year) and high-normophosphatemia (0.06±0.10 fractures/year, 0.05±0.10 surgeries/year) (P≤0.02). The patients in the frank hypophosphatemia and low-normophosphatemia groups had a higher prevalence of moderate-severe scoliosis (defined as Cobb angle ≥30 degrees) compared to those in the high-normophosphatemia group (P=0.003 and P=0.003 respectively). In a sub-analysis of patients matched for Skeletal Burden Score of ≥30; fracture rates, surgery rates, and the prevalence of moderate-severe scoliosis remained higher in frankly hypophosphatemic vs high-normophosphatemic patients (P<0.05), suggesting the association between phosphorus and skeletal complications is not explained by differences in FD burden alone.

Conclusion: Both frankly low and low-normal phosphorus levels are associated with increased skeletal complications in patients with FD. These findings will allow clinicians to identify patients at higher risk and inform the development of target phosphorus levels in patients receiving treatment.