The following is a summary of “Serum Phosphorus as a Driver of Skeletal Morbidity in Fibrous Dysplasia,” published in the May 2024 issue of Endocrinology by Gun, et al.
Fibrous dysplasia (FD) leads to fractures, pain, and deformities. Overproduction of FGF23 by abnormal osteoprogenitor cells results in hyperphosphaturia in most patients and hypophosphatemia in some. Hypophosphatemia has been linked to increased FD-related morbidity, but the relationship between phosphorus levels and skeletal complications has not been explored, nor has the optimal therapeutic target. For a study, researchers sought to characterize the impact of serum phosphorus on FD-related morbidity and identify phosphorus levels associated with increased skeletal complications.
A natural history study was conducted with 240 subjects at a clinical research center, each with at least one fasting phosphorus level measured as age- and sex-adjusted Z-scores. Subjects were categorized into three groups: frank hypophosphatemia (Z-score ≤ −2; n = 48), low-normophosphatemia (> −2 to ≤ −1; n = 66), and high-normophosphatemia (> −1 to ≤ 2; n = 125). The primary outcomes measured were fractures, orthopedic surgeries, and scoliosis.
Subjects with frank and low-normophosphatemia exhibited higher rates of fractures and surgeries compared to those with high-normophosphatemia. Moderate to severe scoliosis was also greater in the frank and low-normophosphatemia groups. In a subanalysis of patients with a Skeletal Burden Score ≥35, fracture and surgery rates remained higher in the frank hypophosphatemia group, indicating that the association between phosphorus levels and skeletal complications is independent of FD burden.
Both frank hypophosphatemia and low-normophosphatemia were linked to increased FD-related complications. It suggested that FGF23-mediated hypophosphatemia contributed significantly to skeletal morbidity, potentially affecting more individuals with FD/McCune-Albright syndrome than previously recognized. The findings helped clinicians identify at-risk patients and guide the development of prospective studies to determine optimal therapeutic targets.
Reference: academic.oup.com/jcem/article-abstract/109/5/1334/7425417