CONTEXT Fibrous dysplasia (FD) results in fractures, pain, and deformities. Abnormal osteoprogenitor cells overproduce FGF23, leading to hyperphosphaturia in most patients and frank hypophosphatemia in a subset. Studies suggest hypophosphatemia is associated with increased FD-related morbidity. However, the relationship between phosphorus and skeletal complications has not been investigated, and the optimal therapeutic target has not been determined. OBJECTIVES Characterize the impact of serum phosphorus on FD-related morbidity and identify levels associated with increased skeletal complications. DESIGN Natural history study. SETTING Clinical Research Center. PATIENTS 240 subjects had ≥1 fasting phosphorus level, determined as age- and sex-adjusted Z-scores. Subjects were categorized based on frank hypophosphatemia (Z-score ≤-2)(n=48); low-normophosphatemia (>-2 to ≤-1)(n=66); and high-normophosphatemia (>-1 to ≤ 2)(n=125). MAIN OUTCOME MEASURES Fractures, orthopedic surgeries, scoliosis. RESULTS Subjects with frank and low-normophosphatemia had increased fracture and surgery rates compared to the high-normophosphatemia group. The prevalence of moderate-severe scoliosis was similarly higher in the frank and low-normophosphatemia groups. In a subanalysis of patients matched for Skeletal Burden Score ≥35, fracture and surgery rates remained higher in the frank hypophosphatemia group, suggesting the association between phosphorus and skeletal complications is not explained by differences in FD burden alone. CONCLUSIONS Both frank hypophosphatemia and low-normophosphatemia are associated with increased FD-related complications. This supports FGF23-mediated hypophosphatemia as a driver of skeletal morbidity, which may impact a larger proportion of the FD/MAS population than previously recognized. These findings will allow clinicians to identify at-risk patients, and will inform the development of prospective studies to determine optimal therapeutic targets.

中文翻译：

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血清磷是纤维发育不良骨骼发病的驱动因素。

背景 纤维发育不良 (FD) 会导致骨折、疼痛和畸形。异常的骨祖细胞过度产生 FGF23，导致大多数患者出现高磷酸盐尿症，部分患者出现明显的低磷血症。研究表明低磷血症与 FD 相关发病率增加有关。然而，磷与骨骼并发症之间的关系尚未被研究，最佳治疗靶点尚未确定。目的 描述血清磷对 FD 相关发病率的影响，并确定与骨骼并发症增加相关的水平。设计自然历史研究。设置临床研究中心。患者 240 名受试者的空腹磷水平≥1，根据年龄和性别调整的 Z 分数确定。根据明显的低磷血症对受试者进行分类（Z 分数≤-2）（n=48）；低磷血症（>-2 至 ≤-1）（n=66）；和高磷血症（>-1 至 ≤ 2）（n=125）。主要观察指标 骨折、矫形手术、脊柱侧弯。结果 与高磷血症组相比，患有正常磷血症和低磷血症的受试者骨折和手术率增加。在正常磷酸盐血症组和低磷酸盐血症组中，中重度脊柱侧凸的患病率同样较高。在对骨骼负担评分≥35 匹配的患者进行的亚组分析中，明显低磷血症组的骨折和手术率仍然较高，这表明磷与骨骼并发症之间的关联不能仅用 FD 负担的差异来解释。结论 明显的低磷血症和低正常磷血症均与 FD 相关并发症的增加有关。这支持 FGF23 介导的低磷血症是骨骼发病的驱动因素，这可能会影响比以前认识到的更大比例的 FD/MAS 人群。这些发现将使临床医生能够识别高危患者，并为前瞻性研究的发展提供信息，以确定最佳治疗目标。