Bilateral Lesions Are Linked to Postoperative Regrowth in Craniofacial Fibrous Dysplasia: Alkaline Phosphatase as a Marker of Clinical Phenotype

<b>Objectives:</b> This study aimed to evaluate phenotypic associations between preoperative alkaline phosphatase (ALP) levels and clinical characteristics, and explore clinical factors associated for postoperative regrowth in craniofacial fibrous dysplasia. <b>Methods:</b> In this retrospective cohort (2003-2024), 71 surgically treated fibrous dysplasia patients were analyzed. Relationships between preoperative ALP (using age-stratified reference ranges) and key phenotypes (age at surgery, onset age, laterality, lesion type) were assessed via nonparametric tests. Associations with postoperative regrowth were assessed using Mann-Whitney U or Kruskal-Wallis tests for non-normally distributed continuous variables and χ² or Fisher's exact tests for categorical variables. <b>Results:</b> Preoperative ALP levels significantly correlated with younger surgical age (16-19 vs. ≥19 years: 244.0 vs. 107.0 U/L, <i>p</i> < 0.001), earlier onset (0-16 vs. >16 years: 114.0 vs. 83.0 U/L, <i>p</i> = 0.030), bilateral lesions (176.0 vs. 106.2 U/L, <i>p</i> = 0.006), and polyostotic subtype (polyostotic fibrous dysplasia vs. monostotic fibrous dysplasia: 162.0 vs. 87.5 U/L, <i>p</i> < 0.001). However, neither ALP levels (<i>p</i> = 0.061) nor abnormal ALP rates (<i>p</i> = 0.090) predicted regrowth. Crucially, bilateral lesions were significantly associated with regrowth (83.3% (5/6) vs. 21.5% (14/65); <i>p</i> = 0.005). The overall regrowth rate was 8.5% (6/71). <b>Conclusions:</b> Bilateral lesions demonstrate significant association with postoperative regrowth risk, potentially guiding surveillance intensity. ALP correlates with phenotypic burden but shows limited prognostic utility. These findings, interpreted considering retrospective constraints, warrant validation in larger cohorts.