OBJECTIVES: XLH is a rare genetic disorder in which adults typically experience significant symptoms including skeletal pain, stiffness, and impaired mobility. To date, no validated measures exist to quantify these symptoms from the patient's perspective. The current study evaluated the psychometric properties of the BPI-SF and WOMAC® to assess their suitability for use as clinical trial endpoints to measure pain, stiffness, and physical functioning in adults with XLH. METHODS: Data from an online burden of illness (BOI) study (n=201) and data from an open-label phase 2b clinical trial (n=20) were used to evaluate the psychometric properties of the BPI-SF and WOMAC in adult patients with XLH. Psychometric analyses included construct validity (confirmatory factor analysis, known groups method, convergent and discriminant validity), reliability (inter-rater, test-retest reliability) and ability to detect change. Exploratory analyses were also conducted to define meaningful change on the BPI-SF and WOMAC. RESULTS: Confirmatory Factor Analysis demonstrated appropriate item-score groupings for both the BPI-SF and WOMAC with the majority of model fit statistics surpassing a-priori thresholds. BPI-SF and WOMAC scores were able to significantly differentiate between groups of patients defined according to a range of clinical and demographic characteristics. BPI-SF and WOMAC scores were positively and strongly correlated with measures of similar concepts in the BOI sample. Strong reliability (internal consistency (α = 0.81-0.96), test-retest (= 0.43-0.82)) was also established for both instruments. The responsiveness analysis was limited due to the small sample size in the trial population. MID values (anchor and distribution-based) were most consistent for the BPI-SF pain severity (0.91-1.62), BPI-SF pain interference (0.59-1.86), and WOMAC Pain scores (7.24-11.28). CONCLUSIONS: These findings provide evidence that the BPI-SF and WOMAC are valid and reliable measures of pain, stiffness, and physical functioning impairments in XLH.