OBJECTIVES: To examine the relationships between heterotopic ossification (HO) volume and functional and quality of life (QoL) endpoints in patients with FOP, an ultra-rare severely debilitating genetic disease associated with progressive restriction of movement.

METHODS: Data from 171 patients from the FOP Natural History Study (NCT02322255) and the MOVE trial (NCT03312634) were used to analyze the relationships between HO volume and the Cumulative Analogue Joint Involvement Scale (CAJIS), the FOP-Physical Function Questionnaire (PFQ), and the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Scale. Total and summary scores distinguishing between upper and lower body extremities were used for HO, CAJIS, and FOP-PFQ. For HO, additional scores were used for the related body regions. Simple correlation analyses were conducted, and mixed effect models were fitted longitudinally. Statistically significant relationships are reported for the models with the best fit per Akaike information criterion and Bayesian information criterion.

RESULTS: HO volume in extremities had moderate to high correlations with CAJIS and FOP-PFQ scores. As expected, regression coefficients generally confirmed positive relationships between HO volume and CAJIS/FOP-PFQ, and negative relationships between HO volume and PROMIS. Statistically significant relationships were found between HO volume in certain body regions and endpoint scores (chest: upper extremity CAJIS, change in total CAJIS; arms: total and upper extremity CAJIS, PROMIS mental health; hips and legs: lower extremity CAJIS, change in total CAJIS; hips: total CAJIS, change in PROMIS mental health). HO volume in the upper or lower extremities was significantly associated with change in upper extremity CAJIS scores, observed FOP-PFQ scores, and changes in FOP-PFQ scores.

CONCLUSIONS: Cross-sectional and longitudinal data confirm logical significant relationships between HO volume in body regions and CAJIS and FOP-PFQ. These results help to better understand the associations between HO volume and functional and QoL endpoints in FOP.