Reliability and Validity of the 6-Minute Walk Test in Hypophosphatasia.

This investigation evaluated the reliability and validity of the 6-Minute Walk Test (6MWT) in patients with pediatric hypophosphatasia (HPP). Children (aged 6 to 12 years; n = 11), adolescents (13 to 17 years; n = 4), and adults (18 to 65 years; n = 9) completed the 6MWT at screening and baseline in two clinical studies of asfotase alfa. Test-retest reliability of the 6MWT, evaluated with Pearson's correlation coefficients (r) for screening versus baseline, was high for children (r = 0.95; p < 0.0001), adolescents (r = 0.81; p = 0.125), and adults (r = 0.94; p = 0.0001). The most conservative minimal clinically important differences, estimated using distribution-based methods, were 31 m (children and adults) and 43 m (adolescents). In children, the 6MWT correlated significantly with scores on measures of skeletal disease, which included the Radiographic Global Impression of Change scale (r = 0.50; p < 0.0001) and the Rickets Severity Scale (r = -0.78; p < 0.0001), such that distance walked increased as the severity of skeletal disease decreased. Significant (p < 0.0001) correlations with the 6MWT distance walked were also observed for children with scores on parent-reported measures of disability (r = -0.67), ability to function in activities of daily living (r = 0.71 to 0.77), and parent-reported measures of pain (r = -0.39). In adolescents and adults, 6MWT distance walked correlated significantly (p < 0.05) with measures of lower extremity function (r = 0.83 and 0.60, respectively), total pain severity (r = -0.41 and -0.36, respectively), and total pain interference (r = -0.41 and -0.49, respectively). Collectively, these data indicate that the 6MWT is a reliable, valid measure of physical functioning in patients with pediatric HPP. © 2018 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.