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.