Development of a radiographic vertebral severity score for evaluation of disease progression in alkaptonuria

Alkaptonuria is associated with progressive spine disease beginning in young adulthood. Characteristic radiographic changes in the intervertebral discs are often the earliest detectable skeletal manifestations. We developed a radiographic severity score measuring spine disease at 13 levels (C2-C7, T10-S1) based upon three parameters: 1) narrowing; 2) calcification; 3) vacuum disc phenomenon. 409 sets of radiographs from 136 participants were scored and divided into: 1) a cross-sectional cohort, with the most recent visit of each individual; 2) a longitudinal cohort, for participants with multiple visits. Correlations with age, sex, clinical measurements and patient-reported outcomes were performed. Both cohorts showed correlation of spinal disease score with age. Correlations were found with pain (SF-36, Pain Disability Index) and physical function (Schober's test, SF-36, Human Activity Profile). Intra- and inter-rater reliability were high for the total score (ICC > 0.95, p < 0.001), with a minimal detectable change of 2.6 points out of a total possible score of 78. This radiographic severity score is highly reliable, correlates with age, sex, and several clinical measures of physical function and pain, and allows for the detection of clinically meaningful changes. It can also be used as an outcome measure to monitor disease progression and response to therapy.