Radiological evolution of spinal disease in alkaptonuria and the effect of nitisinone

Abstract

ObjectivesOchronotic spondyloarthropathy represents one of the main clinical manifestations of alkaptonuria (AKU); however, prospective data and description of the effect of nitisinone treatment are lacking.MethodsPatients with AKU aged 25 years or older were randomly assigned to receive either oral nitisinone 10 mg/day (N=69) or no treatment (N=69). Spine radiographs were recorded yearly at baseline, 12, 24, 36 and 48 months, and the images were scored for the presence of intervertebral space narrowing, soft tissue calcifications, vacuum phenomena, osteophytes/hyperostosis and spinal fusion in the cervical, thoracic and lumbosacral segment at each of the time points.ResultsAt baseline, narrowing of the intervertebral spaces, the presence of osteophytes/hyperostosis and calcifications were the three most frequent radiographic features in AKU. The rate of progression of the five main features during the 4 years, ranked from the highest to lowest was as follows: intervertebral spaces narrowing, calcifications, vacuum phenomena, osteophytes/hyperostosis and fusions. The rate of progression did not differ between the treated and untreated groups in any of the five radiographic parameters except for a slower rate of progression (sum of all five features) in the treatment group compared with the control group (0.45 (1.11) nitisinone vs 0.74 (1.11) controls, p=0.049) in the thoracic segment.ConclusionThe present study shows a relatively slow but significant worsening of radiographic features in patients with AKU over 4 years. Our results demonstrate a modest beneficial effect of 10 mg/day of nitisinone on the slowly progressing spondylosis in AKU during the relatively limited follow-up time.Trial registration numberNCT01916382.

Analysis of the Phenotype Differences in Siblings with Alkaptonuria

“…Spine radiographs, consisting of images of cervical, thoracic, and lumbosacral segments in the anteroposterior and lateral projections, were recorded using GE Optima XR646 in (General Electric Company, Boston, MA, USA) or Kodak DirectView DR7500 (Carestream Health, Rochester, NY, USA) and scored for the presence of narrowing of the intervertebral space, soft tissue calcifications in intervertebral discs and spinal ligaments, vacuum phenomena, osteophytes and/or hyperostosis, and spinal fusion as described elsewhere (manuscript submitted [ 26 ]).…”

Alkaptonuria Presenting With Lumbar Disc Herniation: A Case Report

“…The three most common radiological findings in AKU were a narrowed disc space, the presence of osteophytes, and calcification, which, if present, causes the most rapid radiographic progression [ 15 ]. Though degenerative changes can happen in any part of the spine, the lumbar portion is most affected, followed by the dorsal and cervical regions.…”