Whole-body Computed Tomography Versus Dual Energy X‑ray Absorptiometry for Assessing Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva

Abstract

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder that leads to heterotopic ossification (HO), resulting in progressive restriction of physical function. In this study, low-dose, whole-body computed tomography (WBCT) and dual energy X-ray absorptiometry (DXA) were evaluated to determine the preferred method for assessing total body burden of HO in patients with FOP. This was a non-interventional, two-part natural history study in patients with FOP (NCT02322255; date of registration: December 2014). In Part A (described here), WBCT and DXA scans were individually assessed for HO presence and severity across 15 anatomical regions. All images were independently reviewed by an expert imaging panel. Ten adult patients were enrolled across four sites. The sensitivity to HO presence and severity varied considerably between the two imaging modalities, with WBCT demonstrating HO in more body regions than DXA (76/138 [55%] versus 47/113 [42%]) evaluable regions). Inability to evaluate HO presence, due to overlapping body regions (positional ambiguity), occurred less frequently by WBCT than by DXA (mean number of non-evaluable regions per scan 1.2 [standard deviation: 1.5] versus 2.4 [1.4]). Based on the increased sensitivity and decreased positional ambiguity of low-dose WBCT versus DXA in measuring HO in patients with FOP, low-dose WBCT was chosen as the preferred imaging for measuring HO. Therefore, low-dose WBCT was carried forward to Part B of the natural history study, which evaluated disease progression over 36 months in a larger population of patients with FOP.

Monitoring and Management of Fibrodysplasia Ossificans Progressiva: Current Perspectives

“…Sequential CT-scan can be used to evaluate heterotopic bone volume increase, providing an objective outcome measure for therapeutic interventions. 9 , 27 The evaluation of a CT-scan in FOP patients is often challenging because of the disrupted anatomy due to the ankyloses and deformities. In FOP a CT-scan can be used to measure bone when it has been fully formed, but it does not contribute to finding bone which is still being formed and less calcified.…”

Study methodology and insights from the palovarotene clinical development program in fibrodysplasia ossificans progressiva

“…Prior to the NHS, the optimum imaging modality for assessing the total body burden of HO and HO progression was unknown. Both whole-body dual-energy X-ray absorptiometry (DXA) and low-dose WBCT imaging were compared in the first 10 participants enrolled in the NHS, and it was determined that low-dose WBCT was the preferred imaging modality [ 31 ]. Therefore, this imaging approach was used to assess the progression of HO in the remaining participants in the NHS and for all participants in PVO-1A-202.…”

“…• Comparison of DXA and low-dose WBCT (excluding the head) determined that low-dose WBCT was the preferred imaging modality for measuring HO [ 31 ]. When measured by low-dose WBCT, total HO volume increased substantially over the course of the study, suggesting the usefulness of this approach as a meaningful endpoint to measure disease progression [ 24 ]…”