Abstract

BackgroundIt is currently unknown whether bone erosion in gout occurs through an ‘inside-out’ mechanism due to direct intra-osseous crystal deposition or through an ‘outside-in’ mechanism from the surface of bone. The aim of this study was to examine the mechanism (‘outside-in’ vs. ‘inside-out’) of monosodium urate (MSU) crystal deposition in bone erosion in gout. Specifically, we used three-dimensional dual-energy computed tomography (DECT) to analyse the positional relationship between bone and MSU crystal deposition in tophaceous gout, and to determine whether intra-osseous crystal deposition occurs in the absence of erosion.MethodsOne hundred forty-four participants with gout and at least one palpable tophus had a DECT scan of both feet. Two readers independently scored all metatarsal heads (1433 bones available for scoring). For bones in contact with urate, the bone was scored for whether urate was present within an erosion, on the surface of bone or within bone only (true intra-osseous deposit). Data were analysed using generalised estimating equations.ResultsUrate in contact with bone was present in 370 (54.3 %) of 681 joints with urate deposition. For those bones in contact with urate, deposition was present on the surface of bone in 143 (38.6 %) of 370 joints and within erosion in 227 (61.4 %) of 370. True intra-osseous urate deposition was not observed at any site (p < 0.0001). For all bones with apparent intra-osseous deposition in one plane, examination in other planes revealed urate deposition within an en face erosion.ConclusionsIn tophaceous gout, MSU crystal deposition is present within the joint, on the bone surface and within bone erosion, but it is not observed within bone in the absence of a cortical break. These data support the concept that MSU crystals deposit outside bone and contribute to bone erosion through an ‘outside-in’ mechanism.

Highlights

  • It is currently unknown whether bone erosion in gout occurs through an ‘inside-out’ mechanism due to direct intra-osseous crystal deposition or through an ‘outside-in’ mechanism from the surface of bone

  • Advanced imaging techniques such as conventional computed tomography and magnetic resonance imaging have demonstrated a close relationship between tophus and bone erosion [1, 2]

  • True intra-osseous urate deposition was not observed at any site

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Summary

Introduction

It is currently unknown whether bone erosion in gout occurs through an ‘inside-out’ mechanism due to direct intra-osseous crystal deposition or through an ‘outside-in’ mechanism from the surface of bone. The aim of this study was to examine the mechanism (‘outside-in’ vs ‘inside-out’) of monosodium urate (MSU) crystal deposition in bone erosion in gout. We used three-dimensional dual-energy computed tomography (DECT) to analyse the positional relationship between bone and MSU crystal deposition in tophaceous gout, and to determine whether intra-osseous crystal deposition occurs in the absence of erosion. Bone erosion is a frequent consequence of tophaceous gout Advanced imaging techniques such as conventional computed tomography and magnetic resonance imaging have demonstrated a close relationship between tophus and bone erosion [1, 2]. Histological and imaging studies have implicated both invasion of inflamed synovial tissue or pannus into bone (‘outside-in’) and cytokine-mediated osteitis visualized as bone marrow oedema (‘inside-out’) as potential mechanisms for bone erosion in RA [6–8].

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