Background/Purpose:  Imaging and pathology studies have shown that bone erosion is closely associated with monosodium urate (MSU) crystal deposition in tophaceous gout.  It is currently unknown whether bone erosion in gout occurs through an inside-out mechanism with direct intra-osseous crystal deposition, or through an outside-in mechanism, whereby crystals deposit on the surface of articular cartilage surface or within synovium and then interact with bone to promote erosion.  The aim of this study was to analyse the relationship between bone and MSU crystal deposition using dual energy computed tomography (DECT) in people with tophaceous gout.

Methods:  One hundred and forty four participants were recruited from rheumatology clinics.  All participants had gout according to the 1977 American Rheumatism Association classification criteria and at least one palpable tophus.  DECT scans of both feet were performed on a dual X-ray tube 128 detector row scanner.  Two readers independently scored all metatarsal heads (1433 bones available for scoring).  Each site was initially scored for the presence or absence of urate deposition within the joint. If urate was present within the joint, the presence of urate in contact with bone was then scored.  For bones in contact with urate, the site was then scored for whether urate was present within an erosion, on the surface of bone or within bone only (true intra-osseous deposit).  In the case of reader disagreement, agreement was reached in a consensus re-scoring exercise.  Pre-consensus inter-reader kappa for all scoring was >0.93.  Differences between the location of urate deposits in each and all metatarsal heads were modelled taking into account clustering of results within individuals by general estimating equations using the GENMOD procedure of SAS v9.4. 

Results:  Urate deposition in the joint was present in 681/1433 (47.5%) sites. Urate in contact with bone was present in 370/681 (54.3%) joints with urate deposition.  For those bones in contact with urate, deposition was present on the surface of bone in 143/370 (39%, 95% CI 34, 44%) and within erosion in 227/370 (61%, 95% CI 56, 66%).  True intra-osseous urate deposition was not observed at any site (0%, 95% CI 0, 1%), GENMOD P<0.0001.  For all bones with apparent intra-osseous deposition in one plane, examination in other planes demonstrated urate deposition within an en face erosion (Figure). 

Conclusion:  In tophaceous gout, MSU crystal deposition is present within the joint, on the bone surface and within bone erosion, but 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. Figure. Example of apparent metatarsal intra-osseous urate deposit in axial plane, with images in other planes showing urate within an erosion. Urate is colour coded as green and bone as purple.