Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2016

Open Access 01-12-2016 | Research article

Urate crystal deposition and bone erosion in gout: ‘inside-out’ or ‘outside-in’? A dual-energy computed tomography study

Authors: Patapong Towiwat, Anthony J. Doyle, Gregory D. Gamble, Paul Tan, Opetaia Aati, Anne Horne, Lisa K. Stamp, Nicola Dalbeth

Published in: Arthritis Research & Therapy | Issue 1/2016

Login to get access

Abstract

Background

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. 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.

Methods

One 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.

Results

Urate 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.

Conclusions

In 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.
Literature
1.
go back to reference McQueen FM, Doyle A, Reeves Q, Gao A, Tsai A, Gamble GD, et al. Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study. Rheumatology (Oxford). 2014;53:95–103.CrossRef McQueen FM, Doyle A, Reeves Q, Gao A, Tsai A, Gamble GD, et al. Bone erosions in patients with chronic gouty arthropathy are associated with tophi but not bone oedema or synovitis: new insights from a 3 T MRI study. Rheumatology (Oxford). 2014;53:95–103.CrossRef
2.
go back to reference Dalbeth N, Clark B, Gregory K, Gamble G, Sheehan T, Doyle A, et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis. 2009;68:1290–5.CrossRefPubMed Dalbeth N, Clark B, Gregory K, Gamble G, Sheehan T, Doyle A, et al. Mechanisms of bone erosion in gout: a quantitative analysis using plain radiography and computed tomography. Ann Rheum Dis. 2009;68:1290–5.CrossRefPubMed
3.
go back to reference Dalbeth N, Pool B, Gamble GD, Smith T, Callon KE, McQueen FM, et al. Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum. 2010;62:1549–56.CrossRefPubMed Dalbeth N, Pool B, Gamble GD, Smith T, Callon KE, McQueen FM, et al. Cellular characterization of the gouty tophus: a quantitative analysis. Arthritis Rheum. 2010;62:1549–56.CrossRefPubMed
4.
go back to reference Choi HK, Al-Arfaj AM, Eftekhari A, Munk PL, Shojania K, Reid G, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis. 2009;68:1609–12.CrossRefPubMed Choi HK, Al-Arfaj AM, Eftekhari A, Munk PL, Shojania K, Reid G, et al. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis. 2009;68:1609–12.CrossRefPubMed
5.
go back to reference Dalbeth N, Aati O, Kalluru R, Gamble GD, Horne A, Doyle AJ, et al. Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study. Ann Rheum Dis. 2015;74:1030–6.CrossRefPubMed Dalbeth N, Aati O, Kalluru R, Gamble GD, Horne A, Doyle AJ, et al. Relationship between structural joint damage and urate deposition in gout: a plain radiography and dual-energy CT study. Ann Rheum Dis. 2015;74:1030–6.CrossRefPubMed
6.
go back to reference Dalbeth N, Smith T, Gray S, Doyle A, Antill P, Lobo M, et al. Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease. Ann Rheum Dis. 2009;68:279–82.CrossRefPubMed Dalbeth N, Smith T, Gray S, Doyle A, Antill P, Lobo M, et al. Cellular characterisation of magnetic resonance imaging bone oedema in rheumatoid arthritis; implications for pathogenesis of erosive disease. Ann Rheum Dis. 2009;68:279–82.CrossRefPubMed
7.
go back to reference Tan AL, Tanner SF, Conaghan PG, Radjenovic A, O’Connor P, Brown AK, et al. Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis. Arthritis Rheum. 2003;48:1214–22.CrossRefPubMed Tan AL, Tanner SF, Conaghan PG, Radjenovic A, O’Connor P, Brown AK, et al. Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis. Arthritis Rheum. 2003;48:1214–22.CrossRefPubMed
8.
go back to reference Jimenez-Boj E, Nobauer-Huhmann I, Hanslik-Schnabel B, Dorotka R, Wanivenhaus AH, Kainberger F, et al. Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum. 2007;56:1118–24.CrossRefPubMed Jimenez-Boj E, Nobauer-Huhmann I, Hanslik-Schnabel B, Dorotka R, Wanivenhaus AH, Kainberger F, et al. Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum. 2007;56:1118–24.CrossRefPubMed
9.
go back to reference Larmon WA, Kurtz JF. The surgical management of chronic tophaceous gout. J Bone Joint Surg. 1958;40:743–72.PubMed Larmon WA, Kurtz JF. The surgical management of chronic tophaceous gout. J Bone Joint Surg. 1958;40:743–72.PubMed
10.
11.
go back to reference Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford). 2007;46:1116–21.CrossRef Thiele RG, Schlesinger N. Diagnosis of gout by ultrasound. Rheumatology (Oxford). 2007;46:1116–21.CrossRef
12.
go back to reference Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977;20:895–900.CrossRefPubMed Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ, Yu TF. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum. 1977;20:895–900.CrossRefPubMed
14.
go back to reference Resnick D, Broderick TW. Intraosseous calcifications in tophaceous gout. AJR Am J Roentgenol. 1981;137:1157–61.CrossRefPubMed Resnick D, Broderick TW. Intraosseous calcifications in tophaceous gout. AJR Am J Roentgenol. 1981;137:1157–61.CrossRefPubMed
15.
go back to reference Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, et al. Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells. Arthritis Rheum. 2008;58:1854–65.CrossRefPubMed Dalbeth N, Smith T, Nicolson B, Clark B, Callon K, Naot D, et al. Enhanced osteoclastogenesis in patients with tophaceous gout: urate crystals promote osteoclast development through interactions with stromal cells. Arthritis Rheum. 2008;58:1854–65.CrossRefPubMed
16.
go back to reference Schweyer S, Hemmerlein B, Radzun HJ, Fayyazi A. Continuous recruitment, co-expression of tumour necrosis factor-α and matrix metalloproteinases, and apoptosis of macrophages in gout tophi. Virchows Arch. 2000;437:534–9.CrossRefPubMed Schweyer S, Hemmerlein B, Radzun HJ, Fayyazi A. Continuous recruitment, co-expression of tumour necrosis factor-α and matrix metalloproteinases, and apoptosis of macrophages in gout tophi. Virchows Arch. 2000;437:534–9.CrossRefPubMed
17.
go back to reference Chhana A, Callon KE, Pool B, Naot D, Gamble GD, Dray M, et al. The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout. J Rheumatol. 2013;40:2067–74.CrossRefPubMed Chhana A, Callon KE, Pool B, Naot D, Gamble GD, Dray M, et al. The effects of monosodium urate monohydrate crystals on chondrocyte viability and function: implications for development of cartilage damage in gout. J Rheumatol. 2013;40:2067–74.CrossRefPubMed
18.
go back to reference Hsieh MS, Ho HC, Chou DT, Pan S, Liang YC, Hsieh TY, et al. Expression of matrix metalloproteinase-9 (gelatinase B) in gouty arthritis and stimulation of MMP-9 by urate crystals in macrophages. J Cell Biochem. 2003;89:791–9.CrossRefPubMed Hsieh MS, Ho HC, Chou DT, Pan S, Liang YC, Hsieh TY, et al. Expression of matrix metalloproteinase-9 (gelatinase B) in gouty arthritis and stimulation of MMP-9 by urate crystals in macrophages. J Cell Biochem. 2003;89:791–9.CrossRefPubMed
19.
go back to reference McMillan RM, Vater CA, Hasselbacher P, Hahn J, Harris Jr ED. Induction of collagenase and prostaglandin synthesis in synovial fibroblasts treated with monosodium urate crystals. J Pharm Pharmacol. 1981;33:382–3.CrossRefPubMed McMillan RM, Vater CA, Hasselbacher P, Hahn J, Harris Jr ED. Induction of collagenase and prostaglandin synthesis in synovial fibroblasts treated with monosodium urate crystals. J Pharm Pharmacol. 1981;33:382–3.CrossRefPubMed
20.
go back to reference Melzer R, Pauli C, Treumann T, Krauss B. Gout tophus detection—a comparison of dual-energy CT (DECT) and histology. Semin Arthritis Rheum. 2014;43:662–5.CrossRefPubMed Melzer R, Pauli C, Treumann T, Krauss B. Gout tophus detection—a comparison of dual-energy CT (DECT) and histology. Semin Arthritis Rheum. 2014;43:662–5.CrossRefPubMed
Metadata
Title
Urate crystal deposition and bone erosion in gout: ‘inside-out’ or ‘outside-in’? A dual-energy computed tomography study
Authors
Patapong Towiwat
Anthony J. Doyle
Gregory D. Gamble
Paul Tan
Opetaia Aati
Anne Horne
Lisa K. Stamp
Nicola Dalbeth
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-016-1105-z

Other articles of this Issue 1/2016

Arthritis Research & Therapy 1/2016 Go to the issue