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Mechanisms of joint damage in gout: evidence from cellular and imaging studies

Abstract

The clinical course of gout is initially characterized by acute self-limited joint inflammation, but long-standing disease is often associated with chronic inflammation followed by the development of erosive joint damage, which can result in long-term functional impairment. Preventing joint damage is now a major focus of therapeutic intervention in gout. New light has been shed on the mechanisms leading to cartilage and bone damage in patients with this disease. Here, we discuss basic science studies focusing on the cellular immunology of bone and cartilage in gout and the effects of monosodium urate crystals on signaling pathways, cytokine release and the function of osteoclasts, osteoblasts and chondrocytes. We then explore the use of advanced imaging modalities (including MRI, ultrasonography, CT and dual-energy CT) to investigate pathology in gout, as they provide new ways to visualize joint tissues. These modalities vary in their ability to detect the various pathological features of gout and have different clinical applications. Imaging provides information about the inflammatory nature of the joint lesion, position and size of tophaceous deposits, and extent of bone and cartilage damage. Imaging is also increasingly being used to monitor the progression of joint damage and regression of tophi with effective urate-lowering therapy.

Key Points

  • Bone erosion in patients with gout is likely mediated by activated osteoclasts

  • Osteoblast viability and function are inhibited by contact with monosodium urate crystals

  • Chondrocytes might contribute to cartilage damage in patients with gout

  • Advanced imaging techniques, including MRI, CT, ultrasound and dual-energy CT, allow improved detection of joint damage and tophi

  • Tophus volume can be measured using these modalities and can be used to monitor urate-lowering therapy

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Figure 1: Tartrate-resistant acid phosphatase immunohistological analysis of bone from a gouty joint demonstrating the presence of osteoclasts at the bone–tophus interface.
Figure 2: Evidence for impaired repair mechanisms in tophaceous gout.
Figure 3: Comparison of bone remodeling in normal and gout-affected bone.
Figure 4: Plain radiography of the feet of a patient with chronic tophaceous gout.
Figure 5: MRI of the wrist of a man with tophaceous gout.
Figure 6: Dual-energy CT image of the first metatarsophalangeal joint from a patient with tophaceous gout showing monosodium urate crystals present within a bone erosion.

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McQueen, F., Chhana, A. & Dalbeth, N. Mechanisms of joint damage in gout: evidence from cellular and imaging studies. Nat Rev Rheumatol 8, 173–181 (2012). https://doi.org/10.1038/nrrheum.2011.207

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