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02-02-2017 | Osteoarthritis | Review | Article

Synovitis in osteoarthritis: current understanding with therapeutic implications

Journal: Arthritis Research & Therapy

Authors: Alexander Mathiessen, Philip G. Conaghan

Publisher: BioMed Central

Abstract

Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically.

Division UNDoEaSAP. World Population Prospects: The 2015 Revision, Key Findings and Advance Tables. 2016. https://esa.un.org/unpd/wpp/.

Thomas E, Peat G, Croft P. Defining and mapping the person with osteoarthritis for population studies and public health. Rheumatology (Oxford). 2014;53(2):338–45.CrossRef

Goldenberg DL, Egan MS, Cohen AS. Inflammatory synovitis in degenerative joint disease. J Rheumatol. 1982;9(2):204–9.PubMed

Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1):16–21.CrossRefPubMed

Sellam J, Berenbaum F. The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis. Nat Rev Rheumatol. 2010;6(11):625–35.CrossRefPubMed

Scanzello CR, Goldring SR. The role of synovitis in osteoarthritis pathogenesis. Bone. 2012;51(2):249–57.CrossRefPubMedPubMedCentral

Smith MD. The normal synovium. Open Rheumatol J. 2011;5:100–6.CrossRefPubMedPubMedCentral

Prieto-Potin I, Largo R, Roman-Blas JA, et al. Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis. BMC Musculoskelet Disord. 2015;16:226.CrossRefPubMedPubMedCentral

Klein-Wieringa IR, de Lange-Brokaar BJ, Yusuf E, et al. Inflammatory cells in patients with endstage knee osteoarthritis: a comparison between the synovium and the infrapatellar fat pad. J Rheumatol. 2016;43(4):771–8.CrossRefPubMed

10.

Deligne C, Casulli S, Pigenet A, et al. Differential expression of interleukin-17 and interleukin-22 in inflamed and non-inflamed synovium from osteoarthritis patients. Osteoarthritis Cartilage. 2015;23(11):1843–52.CrossRefPubMed

11.

de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage. 2012;20(12):1484–99.CrossRefPubMed

12.

Sokolove J, Lepus CM. Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations. Ther Adv Musculoskelet Dis. 2013;5(2):77–94.CrossRefPubMedPubMedCentral

13.

Goldring MB. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther Adv Musculoskelet Dis. 2012;4(4):269–85.CrossRefPubMedPubMedCentral

14.

Ponchel F, Burska AN, Hensor EM, et al. Changes in peripheral blood immune cell composition in osteoarthritis. Osteoarthritis Cartilage. 2015;23(11):1870–8.CrossRefPubMedPubMedCentral

15.

Siebuhr AS, Bay-Jensen AC, Jordan JM, et al. Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment? Scand J Rheumatol. 2016;45(2):87–98.CrossRefPubMed

16.

Wojdasiewicz P, Poniatowski LA, Szukiewicz D. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis. Mediators Inflamm. 2014;2014:561459.CrossRefPubMedPubMedCentral

17.

Hamilton JA, Cook AD, Tak PP. Anti-colony-stimulating factor therapies for inflammatory and autoimmune diseases. Nat Rev Drug Discov. 2017;16(1):53–70.CrossRef

18.

Pustjens MF, Mastbergen SC, Steen-Louws C, et al. IL4-10 synerkine induces direct and indirect structural cartilage repair in osteoarthritis. Osteoarthritis Cartilage. 2016;24:S532.CrossRef

19.

Guermazi A, Roemer FW, Haugen IK, et al. MRI-based semiquantitative scoring of joint pathology in osteoarthritis. Nat Rev Rheumatol. 2013;9(4):236–51.CrossRefPubMed

20.

Pearle AD, Scanzello CR, George S, et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage. 2007;15(5):516–23.CrossRefPubMed

21.

de Lange-Brokaar BJ, Ioan-Facsinay A, Yusuf E, et al. Degree of synovitis on MRI by comprehensive whole knee semi-quantitative scoring method correlates with histologic and macroscopic features of synovial tissue inflammation in knee osteoarthritis. Osteoarthritis Cartilage. 2014;22(10):1606–13.CrossRefPubMed

22.

Loeuille D, Sauliere N, Champigneulle J, et al. Comparing non-enhanced and enhanced sequences in the assessment of effusion and synovitis in knee OA: associations with clinical, macroscopic and microscopic features. Osteoarthritis Cartilage. 2011;19(12):1433–9.CrossRefPubMed

23.

Neogi T, Guermazi A, Roemer F, et al. Association of joint inflammation with pain sensitization in knee osteoarthritis: the Multicenter Osteoarthritis Study. Arthritis Rheumatol. 2016;68(3):654–61.CrossRefPubMed

24.

Guermazi A, Hayashi D, Roemer FW, et al. Synovitis in knee osteoarthritis assessed by contrast-enhanced magnetic resonance imaging (MRI) is associated with radiographic tibiofemoral osteoarthritis and MRI-detected widespread cartilage damage: the MOST study. J Rheumatol. 2014;41(3):501–8.CrossRefPubMed

25.

Baker K, Grainger A, Niu J, et al. Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann Rheum Dis. 2010;69(10):1779–83.CrossRefPubMed

26.

Haugen IK, Boyesen P, Slatkowsky-Christensen B, et al. Associations between MRI-defined synovitis, bone marrow lesions and structural features and measures of pain and physical function in hand osteoarthritis. Ann Rheum Dis. 2012;71(6):899–904.CrossRefPubMed

27.

Sarmanova A, Hall M, Moses J, et al. Synovial changes detected by ultrasound in people with knee osteoarthritis—a meta-analysis of observational studies. Osteoarthritis Cartilage. 2016;24(8):1376–83.CrossRefPubMedPubMedCentral

28.

D’Agostino MA, Conaghan P, Le Bars M, et al. EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: prevalence of inflammation in osteoarthritis. Ann Rheum Dis. 2005;64(12):1703–9.CrossRefPubMedPubMedCentral

29.

Mathiessen A, Slatkowsky-Christensen B, Kvien TK, et al. Ultrasound-detected inflammation predicts radiographic progression in hand osteoarthritis after 5 years. Ann Rheum Dis. 2016;75(5):825–30.CrossRefPubMed

30.

Kortekaas MC, Kwok WY, Reijnierse M, et al. Pain in hand osteoarthritis is associated with inflammation: the value of ultrasound. Ann Rheum Dis. 2010;69(7):1367–9.CrossRefPubMed

31.

Roze RH, Bierma-Zeinstra SM, Agricola R, et al. Differences in MRI features between two different osteoarthritis subpopulations: data from the Osteoarthritis Initiative. Osteoarthritis Cartilage. 2016;24(5):822–6.CrossRefPubMed

32.

Kortekaas MC, Kwok WY, Reijnierse M, et al. In erosive hand osteoarthritis more inflammatory signs on ultrasound are found than in the rest of hand osteoarthritis. Ann Rheum Dis. 2013;72(6):930–4.CrossRefPubMed

33.

de Lange-Brokaar BJ, Ioan-Facsinay A, Yusuf E, et al. Association of pain in knee osteoarthritis with distinct patterns of synovitis. Arthritis Rheumatol. 2015;67(3):733–40.CrossRefPubMed

34.

Wang X, Jin X, Han W, et al. Cross-sectional and longitudinal associations between knee joint effusion synovitis and knee pain in older adults. J Rheumatol. 2016;43(1):121–30.CrossRefPubMed

35.

Yusuf E, Kortekaas MC, Watt I, et al. Do knee abnormalities visualised on MRI explain knee pain in knee osteoarthritis? A systematic review. Ann Rheum Dis. 2011;70(1):60–7.CrossRefPubMed

36.

Riis RG, Gudbergsen H, Henriksen M, et al. Synovitis assessed on static and dynamic contrast-enhanced magnetic resonance imaging and its association with pain in knee osteoarthritis: a cross-sectional study. Eur J Radiol. 2016;85(6):1099–108.CrossRefPubMed

37.

Hill CL, Hunter DJ, Niu J, et al. Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis. Ann Rheum Dis. 2007;66(12):1599–603.CrossRefPubMedPubMedCentral

38.

Zhang Y, Nevitt M, Niu J, et al. Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging. Arthritis Rheum. 2011;63(3):691–9.CrossRefPubMed

39.

de Lange-Brokaar BJ, Ioan-Facsinay A, Yusuf E, et al. Evolution of synovitis in osteoarthritic knees and its association with clinical features. Osteoarthritis Cartilage. 2016;24(11):1867–74.CrossRefPubMed

40.

Haugen IK, Slatkowsky Christensen B, Boyesen P, et al. Increasing synovitis and bone marrow lesions are associated with incident joint tenderness in hand osteoarthritis. Ann Rheum Dis. 2016;75(4):702–8.CrossRefPubMed

41.

Felson DT, Niu J, Neogi T, et al. Synovitis and the risk of knee osteoarthritis: the MOST Study. Osteoarthritis Cartilage. 2016;24(3):458–64.CrossRefPubMed

42.

Roemer FW, Guermazi A, Felson DT, et al. Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study. Ann Rheum Dis. 2011;70(10):1804–9.CrossRefPubMedPubMedCentral

43.

Atukorala I, Kwoh CK, Guermazi A, et al. Synovitis in knee osteoarthritis: a precursor of disease? Ann Rheum Dis. 2016;75(2):390–5.CrossRefPubMed

44.

Roemer FW, Kwoh CK, Hannon MJ, et al. What comes first? Multitissue involvement leading to radiographic osteoarthritis: magnetic resonance imaging-based trajectory analysis over four years in the osteoarthritis initiative. Arthritis Rheumatol. 2015;67(8):2085–96.CrossRefPubMedPubMedCentral

45.

Conaghan PG, D’Agostino MA, Le Bars M, et al. Clinical and ultrasonographic predictors of joint replacement for knee osteoarthritis: results from a large, 3-year, prospective EULAR study. Ann Rheum Dis. 2010;69(4):644–7.CrossRefPubMed

46.

Collins JE, Losina E, Nevitt MC, et al. Semi-quantitative imaging biomarkers of knee osteoarthritis progression: data from the FNIH OA Biomarkers Consortium. Arthritis Rheumatol. 2016;68(10):2422–31.CrossRefPubMed

47.

Kortekaas MC, Kwok WY, Reijnierse M, et al. Inflammatory ultrasound features show independent associations with progression of structural damage after over 2 years of follow-up in patients with hand osteoarthritis. Ann Rheum Dis. 2015;74(9):1720–4.CrossRefPubMed

48.

Haugen IK, Slatkowsky-Christensen B, Boyesen P, et al. MRI findings predict radiographic progression and development of erosions in hand osteoarthritis. Ann Rheum Dis. 2016;75(1):117–23.CrossRefPubMed

49.

Damman W, Liu R, Bloem JL, et al. Bone marrow lesions and synovitis on MRI associate with radiographic progression after 2 years in hand osteoarthritis. Ann Rheum Dis. 2017;76(1):214–17.CrossRefPubMed

50.

O’Neill TW, Parkes MJ, Maricar N, et al. Synovial tissue volume: a treatment target in knee osteoarthritis (OA). Ann Rheum Dis. 2016;75(1):84–90.CrossRefPubMed

51.

Gait AD, Hodgson R, Parkes MJ, et al. Synovial volume vs synovial measurements from dynamic contrast enhanced MRI as measures of response in osteoarthritis. Osteoarthritis Cartilage. 2016;24(8):1392–8.CrossRefPubMedPubMedCentral

52.

Wenham CY, Balamoody S, Grainger AJ, et al. The responsiveness of novel, dynamic, contrast-enhanced magnetic resonance measures of total knee synovitis after intra-articular corticosteroid for painful osteoarthritis. Osteoarthritis Cartilage. 2014;22(10):1614–8.CrossRefPubMed

53.

Zhang W, Nuki G, Moskowitz RW, et al. OARSI recommendations for the management of hip and knee osteoarthritis: part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis Cartilage. 2010;18(4):476–99.CrossRefPubMed

54.

Robinson P, Keenan AM, Conaghan PG. Clinical effectiveness and dose response of image-guided intra-articular corticosteroid injection for hip osteoarthritis. Rheumatology (Oxford). 2007;46(2):285–91.CrossRef

55.

Wenham CY, Hensor EM, Grainger AJ, et al. A randomized, double-blind, placebo-controlled trial of low-dose oral prednisolone for treating painful hand osteoarthritis. Rheumatology (Oxford). 2012;51(12):2286–94.CrossRef

56.

Keen HI, Wakefield RJ, Hensor EM, et al. Response of symptoms and synovitis to intra-muscular methylprednisolone in osteoarthritis of the hand: an ultrasonographic study. Rheumatology (Oxford). 2010;49(6):1093–100.CrossRef

57.

Conaghan PG, Cohen S, Jordan J, et al. Sustained and profound analgesic benefits in people with osteoarthritis of the knee using FX006, an intra-articular extended-release formulation of triamcinolone acetonide: results from a double-blind, randomized, parallel-group, dose-ranging study. Osteoarthritis Cartilage. 2016;24:S49–50.CrossRef

58.

Wenham CY, Grainger AJ, Hensor EM, et al. Methotrexate for pain relief in knee osteoarthritis: an open-label study. Rheumatology (Oxford). 2013;52(5):888–92.CrossRef

59.

Wenham CY, McDermott M, Conaghan PG. Biological therapies in osteoarthritis. Curr Pharm Des. 2015;21(17):2206–15.CrossRefPubMed

60.

Kloppenburg M, Ramonda R, Kwok W-Y, et al. OP0095 Randomized, placebo-controlled trial to evaluate clinical efficacy and structure modifying properties of subcutaneous etanercept (ETN) in patients with erosive inflammatory hand osteoarthritis (OA). Ann Rheum Dis. 2016;75 Suppl 2:90–1.CrossRef

61.

Larsson S, Englund M, Struglics A, et al. Interleukin-6 and tumor necrosis factor alpha in synovial fluid are associated with progression of radiographic knee osteoarthritis in subjects with previous meniscectomy. Osteoarthritis Cartilage. 2015;23(11):1906–14.CrossRefPubMed

62.

Hayashi D, Roemer FW, Katur A, et al. Imaging of synovitis in osteoarthritis: current status and outlook. Semin Arthritis Rheum. 2011;41(2):116–30.CrossRefPubMed

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