Abstract
Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder that occurs in patients with psoriasis and predominantly affects musculoskeletal structures, skin, and nails. The etiology of PsA is not well understood but evidence supports an interplay of genetic, immunologic, and environmental factors which promote pathological bone remodeling and joint damage in PsA. Localized and systemic bone loss due to increased activity of osteoclasts is well established in PsA based on animal models and translational studies. In contrast, the mechanisms responsible for pathological bone remodeling in PsA remain enigmatic although new candidate molecules and pathways have been identified. Recent reports have revealed novel findings related to bone erosion and pathologic bone formation in PsA. Many associated risk factors and contributing molecular mechanisms have also been identified. In this review, we discuss new developments in the field, point out unresolved questions regarding the pathogenetic origins of the wide array of bone phenotypes in PsA, and discuss new directions for investigation.
Similar content being viewed by others
References
Rachakonda TD, Schupp CW, Armstrong AW (2014) Psoriasis prevalence among adults in the United States. J Am Acad Dermatol 70:512–516
Ritchlin CT, Colbert RA, Gladman DD (2017) Psoriatic arthritis. N Engl J Med 376:2095–2096
Haroon M, Gallagher P, FitzGerald O (2015) Diagnostic delay of more than 6 months contributes to poor radiographic and functional outcome in psoriatic arthritis. Ann Rheum Dis 74:1045–1050
Paparo F, Revelli M, Semprini A, Camellino D, Garlaschi A, Cimmino MA, Rollandi GA, Leone A (2014) Seronegative spondyloarthropathies: what radiologists should know. Radiol Med 119:156–163
Narvaez J, Narvaez JA, de Albert M, Gomez-Vaquero C, Nolla JM (2012) Can magnetic resonance imaging of the hand and wrist differentiate between rheumatoid arthritis and psoriatic arthritis in the early stages of the disease? Semin Arthritis Rheum 42:234–245
Brockbank JE, Stein M, Schentag CT, Gladman DD (2005) Dactylitis in psoriatic arthritis: a marker for disease severity? Ann Rheum Dis 64:188–190
Simon D, Faustini F, Kleyer A, Haschka J, Englbrecht M, Kraus S, Hueber AJ, Kocijan R, Sticherling M, Schett G et al (2016) Analysis of periarticular bone changes in patients with cutaneous psoriasis without associated psoriatic arthritis. Ann Rheum Dis 75:660–666
Llopis E, Kroon HM, Acosta J, Bloem JL (2017) Conventional radiology in rheumatoid arthritis. Radiol Clin North Am 55:917–941
Stavre Z, Upchurch K, Kay J, Gravallese EM (2016) Differential effects of inflammation on bone and response to biologics in rheumatoid arthritis and spondyloarthritis. Curr Rheumatol Rep 18:72
Siannis F, Farewell VT, Cook RJ, Schentag CT, Gladman DD (2006) Clinical and radiological damage in psoriatic arthritis. Ann Rheum Dis 65:478–481
Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473:139–146
Paine A, Ritchlin C (2016) Bone remodeling in psoriasis and psoriatic arthritis: an update. Curr Opin Rheumatol 28:66–75
Sudol-Szopinska I, Matuszewska G, Kwiatkowska B, Pracon G (2016) Diagnostic imaging of psoriatic arthritis. Part I: etiopathogenesis, classifications and radiographic features. J Ultrason 16:65–77
Wright V (1978) Seronegative polyarthritis: a unified concept. Arthritis Rheum 21:619–633
McGonagle D (2005) Imaging the joint and enthesis: insights into pathogenesis of psoriatic arthritis. Ann Rheum Dis 64(Suppl 2):ii58–i60
Goldring SR (2016) Differential mechanisms of de-regulated bone formation in rheumatoid arthritis and spondyloarthritis. Rheumatology 55:ii56–ii60
Szentpetery A, Heffernan E, Haroon M, Kilbane M, Gallagher P, McKenna MJ, FitzGerald O (2016) Striking difference of periarticular bone density change in early psoriatic arthritis and rheumatoid arthritis following anti-rheumatic treatment as measured by digital X-ray radiogrammetry. Rheumatology 55:891–896
Finzel S, Englbrecht M, Engelke K, Stach C, Schett G (2011) A comparative study of periarticular bone lesions in rheumatoid arthritis and psoriatic arthritis. Ann Rheum Dis 70:122–127
Ogdie A, Harter L, Shin D, Baker J, Takeshita J, Choi HK, Love TJ, Gelfand JM (2017) The risk of fracture among patients with psoriatic arthritis and psoriasis: a population-based study. Ann Rheum Dis 76:882–885
Reddy SM, Anandarajah AP, Fisher MC, Mease PJ, Greenberg JD, Kremer JM, Reed G, Chen R, Messing S, Kaukeinen K et al (2010) Comparative analysis of disease activity measures, use of biologic agents, body mass index, radiographic features, and bone density in psoriatic arthritis and rheumatoid arthritis patients followed in a large U.S. disease registry. J Rheumatol 37:2566–2572
Modalsli EH, Asvold BO, Romundstad PR, Langhammer A, Hoff M, Forsmo S, Naldi L, Saunes M (2017) Psoriasis, fracture risk and bone mineral density: the HUNT Study, Norway. Br J Dermatol 176:1162–1169
Chandran S, Aldei A, Johnson SR, Cheung AM, Salonen D, Gladman DD (2016) Prevalence and risk factors of low bone mineral density in psoriatic arthritis: A systematic review. Semin Arthritis Rheum 46:174–182
Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H (2016) RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. Ann Rheum Dis 75:1187–1195
Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM (2003) Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Investig 111:821–831
Amin TE, ElFar NN, Ghaly NR, Hekal MM, Hassan AM, Elsaadany HM (2016) Serum level of receptor activator of nuclear factor kappa-B ligand in patients with psoriasis. Int J Dermatol 55:e227–e233
Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Investig 106:1481–1488
Zhao B, Grimes SN, Li S, Hu X, Ivashkiv LB (2012) TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J. J Exp Med 209:319–334
Yarilina A, Xu K, Chen J, Ivashkiv LB (2011) TNF activates calcium-nuclear factor of activated T cells (NFAT)c1 signaling pathways in human macrophages. Proc Natl Acad Sci USA 108:1573–1578
Yao Z, Li P, Zhang Q, Schwarz EM, Keng P, Arbini A, Boyce BF, Xing L (2006) Tumor necrosis factor-alpha increases circulating osteoclast precursor numbers by promoting their proliferation and differentiation in the bone marrow through up-regulation of c-Fms expression. J Biol Chem 281:11846–11855
Partsch G, Wagner E, Leeb BF, Dunky A, Steiner G, Smolen JS (1998) Upregulation of cytokine receptors sTNF-R55, sTNF-R75, and sIL-2R in psoriatic arthritis synovial fluid. J Rheumatol 25:105–110
Anandarajah AP, Schwarz EM, Totterman S, Monu J, Feng CY, Shao T, Haas-Smith SA, Ritchlin CT (2008) The effect of etanercept on osteoclast precursor frequency and enhancing bone marrow oedema in patients with psoriatic arthritis. Ann Rheum Dis 67:296–301
Taurog JD, Chhabra A, Colbert RA (2016) Ankylosing spondylitis and axial spondyloarthritis. N Engl J Med 375:1303
McEwen C, DiTata D, Lingg C, Porini A, Good A, Rankin T (1971) Ankylosing spondylitis and spondylitis accompanying ulcerative colitis, regional enteritis, psoriasis and Reiter’s disease. A comparative study. Arthritis Rheum 14:291–318
Gladman DD, Brubacher B, Buskila D, Langevitz P, Farewell VT (1993) Differences in the expression of spondyloarthropathy: a comparison between ankylosing spondylitis and psoriatic arthritis. Clin Invest Med 16:1–7
Jadon DR, Sengupta R, Nightingale A, Lindsay M, Korendowych E, Robinson G, Jobling A, Shaddick G, Bi J, Winchester R et al (2017) Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis. Ann Rheum Dis 76:701–707
Helliwell PS, Hickling P, Wright V (1998) Do the radiological changes of classic ankylosing spondylitis differ from the changes found in the spondylitis associated with inflammatory bowel disease, psoriasis, and reactive arthritis? Ann Rheum Dis 57:135–140
Benham H, Norris P, Goodall J, Wechalekar MD, FitzGerald O, Szentpetery A, Smith M, Thomas R, Gaston H (2013) Th17 and Th22 cells in psoriatic arthritis and psoriasis. Arthritis Res Ther 15:R136
Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT et al (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Investig 103:1345–1352
Zheng L, Wang W, Ni J, Mao X, Song D, Liu T, Wei J, Zhou H (2017) Role of autophagy in tumor necrosis factor-alpha-induced apoptosis of osteoblast cells. J Investig Med 65:1014–1020
Yago T, Nanke Y, Ichikawa N, Kobashigawa T, Mogi M, Kamatani N, Kotake S (2009) IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17. J Cell Biochem 108:947–955
Kitami S, Tanaka H, Kawato T, Tanabe N, Katono-Tani T, Zhang F, Suzuki N, Yonehara Y, Maeno M (2010) IL-17A suppresses the expression of bone resorption-related proteinases and osteoclast differentiation via IL-17RA or IL-17RC receptors in RAW264.7 cells. Biochimie 92:398–404
van der Heijde D, Landewe RB, Mease PJ, McInnes IB, Conaghan PG, Pricop L, Ligozio G, Richards HB, Mpofu S (2016) Brief report: secukinumab provides significant and sustained inhibition of joint structural damage in a phase III study of active psoriatic arthritis. Arthritis Rheumatol 68:1914–1921
van Kuijk AW, Reinders-Blankert P, Smeets TJ, Dijkmans BA, Tak PP (2006) Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment. Ann Rheum Dis 65:1551–1557
Celis R, Planell N, Fernandez-Sueiro JL, Sanmarti R, Ramirez J, Gonzalez-Alvaro I, Pablos JL, Canete JD (2012) Synovial cytokine expression in psoriatic arthritis and associations with lymphoid neogenesis and clinical features. Arthritis Res Ther 14:R93
Kudo O, Sabokbar A, Pocock A, Itonaga I, Fujikawa Y, Athanasou NA (2003) Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism. Bone 32:1–7
Ogata A, Kumanogoh A, Tanaka T (2012) Pathological role of interleukin-6 in psoriatic arthritis. Arthritis 2012:713618
Mease PJ, Gottlieb AB, Berman A, Drescher E, Xing J, Wong R, Banerjee S (2016) The efficacy and safety of clazakizumab, an anti-interleukin-6 monoclonal antibody, in a Phase IIB study of adults with active psoriatic arthritis. Arthritis Rheumatol 68:2163–2173
Yokota K, Sato K, Miyazaki T, Kitaura H, Kayama H, Miyoshi F, Araki Y, Akiyama Y, Takeda K, Mimura T (2014) Combination of tumor necrosis factor alpha and interleukin-6 induces mouse osteoclast-like cells with bone resorption activity both in vitro and in vivo. Arthritis Rheumatol 66:121–129
O’Brien W, Fissel BM, Maeda Y, Yan J, Ge X, Gravallese EM, Aliprantis AO, Charles JF (2016) RANK-independent osteoclast formation and bone erosion in inflammatory arthritis. Arthritis Rheumatol 68:2889–2900
Polachek A, Li S, Chandran V, Gladman DD (2016) Clinical enthesitis in a prospective longitudinal psoriatic arthritis cohort: incidence, prevalence, characteristics, and outcome. Arthritis Care Res (Hoboken) 69:1685–1691
Gladman DD (2006) Clinical, radiological, and functional assessment in psoriatic arthritis: is it different from other inflammatory joint diseases? Ann Rheum Dis 65(Suppl 3):iii22–i24
Ory PA, Gladman DD, Mease PJ (2005) Psoriatic arthritis and imaging. Ann Rheum Dis 64(Suppl 2):ii55–i57
Schett G, Coates LC, Ash ZR, Finzel S, Conaghan PG (2011) Structural damage in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: traditional views, novel insights gained from TNF blockade, and concepts for the future. Arthritis Res Ther 13(Suppl 1):S4
Cao X, Chen D (2005) The BMP signaling and in vivo bone formation. Gene 357:1–8
Yuan TL, Chen J, Tong YL, Zhang Y, Liu YY, Wei JC, Liu Y, Zhao Y, Herrmann M (2016) Serum heme oxygenase-1 and BMP-7 are potential biomarkers for bone metabolism in patients with rheumatoid arthritis and ankylosing Spondylitis. Biomed Res Int 2016:7870925
Lories RJ, Derese I, Luyten FP (2005) Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J Clin Investig 115:1571–1579
Abd-Elsalam N, Kamel N, Zamzam M, El-Hilaly R, Sobhib M, Sabryc M (2013) The relation between serum bone morphogenetic protein-7 and severity of enthesitis in psoriatic arthritis. Egypt Rheumatol Rehabil 40:129–133
Lories RJ, Matthys P, de Vlam K, Derese I, Luyten FP (2004) Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Ann Rheum Dis 63:595–598
Lin GL, Hankenson KD (2011) Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J Cell Biochem 112:3491–3501
Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky MS, Dwyer D, Korb A, Smolen J, Hoffmann M, Scheinecker C et al (2007) Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13:156–163
Rossini M, Viapiana O, Adami S, Fracassi E, Idolazzi L, Dartizio C, Povino MR, Orsolini G, Gatti D (2015) In patients with rheumatoid arthritis, Dickkopf-1 serum levels are correlated with parathyroid hormone, bone erosions and bone mineral density. Clin Exp Rheumatol 33:77–83
Heiland GR, Appel H, Poddubnyy D, Zwerina J, Hueber A, Haibel H, Baraliakos X, Listing J, Rudwaleit M, Schett G et al (2012) High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis. Ann Rheum Dis 71:572–574
Fassio A, Idolazzi L, Viapiana O, Benini C, Vantaggiato E, Bertoldo F, Rossini M, Gatti D (2017) In psoriatic arthritis Dkk-1 and PTH are lower than in rheumatoid arthritis and healthy controls. Clin Rheumatol 36:2377–2381
Dalbeth N, Pool B, Smith T, Callon KE, Lobo M, Taylor WJ, Jones PB, Cornish J, McQueen FM (2010) Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion. Arthritis Res Ther 12:R164
Daoussis D, Liossis SN, Solomou EE, Tsanaktsi A, Bounia K, Karampetsou M, Yiannopoulos G, Andonopoulos AP (2010) Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthritis Rheum 62:150–158
Gilbert L, He X, Farmer P, Boden S, Kozlowski M, Rubin J, Nanes MS (2000) Inhibition of osteoblast differentiation by tumor necrosis factor-alpha. Endocrinology 141:3956–3964
Gilbert L, He X, Farmer P, Rubin J, Drissi H, van Wijnen AJ, Lian JB, Stein GS, Nanes MS (2002) Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2alpha A) is inhibited by tumor necrosis factor-alpha. J Biol Chem 277:2695–2701
Lu X, Gilbert L, He X, Rubin J, Nanes MS (2006) Transcriptional regulation of the osterix (Osx, Sp7) promoter by tumor necrosis factor identifies disparate effects of mitogen-activated protein kinase and NF kappa B pathways. J Biol Chem 281:6297–6306
Ghali O, Chauveau C, Hardouin P, Broux O, Devedjian JC (2010) TNF-alpha’s effects on proliferation and apoptosis in human mesenchymal stem cells depend on RUNX2 expression. J Bone Miner Res 25:1616–1626
Gilbert LC, Rubin J, Nanes MS (2005) The p55 TNF receptor mediates TNF inhibition of osteoblast differentiation independently of apoptosis. Am J Physiol Endocrinol Metab 288:E1011–E1018
Hess K, Ushmorov A, Fiedler J, Brenner RE, Wirth T (2009) TNFalpha promotes osteogenic differentiation of human mesenchymal stem cells by triggering the NF-kappaB signaling pathway. Bone 45:367–376
Lu Z, Wang G, Dunstan CR, Zreiqat H (2012) Short-term exposure to tumor necrosis factor-alpha enables human osteoblasts to direct adipose tissue-derived mesenchymal stem cells into osteogenic differentiation. Stem Cells Dev 21:2420–2429
Marupanthorn K, Tantrawatpan C, Tantikanlayaporn D, Kheolamai P, Manochantr S (2015) The effects of TNF-alpha on osteogenic differentiation of umbilical cord derived mesenchymal stem cells. J Med Assoc Thai 98(Suppl 3):S34–S40
Cho HH, Shin KK, Kim YJ, Song JS, Kim JM, Bae YC, Kim CD, Jung JS (2010) NF-kappaB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression. J Cell Physiol 223:168–177
Glass GE, Chan JK, Freidin A, Feldmann M, Horwood NJ, Nanchahal J (2011) TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc Natl Acad Sci USA 108:1585–1590
Huang H, Zhao N, Xu X, Xu Y, Li S, Zhang J, Yang P (2011) Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells. Cell Prolif 44:420–427
Wang Z, Jia Y, Du F, Chen M, Dong X, Chen Y, Huang W (2017) IL-17A inhibits osteogenic differentiation of bone mesenchymal stem cells via WNT signaling pathway. Med Sci Monit 23:4095–4101
Zhang JR, Pang DD, Tong Q, Liu X, Su DF, Dai SM (2017) Different modulatory effects of IL-17, IL-22, and IL-23 on osteoblast differentiation. Mediators Inflamm 2017:5950395
Osta B, Lavocat F, Eljaafari A, Miossec P (2014) Effects of interleukin-17A on osteogenic differentiation of isolated human mesenchymal stem cells. Front Immunol 5:425
Croes M, Oner FC, van Neerven D, Sabir E, Kruyt MC, Blokhuis TJ, Dhert WJ, Alblas J (2016) Proinflammatory T cells and IL-17 stimulate osteoblast differentiation. Bone 84:262–270
Huang H, Kim HJ, Chang EJ, Lee ZH, Hwang SJ, Kim HM, Lee Y, Kim HH (2009) IL-17 stimulates the proliferation and differentiation of human mesenchymal stem cells: implications for bone remodeling. Cell Death Differ 16:1332–1343
Huang W, La Russa V, Alzoubi A, Schwarzenberger P (2006) Interleukin-17A: a T-cell-derived growth factor for murine and human mesenchymal stem cells. Stem Cells 24:1512–1518
Kocic J, Santibanez JF, Krstic A, Mojsilovic S, Dordevic IO, Trivanovic D, Ilic V, Bugarski D (2012) Interleukin 17 inhibits myogenic and promotes osteogenic differentiation of C2C12 myoblasts by activating ERK1,2. Biochim Biophys Acta 1823:838–849
Nam D, Mau E, Wang Y, Wright D, Silkstone D, Whetstone H, Whyne C, Alman B (2012) T-lymphocytes enable osteoblast maturation via IL-17F during the early phase of fracture repair. PLoS One 7:e40044
Shaw AT, Maeda Y, Gravallese EM (2016) IL-17A deficiency promotes periosteal bone formation in a model of inflammatory arthritis. Arthritis Res Ther 18:104
Uluckan O, Jimenez M, Karbach S, Jeschke A, Grana O, Keller J, Busse B, Croxford AL, Finzel S, Koenders M et al (2016) Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts. Sci Transl Med 8:330ra337
Ono T, Okamoto K, Nakashima T, Nitta T, Hori S, Iwakura Y, Takayanagi H (2016) IL-17-producing gammadelta T cells enhance bone regeneration. Nat Commun 7:10928
Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, Gorman DM, Bowman EP, McClanahan TK, Yearley JH et al (2012) IL-23 induces spondyloarthropathy by acting on ROR-gammat + CD3 + CD4-CD8- entheseal resident T cells. Nat Med 18:1069–1076
El-Zayadi AA, Jones EA, Churchman SM, Baboolal TG, Cuthbert RJ, El-Jawhari JJ, Badawy AM, Alase AA, El-Sherbiny YM, McGonagle D (2017) Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology 56:488–493
O’Rielly DD, Rahman P (2015) Genetic, epigenetic and pharmacogenetic aspects of psoriasis and psoriatic arthritis. Rheum Dis Clin North Am 41:623–642
Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD (1973) Ankylosing spondylitis and HL-A 27. Lancet 1:904–907
FitzGerald O, Haroon M, Giles JT, Winchester R (2015) Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Res Ther 17:115
Bowes J, Ashcroft J, Dand N, Jalali-Najafabadi F, Bellou E, Ho P, Marzo-Ortega H, Helliwell PS, Feletar M, Ryan AW et al (2017) Cross-phenotype association mapping of the MHC identifies genetic variants that differentiate psoriatic arthritis from psoriasis. Ann Rheum Dis 76:1774–1779
Ogdie A, Weiss P (2015) The epidemiology of psoriatic arthritis. Rheum Dis Clin North Am 41:545–568
Raimondo A, Lembo S, Di Caprio R, Donnarumma G, Monfrecola G, Balato N, Ayala F, Balato A (2017) Psoriatic cutaneous inflammation promotes human monocyte differentiation into active osteoclasts, facilitating bone damage. Eur J Immunol 47:1062–1074
Yamamoto M, Nakajima K, Takaishi M, Kitaba S, Magata Y, Kataoka S, Sano S (2015) Psoriatic inflammation facilitates the onset of arthritis in a mouse model. J Investig Dermatol 135:445–453
Sagi L, Trau H (2011) The Koebner phenomenon. Clin Dermatol 29:231–236
Punzi L, Pianon M, Bertazzolo N, Fagiolo U, Rizzi E, Rossini P, Todesco S (1998) Clinical, laboratory and immunogenetic aspects of post-traumatic psoriatic arthritis: a study of 25 patients. Clin Exp Rheumatol 16:277–281
McGonagle D, Ash Z, Dickie L, McDermott M, Aydin SZ (2011) The early phase of psoriatic arthritis. Ann Rheum Dis 70(Suppl 1):i71–i76
Thorarensen SM, Lu N, Ogdie A, Gelfand JM, Choi HK, Love TJ (2017) Physical trauma recorded in primary care is associated with the onset of psoriatic arthritis among patients with psoriasis. Ann Rheum Dis 76:521–525
Round JL, Mazmanian SK (2009) The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9:313–323
Horta-Baas G, Romero-Figueroa MDS, Montiel-Jarquin AJ, Pizano-Zarate ML, Garcia-Mena J, Ramirez-Duran N (2017) Intestinal dysbiosis and rheumatoid arthritis: a link between gut microbiota and the pathogenesis of rheumatoid arthritis. J Immunol Res 2017:4835189
Diamanti AP, Manuela Rosado M, Lagana B, D’Amelio R (2016) Microbiota and chronic inflammatory arthritis: an interwoven link. J Transl Med 14:233
Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernandez-Sueiro JL, Balish E, Hammer RE (1994) The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med 180:2359–2364
Manasson J, Scher JU (2015) Spondyloarthritis and the microbiome: new insights from an ancient hypothesis. Curr Rheumatol Rep 17:10
Scher JU, Littman DR, Abramson SB (2016) Microbiome in Inflammatory Arthritis and Human Rheumatic Diseases. Arthritis Rheumatol 68:35–45
Costello ME, Ciccia F, Willner D, Warrington N, Robinson PC, Gardiner B, Marshall M, Kenna TJ, Triolo G, Brown MA (2015) Brief report: intestinal dysbiosis in ankylosing spondylitis. Arthritis Rheumatol 67:686–691
Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T et al (2015) Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol 67:128–139
Ciccia F, Guggino G, Ferrante A, Raimondo S, Bignone R, Rodolico V, Peralta S, Van Tok M, Cannizzaro A, Schinocca C et al (2016) Interleukin-9 overexpression and Th9 polarization characterize the inflamed gut, the synovial tissue, and the peripheral Blood of patients with psoriatic arthritis. Arthritis Rheumatol 68:1922–1931
Elyaman W, Bradshaw EM, Uyttenhove C, Dardalhon V, Awasthi A, Imitola J, Bettelli E, Oukka M, van Snick J, Renauld JC et al (2009) IL-9 induces differentiation of TH17 cells and enhances function of FoxP3 + natural regulatory T cells. Proc Natl Acad Sci USA 106:12885–12890
Kundu-Raychaudhuri S, Abria C, Raychaudhuri SP (2016) IL-9, a local growth factor for synovial T cells in inflammatory arthritis. Cytokine 79:45–51
Love TJ, Zhu Y, Zhang Y, Wall-Burns L, Ogdie A, Gelfand JM, Choi HK (2012) Obesity and the risk of psoriatic arthritis: a population-based study. Ann Rheum Dis 71:1273–1277
Gladman DD, Callen JP (2010) Early-onset obesity and risk for psoriatic arthritis. JAMA 304:787–788
di Minno MN, Peluso R, Iervolino S, Lupoli R, Russolillo A, Scarpa R, di Minno G (2013) Obesity and the prediction of minimal disease activity: a prospective study in psoriatic arthritis. Arthritis Care Res (Hoboken) 65:141–147
Eder L, Thavaneswaran A, Chandran V, Cook RJ, Gladman DD (2015) Obesity is associated with a lower probability of achieving sustained minimal disease activity state among patients with psoriatic arthritis. Ann Rheum Dis 74:813–817
Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y (2014) Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev 13:981–1000
Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J (2003) Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res 11:525–531
Eder L, Jayakar J, Pollock R, Pellett F, Thavaneswaran A, Chandran V, Rosen CF, Gladman DD (2013) Serum adipokines in patients with psoriatic arthritis and psoriasis alone and their correlation with disease activity. Ann Rheum Dis 72:1956–1961
Urruticoechea-Arana A, Martin-Martinez MA, Castaneda S, Piedra CA, Gonzalez-Juanatey C, Llorca J, Diaz-Gonzalez F, Gonzalez-Gay MA, Group CPC (2015) Vitamin D deficiency in chronic inflammatory rheumatic diseases: results of the cardiovascular in rheumatology [CARMA] study. Arthritis Res Ther 17:211
van der Helm-van Mil AH, van der Kooij SM, Allaart CF, Toes RE, Huizinga TW (2008) A high body mass index has a protective effect on the amount of joint destruction in small joints in early rheumatoid arthritis. Ann Rheum Dis 67:769–774
Westhoff G, Rau R, Zink A (2007) Radiographic joint damage in early rheumatoid arthritis is highly dependent on body mass index. Arthritis Rheum 56:3575–3582
Vidal C, Barnetche T, Morel J, Combe B, Daien C (2015) Association of body mass index categories with disease activity and radiographic joint damage in rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol 42:2261–2269
Klein-Wieringa IR, van der Linden MP, Knevel R, Kwekkeboom JC, van Beelen E, Huizinga TW, van der Helm-van Mil A, Kloppenburg M, Toes RE, Ioan-Facsinay A (2011) Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthritis. Arthritis Rheum 63:2567–2574
Giles JT, van der Heijde DM, Bathon JM (2011) Association of circulating adiponectin levels with progression of radiographic joint destruction in rheumatoid arthritis. Ann Rheum Dis 70:1562–1568
Ebina K, Fukuhara A, Ando W, Hirao M, Koga T, Oshima K, Matsuda M, Maeda K, Nakamura T, Ochi T et al (2009) Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction. Clin Rheumatol 28:445–451
Li W, Han J, Qureshi AA (2012) Smoking and risk of incident psoriatic arthritis in US women. Ann Rheum Dis 71:804–808
Tillett W, Jadon D, Shaddick G, Cavill C, Korendowych E, de Vries CS, McHugh N (2013) Smoking and delay to diagnosis are associated with poorer functional outcome in psoriatic arthritis. Ann Rheum Dis 72:1358–1361
Hojgaard P, Glintborg B, Hetland ML, Hansen TH, Lage-Hansen PR, Petersen MH, Holland-Fischer M, Nilsson C, Loft AG, Andersen BN et al (2015) Association between tobacco smoking and response to tumour necrosis factor alpha inhibitor treatment in psoriatic arthritis: results from the DANBIO registry. Ann Rheum Dis 74:2130–2136
Petrescu F, Voican SC, Silosi I (2010) Tumor necrosis factor-alpha serum levels in healthy smokers and nonsmokers. Int J Chron Obstruct Pulmon Dis 5:217–222
Redlich K, Hayer S, Ricci R, David JP, Tohidast-Akrad M, Kollias G, Steiner G, Smolen JS, Wagner EF, Schett G (2002) Osteoclasts are essential for TNF-alpha-mediated joint destruction. J Clin Investig 110:1419–1427
Bond SJ, Farewell VT, Schentag CT, Gladman DD (2007) Predictors for radiological damage in psoriatic arthritis: results from a single centre. Ann Rheum Dis 66:370–376
van der Heijde D, Kavanaugh A, Gladman DD, Antoni C, Krueger GG, Guzzo C, Zhou B, Dooley LT, de Vlam K, Geusens P et al (2007) Infliximab inhibits progression of radiographic damage in patients with active psoriatic arthritis through one year of treatment: Results from the induction and maintenance psoriatic arthritis clinical trial 2. Arthritis Rheum 56:2698–2707
Kavanaugh A, Krueger GG, Beutler A, Guzzo C, Zhou B, Dooley LT, Mease PJ, Gladman DD, de Vlam K, Geusens PP et al (2007) Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann Rheum Dis 66:498–505
Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, Salonen D, Rubenstein J, Sharp JT, Tsuji W (2004) Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 50:2264–2272
Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, Salonen D, Rubenstein J, Sharp JT, Dunn M et al (2006) Continued inhibition of radiographic progression in patients with psoriatic arthritis following 2 years of treatment with etanercept. J Rheumatol 33:712–721
Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, Sharp JT, Ory PA, Perdok RJ, Weinberg MA et al (2005) Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 52:3279–3289
Gladman DD, Mease PJ, Cifaldi MA, Perdok RJ, Sasso E, Medich J (2007) Adalimumab improves joint-related and skin-related functional impairment in patients with psoriatic arthritis: patient-reported outcomes of the Adalimumab Effectiveness in Psoriatic Arthritis Trial. Ann Rheum Dis 66:163–168
Kavanaugh A, Husni ME, Harrison DD, Kim L, Lo KH, Leu JH, Hsia EC (2017) Safety and efficacy of intravenous golimumab in patients with active psoriatic arthritis: Results through week 24 of the GO-VIBRANT study. Arthritis Rheumatol 69:2151–2161
Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, Woltering F, Stach C, Hoepken B, Arledge T et al (2014) Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis 73:48–55
Ritchlin C, Rahman P, Kavanaugh A, McInnes IB, Puig L, Li S, Wang Y, Shen YK, Doyle MK, Mendelsohn AM et al (2014) Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis 73:990–999
McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, Brodmerkel C, Li S, Wang Y, Mendelsohn AM et al (2013) Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 382:780–789
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, van der Heijde D, Landewe R, Conaghan PG, Gottlieb AB et al (2015) Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 386:1137–1146
Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, Landewe R, Nash P, Pricop L, Yuan J et al (2015) Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med 373:1329–1339
Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler CL, Lin CY, Braun DK, Lee CH, Gladman DD et al (2017) Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis 76:79–87
Mease P, Hall S, FitzGerald O, van der Heijde D, Merola JF, Avila-Zapata F, Cieslak D, Graham D, Wang C, Menon S et al (2017) Tofacitinib or adalimumab versus placebo for psoriatic arthritis. N Engl J Med 377:1537–1550
Gladman D, Rigby W, Azevedo VF, Behrens F, Blanco R, Kaszuba A, Kudlacz E, Wang C, Menon S, Hendrikx T et al (2017) Tofacitinib for Psoriatic Arthritis in Patients with an Inadequate Response to TNF Inhibitors. N Engl J Med 377:1525–1536
Kavanaugh A, Ritchlin C, Rahman P, Puig L, Gottlieb AB, Li S, Wang Y, Noonan L, Brodmerkel C, Song M et al (2014) Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials. Ann Rheum Dis 73:1000–1006
Funding
Ananta Paine’s research works are supported by Health Sciences Research Using High Performance Computational Resources (HSCCI) Pilot Grant, Lung Biology Strategic Plan High Risk Project Pilot Research Award, and Department of Medicine Research Pilot Projects Award from University of Rochester. Christopher Ritchlin’s research works are supported by funds from the National Institutes of Health (NIH) AR0169000, P30AR069655, and 5UL1TR000042-09 Grants.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Christopher Ritchlin has research grants from Amgen, Abbvie, and UCB. He is also a consultant for Amgen, Abbvie, Boehringer Ingelheim, Celgene, Janssen, and Novartis. Ananta Paine has no conflicts of interest.
Rights and permissions
About this article
Cite this article
Paine, A., Ritchlin, C. Altered Bone Remodeling in Psoriatic Disease: New Insights and Future Directions. Calcif Tissue Int 102, 559–574 (2018). https://doi.org/10.1007/s00223-017-0380-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00223-017-0380-2