Clinical Rheumatology

, 29:123

Is osteoarthritis a heterogeneous disease that can be stratified into subsets?

  • Jeffrey B. Driban
  • Michael R. Sitler
  • Mary F. Barbe
  • Easwaran Balasubramanian
Review Article

Abstract

Osteoarthritis is a heterogeneous disease characterized by variable clinical features, biochemical/genetic characteristics, and responses to treatments. To optimize palliative effects of current treatments and develop efficacious disease-modifying interventions, treatments may need to be tailored to the individual or a subset of osteoarthritic joints. The purpose of this review is to explore the current literature on the clinical and physiological variability in osteoarthritis and potential for stratifying patients. Several stratifications have been reported, including mechanism of onset, stage of disease progression, involved joints, inflammatory levels, and effusion. Most of these methods revealed two to three unique subsets of osteoarthritis. Osteoarthritic joints may be stratified by an array of variables, some transient and others consistent throughout the disease process. Future research needs to continue to explore stratification techniques since these may be the key to optimizing palliative interventions and developing disease-modifying interventions for subsets within this heterogeneous disease.

Keywords

Diagnosis Stratification Therapeutics 

References

  1. 1.
    Symmons D, Mathers C, Pfleger B. Global burden of osteoarthritis in the year 2000. World Health Organization. Available via URL:http://www.who.int/healthinfo/statistics/bod_osteoarthritis.pdf. Accessed 2008
  2. 2.
    Internet Data Base (IDB). United States Census Bureau. Available via URL:http://www.census.gov/ipc/www/idb/worldpop.html. Accessed 2008
  3. 3.
    Press Release: POP/952. United Nations. Available via URL:http://www.un.org/News/Press/docs//2007/pop952.doc.htm. Accessed 2008
  4. 4.
    Le PC, Reygrobellet C, Gerentes I (2005) Financial cost of osteoarthritis in France. The "COART" France study. Jt Bone Spine 72:567–570CrossRefGoogle Scholar
  5. 5.
    Brown TD, Johnston RC, Saltzman CL, Marsh JL, Buckwalter JA (2006) Posttraumatic osteoarthritis: a first estimate of incidence, prevalence, and burden of disease. J Orthop Trauma 20:739–744CrossRefPubMedGoogle Scholar
  6. 6.
    Zhang W, Moskowitz RW, Nuki G, Abramson S, Altman RD, Arden N et al (2008) OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage 16:137–162CrossRefPubMedGoogle Scholar
  7. 7.
    Bingham CO III, Bird SR, Smugar SS, Xu X, Tershakovec AM (2008) Responder analysis and correlation of outcome measures: pooled results from two identical studies comparing etoricoxib, celecoxib, and placebo in osteoarthritis. Osteoarthritis Cartilage 16:1289–1293CrossRefPubMedGoogle Scholar
  8. 8.
    Kovac SH, Saag KG, Curtis JR, Allison J (2008) Association of health-related quality of life with dual use of prescription and over-the-counter nonsteroidal antiinflammatory drugs. Arthritis Rheum 59:227–233CrossRefPubMedGoogle Scholar
  9. 9.
    Brooks PM (2006) The burden of musculoskeletal disease—a global perspective. Clin Rheumatol 25:778–781CrossRefPubMedGoogle Scholar
  10. 10.
    Hunter DJ, Hellio Le Graverand-Gastineau MP (2008) How close are we to having structure-modifying drugs available? Rheum Dis Clin North Am 34:789–802CrossRefPubMedGoogle Scholar
  11. 11.
    Ciombor DM, Aaron RK, Wang S, Simon B (2003) Modification of osteoarthritis by pulsed electromagnetic field—a morphological study. Osteoarthritis Cartilage 11:455–462CrossRefPubMedGoogle Scholar
  12. 12.
    Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K et al (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29:1039–1049CrossRefPubMedGoogle Scholar
  13. 13.
    Martel-Pelletier J, Lajeunesse D, Fahmi H, Tardif G, Pelletier JP (2006) New thoughts on the pathophysiology of osteoarthritis: one more step toward new therapeutic targets. Curr Rheumatol Rep 8:30–36CrossRefPubMedGoogle Scholar
  14. 14.
    Herrero-Beaumont G, Roman-Blas JA, Castaneda S, Jimenez SA (2009) Primary osteoarthritis no longer primary: three subsets with distinct etiological, clinical, and therapeutic characteristics. Semin Arthritis Rheum. doi:10.1016/j.semarthrit.2009.03.006 PubMedGoogle Scholar
  15. 15.
    Doss F, Menard J, Hauschild M, Kreutzer HJ, Mittlmeier T, Muller-Steinhardt M et al (2007) Elevated IL-6 levels in the synovial fluid of osteoarthritis patients stem from plasma cells. Scand J Rheumatol 36:136–139CrossRefPubMedGoogle Scholar
  16. 16.
    Haynes MK, Hume EL, Smith JB (2002) Phenotypic characterization of inflammatory cells from osteoarthritic synovium and synovial fluids. Clin Immunol 105:315–325CrossRefPubMedGoogle Scholar
  17. 17.
    Roach HI, Aigner T, Soder S, Haag J, Welkerling H (2007) Pathobiology of osteoarthritis: pathomechanisms and potential therapeutic targets. Curr Drug Targets 8:271–282CrossRefPubMedGoogle Scholar
  18. 18.
    Ratcliffe A, Israel HA, Saed-Nejad F, Diamond B (1998) Proteoglycans in the synovial fluid of the temporomandibular joint as an indicator of changes in cartilage metabolism during primary and secondary osteoarthritis. J Oral Maxillofac Surg 56:204–208CrossRefPubMedGoogle Scholar
  19. 19.
    Ostalowska A, Birkner E, Wiecha M, Kasperczyk S, Kasperczyk A, Kapolka D et al (2006) Lipid peroxidation and antioxidant enzymes in synovial fluid of patients with primary and secondary osteoarthritis of the knee joint. Osteoarthritis Cartilage 14:139–145CrossRefPubMedGoogle Scholar
  20. 20.
    Brandt KD, Dieppe P, Radin E (2009) Etiopathogenesis of osteoarthritis. Med Clin North Am 93:1–24 xvCrossRefPubMedGoogle Scholar
  21. 21.
    Englund M, Guermazi A, Gale D, Hunter DJ, Aliabadi P, Clancy M et al (2008) Incidental meniscal findings on knee MRI in middle-aged and elderly persons. N Engl J Med 359:1108–1115CrossRefPubMedGoogle Scholar
  22. 22.
    Carroll GJ, Breidahl WH, Jazayeri J (2009) Confirmation of two major polyarticular osteoarthritis (POA) phenotypes—differentiation on the basis of joint topography. Osteoarthritis Cartilage 17:877–881CrossRefGoogle Scholar
  23. 23.
    Kraus VB, Jordan JM, Doherty M, Wilson AG, Moskowitz R, Hochberg M et al (2007) The Genetics of Generalized Osteoarthritis (GOGO) study: study design and evaluation of osteoarthritis phenotypes. Osteoarthritis Cartilage 15:120–127CrossRefPubMedGoogle Scholar
  24. 24.
    Solovieva S, Kamarainen OP, Hirvonen A, Hamalainen S, Laitala M, Vehmas T et al (2009) Association between interleukin 1 gene cluster polymorphisms and bilateral distal interphalangeal osteoarthritis. J Rheumatol 36:1977–1986CrossRefPubMedGoogle Scholar
  25. 25.
    MacGregor AJ, Li Q, Spector TD, Williams FM (2009) The genetic influence on radiographic osteoarthritis is site specific at the hand, hip and knee. Rheumatology (Oxford) 48:277–280CrossRefGoogle Scholar
  26. 26.
    Chen HC, Shah S, Stabler TV, Li YJ, Kraus VB (2008) Biomarkers associated with clinical phenotypes of hand osteoarthritis in a large multigenerational family: the CARRIAGE family study. Osteoarthritis Cartilage 16:1054–1059CrossRefPubMedGoogle Scholar
  27. 27.
    Huch K (2001) Knee and ankle: human joints with different susceptibility to osteoarthritis reveal different cartilage cellularity and matrix synthesis in vitro. Arch Orthop Trauma Surg 121:301–306CrossRefPubMedGoogle Scholar
  28. 28.
    Emrani PS, Katz JN, Kessler CL, Reichmann WM, Wright EA, McAlindon TE et al (2008) Joint space narrowing and Kellgren–Lawrence progression in knee osteoarthritis: an analytic literature synthesis. Osteoarthritis Cartilage 16:873–882CrossRefPubMedGoogle Scholar
  29. 29.
    Link TM, Steinbach LS, Ghosh S, Ries M, Lu Y, Lane N et al (2003) Osteoarthritis: MR imaging findings in different stages of disease and correlation with clinical findings. Radiology 226:373–381CrossRefPubMedGoogle Scholar
  30. 30.
    Kellgren J, Lawrence J (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16:494–502CrossRefPubMedGoogle Scholar
  31. 31.
    Hart DJ, Spector TD, Brown P, Wilson P, Doyle DV, Silman AJ (1991) Clinical signs of early osteoarthritis: reproducibility and relation to X ray changes in 541 women in the general population. Ann Rheum Dis 50:467–470CrossRefPubMedGoogle Scholar
  32. 32.
    Peterfy CG, Guermazi A, Zaim S, Tirman PF, Miaux Y, White D et al (2004) Whole-Organ Magnetic Resonance Imaging Score (WORMS) of the knee in osteoarthritis. Osteoarthritis Cartilage 12:177–190CrossRefPubMedGoogle Scholar
  33. 33.
    Phan CM, Link TM, Blumenkrantz G, Dunn TC, Ries MD, Steinbach LS et al (2006) MR imaging findings in the follow-up of patients with different stages of knee osteoarthritis and the correlation with clinical symptoms. Eur Radiol 16:608–618CrossRefPubMedGoogle Scholar
  34. 34.
    Aigner T, Fundel K, Saas J, Gebhard PM, Haag J, Weiss T et al (2006) Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum 54:3533–3544CrossRefPubMedGoogle Scholar
  35. 35.
    Gobezie R, Kho A, Krastins B, Sarracino DA, Thornhill TS, Chase M et al (2007) High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis. Arthritis Res Ther 9:R36CrossRefPubMedGoogle Scholar
  36. 36.
    Zien A, Gebhard PM, Fundel K, Aigner T (2007) Phenotyping of chondrocytes in vivo and in vitro using cDNA array technology. Clin Orthop Relat Res 460:226–233PubMedGoogle Scholar
  37. 37.
    Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, Dicarlo EF et al (2009) Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease. Osteoarthritis Cartilage 17:1040–1048CrossRefPubMedGoogle Scholar
  38. 38.
    Honsawek S, Tanavalee A, Sakdinakiattikoon M, Chayanupatkul M, Yuktanandana P (2009) Correlation of plasma and synovial fluid osteopontin with disease severity in knee osteoarthritis. Clin Biochem 42:808–812CrossRefPubMedGoogle Scholar
  39. 39.
    D'Agostino MA, Conaghan P, Le BM, Baron G, Grassi W, Martin-Mola E et al (2005) EULAR report on the use of ultrasonography in painful knee osteoarthritis. Part 1: prevalence of inflammation in osteoarthritis. Ann Rheum Dis 64:1703–1709CrossRefPubMedGoogle Scholar
  40. 40.
    Kornaat PR, Bloem JL, Ceulemans RY, Riyazi N, Rosendaal FR, Nelissen RG et al (2006) Osteoarthritis of the knee: association between clinical features and MR imaging findings. Radiology 239:811–817CrossRefPubMedGoogle Scholar
  41. 41.
    Scott-Lennox JA, Laughlin-Miley C, Lennox RD, Bohlig AM, Cutler BL, Yan C et al (2001) Stratification of flare intensity identifies placebo responders in a treatment efficacy trial of patients with osteoarthritis. Arthritis Rheum 44:1599–1607CrossRefPubMedGoogle Scholar
  42. 42.
    Toncheva A, Remichkova M, Ikonomova K, Dimitrova P, Ivanovska N (2009) Inflammatory response in patients with active and inactive osteoarthritis. Rheumatol Int 29:1197–1203CrossRefPubMedGoogle Scholar
  43. 43.
    Pearle AD, Scanzello CR, George S, Mandl LA, Dicarlo EF, Peterson M et al (2007) Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis Cartilage 15:516–523CrossRefPubMedGoogle Scholar
  44. 44.
    Eckstein F, Wirth W, Hudelmaier MI, Maschek S, Hitzl W, Wyman BT et al (2009) Relationship of compartment-specific structural knee status at baseline with change in cartilage morphology: a prospective observational study using data from the osteoarthritis initiative. Arthritis Res Ther 11:R90CrossRefPubMedGoogle Scholar
  45. 45.
    Dam EB, Loog M, Christiansen C, Byrjalsen I, Folkesson J, Nielsen M et al (2009) Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers. Arthritis Res Ther 11:R115CrossRefPubMedGoogle Scholar
  46. 46.
    Gineyts E, Mo JA, Ko A, Henriksen DB, Curtis SP, Gertz BJ et al (2004) Effects of ibuprofen on molecular markers of cartilage and synovium turnover in patients with knee osteoarthritis. Ann Rheum Dis 63:857–861CrossRefPubMedGoogle Scholar
  47. 47.
    Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA et al (2008) Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: part II. Arthritis Rheum 58:26–35CrossRefPubMedGoogle Scholar
  48. 48.
    Amin S, Baker K, Niu J, Clancy M, Goggins J, Guermazi A et al (2009) Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis. Arthritis Rheum 60:189–198CrossRefPubMedGoogle Scholar
  49. 49.
    Barker K, Lamb SE, Toye F, Jackson S, Barrington S (2004) Association between radiographic joint space narrowing, function, pain and muscle power in severe osteoarthritis of the knee. Clin Rehabil 18:793–800CrossRefPubMedGoogle Scholar
  50. 50.
    Jordan KM, Arden NK, Doherty M, Bannwarth B, Bijlsma JW, Dieppe P et al (2003) EULAR Recommendations 2003: an evidence based approach to the management of knee osteoarthritis: report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Ann Rheum Dis 62:1145–1155CrossRefPubMedGoogle Scholar
  51. 51.
    [No authors listed] (2000) Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 43(9):1905–1915Google Scholar
  52. 52.
    Noack W, Fischer M, Forster KK, Rovati LC, Setnikar I (1994) Glucosamine sulfate in osteoarthritis of the knee. Osteoarthritis Cartilage 2:51–59CrossRefPubMedGoogle Scholar
  53. 53.
    Walker JS, Sheather-Reid RB, Carmody JJ, Vial JH, Day RO (1997) Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis: support for the concept of "responders" and "nonresponders". Arthritis Rheum 40:1944–1954CrossRefPubMedGoogle Scholar
  54. 54.
    Lavigne P, Benderdour M, Lajeunesse D, Shi Q, Fernandes JC (2004) Expression of ICAM-1 by osteoblasts in healthy individuals and in patients suffering from osteoarthritis and osteoporosis. Bone 35:463–470CrossRefPubMedGoogle Scholar
  55. 55.
    Massicotte F, Fernandes JC, Martel-Pelletier J, Pelletier JP, Lajeunesse D (2006) Modulation of insulin-like growth factor 1 levels in human osteoarthritic subchondral bone osteoblasts. Bone 38:333–341CrossRefPubMedGoogle Scholar
  56. 56.
    Massicotte F, Lajeunesse D, Benderdour M, Pelletier JP, Hilal G, Duval N et al (2002) Can altered production of interleukin-1beta, interleukin-6, transforming growth factor-beta and prostaglandin E(2) by isolated human subchondral osteoblasts identify two subgroups of osteoarthritic patients. Osteoarthritis Cartilage 10:491–500CrossRefPubMedGoogle Scholar
  57. 57.
    Tat SK, Pelletier JP, Lajeunesse D, Fahmi H, Duval N, Martel-Pelletier J (2008) Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. Bone 43:284–291CrossRefPubMedGoogle Scholar
  58. 58.
    Tat SK, Pelletier JP, Lajeunesse D, Fahmi H, Lavigne M, Martel-Pelletier J (2008) The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin Exp Rheumatol 26:295–304Google Scholar

Copyright information

© Clinical Rheumatology 2009

Authors and Affiliations

  • Jeffrey B. Driban
    • 1
  • Michael R. Sitler
    • 1
  • Mary F. Barbe
    • 2
    • 3
  • Easwaran Balasubramanian
    • 4
  1. 1.Department of KinesiologyTemple UniversityPhiladelphiaUSA
  2. 2.Department of Physical TherapyTemple UniversityPhiladelphiaUSA
  3. 3.Department of Anatomy and Cell BiologyTemple University School of MedicinePhiladelphiaUSA
  4. 4.Department of Clinical Orthopedic SurgeryTemple UniversityPhiladelphiaUSA

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