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Metabolic Syndrome, Obesity, and Osteoarthritis

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Book cover Diagnosis and Management of Hip Disease

Abstract

Patients with osteoarthritis (OA) experience a high prevalence of cardiovascular comorbidities. Both OA and cardiovascular disease are characterized by obesity, hypertension, type II diabetes, and hypercoagulation and inflammatory proteins. This coincidence has suggested potentially important pathophysiological relationships between OA and the metabolic syndrome (MS). This chapter reviews epidemiologic, pathologic, and physiologic relationships among the MS and OA. Epidemiological and observational evidence suggests associations among OA, vascular pathology, and hypercoagulability. Concordance between peripheral vascular disease and OA is presented including changes in peripheral blood flow and velocity and intimal wall thickness. These observations suggest common mechanisms between OA and peripheral vascular disease as an end product of the MS.

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Abbreviations

BMI:

Body mass index

BMP:

Bone morphogenetic proteins

CRP:

C-reactive protein

ECM:

Extracellular matrix

FGF:

Fibroblast growth factors

GLUT-1:

Glucose transporter-1

HDL:

High-density lipoprotein

HOMA-IR:

Homeostatic model assessment of insulin resistance

IGF-1:

Insulin growth factor-1

IL:

Interleukin

IMT:

Intima-media wall thickness

JSW:

Joint space width

KL:

Kellgren–Lawrence

LA:

Lupus anticoagulant

LS:

Least square

MMP:

Matrix metalloproteinase 9

MRI:

Magnetic resonance imaging

MS:

Metabolic syndrome

NCEP:

National Cholesterol Education Program

NHANES III:

National Health and Nutrition Examination Survey

OA:

Osteoarthritis

PAI-1:

Plasminogen activator inhibitor -1

ROAD:

Research on osteoarthritis/osteoporosis against disability

ROS:

Reactive oxidative species

TGF-β:

Transforming growth factor beta

THR:

Total hip replacements

TKR:

Total knee replacements

TNF-α:

Tumor necrosis alpha

VEGF:

Vascular endothelial growth factor

WHO:

World Health Organization

WOMAC:

Western Ontario and McMaster Universities Arthritis Index

References

  1. Marks R, Allegrante JP. Comorbid disease profiles of adults with end-stage hip osteoarthritis. Med Sci Monit. 2002;8(4):CR305–9.

    PubMed  Google Scholar 

  2. Weinberger M, Tierney WM, Booher P. Common problems experienced by adults with osteoarthritis. Arthritis Care Res. 1989;2(3):94–100.

    Article  CAS  PubMed  Google Scholar 

  3. Conaghan P, Vanharanta H, Dieppe P. Is progressive osteoarthritis an atheromatous vascular disease? Ann Rheum Dis. 2005;64:1539–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Puenpatom RA, Victor TW. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med. 2009;121(6):9–20.

    Article  PubMed  Google Scholar 

  5. Sowers M, Karvonen-Gutierrez CA, Palmieri-Smith R, Jacobson JA, Jiang Y, Ashton-Miller JA. Knee osteoarthritis in obese women with cardiometabolic clustering. Arthritis Rheum. 2009;61(10):1328–36.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Yoshimura N, Muraki S, Oka H, Tanaka S, Kawaguchi H, Nakamura K, et al. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis Cartilage. 2012;20(11):1217–26.

    Article  CAS  PubMed  Google Scholar 

  7. Ghosh P, Cheras PA. Vascular mechanisms in osteoarthritis. Best Pract Res Clin Rheumatol. 2001;15(5):693–709.

    Article  CAS  PubMed  Google Scholar 

  8. Reilly MP, Rader DJ. The metabolic syndrome: more than the sum of its parts? Circulation. 2003;108(13):1546–51.

    Article  PubMed  Google Scholar 

  9. Grundy SM, Brewer Jr HB, Cleeman JI, Smith Jr SC, Lenfant C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation. 2004;109(3):433–8.

    Article  PubMed  Google Scholar 

  10. Pereira RM, de Carvalho JF, Bonfa E. Metabolic syndrome in rheumatological diseases. Autoimmun Rev. 2009;8(5):415–9.

    Article  CAS  PubMed  Google Scholar 

  11. Visser AW, de Mutsert R, le Cessie S, den Heijer M, Rosendaal FR, Kloppenburg M. The relative contribution of mechanical stress and systemic processes in different types of osteoarthritis: the NEO study. Ann Rheum Dis. 2014;20.

    Google Scholar 

  12. Hussain SM, Cicuttini FM, Bell RJ, Robinson PJ, Davis SR, Giles GG, et al. Incidence of total knee and hip replacement for osteoarthritis in relation to circulating sex steroid hormone concentrations in women. Arthritis Rheumatol. 2014;66(8):2144–51.

    Article  PubMed  Google Scholar 

  13. Engstrom G, Gerhardsson de Verdier M, Rollof J, Nilsson PM, Lohmander LS. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study. Osteoarthritis Cartilage. 2009;17(2):168–73.

    Google Scholar 

  14. Gandhi R, Razak F, Davey JR, Mahomed NN. Metabolic syndrome and the functional outcomes of hip and knee arthroplasty. J Rheumatol. 2010;37(9):1917–22.

    Article  PubMed  Google Scholar 

  15. Katz JD, Agrawal S, Velasquez M. Getting to the heart of the matter: osteoarthritis takes its place as part of the metabolic syndrome. Curr Opin Rheumatol. 2010;22(5):512–9.

    Article  PubMed  Google Scholar 

  16. Gustafson B. Adipose tissue, inflammation and atherosclerosis. J Atheroscler Thromb. 2010;17(4):332–41.

    Article  CAS  PubMed  Google Scholar 

  17. Kirilmaz B, Asgun F, Alioglu E, Ercan E, Tengiz I, Turk U, et al. High inflammatory activity related to the number of metabolic syndrome components. J Clin Hypertens (Greenwich). 2010;12(2):136–44.

    Article  CAS  Google Scholar 

  18. Oregon-Romero E, Vazquez-Del Mercado M, Navarro-Hernandez RE, Torres-Carrillo N, Martinez-Bonilla G, Estrada-Garcia I, et al. Tumor necrosis factor receptor 2 M196R polymorphism in rheumatoid arthritis and osteoarthritis: relationship with sTNFR2 levels and clinical features. Rheumatol Int. 2006;27(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  19. Attur M, Belitskaya-Levy I, Oh C, Krasnokutsky S, Greenberg J, Samuels J, et al. Increased interleukin-1beta gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum. 2011;63(7):1908–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Lewis Jr JS, Furman BD, Zeitler E, Huebner JL, Kraus VB, Guilak F, et al. Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL/MpJ mice. Arthritis Rheum. 2013;65(3):660–70.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Loeser RF. Osteoarthritis year in review 2013: biology. Osteoarthritis Cartilage. 2013;21(10):1436–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Davies-Tuck ML, Hanna F, Davis SR, Bell RJ, Davison SL, Wluka AE, et al. Total cholesterol and triglycerides are associated with the development of new bone marrow lesions in asymptomatic middle-aged women – a prospective cohort study. Arthritis Res Ther. 2009;11(6):R181.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Soran N, Altindag O, Cakir H, Celik H, Demirkol A, Aksoy N. Assessment of paraoxonase activities in patients with knee osteoarthritis. Redox Rep. 2008;13(5):194–8.

    Article  CAS  PubMed  Google Scholar 

  25. Findlay DM. Vascular pathology and osteoarthritis. Rheumatology. 2007;46(12):1763–8.

    Article  CAS  PubMed  Google Scholar 

  26. Rosa SC, Goncalves J, Judas F, Mobasheri A, Lopes C, Mendes AF. Impaired glucose transporter-1 degradation and increased glucose transport and oxidative stress in response to high glucose in chondrocytes from osteoarthritic versus normal human cartilage. Arthritis Res Ther. 2009;11(3):R80.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Kim J, Xu M, Xo R, Mates A, Wilson GL, Pearsall AW, et al. Mitochondrial DNA damage is involved in apoptosis caused by pro-inflammatory cytokines in human OA chondrocytes. Osteoarthritis Cartilage. 2010;18(3):424–32.

    Article  CAS  PubMed  Google Scholar 

  28. Lago R, Gomez R, Lago F, Gomez-Reino J, Gualillo O. Leptin beyond body weight regulation—current concepts concerning its role in immune function and inflammation. Cell Immunol. 2008;252(1–2):139–45.

    Article  CAS  PubMed  Google Scholar 

  29. Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, et al. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118–29.

    Article  CAS  PubMed  Google Scholar 

  30. Vuolteenaho K, Koskinen A, Kukkonen M, Nieminen R, Päivärinta U, Moilanen T, et al. Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage—mediator role of NO in leptin-induced, IL-6, and IL-8 production. Mediators Inflamm. 2009;2009:10.

    Article  Google Scholar 

  31. Wildman RP, Kaplan R, Manson JE, Rajkovic A, Connelly SA, Mackey RH, et al. Body size phenotypes and inflammation in the Women's Health Initiative Observational Study. Obesity (Silver Spring). 2011;19(7):1482–91.

    Article  CAS  Google Scholar 

  32. Watt I. Osteoarthritis revisited—again! Skeletal Radiol. 2009;38(5):419–23.

    Article  PubMed  Google Scholar 

  33. Lawrence JS. Hypertension in relation to musculoskeletal disorders. Ann Rheum Dis. 1975;34(5):451–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Philbin EF, Groff GD, Ries MD, Miller TE. Cardiovascular fitness and health in patients with end-stage osteoarthritis. Arthritis Rheum. 1995;38(6):799–805.

    Article  CAS  PubMed  Google Scholar 

  35. Tepper S, Hochberg MC. Factors associated with hip osteoarthritis: data from the First National Health and Nutrition Examination Survey (NHANES-I). Am J Epidemiol. 1993;137(10):1081–8.

    CAS  PubMed  Google Scholar 

  36. Hoeven TA, Kavousi M, Clockaerts S, Kerkhof HJ, van Meurs JB, Franco O, et al. Association of atherosclerosis with presence and progression of osteoarthritis: the Rotterdam Study. Ann Rheum Dis. 2013;72(5):646–51.

    Article  PubMed  Google Scholar 

  37. Boyaci A, Tutoglu A, Boyaci N, Koca I, Aridici R, Daglioglu E, et al. Assessment of lower extremity arterial blood flow in females with knee osteoarthritis. Clin Rheumatol. 2015;34:329–35.

    Article  PubMed  Google Scholar 

  38. Kornaat PR, Sharma R, van der Geest RJ, Lamb HJ, Kloppenburg M, Hellio le Graverand MP, et al. Positive association between increased popliteal artery vessel wall thickness and generalized osteoarthritis: is OA also part of the metabolic syndrome? Skeletal Radiol. 2009;38(12):1147–51.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Holland CK, Brown JM, Scoutt LM, Taylor KJW. Lower extremity volumetric arterial blood flow in normal subjects. Ultrasound Med Biol. 1998;24(8):1079–86.

    Article  CAS  PubMed  Google Scholar 

  40. Cheras PA, Whitaker AN, Blackwell EA, Sinton TJ, Chapman MD, Peacock KA. Hypercoagulability and hypofibrinolysis in primary osteoarthritis. Clin Orthop Relat Res. 1997;(334):57–67.

    Google Scholar 

  41. Schafer K, Fujisawa K, Konstantinides S, Loskutoff D. Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice. FASEB J. 2001;15(10):1840–2.

    CAS  PubMed  Google Scholar 

  42. So AK, Varisco PA, Kemkes-Matthes B, Herkenne-Morard C, Chobaz-Peclat V, Gerster JC, et al. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J Thromb Haemost. 2003;1(12):2510–5.

    Article  CAS  PubMed  Google Scholar 

  43. Mileno MD, Margolis NH, Clark BD, Dinarello CA, Burke JF, Gelfand JA. Coagulation of whole blood stimulates interleukin-1 beta gene expression. J Infect Dis. 1995;172(1):308–11.

    Article  CAS  PubMed  Google Scholar 

  44. Dosne AM, Dubor F, Lutcher F, Parant M, Chedid L. Tumor necrosis factor (TNF) stimulates plasminogen activator inhibitor (PAI) production by endothelial cells and decreases blood fibrinolytic activity in the rat. Thromb Res Suppl. 1988;8:115–22.

    Article  CAS  PubMed  Google Scholar 

  45. Furmaniak-Kazmierczak E, Cooke TD, Manuel R, Scudamore A, Hoogendorn H, Giles AR, et al. Studies of thrombin-induced proteoglycan release in the degradation of human and bovine cartilage. J Clin Invest. 1994;94(2):472–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Martel-Pelletier J, Faure MP, McCollum R, Mineau F, Cloutier JM, Pelletier JP. Plasmin, plasminogen activators and inhibitor in human osteoarthritic cartilage. J Rheumatol. 1991;18(12):1863–71.

    CAS  PubMed  Google Scholar 

  47. Imhof H, Sulzbacher I, Grampp S, Czerny C, Youssefzadeh S, Kainberger F. Subchondral bone and cartilage disease: a rediscovered functional unit. Invest Radiol. 2000;35(10):581–8.

    Article  CAS  PubMed  Google Scholar 

  48. Burr DB. The importance of subchondral bone in osteoarthrosis. Curr Opin Rheumatol. 1998;10(3):256–62.

    Article  CAS  PubMed  Google Scholar 

  49. Gross TS, Akeno N, Clemens TL, Komarova S, Srinivasan S, Weimer DA, et al. Selected Contribution: Osteocytes upregulate HIF-1alpha in response to acute disuse and oxygen deprivation. J Appl Physiol (1985). 2001;90(6):2514–9.

    Google Scholar 

  50. Warren SM, Steinbrech DS, Mehrara BJ, Saadeh PB, Greenwald JA, Spector JA, et al. Hypoxia regulates osteoblast gene expression. J Surg Res. 2001;99(1):147–55.

    Article  CAS  PubMed  Google Scholar 

  51. Hilal G, Martel-Pelletier J, Pelletier JP, Ranger P, Lajeunesse D. Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis. Arthritis Rheum. 1998;41(5):891–9.

    Article  CAS  PubMed  Google Scholar 

  52. Prasadam I, van Gennip S, Friis T, Shi W, Crawford R, Xiao Y. ERK-1/2 and p38 in the regulation of hypertrophic changes of normal articular cartilage chondrocytes induced by osteoarthritic subchondral osteoblasts. Arthritis Rheum. 2010;62(5):1349–60.

    Article  CAS  PubMed  Google Scholar 

  53. Westacott CI, Webb GR, Warnock MG, Sims JV, Elson CJ. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum. 1997;40(7):1282–91.

    Article  CAS  PubMed  Google Scholar 

  54. Sanchez C, Deberg MA, Piccardi N, Msika P, Reginster JY, Henrotin YE. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthritis Cartilage. 2005;13(11):979–87.

    Article  CAS  PubMed  Google Scholar 

  55. Sanchez C, Deberg MA, Piccardi N, Msika P, Reginster JY, Henrotin YE. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthritis Cartilage. 2005;13(11):988–97.

    Article  CAS  PubMed  Google Scholar 

  56. Ashraf S, Walsh DA. Angiogenesis in osteoarthritis. Curr Opin Rheumatol. 2008;20(5):573–80.

    Article  PubMed  Google Scholar 

  57. Murata M, Yudoh K, Masuko K. The potential role of vascular endothelial growth factor (VEGF) in cartilage: how the angiogenic factor could be involved in the pathogenesis of osteoarthritis? Osteoarthritis Cartilage. 2008;16(3):279–86.

    Article  CAS  PubMed  Google Scholar 

  58. Lyons TJ, McClure SF, Stoddart RW, McClure J. The normal human chondro-osseous junctional region: evidence for contact of uncalcified cartilage with subchondral bone and marrow spaces. BMC Musculoskelet Disord. 2006;7:52.

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Family Medicine and Epidemiology, Warren Alpert Medical School of Brown University, Providence, RI, 02906, USA

    Charles Eaton MD

  2. Department of Orthopedics, Warren Alpert Medical School of Brown University, 100 Butler Drive, Providence, RI, 02906, USA

    Roy K. Aaron MD

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  1. Charles Eaton MD
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Correspondence to Roy K. Aaron MD .

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  1. Department of Orthopedics, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA

    Roy K. Aaron

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Eaton, C., Aaron, R.K. (2015). Metabolic Syndrome, Obesity, and Osteoarthritis. In: Aaron, R. (eds) Diagnosis and Management of Hip Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-19905-4_3

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  • DOI: https://doi.org/10.1007/978-3-319-19905-4_3

  • Publisher Name: Springer, Cham

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