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The synovial fluid adiponectin-leptin ratio predicts pain with knee osteoarthritis

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Abstract

The relationship between adipokines, such as leptin and adiponectin, and cartilage degeneration is being increasingly recognized. We asked what the relationship is between these hormones and patient-reported knee osteoarthritis (OA) pain. We collected demographic data, Short Form McGill Pain scores, Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores, and synovial fluid (SF) samples from 60 consecutive patients with severe knee OA at the time of joint replacement surgery. SF samples were analyzed for leptin and adiponectin using specific ELISA. Non-parametric correlations and linear regression modeling were used to identify the relationship between the adipokines and pain levels. The correlations between the individual adipokines and the pain scales were low to moderate and consistently less than that for the corresponding adiponectin/leptin (A/L) ratio. Linear regression modeling showed that the A/L ratio was a significant predictor of a greater level of pain on the MPQ-SF (p = 0.03) but not the WOMAC pain scale (p = 0.77). A greater A/L ratio was associated with less pain with severe knee OA and this metabolic pathway may represent a target for novel therapeutics.

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References

  1. Sowers MF, Yosef M, jamadar D, Jacobson J, Karvonen-gutierrez C, Jaffe M (2008) BMI vs. body composition and radiographically defined osteoarthritis of the knee in women: a 4-year follow-up study. Osteoathr Cartil 16(3):367–372

    Article  CAS  Google Scholar 

  2. Grotle M, Hagen KB, Natvig B, Dahl FA, Kvien TK (2008) Obesity and osteoarthritis in knee, hip, and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord 9(1):132

    Article  PubMed  Google Scholar 

  3. Bourne R, Mukhi S, Zhu N, Keresteci M, Marin M (2007) Role of obesity on the risk for total hip or knee arthroplasty. Clin Orthop Relat Res 465:185–188

    PubMed  Google Scholar 

  4. Toussirot E, Streit G, Wendling D (2007) The contribution of adipose tissue and adipokines to inflammation in joint diseases. Curr Med Chem 14(10):1095–1100

    Article  CAS  PubMed  Google Scholar 

  5. Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P (2003) Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum 48(11):3118–3129

    Article  CAS  PubMed  Google Scholar 

  6. Simopoulou T, Malizos KN, Iliopoulos D, Stefanou N, Papatheodorou L, Ioannou M, Tsezou A (2007) Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthr Cartil 15(8):872–883

    Article  CAS  PubMed  Google Scholar 

  7. Otero M, Lago R, Lago F, Reino JJ, Gualillo O (2005) Signaling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1. Arthritis Res Ther 7:581e91

    Article  Google Scholar 

  8. Waldron HA (1997) Association between osteoarthritis of the hand and knee in a population of skeletons from London. Ann Rheum Dis 56:116–118

    Article  CAS  PubMed  Google Scholar 

  9. Hart DJ, Spector TD (1993) The relationship of obesity, fat distribution, and osteoarthritis in women in the general population: the Chingford Study. J Rheumatol 20(2):331–335

    CAS  PubMed  Google Scholar 

  10. Sattar N, Wannamethee G, Sarwar N, Chernova J, Lawlor DA, Kelly A, Wallace AM, Danesh J, Whincup PH (2009) Leptin and coronary heart disease: prospective study and systematic review. J Am Coll Cardiol 53(2):167–175

    Article  CAS  PubMed  Google Scholar 

  11. Soderberg S, Colquhoun D, Keech A, Yallop J, Barnes EH, Pollicino C, Simes J, Tonkin AM, Nestel P (2009) Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men: results from the LIPID study. Int J Obes (Lond) 33(1):123–130

    Article  CAS  Google Scholar 

  12. Liu J, Butler KR, Buxbaum SF, Sung JH, Campbell BW, Taylor HA (2010) Leptinemia and its association with stroke and coronary heart disease in the Jackson Heart Study. Clin Endocrinol 72(1):32–37

    Article  CAS  Google Scholar 

  13. Figenschau Y, Knutsen G, Shahazcydi S, Johansen O, Sveinbjornson B (2001) Human articular chondrocytes express functional leptin receptors. Biochem Biophys Res Commun 287:190–197

    Article  CAS  PubMed  Google Scholar 

  14. Gualillo O, Gonzalez-Juanatey JR, Lago F (2007) The emerging role of adipokines as mediators of cardiovascular diseases: physiological and clinical perspectives. Trends Cardiovasc Med 17:277e85

    Article  Google Scholar 

  15. Lago R, Gomez R, Otero M, Lago F, Gallega R, Dieguez C, Gomez-Reino JJ, Gualillo O (2008) A new player in cartilage homeostatsis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarth Cartil 16:1101–1109

    Article  CAS  Google Scholar 

  16. Norata GD, Raselli S, Grigore L, Garlaschelli K, Dozio E, Magni P, Catapano AL (2007) Leptin:adiponectin ratio is an independent predictor of intima media thickness of the common carotid artery. Stroke 38:2844–2846

    Article  CAS  PubMed  Google Scholar 

  17. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783

    Article  CAS  PubMed  Google Scholar 

  18. Ehling A, Schaffler A, Herfarth H, Tarner IH, Anders S, Distler O, Paul G, Distler J, Gay S, Scholmerich J, Neumann E, Muller-Ladner U (2006) The potential of adiponectin in driving arthritis. J Immunol 176(7):4468–4478

    CAS  PubMed  Google Scholar 

  19. Galluccio E, Piatti P, Citterio L, Lucotti PCG, Setola E, Cassina L, Oldani M, Zavaroni I, Bosi E, Columbo A, Alfieri O, Casari G, Reaven GM, Monti LD (2008) Hyperinsulinemia and impaired leptin-adiponectin ratio associate with endothelial nitric oxide synthase polymorphisms in subjects with in-stent restenosis. Am J Physiol Endocrinol Metab 294:E978–E986

    Article  CAS  PubMed  Google Scholar 

  20. Satoh N, Naruse M, Usui T, Tagami T, Suganami T, Yamada K, Kuzuya H, Shimatsu A, Ogawa Y (2004) Leptin-to-Adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care 27(10):2488–2490

    Article  CAS  PubMed  Google Scholar 

  21. 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. Arthritis Rheum 29:1039–1049

    Article  CAS  PubMed  Google Scholar 

  22. Linn BS, Linn MW, Gurel L (1968) Cumulative illness rating scale. J Am Geriatr Soc 16:622–626

    CAS  PubMed  Google Scholar 

  23. Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, Mulsant B, Reynolds CF 3rd (1992) Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 41:237–248

    Article  CAS  PubMed  Google Scholar 

  24. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW (1998) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes following total hip or knee arthroplasty in osteoarthritis. J Rheumatol 15:1833–1840

    Google Scholar 

  25. Melzack R (1987) The Short-Form McGill Pain Questionnaire. Pain 30:191–197

    Article  CAS  PubMed  Google Scholar 

  26. Creamer P, Lethbridge-Cejku M, Hockberg MC (1999) Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures. J Rheumatol 26(8):1785–1792

    CAS  PubMed  Google Scholar 

  27. Hardie LJ, Rayner DV, Holmes S, Trayhurn P (1996) Circulating leptin levels are modulated by fasting, cold exposure and insulin administration in lean but not Zucker (fa/fa) rats as measured by ELISA. Biochem Biophys Res Commun 223:660–665

    Article  CAS  PubMed  Google Scholar 

  28. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, Marco C, Caro JF (1996) Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 97(5):1344–1347

    Article  CAS  PubMed  Google Scholar 

  29. Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Lawrence Erlbaum, Hillsdale

    Google Scholar 

  30. Harrell FE (2001) Chapter 4.4 Overfitting and limits on number of predictors. In: Multivariable modeling strategies, 2nd edn. Springer, New York

    Google Scholar 

  31. Simopoulou T, Malizos KN, Iliopoulos D, Stefanou N, Papatheodorou L, Ioannou M, Tsezou A (2007) Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarth Cartil 15(8):872–883

    Article  CAS  Google Scholar 

  32. Kumagai S, Kishimoto H, Suwa M, Zou B, Sasaki H (2005) The leptin to adiponectin ratio is a good biomarker for the prevalence of metabolic syndrome, dependent on visceral fat accumulation and endurance fitness in obese patients with diabetes mellitus. Metab Syndr Relat Disord 3(2):85–94

    Article  CAS  PubMed  Google Scholar 

  33. Matsubara M, Maruoka S, Katayose S (2003) Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 148(3):343–350

    Article  CAS  PubMed  Google Scholar 

  34. Otero M, Gomez Reino JJ, Gualillo O (2003) Synergistic induction of nitric oxide synthase type II: in vitro effect of leptin and interferon-γ in human chondrocytes and ATDC5 chondrogenic cells. Arthritis Rheum 48(2):404–409

    Article  CAS  PubMed  Google Scholar 

  35. Otero M, Lago R, Lago F, Reino JJ, Gualillo O (2005) Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1. Arth Res & Therapy 7(3):R581–R591

    Article  Google Scholar 

  36. Goldring MB, Berenbaum F (2004) The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clin Orthop Relat Res 427:S37e46

    Google Scholar 

  37. Tong KM, Shieh DC, Chen CP, Tzeng CY, Wang SP, Huang KC, Chiu YC, Fong YC, Tang CH (2008) Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts. Cell Signal 20(8):1478–1488

    Article  CAS  PubMed  Google Scholar 

  38. Ilipoulos D, Malizos KN, Tsezou A (2007) Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann Rheum Dis 66:1616–1621

    Article  Google Scholar 

  39. Vuolteenaho K, Koskinen A, Kukkonen M, Nieminen R, Paivarinta U, Moilanen T, Moilanen E (2009) Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production. Mediat Inflamm 2009:345838

    Google Scholar 

  40. Chen TH, Chen L, Hsieh MS, Chang CP, Chou DT, Tsai SH (2006) Evidence for a protective role for adiponectin in osteoarthritis. Biochim Biophys Acta 1762(8):711–718

    CAS  PubMed  Google Scholar 

  41. Sturmer T, Brenner H, Koenig W, Gunther KP (2004) Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C Reactive protein. Ann Rheum Dis 63:200–205

    Article  CAS  PubMed  Google Scholar 

  42. Pearle AD, Scanzello CR, George S, Mandl LA, DiCarlo EF, Peterson M, Sculco TP, Crow MK (2007) Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarth Cartil 15:516–523

    Article  CAS  Google Scholar 

  43. Hawker GA, Stewart L, French MR, Cibere J, Jordan JM, March L, Suarez-Almazor M, Gooberman-Hill R (2008) Understanding the pain experience in hip and knee osteoarthritis—an OARSI/OMERACT initiative. Osteoarth Cartil 16:415–422

    Article  CAS  Google Scholar 

  44. Felson DT (2005) The sources of pain in knee osteoarthritis. Curr Opin Rheumatol 17:624–628

    Article  PubMed  Google Scholar 

  45. Kidd BL (2006) Osteoarthritis and joint pain. Pain 123:6–9

    Article  PubMed  Google Scholar 

  46. Spencer EA, Appleby PN, Davey GK, Key TJ (2004) Accuracy of self-reported waist and hip measurements in 4492 EPIC-Oxford participants. Public Health Nutr 7(6):723–727

    Article  PubMed  Google Scholar 

  47. Bolton-Smith C, Woodward M, Tunstall-Pedoe H, Morrison C (2000) Accuracy of the estimated prevalence of obesity from self-reported height and weight in an adult Scottish population. J Epidemiol Community Health 54(2):143–148

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Orthopaedic Surgery, University Health Network, 399 Bathurst Street, East Wing 1-439, Toronto, ON, M5T-2S8, Canada

    Rajiv Gandhi, Holly Smith, Randy Rizek & Nizar N. Mahomed

  2. Department of Surgery, University of Toronto, Toronto, Canda

    Rajiv Gandhi, Holly Smith & Randy Rizek

  3. MaRS Discovery Institute, University of Toronto, Toronto, Canada

    Mark Takahashi

  4. Division of Health Care and Outcomes Research and Arthritis Community Research and Evaluation Unit, Toronto Western Research Institute, Toronto, Canada

    Nizar N. Mahomed

  5. Department of Health Policy, Management and Evaluation and Department of Surgery, University of Toronto, Toronto, Canada

    Nizar N. Mahomed

  6. Toronto Western Hospital, University Health Network, 399 Bathurst Street, East Wing 1-439, Toronto, ON, M5T-2S8, Canada

    Rajiv Gandhi

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  1. Rajiv Gandhi
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  2. Mark Takahashi
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  5. Nizar N. Mahomed
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Correspondence to Rajiv Gandhi.

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Gandhi, R., Takahashi, M., Smith, H. et al. The synovial fluid adiponectin-leptin ratio predicts pain with knee osteoarthritis. Clin Rheumatol 29, 1223–1228 (2010). https://doi.org/10.1007/s10067-010-1429-z

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  • DOI: https://doi.org/10.1007/s10067-010-1429-z

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