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International Orthopaedics
Published in: International Orthopaedics 10/2013

01-10-2013 | Original Paper

Do synovial leptin levels correlate with pain in end stage arthritis?

Authors: Anne Lübbeke, Axel Finckh, Gabor J. Puskas, Domizio Suva, Alexandre Lädermann, Sylvette Bas, Daniel Fritschy, Cem Gabay, Pierre Hoffmeyer

Published in: International Orthopaedics | Issue 10/2013

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Abstract

Purpose

We evaluated whether synovial fluid (SF) leptin concentrations correlate with pain severity in patients with hip or knee endstage osteoarthritis (OA) and whether they mediate the association between increased joint pain and (1) female gender and (2) obesity.

Methods

We conducted a cross-sectional study including patients with primary hip and knee OA undergoing joint replacement between January and December 2010. SF leptin concentrations obtained on the day of surgery were assessed. Main outcome was pain severity measured pre-operatively using WOMAC and VAS pain scales.

Results

A total of 219 patients were included, 123 hip and 96 knee arthroplasties. Mean age was 72 years, 59 % were women. Mean SF leptin levels were 22.9 (±25.6) ng/ml in women and 5.4 (±5.9) ng/ml in men. Levels >19.6 ng/ml (highest quartile) were significantly associated with increased pain on both WOMAC (mean difference −9.6, 95 % CI −15.1 to −4.0) and VAS scale (mean difference 0.8, 95 % CI 0.2–1.3). Associations remained unchanged after adjusting for age, co-morbidities, contra-lateral arthritic joint, OA site, and disability. The associations observed between increased pain and female gender or obesity were substantially reduced after adjusting for SF leptin.

Conclusion

Joint pain is associated with SF leptin concentrations. Increased pre-operative pain observed in women and obese may be related to high intra-articular leptin levels.
Literature
1.
Creamer P (2004) Current perspectives on the clinical presentation of joint pain in human OA. Novartis Found Symp 260:64–74, discussion 74–8, 100–4, 277–9PubMedCrossRef
2.
Dieppe PA, Lohmander LS (2005) Pathogenesis and management of pain in osteoarthritis. Lancet 365(9463):965–973PubMedCrossRef
3.
Hunter DJ (2009) Insights from imaging on the epidemiology and pathophysiology of osteoarthritis. Radiol Clin North Am 47(4):539–551PubMedCrossRef
4.
Wenham CY, Conaghan PG (2009) Imaging the painful osteoarthritic knee joint: what have we learned? Nat Clin Pract Rheumatol 5(3):149–158PubMedCrossRef
5.
Bedson J, Croft PR (2008) The discordance between clinical and radiographic knee osteoarthritis: a systematic search and summary of the literature. BMC Musculoskelet Disord 9:116PubMedCrossRef
6.
Aspden RM, Scheven BA, Hutchison JD (2001) Osteoarthritis as a systemic disorder including stromal cell differentiation and lipid metabolism. Lancet 357(9262):1118–1120PubMedCrossRef
7.
Dumond H, Presle N, Terlain B, Mainard D et al (2003) Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum 48(11):3118–3129PubMedCrossRef
8.
Figenschau Y, Knutsen G, Shahazeydi S, Johansen O et al (2001) Human articular chondrocytes express functional leptin receptors. Biochem Biophys Res Commun 287(1):190–197PubMedCrossRef
9.
Griffin TM, Huebner JL, Kraus VB, Guilak F (2009) Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum 60(10):2935–2944PubMedCrossRef
10.
Simopoulou T, Malizos KN, Iliopoulos D, Stefanou N et al (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):872–883PubMedCrossRef
11.
de Boer TN, van Spil WE, Huisman AM, Polak AA et al (2012) Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthr Cartil 20(8):846–853PubMedCrossRef
12.
Vuolteenaho K, Koskinen A, Moilanen T, Moilanen E (2012) Leptin levels are increased and its negative regulators, SOCS-3 and sOb-R are decreased in obese patients with osteoarthritis: a link between obesity and osteoarthritis. Ann Rheum Dis 71:1912–1913PubMedCrossRef
13.
Jacobsen S, Sonne-Holm S (2005) Increased body mass index is a predisposition for treatment by total hip replacement. Int Orthop 29(4):229–234PubMedCrossRef
14.
Christensen R, Astrup A, Bliddal H (2005) Weight loss: the treatment of choice for knee osteoarthritis? A randomized trial. Osteoarthr Cartil 13:20–27PubMedCrossRef
15.
Toda Y, Toda T, Takemura S, Wada T et al (1998) Change in body fat, but not body weight or metabolic correlates of obesity, is related to symptomatic relief of obese patients with knee osteoarthritis after a weight control program. J Rheumatol 25:2181–2186PubMed
16.
Miller GD, Nicklas BJ, Loeser RF (2008) Inflammatory biomarkers and physical function in older, obese adults with knee pain and self-reported osteoarthritis after intensive weight-loss therapy. J Am Geriatr Soc 56:644–651PubMedCrossRef
17.
Monzillo LU, Hamdy O, Horton ES, Ledbury S et al (2003) Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res 11:1048–1054PubMedCrossRef
18.
Sheu WH, Chang TM, Lee WJ, Ou HC et al (2008) Effect of weight loss on proinflammatory state of mononuclear cells in obese women. Obesity (Silver Spring) 16:1033–1038CrossRef
19.
Presle N, Pottie P, Dumond H, Guillaume C et al (2006) Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. Osteoarthr Cartil 14:690–695PubMedCrossRef
20.
Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L et al (2007) Studying sex and gender differences in pain and analgesia: a consensus report. Pain 132(Suppl 1):S26–S45PubMedCrossRef
21.
Creamer P, Lethbridge-Cejku M, Hochberg MC (1999) Determinants of pain severity in knee osteoarthritis: effect of demographic and psychosocial variables using 3 pain measures. J Rheumatol 26:1785–1792PubMed
22.
Tonelli SM, Rakel BA, Cooper NA, Angstom WL et al (2011) Women with knee osteoarthritis have more pain and poorer function than men, but similar physical activity prior to total knee replacement. Biol Sex Differ 2:12PubMedCrossRef
23.
Cho HJ, Chang CB, Yoo JH, Kim SJ et al (2010) Gender differences in the correlation between symptom and radiographic severity in patients with knee osteoarthritis. Clin Orthop Relat Res 468:1749–1758PubMedCrossRef
24.
Holtzman J, Saleh K, Kane R (2002) Gender differences in functional status and pain in a Medicare population undergoing elective total hip arthroplasty. Med Care 40:461–470PubMedCrossRef
25.
Katz JN, Wright EA, Guadagnoli E, Liang MH et al (1994) Differences between men and women undergoing major orthopedic surgery for degenerative arthritis. Arthritis Rheum 37:687–694PubMedCrossRef
26.
Lubbeke A, Duc S, Garavaglia G, Finckh A et al (2009) BMI and severity of clinical and radiographic signs of hip osteoarthritis. Obesity (Silver Spring) 17:1414–1419
27.
Bedaiwy MA, Falcone T, Goldberg JM, Sharma RK et al (2006) Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients. Hum Reprod 21:788–791PubMedCrossRef
28.
Lim G, Wang S, Zhang Y, Tian Y et al (2009) Spinal leptin contributes to the pathogenesis of neuropathic pain in rodents. J Clin Invest 119:295–304PubMed
29.
Maeda T, Kiguchi N, Kobayashi Y, Ikuta T et al (2009) Leptin derived from adipocytes in injured peripheral nerves facilitates development of neuropathic pain via macrophage stimulation. Proc Natl Acad Sci USA 106:13076–13081PubMedCrossRef
30.
Tian Y, Wang S, Ma Y, Lim G et al (2011) Leptin enhances NMDA-induced spinal excitation in rats: a functional link between adipocytokine and neuropathic pain. Pain 152:1263–1271PubMedCrossRef
31.
Gandhi R, Takahashi M, Smith H, Rizek R et al (2010) The synovial fluid adiponectin-leptin ratio predicts pain with knee osteoarthritis. Clin Rheumatol 29:1223–1228PubMedCrossRef
32.
Massengale M, Lu B, Pan JJ, Katz JN et al (2012) Adipokine hormones and hand osteoarthritis: radiographic severity and pain. PLoS One 7(10):e47860PubMedCrossRef
33.
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J et al (1988) Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840PubMed
34.
Harris WH (1969) Traumatic arthritis of the hip after dislocation and acetabular fractures: treatment by mold arthroplasty. An end-result study using a new method of result evaluation. J Bone Joint Surg Am 51(4):737–755PubMed
35.
Insall JN, Dorr LD, Scott RD, Scott WN (1989) Rationale of the Knee Society clinical rating system. Clin Orthop Relat Res 248:13–14
36.
Ware J Jr, Kosinski M, Keller SD (1996) A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Med Care 34:220–233PubMedCrossRef
37.
Charnley J (1979) Numerical grading of clinical results. In: Charnley J (ed) Low friction arthroplasty of the hip: Theory and practice. Springer Verlag, Berlin, pp 20–24CrossRef
38.
Kellgren JH, Lawrence JS (1957) Radiological assessment of osteo-arthrosis. Ann Rheum Dis 16(4):494–502PubMedCrossRef
39.
Goldring MB (2009) The link between structural damage and pain in a genetic model of osteoarthritis and intervertebral disc degeneration: a joint misadventure. Arthritis Rheum 60(9):2550–2552PubMedCrossRef
40.
Hunter DJ, McDougall JJ, Keefe FJ (2008) The symptoms of osteoarthritis and the genesis of pain. Rheum Dis Clin North Am 34:623–643PubMedCrossRef
41.
Im HJ, Kim JS, Li X, Kotwal N et al (2010) Alteration of sensory neurons and spinal response to an experimental osteoarthritis pain model. Arthritis Rheum 62:2995–3005PubMedCrossRef
42.
Schaible HG, Ebersberger A, Von Banchet GS (2002) Mechanisms of pain in arthritis. Ann NY Acad Sci 966:343–354PubMedCrossRef
43.
Schaible HG, Richter F, Ebersberger A, Boettger MK et al (2009) Joint pain. Exp Brain Res 196:153–162PubMedCrossRef
44.
Bernotiene E, Palmer G, Gabay C (2006) The role of leptin in innate and adaptive immune responses. Arthritis Res Ther 8:217PubMedCrossRef
45.
Otero M, Lago R, Gomez R, Dieguez C et al (2006) Towards a pro-inflammatory and immunomodulatory emerging role of leptin. Rheumatol (Oxford) 45:944–950CrossRef
46.
Hoff P, Buttgereit F, Burmester GR, Jakstadt M et al (2013) Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytes. Int Orthop 37(1):145–151PubMedCrossRef
47.
Vuolteenaho K, Koskinen A, Kukkonen M, Nieminen R et al (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 2009:345838CrossRef
48.
Hochman JR, French MR, Bermingham SL, Hawker GA (2010) The nerve of osteoarthritis pain. Arthritis Care Res (Hoboken) 62:1019–1023CrossRef
49.
Hochman JR, Gagliese L, Davis AM, Hawker GA (2011) Neuropathic pain symptoms in a community knee OA cohort. Osteoarthr Cartil 19:647–654PubMedCrossRef
50.
Roubos EW, Dahmen M, Kozicz T, Xu L (2012) Leptin and the hypothalamo-pituitary-adrenal stress axis. Gen Comp Endocrinol 177(1):28–36PubMedCrossRef
51.
Dawson J, Fitzpatrick R, Murray D, Carr A (1996) The problem of ‘noise’ in monitoring patient-based outcomes: generic, disease-specific and site-specific instruments for total hip replacement. J Health Serv Res Policy 1:224–231PubMed
52.
Hawker GA, Gignac MA, Badley E, French MR et al (2011) A longitudinal study to explain the pain-depression link in older adults with osteoarthritis. Arthritis Care Res (Hoboken) 63:1382–1390CrossRef
53.
Mallen CD, Peat G, Thomas E, Dunn KM et al (2007) Prognostic factors for musculoskeletal pain in primary care: a systematic review. Br J Gen Pract 57:655–661PubMed
54.
Wylde V, Hewlett S, Learmonth ID, Dieppe P (2011) Persistent pain after joint replacement: prevalence, sensory qualities, and postoperative determinants. Pain 152:566–572PubMedCrossRef
Metadata
Title
Do synovial leptin levels correlate with pain in end stage arthritis?
Authors
Anne Lübbeke
Axel Finckh
Gabor J. Puskas
Domizio Suva
Alexandre Lädermann
Sylvette Bas
Daniel Fritschy
Cem Gabay
Pierre Hoffmeyer
Publication date
01-10-2013
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 10/2013
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-013-1982-6

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