International Journal of Biometeorology

, Volume 59, Issue 11, pp 1691–1700 | Cite as

Circulating levels of adiponectin, resistin, and visfatin after mud-bath therapy in patients with bilateral knee osteoarthritis

  • Antonella FioravantiEmail author
  • Chiara Giannitti
  • Sara Cheleschi
  • Antonella Simpatico
  • Nicola Antonio Pascarelli
  • Mauro Galeazzi
Original Paper


Adipocytokines, including adiponectin, resistin, and visfatin may play an important role in the pathophysiology of osteoarthritis (OA). Spa therapy is one of the most commonly used non-pharmacological approaches for OA, but its mechanisms of action are not completely known. The aim of the present study was to assess whether a cycle of mud-bath therapy (MBT) influences the serum levels of adiponectin, resistin, and visfatin in patients with knee OA. As part of a prospective randomized, single blind-controlled trial evaluating the efficacy of MBT in knee OA, we included in this study 95 outpatients. One group (n = 49) received a cycle of MBT at the spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group (control group; n = 46) continued their regular care routine alone. Patients were assessed at basal time and at the end of the study (15 days) for clinical and biochemical parameters. Clinical assessments included spontaneous pain on a visual analog scale (VAS) score and the Western Ontario and McMaster Universities index (WOMAC) subscores for knee OA evaluated as total pain score (W-TPS), total stiffness score (W-TSS), and total physical function score (W-TPFS). Adiponectin, resistin and visfatin serum levels were assessed by enzyme immunoassay methods. At the end of the mud-bath therapy, serum adiponectin levels showed a significant decrease (p < 0.001), while no significant modifications were found in the control group at day 15. Serum resistin showed a significant decrease (p < 0.0001) in the MBT group at the end of the study and a significant increase in the control patients (p < 0.001). No significant modifications of visfatin were found in MBT. Furthermore, we tested the relationships between demographic and clinical parameters and adipocytokine concentrations measured in the MBT group at basal and at the end of the study. In conclusion, the present study shows that a cycle of MBT can modify serum levels of adiponectin and resistin but not the circulating levels of visfatin. In view of the recent evidences about the involvement of adiponectin and resistin in the pathogenesis and progression of OA, the decrease of these adipokines after mud-bath therapy may play a protective role in the course of the disease. However, it remains to be clarified which of the mechanisms of action of MBT may have determined the changes in serum levels of adiponectin and resistin that we observed.


Osteoarthritis Adiponectin Resistin Visfatin Mud-bath therapy 







Tumor necrosis factor-α




Prostaglandin E2


Thrombospondin motifs


Pre-B cell colony-enhancing factor


Nicotinalide phosphoribosyltransferase


Mud-bath therapy


High-sensitivity C-reactive protein


American College of Rheumatology


Body mass index


Non-steroidal anti-inflammatory drugs


Symptomatic slow-acting drugs for OA


Visual analog scale


Western Ontario and McMaster Universities index


Total pain score


Total stiffness score


Total physical function score


High-density lipoprotein cholesterol


Low-density lipoprotein cholesterol


Competing interest statement



This study was funded by Regione Toscana. This study sponsor did not participate in the study design, in the collection, analysis, or the interpretation of data.

Supplementary material

484_2015_977_MOESM1_ESM.docx (12 kb)
ESM 1 (DOCX 12 kb)


  1. Altman R, Asch E, Bloch D 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 29:1039–1049CrossRefGoogle Scholar
  2. Bellamy N (2009) WOMAC osteoarthritis index: user guide IX. WOMAC, QueenslandGoogle Scholar
  3. 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 to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 15:1833–1840Google Scholar
  4. Bellometti S, Cecchettin M, Galzigna L (1997) Mud pack therapy in osteoarthrosis. Changes in serum levels of chondrocyte markers. Clin Chim Acta 268:101–106CrossRefGoogle Scholar
  5. Bellometti S, Galzigna L, Richelmi P, Gregotti C, Bertè F (2002) Both serum receptors of tumor necrosis factor are influenced by mud pack treatment in osteoarthrotic patients. Int J Tissue React 24:57–64Google Scholar
  6. Cantarini L, Brucato A, Simonini G et al (2013) Leptin, adiponectin, resistin, visfatin serum levels and idiopathic recurrent pericarditis: biomarkers of disease activity? A preliminary report. Clin Exp Rheumatol 31:207–212Google Scholar
  7. Cima L, Cozzi F, Giusti P, Guidetti G, Todesco S (1992) Neuroendocrin effects of a cycle of fangotherapy. Pharmacol Rhes 26(suppl 1):302Google Scholar
  8. Conde J, Scotece M, Gómez R, Lopez V, Gómez-Reino JJ, Gualillo O (2011) Adipokines and osteoarthritis: novel molecules involved in the pathogenesis and progression of disease. Arthritis 2011:203901. doi: 10.1155/2011/203901 CrossRefGoogle Scholar
  9. Delaigle AM, Jonas JC, Bauche IB, Cornu O, Brichard SM (2004) Induction of adiponectin in skeletal muscle by inflammatory cytokines: in vivo and in vitro studies. Endocrinology 145:5589–5597CrossRefGoogle Scholar
  10. Fantuzzi G (2005) Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 115:911–919CrossRefGoogle Scholar
  11. Fioravanti A, Cantarini L, Guidelli GM, Galeazzi M (2011a) Mechanisms of action of spa therapies in rheumatic diseases: what scientific evidence is there? Rheumatol Int 31:1–8. doi: 10.1007/s00296-010-1628-6 CrossRefGoogle Scholar
  12. Fioravanti A, Cantarini L, Bacarelli MR, de Lalla A, Ceccatelli L, Blardi P (2011b) Effects of spa therapy on serum leptin and adiponectin levels in patients with knee osteoarthritis. Rheumatol Int 31:879–882. doi: 10.1007/s00296-010-1401-x CrossRefGoogle Scholar
  13. Fioravanti A, Adamczyk P, Pascarelli NA, Giannitti C, Urso R, Tołodziecki M, Ponikowska I (2014) Clinical and biochemical effects of a 3-week program of diet combined with spa therapy in obese and diabetic patients: a pilot open study. Int J BiometeorolGoogle Scholar
  14. Fioravanti A, Bacaro G, Giannitti C, Tenti S, Cheleschi S, Guidelli GM, Pascarelli NA, Galeazzi M (2014) One year follow-up of mud-bath therapy in patients with bilateral knee osteoarthritis: a randomized, single-blind controlled trial. Int J Biometeorol [Accepted]Google Scholar
  15. Francin PJ, Abot A, Guillaume C et al (2014) Association between adiponectin and cartilage degradation in human osteoarthritis. Osteoarthr Cartil 22:519–526. doi: 10.1016/j.joca.2014.01.002 CrossRefGoogle Scholar
  16. Fukuhara A, Matsuda M, Nishizawa M et al (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430CrossRefGoogle Scholar
  17. Gabay O, Berenbaum F (2009) Adipokines in arthritis: new kids on the block. Curr Rheumatol Rev 5:226–232CrossRefGoogle Scholar
  18. Gomez R, Conde J, Scotece M, Gomez-Reino JJ, Lago F, Gualillo O (2011) What’s new in our understanding of the role of adipokines in rheumatic diseases? Nat Rev Rheumatol 7:528–536CrossRefGoogle Scholar
  19. Gonzalez-Gay MA, Llorca J, Garcia-Unzueta MT et al (2008) High-grade inflammation, circulating adiponectin oncentrations and cardiovascular risk factors in severe rheumatoid arthritis. Clin Exp Rheumatol 26:596–603Google Scholar
  20. Goossens GH, Jocken JW, van Baak MA, Jansen EH, Saris WH, Blaak EE (2008) Short-term beta-adrenergic regulation of leptin, adiponectin and interleukin-6 secretion in vivo in lean and obese subjects. Diabetes Obes Metab 10:1029–1038. doi: 10.1111/j.1463-1326.2008.00856.x CrossRefGoogle Scholar
  21. Gosset M, Berenbaum F, Salvat C, Sautet A, Pigenet A, Tahiri K, Jacques C (2008) Crucial role of visfatin/pre-B cell colony enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis. Arthritis Rheum 58:1399–1409. doi: 10.1002/art.23431 CrossRefGoogle Scholar
  22. Hochberg MC, Altman RD, April KT, American College of Rheumatology et al (2012) Recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res 64:465–474CrossRefGoogle Scholar
  23. Hu PF, Bao JP, Wu LD (2011) The emerging role of adipokines in osteoarthritis: a narrative review. Mol Biol Rep 38:873–878. doi: 10.1007/s11033-010-0179-y CrossRefGoogle Scholar
  24. Imbeault P, Dépault I, Haman F (2009) Cold exposure increases adiponectin levels in men. Metabolism 58:552–559. doi: 10.1016/j.metabol.2008.11.017 CrossRefGoogle Scholar
  25. Iwen KA, Wenzel ET, Ott V et al (2011) Cold-induced alteration of adipokine profile in humans. Metabolism 60:430–437. doi: 10.1016/j.metabol.2010.03.011 CrossRefGoogle Scholar
  26. Jankovic A, Korac A, Buzadzic B et al (2013) Endocrine and metabolic signaling in retroperitoneal white adipose tissue remodeling during cold acclimation. J Obes 2013:937572. doi: 10.1155/2013/937572 CrossRefGoogle Scholar
  27. Jensen MP, Karoly P, Braver S (1986) The measurement of clinical pain intensity: a comparison of six methods. Pain 27:117–126CrossRefGoogle Scholar
  28. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792CrossRefGoogle Scholar
  29. Kaser S, Kaser A, Sandhofer A, Ebenbichler CF, Tilg H, Patsch JR (2003) Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro. Biochem Biophys Res Commun 309:286–290CrossRefGoogle Scholar
  30. Kellgren JH, Lawrence JS (1957) Radiological assessment of osteoarthrosis. Ann Rheum Dis 16:494–502CrossRefGoogle Scholar
  31. Koskinen A, Juslin S, Nieminen R, Moilanen T, Vuolteenaho K, Moilanen E (2011) Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen activated protein kinase pathways. Arthritis Res Ther 13:R184. doi: 10.1186/ar3512 CrossRefGoogle Scholar
  32. Koskinen A, Vuolteenaho K, Moilanen T, Moilanen E (2014) Resistin as a factor in osteoarthritis: synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases MMP-1 and MMP-3. Scand J Rheumatol 43:249–253. doi: 10.3109/03009742.2013.853096 CrossRefGoogle Scholar
  33. Laatikainen T, Salminen K, Kohvakka A, Pettersson J (1988) Response of plasma endorphins, prolactin and catecholamines in women to intense heat in a sauna. Eur J Appl Physiol Occup Physiol 57:98–102CrossRefGoogle Scholar
  34. Lago R, Gomez R, Otero M et al (2008) A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthr Cartil 16:1101–1109. doi: 10.1016/j.joca.2007.12.008 CrossRefGoogle Scholar
  35. Laiguillon MC, Houard X, Bougault C et al (2014) Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis. Arthritis Res Ther 16:R38. doi: 10.1186/ar4467 CrossRefGoogle Scholar
  36. Lee JH, Ort T, Ma K et al (2009) Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro. Osteoarthr Cartil 17:613–620. doi: 10.1016/j.joca.2008.08.007 CrossRefGoogle Scholar
  37. Matsuzawa Y (2005) Adiponectin: identification, physiology and clinical relevance in metabolic and vascular disease. Atheroscler Suppl 6:7–14CrossRefGoogle Scholar
  38. McConnell S, Kolopack P, Davis AM (2001) The Western Ontario and McMaster Universities Osteoarthritis index (WOMAC): a review of its utility and measurement properties. Arthritis Rheum 45:453–461CrossRefGoogle Scholar
  39. Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM (1999) Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology 10:161–166CrossRefGoogle Scholar
  40. Ouchi N, Shibata R, Walsh K (2006) Cardioprotection by adiponectin. Trends Cardiovasc Med 16:141–146CrossRefGoogle Scholar
  41. Poonpet T, Honsawek S (2014) Adipokines: biomarkers for osteoarthritis? World J Orthop 5:319–327. doi: 10.5312/wjo.v5.i3.319 CrossRefGoogle Scholar
  42. Presle N, Pottie P, Dumond H et al (2006) Differential distribution of adipokines between plasma and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production. Osteoarthr Cartil 14:690–695CrossRefGoogle Scholar
  43. Puenpatom RA, Victor TW (2009) Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med 121:9–20. doi: 10.3810/pgm.2009.11.2073 CrossRefGoogle Scholar
  44. Puerta M, Abelenda M, Rocha M, Trayhurn P (2002) Effect of acute cold exposure on the expression of the adiponectin, resistin and leptin genes in rat white and brown adipose tissues. Horm Metab Res 34:629–634CrossRefGoogle Scholar
  45. Punzi L, Ramonda R, Deberg M, Frallonardo P, Campana C, Musacchio E, Henrotin Y (2012) Coll2-1, Coll2-1NO2 and myeloperoxidase serum levels in erosive and non-erosive osteoarthritis of the hands. Osteoarthr Cartil 20:557–561. doi: 10.1016/j.joca.2012.02.638 CrossRefGoogle Scholar
  46. Salaffi F, Leardini G, Canesi B et al (2003) Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index in Italian patients with osteoarthritis of the knee. Osteoarthr Cartil 11:551–560CrossRefGoogle Scholar
  47. Senolt L, Housa D, Vernerova Z et al (2007) Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. Ann Rheum Dis 66:458–463CrossRefGoogle Scholar
  48. Shimodozono M, Matsumoto S, Ninomiya K et al (2012) Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: a pilot study. Int J Biometeorol 56:933–939. doi: 10.1007/s00484-011-0502-x CrossRefGoogle Scholar
  49. Srámek P, Simecková M, Janský L, Savlíková J, Vybíral S (2000) Human physiological responses to immersion into water of different temperatures. Eur J Appl Physiol 81:436–442CrossRefGoogle Scholar
  50. Steppan CM, Lazar MA (2002) Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 13:18–23CrossRefGoogle Scholar
  51. Steppan CM, Bailey ST, Bhat S et al (2001) The hormone resistin links obesity to diabetes. Nature 409:307–312CrossRefGoogle Scholar
  52. Sukenik S, Flusser D, Abu-Shakra M (1999) The role of spa therapy in various rheumatic diseases. Rheum Dis Clin N Am 25:883–897CrossRefGoogle Scholar
  53. Sun Z, Lei H, Zhang Z (2013) Pre-B cell colony enhancing factor (PBEF), a cytokine with multiple physiological functions. Cytokine Growth Factor Rev 24:433–442. doi: 10.1016/j.cytogfr.2013.05.006 CrossRefGoogle Scholar
  54. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783CrossRefGoogle Scholar
  55. Verhagen AP, Bierma-Zeinstra SM, Boers M et al (2007) Balneotherapy for osteoarthritis. Cochrane Database Syst Rev 17, CD006864Google Scholar
  56. Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656Google Scholar
  57. Yusuf E, Nelissen RG, Ioan-Facsinay A et al (2010) Association between weight or body mass index and hand osteoarthritis: a systematic review. Ann Rheum Dis 69:761–765CrossRefGoogle Scholar

Copyright information

© ISB 2015

Authors and Affiliations

  • Antonella Fioravanti
    • 1
    Email author
  • Chiara Giannitti
    • 1
  • Sara Cheleschi
    • 1
  • Antonella Simpatico
    • 1
  • Nicola Antonio Pascarelli
    • 1
  • Mauro Galeazzi
    • 1
  1. 1.Department of Medicine, Surgery and Neuroscience, Rheumatology UnitUniversity of SienaSienaItaly

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