1. The Effects of Balneotherapy on Knee Osteoarthritis Prof.Dr. Arif Dönmez İstanbul University, İstanbul Medical Faculty, Department of Medical Ecology and Hydroclimatology III. Hungarian-Turkish Balneological Symposium 1 APRIL 2005

2. 5/25/2015III. Hungarian – Turkish Balneological Symposium 2 The Effects of Balneotherapy on Knee Osteoarthritis  Knee OA and disability  EULAR Recommendations 2003 : an evidence based approach to the management of knee osteoarthritis  Balneotherapy studies on knee osteoarthritis  Problems in balneotherapy studies  Mechanisms of action  Efficacy of balneotherapy in OA  Proposals for high quality studies

3. 5/25/2015III. Hungarian – Turkish Balneological Symposium 3 Knee OA and disability  As an estimation, 10 % of people older than 55 years have disabling knee symptoms ~25 % of them are severely disabled  According to WHO report on global burden of disease, knee OA is likely to be one of the most important global cause of disability in the society Fourth most important in women and eighth most important in men Peat G, Mc Carney R, Croft P. Knee pain and osteoarthritis in older adults: a review of community burden and current use of health care. Ann Rheum Dis 2001;60:91–7 Murray CJL, Lopez AD. The global burden of disease. Geneva: World Health Organization, 1997

4. 5/25/2015III. Hungarian – Turkish Balneological Symposium 4 EULAR Recommendations 2003 Non-pharmacologicalPharmacologicalIntraarticularSurgical EducationParacetamolCorticosteroidArthroscopy ExerciseNSAIDs InsolesOpioid analgesicsHyaluronic acidOsteotomy Orthotic devicesSex hormones Weight LossSYSADOATidal irrigationUni-compartmental LaserPsychotropic drugsknee replacement SpaTopical NSAIDs TelephoneTopical capsaicinTotal knee Vitamins / Mineralsreplacement Pulsed EMF Ultrasound TENS Acupuncture Nutrients Herbal remedies Jordan K M, Arden N K, Doherty M et al. 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 2003;62:1145–1155.

5. 5/25/2015III. Hungarian – Turkish Balneological Symposium 5 Evidence : Categories CategoryEvidence provided from: 1AMeta-analysis of RCTs 1BAt least one RCT 2AAt least one controlled study without randomization 2BAt least one quasi-experimental study 3 Descriptive studies such as comparative, correlation or case-control studies 4 Expert committee reports or opinions and/or clinical experience of respected authorities

6. 5/25/2015III. Hungarian – Turkish Balneological Symposium 6 The strength of recommendation is based on  the level of evidence  the effect size of the intervention  the side effect profile  the applicability of the evidence to the population of interest  practicality of delivery  economic considerations

7. 5/25/2015III. Hungarian – Turkish Balneological Symposium 7 Strength of recommendation and the level of evidence CategoryDirectly based on A category 1 evidence B category 2 evidence OR extrapolated recommendation from category 1 evidence C category 3 evidence OR extrapolated recommendation from category 1 or 2 evidence D category 4 evidence OR extrapolated recommendation from category 2 or 3 evidence

8. 5/25/2015III. Hungarian – Turkish Balneological Symposium 8 Balneotherapy studies on knee osteoarthritis  Observational studies (OSs)  Controlled Clinical Trials (CCTs)  Randomized Controlled Clinical Trials (RCCTs)

9. 5/25/2015III. Hungarian – Turkish Balneological Symposium 9 Observational studies Selected References 1. Dönmez A, Karagülle Z, Turan M: Balneotherapie mit Akratoterme bei Gonartrose. Zeitschrift Naturamed 1995;7-20-3 2. Forestier R.Magnitude and duration of the effects of two spa therapy courses on knee and hip osteoarthritis: an open prospective study in 51 consecutive patients. Joint Bone Spine 2000;67(4):296-304. 3. Guillemin F, Virion JM, Escudier P et al. Effect on osteoarthritis of spa therapy at Bourbonne-les-Bains. Joint Bone Spine 2001 ; 68 : 499-503 4. Fioravanti A, Valenti M, Altobelli E et al. Clinical efficacy and cost- effectiveness evidence of spa therapy in osteoarthritis. The results of "Naiade" Italian Project. Panminerva Med.2003 Sep;45(3):211- 7. 5. Yılmaz B, Goktepe SA, Alaca R et al.Comparison of a generic and a disease specific quality of life scale to assess a comprehensive spa therapy program for knee osteoarthritis. Joint Bone Spine. 2004 Nov;71(6):563-6.

10. 5/25/2015III. Hungarian – Turkish Balneological Symposium 10 Results of Observational studies  Pain  1,2,3,4  Lequesne Knee Index score  1,2  Walking distance  2  Flexion range  2  Quality of life  3,5  Drug consumption  4

11. 5/25/2015III. Hungarian – Turkish Balneological Symposium 11 Controlled Clinical Trials Selected References 1. Wigler I, Elkayam O, Paran D, Yaron M. Spa therapy for gonartrosis: prospective study. Rheumatol Int 1995;15:65-68. 2. Flusser D, Abu-Shakra M, Friger M, et al.Therapy With Mud Compresses for Knee Osteoarthritis Comparison of Natural Mud Preparations With Mineral-Depleted Mud. J Clin Rheumatol 2002;8:197–203 3. Odabaşı E, Karagülle MZ, Karagülle M et al. Comparison of two traditional spa therapy regimens in patients with knee osteoarthritis; an exploratory study. Phys Med Rehab Kuror 2002;12:337-341

12. 5/25/2015III. Hungarian – Turkish Balneological Symposium 12 Results of CCTs  Wigler I, Elkayam O, Paran D, Yaron M. Spa therapy for gonartrosis: prospective study. Rheumatol Int 1995;15:65-68. Mineral water bath and mud pack combination is bettter than: Mineral water bath + rinsed mud pack Tap water bath + rinsed mud pack

13. 5/25/2015III. Hungarian – Turkish Balneological Symposium 13 Results of CCTs  Flusser D, Abu-Shakra M, Friger M, et al. Therapy With Mud Compresses for Knee Osteoarthritis Comparison of Natural Mud Preparations With Mineral-Depleted Mud. J Clin Rheumatol 2002;8:197–203 Mineral mud compresses are far effective than mineral-depleted mud compresses

14. 5/25/2015III. Hungarian – Turkish Balneological Symposium 14 Results of CCTs  Odabaşı E, Karagülle MZ, Karagülle M et al. Comparison of two traditional spa therapy regimens in patients with knee osteoarthritis; an exploratory study. Phys Med Rehab Kuror 2002;12:337-341 Thermal water bath and peloid pack combination is better than twice-a-day thermal water bath application

15. 5/25/2015III. Hungarian – Turkish Balneological Symposium 15 Randomized Controlled Trials Selected References I Balneotherapy group vs. Tap water group 1. Szucs L, Ratko I, Lesko T et al. Double-blind trial on the effectiveness of the Puspokladany thermal water on arthrosis of the knee-joints. J R Soc Health 1989; 109:7–9 2. Kovács I, Bender T. The therapeutic effects of Cserkeszölö thermal water in osteoarthritis of the knee: a double blind,controlled, follow-up study Rheumatol Int (2002) 21: 218–221 3. Balint G, Ádam A, Ratko I et al. Double blind study about the effectivity of the thermal mineral water of Nagybaracska in patient with knee joint osteoarthritis.2.Turkish-Hungarian Balneological Workshop, Pamukkale, Turkey 16-18 September 2004

16. 5/25/2015III. Hungarian – Turkish Balneological Symposium 16 Randomized Controlled Trials Selected References II Balneotherapy group vs. Outpatient medical care group 1. Nguyen M, Revel M, Dougados M. Prolonged effects of 2 week therapy in a spa resort on lumbar spine, knee and hip osteoarthritis: Follow-up after 5 months. A randomized controlled trial. British Journal of Rheumatology1997:36;77-81 2. Tishler M Rosenberg O, Levy O et al. The effect of balneotherapy on osteoarthritis. Is an intermittent regimen effective? Eur J Intern Med 2004 15(2): 93-96 3. Uysal B, Dönmez A, Karagülle MZ et al. Wirksamkeit der Balneotherapie bei Patienten mit Gonarthrose im Kurort Gönen: eine randomisierte kontrollierte Studie. 5.Deutsch-Türkischer Kongress für Balneologie und Medizinische Klimatologie 27-28 Juni 2003 Balneotherapy and control groups stayed at the same area 1. Sukenik S, Flusser D, Codish S. Balneotherapy at the Dead Sea area for knee osteoarthritis IMAJ 1999;1:83-85

17. 5/25/2015III. Hungarian – Turkish Balneological Symposium 17 Systematic Review of RCTs  Brosseau L, Macleay L, Robinson V. Efficiacy of balneotherapy for osteoarthritis f the knee; a systematic review. Physical Therapy Reviews. 2002;7:209-222 “ The results of this review suggest that balneotherapy can be effective on a short-term basis for measures of pain severity and function as well as for improved ROM and timed stair climbing.”

18. 5/25/2015III. Hungarian – Turkish Balneological Symposium 18 Problems in balneotherapy studies  Type of treatment mud pack, sulphur bath, radon and carbon dioxide bath, Dead Sea bath salts, NaCl baths salts, and mineral water bath  Treatment characteristics duration of study, frequency, number of treatments, duration of treatment, temperature  Setting in the sea, hospital, home  Constituents of the treatment agent Na, Ca, K, Cl…  Individual who prepared bath patient, medical staff Brosseau L, Macleay L, Robınson V. Efficacy of balneotherapy for osteoarthritis of the knee: a systematic review. Physical Therapy Reviews 2002; 7: 209–222

19. 5/25/2015III. Hungarian – Turkish Balneological Symposium 19 Problems in balneotherapy studies  Verhagen AP, de Vet HCW, de Bie RA et al. Balneotherapy for rheumatoid arthritis and osteoarthritis (Cochrane Review) In: The Cochrane Library, Issue 2, 2002. Oxford: Update Software. “… the positive findings reported in most trials. However the scientific evidence is weak the poor methodological quality, the absence of an adequate statistical analysis, the absence of most essential outcome measures (pain, quality of life) Therefore, the noted "positive findings" should be viewed with caution.”

20. 5/25/2015III. Hungarian – Turkish Balneological Symposium 20 Mechanisms of action  A combination of mechanical, thermal and chemical effects Heat  Analgesia  Anti inflammatory effect  Muscle tonus decrease  Peripheral vasodilatation  ß-endorphin level  Gate-control theory Buoyancy and hydrostatic pressure  affect muscle tone,  joint mobility  pain intensity by decreasing joint load Mineral water chemical implications  Environmental change  Non-competitive atmosphere  Absence of work duties

21. 5/25/2015III. Hungarian – Turkish Balneological Symposium 21 Efficacy of balneotherapy in OA - I TNF α  *TNF α  *** IL-1  **IL-1  *** IGF-1  *** CRP  *,** Haptoglobulin  *,** *Tütüncü ZN,Turan M, Barut A: Changes in TNF α plasma levels in osteoarthritic patients under balneotherapy with acratotermal water. Phys Rehab Kur Med 1996;6:80-82 **Turan M :Wirkungen der Balneotherapie auf die Akute-Phase-Reaction. IV.Deutsch-Türkischer Ärtzekongress Balneologie und Klimatologie, İzmir,Türkie 2000, Kongressbuch: 39-41 ***Bellometti S, Giannini S, Sartori L, Crepaldi G: Cytokine levels in osteoarthrosis patients undergoing mud bath therapy. Int J Clin Pharmacol Res. 1997;17(4):149-53

22. 5/25/2015III. Hungarian – Turkish Balneological Symposium 22 Efficacy of balneotherapy in OA - II  Beta endorphine  Kubota K, Kurabayashi H, Tamura K, et al (1992) A transient rise in plasma beta-endorphin after a traditional 47 degrees C hot-spring bath in Kusatsu-spa, Japan. Life Sci. 51(24):1877-80.  Beta endorphine (60%) , (30%) , (10%)  Yurtkuran M, Ulus H, Irdesel J (1993) The effect of balneotherapy on plasma beta endorphine level in patient with osteoarthritis. Phys Rehab Kur Med 3:130-132

23. 5/25/2015III. Hungarian – Turkish Balneological Symposium 23 Proposals for high quality studies  Standardization application method, medium, environment. …  Proper/Current outcome measures  Appropriate sampling representative number of patients  Intent-to-treat analysis  Randomization  Blinded studies single, double  Placebo controlled studies

24. 5/25/2015III. Hungarian – Turkish Balneological Symposium 24 THANK YOU