1. Exercise vs. Pharmacological Approach in Musculoskeletal Problems Ilkka Vuori, MD, PhD, FACSM, FECSS Secretary General of the Finnish Bone and Joint Association, Tampere, Finland The International 21th Puijo Synposium, Kuopio, June 29- July 2, 2011

2. Aim of the Presentation To delineate the usefulness of exercise (physical activity) and medicines for prevention and management (treatment, secondary prevention, rehabilitation) of the most prevalent musculoskeletal conditions; practical orientation. The usefulness is estimated on the basis of current scientific evidence on the efficacy/ effectiveness, safety, and feasibility of the means. 6/2011© Ilkka Vuori 6/2011

3. Methods Systematic search and review of scientific publications, and evidence-based clinical guidelines for the last ten years covering the major musculoskeletal conditions; search prepared by a professional librarian. Primary references: current meta-analyses, systematic reviews and evidence-based guidelines 6/2011Ilkka Vuori 6/2011

4. Exclusions The following aspects are touched only in passing or not at all: Direct comparisons of exercise and medications: shortage of data Cost-effectiveness: shortage of data; topic of an other presentation (Valtonen, van Mechelen) Detailed application of exercise: topic of an other presentation (Kujala) 6/2011Ilkka Vuori 6/2011

5. Sarcopenia: prevention, management Evidence on:Exercise: primary meansMedications : none, vitamin D, ACE inhibitors candidates Efficacy/effectivenessResistance, aerobic;strong * muscle mass, strength, power Increased or decline deterred; strong ------------ * muscle-dependent functions Maintained or improved, decline deterred; strong - ----------- * Risk or development of consequences (decreased energy expenditure, malnutrition, increased fat content, insulin resistance, osteoporosis, frailty Decreased, deterred; strong ------------- Safety: side effects, harmsPoorly reported; few, minor ------------- FeasibilityReasonable/good ------------- 6/2011Ilkka Vuori 6/2011

6. Sarcopenia: conclusion In prevention and management of sarcopenia and its consequences esp. resistance exercise is the key means. No drugs are currently recommencded, but nutrition high in protein and vitamin D is another important means. Peterson MD, Gordon PM. Am J Med. 2011;124(3):194-8 Burton LA, Samukadas D. Clinical Interventions in Aging 2010;5:217-228 Visvanathan R, Chapman I. Maturitas 2010;66:383-388. 6/2011Ilkka Vuori 6/2011

7. Fibromyalgia (FM): prevention Exercise: One observational study on unselected female population (n = 15 990), follow-up 11 years. A weak dose-response association between level of PA (for trend, P = 0.13) and risk of FM. In women with highest exercise level, RR 0.77 (0.55-1.07). BMI: independent risk factor; BMI > 25, risk 60 – 70 % higher than in women with normal BMI. PA decreased the risk associated with overweight (Mork et al. Arthritis Care Res. 2010). Medicines: none 6/2011Ilkka Vuori 6/2011

8. Fibromyalgia Evidence on:Exercise: managementMedications: management Efficacy/effectiveness * symptoms: decreased pain, fatigue, depression, ES -0.22 - -0.32, strong Pain, fatigue, depression. About 50 % of treated pt´s experience 30 % reduction of symptoms. * function: improvedfitness ES +0.65, strong * other, e.g. quality of lifeimprovedImproved (well being, sleep) Safety * harms, side-effectsInconsistently reported, few and minor Many drugs in use have many side effects *other Feasibility * adherenceInconsistently reportedTolerability may be limited * otherRegimens realizable 6/2011Ilkka Vuori 6/2011

9. Fibromyalgia: conclusions Prevention: no effective means known, overweight/obesity is a risk factor; PA? Management: both PA, esp. moderate intensity aerobic, and medications indicated and needed. Differences between major clinical guidelines. Häuser W. et al. Arthritis Res Ther. 2010;12(3):R79 Häuser W. et al. European Journal of Pain 2010;14:5-10 (review of major guidelines) Staud R. Drugs 2010;70(1):1-14. 6/2011Ilkka Vuori 6/2011

10. Neck pain (non-specific): prevention Primary prevention: one observational study in unselected population sample (n ~ 30 000), follow- up 11 years. For both males and females, hours of physical exercise per week at base line was linearly and inversely associated with neck pain (women: P- trend = 0.002; men: P-trend < 0.001 (Nilsen et al. Am J Epidemiol. 2011;Jun1). Secondary prevention: in a meta-analysis no exercises were found effective in prevention (Sihawong et al. J Manipulative Physiol Ther.2011;34:62-71 Medications: none 6/2011Ilkka Vuori 6/2011

11. Neck pain, management During the first 12 weeks: exercise is not usefull and not recommended for neck pain. In extended or chronic neck pain: manual therapy plus exercise is more effective on symptoms and function, and the effects last longer compared to exercise only or to manual therapy only. Effects of medications: insufficiently studied. Miller et al. Manual Therapy 2010;15:334-354 Guzman J et al. Spine 2008;33(4 Suppl):S199-213 Hurwitz EL et al. Spine 2008;33(4 Suppl):123-52 6/2011Ilkka Vuori 6/2011

12. Low back pain (non-specific) (LBP): prevention Primary prevention: inconsistent findings in epidemiological studies (Heneweer H. et al. Eur Spine J. 2011;20(6): 826-45, Nilsen TI. et al. Am J Epidemiol. 2011:Jun1) Secondary prevention: free living PA in subjects with LBP is neither associated nor predictive of LBP or disability (Hendrick P. et al. Eur Spine J. 2011;20(3):464-74). Exercise programs: moderate to strong evidence indicates effectiveness in reducing the rate and number of episodes (Bigos SJ et al. The Spine Journal 2009;9:147-168, Choi BKL et al. Cochrane Database of Systematic Reviews 2010, Issue 1). Medications: temporary relief of pain, episodic use 6/2011Ilkka Vuori 6/2011

13. Low back pain: management Acute LBP: most clinical guidelines recommend staying active, exercise not effective, pain relieving medications episodically, Subacute LBP: conflicting results Koes et. Al. Eur. Spine J. 2010;19:2075-94 Pillastrini et al. Joint Bone Spine 2011 May 12 6/2011Ilkka Vuori 6/2011

14. Chronic Low Back Pain: management 1 Most clinical guidelines recommend exercise (Koes et. al. Eur. Spine J. 2010;19:2075-94; May S. Nature Reviews (Rheumatology) 2010;6:199-209; Pillastrini et al. Joint Bone Spine 2011 May 12) Exercise therapy (specific movements) vs. usual care: decreased pain intensity and disability, improved long term function (low evidence). Multidisciplinary and behavioral treatments more effective. Other modalities: insufficient data (van Middelkoop et al. Eur Spin J 2011;20:19-39). 6/2011Ilkka Vuori 6/2011

15. Chronic Low Back Pain: management 2 Physical conditioning programs: reduce slightly sickness absence and work disability in long term (Oesch et al. J Rehabil Med. 2010;42:193- 205; Schaafsma et al. Scand J Work Environ Health 2011;37:1-5; Rantonen et al. Occup Environ Med. 2011 May 20) Cost-effectiveness of exercise as part of management: clear supporting evidence for exercise, none for medications (Lin et al. Eur Spine J 2011;Jan 4 and Jan 13). 6/2011Ilkka Vuori 6/2011

16. Osteoarthritis (OA, knee, hip): prevention In most studies recreational physical activity has not been found either to protect against or to increase risk of knee or hip OA. Hart et al. Clin J Sport Med. 2008;18508-21 Juhakoski et al. Rheumatology 2009;48:83-87 Toivanen et al. Rheumatology 2010;49:308-14 No pharmacological means for prevention available. 6/2011Ilkka Vuori 6/2011

17. Osteoarthritis (knee, hip): management Exercise: in knee OA small to moderate effect on pain and physical function (subjective and objective); in hip OA less evidence; moderate effect on physical activity behaviour (May S. Nature Reviews/Rheumatology 2010;6:199-209). Effect on pain comparable to the effect of non-steroidal and anti-inflammatory drugs (Fransen and McConnell. Cochrane Database of Syst.Rev. 2008;4 (CD004376). Effects of exercise on pain and function: not sustained in the long term without booster sessions (Pisters et al. Arthritis Care & Res. 2007;57:1245-1253). 6/2011Ilkka Vuori 6/2011

18. Osteoarthritis (OA, knee, hip): management Rationale for exercise in knee OA: Low-impact aerobic: statistically significant relief of pain (ES 0.52 (0.34, 0.70)) and decrease of disability (ES 0.46 (0.25, 0.67), clinically important? Quadriceps strengthening: statistically significant relief of pain (ES 0.37 (0.16, 0.59)) and function (ES 0.39 (0.26, 0.50), clinically important? Range of motion/flexibility exercises: no studies, but expert opinion: potential benefits, low cost, limited harms. Zhang et al. Osteoarthritis and Cartilage 2008;16:137-162. American Academy of Orthopaedic Surgeons 2008 (http./www.aaos.org/Research/guidelines/Quidelline OAKnee.asp). Lange et al. Arthritis Care & Research 2008;59:1488-94. Jenkinson et al. BMJ 2009;339:b3170. 6/2011Ilkka Vuori 6/2011

19. Osteoarthritis (knee, hip): management Pharmacological treatments are recommended as adjunctives periodically and in the lowest effective dose for pain (Zhang et al. Osteoarthritis and Cartilage 2008;16:137-162, Lim and Doherty. Int J Rheumatic Diseases 2011;14: 136-144). Paracetamol is a core recommendation for use as an analgesic, but effect very small. For symptomatic OA NSAIDs can be used for short periods; effect on pain but also side effects grater than those of paracetamol. Injections of hyaluronate may provide small symptomatic benefit, but results are variable and effect small. Glucosamine and/or chondroitin do not have a clinically relevant effect on joint pain or joint space narrowing (Wandel et al. BMJ 2010;341:c4675). Intra-articular corticosteroids can be used particularly in knee or hip OA with severe pain not responding satisfactorily to the drugs mentioned above. 6/2011Ilkka Vuori 6/2011

20. Osteoarthritis (knee, hip): exercise vs. pharmacological management Optimal management: combination of non-pharmacological and pharmacological modalities (Zhang et al. Osteoarthritis and Cartilage 2008;16:137-162). Few direct comparisons of exercise and medicines: – Home exercise vs. NSAIDs in knee OA (RT, n = 142 (121 analyzed), 8 weeks): improvement in both groups in WOMAC, SF-36, and pain but no significant differences between the groups (Doi et al. Am J Phys Med Rehabil. 2008;87:258-69). – Home exercise vs. i.a. hyaluronate in knee OA (RT, n = 102, 24 weeks): statistically significant improvement in pain and stiffness but no significant differences between the groups (Kawasaki et al. J Orop Sci 2009;14:182-91). – Home exercise vs. glucosamine or risedronate in knee OA (RT (ex- + hyaluronate, ex. + risedronate, ex- only) n = 142, 18 months): significant improvement in pain and function in all three groups but no significant differences between the groups, i.e. glucossamine and risedronate did not add to the effects of home exercise alone (Kawasaki et al. J Bone Miner Metab. 2008;26:279-287). 6/2011Ilkka Vuori 6/2011

21. Rheumatoid Arthritis (RA): management Evidence on:Exercise: adjuvantMedications: main means Efficacy/effectiveness * symptoms: decreasedPain ES -0.34 (-0.53 - -0.21)Good; strong * function: improvedES 0.37 (0.21 – 0.52)Good; strong * other, e.g. quality of lifeES 0.39 Safety * harms, side-effectsNone seriousMany, variable, partly severe *other Feasibility * adherenceModerate at bestVariable * otherRealizable 6/2011Ilkka Vuori 6/2011

22. Rheumatoid Arthritis: management Conclusion: Strong and increasing evidence to include individualized aerobic and resistance exercise to complement drug therapy in most pt´s with RA to decrease symptoms, and improve function and quality of life without risk of harms. Hurkmans E et al. Cochrane Database Syst. Rev. 2009;4:CD006853 Vliet Vlieland TP, van den Ende CH. Curr Opin Rheumatol. 2011;23:259-64 Forestier R. et al. Joint Bone Spine 2009;76(6):691-8 Baillet A et al. Arthritis Care Res. 2010;62:984-92 Kelley GA ym. Arthritis Care Res. 2011;63(1):79-93. 6/2011Ilkka Vuori 6/2011

23. Osteoporosis (OP): prevention 1 Osteoporosis: defined on the basis of bone mass/density, BMD. Exercise aids to prevent OP by increasing BMD in young people, and helps to maintain or deterr its loss in middle- aged and old people. Also effective although not optimal modes and regimens of exercise are known (Guadalupe-Grau et al. Sports Med. 2009;39:439-68, Martyn-St James and Carroll. Br J Sports Med.2009;43:898-90; Martyn St James and Carroll. J Bone Mieral Metab. 2010;28:251-67). However, clinical significance of OP is based on fractures, and exercise intervention studies with fracture data as endpoint are scanty. BMD is only a surrogate measure of bone strength. Up to 80 % of all low-trauma fractures occur in individuals who are not osteoporotic but have normal BMD or osteopenia. 6/2011Ilkka Vuori 6/2011

24. Osteoporosis (OP): prevention 2 Biomechanical bone strength can be estimated from measurements obtained by various imaging techniques. A meta-analysis of studies with data on whole bone strength of lower extremities: exercise can significantly increase bone strength at loaded sites in children but not in adults. However, the number of studies is still small (Nikander et al.BMC Medicine 2010,8:47). Thus, the real role of exercise in the prevention of osteoporotic fractures is not yet definitively known. 6/2011Ilkka Vuori 6/2011

25. Osteoporosis (OP): prevention 3 Pharmacological prevention: several drugs prevent OP and also fractures (vertebral fractures by 15 – 30 %, hip fractures by 15 - 60 %). However, most drugs can cause serious side effects esp. in individuals with various diseases (Geusens et al. Nature Clinical Practice Rheumatology 2008;4:240-48). The true costs of pharmacological prevention can be much higher than estimated on the basis of RCT´s (Järvinen et al. BMJ 2011;342:d2175 doi), and any risks related to preventive drugs will be magnified if they are prescribed too liberally (Lancet 2011;377(9784):2152, commentary on a new report from the Int. Osteoporosis Foundation and European Federation of Pharmaceutical industry). 6/2011Ilkka Vuori 6/2011

26. Summary Prevention Management Exercise Pharmacol. Exercise Pharmacol. Sarcopenia ++ - - Fibromyalgia -? - + + Neck pain -? - + + Low back pain -/+ - + (chr.) + Osteoarthritis - - ++ + Rheumat. arthritis - - + ++ Osteoporosis +? + + ++ 6/2011Ilkka Vuori 6/2011

27. Conclusions 1 Current evidence regarding exercise: efficacy: mostly small effects; quality of evidence rated mostly as low effectiveness: much more research needed safety: side effects insufficiently reported, but minor when recommendations are followed feasibility: most regimens realizable in various conditions, but adherence incomplete cost-effectiveness: few studies direct comparisons with pharmaceuticals and other means: few, mostly low quality 6/2011Ilkka Vuori 6/2011

28. Conclusions 2 In order to increase the use of exercise in prevention and esp. treatment of musculoskeletal problems, more and higher quality research is needed to convince the professionals and administrators of the health care system. Especially comparative effectiveness research focusing on head to head comparisons of interventions in real life conditions, and that use broad health outcomes (Tinetti and Studenski NEJM 2011, June 22) would bring evidence of the total potential of exercise in prevention and management of chronic non-communicable diseases. 6/2011Ilkka Vuori 6/2011

29. Acknowledgements I thank Birgitta Järvinen (librarian),and Outi Ansamaa (library assistant) at the UKK Institute for Health Promotion Research for their skillful work in searching and providing the literature for this review. 6/2011Ilkka Vuori 6/2011

30. Thank you for your attention! 6/2011Ilkka Vuori 6/2011

31. 6/2011Ilkka Vuori 6/2011

32. Neck pain: management, exercise only (Leaver et al. J Physiotherapy 2010;56:73-85) Evidence on:Exercise (only, specific)Medications (analgesic) Efficacy/effectiveness * symptoms: decreasedModerately, only in short term Moderately, studied only in short term * function: improvedNo effect---------- * other, e.g. quality of life Safety * harms, side-effectsFew, minor---------- *other Feasibility * adherence * other 6/2011Ilkka Vuori 6/2011

33. Neck pain: management, exercise plus manual therapy ( Miller et al. Manual Therapy 2010;15:334-354) Evidence on:ExerciseMedications Efficacy/effectiveness * symptoms: decreasedModerately, long term; low quality evidence * function: improvedModerately, long term; low quality evidence * Global perceived healthModerately Safety * harms, side-effectsBenign, transient *other Feasibility * adherence * other 6/2011Ilkka Vuori 6/2011