“Muscle – not just for athletes!” Muscle mass, disability & quality of life.

1. “Muscle – not just for athletes!” Muscle mass, disability & quality of life. Dr. Andrew Lemmey School of Sport, Health and Exercise Sciences Bangor University, UK

2. Determinants of Muscle Atrophy: Loss of Muscle Fibers→ Reduction of Muscle Fibers Size→

3. Pathophysiology of muscle loss secondary to aging Tomlinson and Irving (1977) Lexell et al. (1988)

4. Cachexia / sarcopenia is associated with poor outcome

5. Consequences of Sarcopenia: Mortality(Kotler et al., 1989)

6. Muscle Atrophy and Mortality Kato et al. (2003)

7. Muscle Atrophy at Admission and Length of Stay in Hospital High FFMI Normal FFMI Low FFMI Pichard et al. (2004)

8. Consequences of Sarcopenia: Disability(Baumgartner, 2000)

9. Muscle Mass and Strength in RA Healthy r = 0.94, p < 0.001 RA r = 0.73, p < 0.001 Healthy r = 0.59, p < 0.01 RA r = 0.40, p = 0.07

10. r = 0.832 Fig. 3. Bivariate linear regression analysis between body composition data and measures of functional capacity. KES, Knee extensor strength. Analysis is based on pooled data for patients and controls. r, Pearson correlation coefficient. *, p < 0.005.

11. r = 0.615 Fig. 2. Bivariate linear regression analysis between body composition data and measures of functional capacity. 30sec SST, 30 second sit to stand chair test. Analysis is based on pooled data for patients and controls. r, Pearson correlation coefficient. *, p < 0.005.

12. The identification of effective means of treating sarcopenia/cachexia (muscle wasting) is very important since increasing muscle mass in individuals with muscle wasting has the potential to decrease disability and morbidity, increase life expectancy, and improve quality of life in these patients

13. Sarcopenia →

14. Muscle Loss Secondary to Disuse(SHUTTLE and MIR missions of 16-28 weeks duration) Le Blanc et al. (2000)

15. Muscle Loss Secondary to Systemic Disease Marcora et al., Journal of Rheumatology (2005) 32(6):1031-1039

16. Standard medical treatment does not completely prevent cachexia

17. Muscle Loss Secondary to Drug Therapy(Androgen Deprivation Therapy in Prostate Cancer Patients) Smith et al. (2001)

18. Muscle Protein Metabolism inHealth and Disease

19. Standard drug therapy, including anti-TNF therapy, neither completely prevents muscle wasting, nor restores muscle mass Consequently, there is a need for anabolic therapy in treating patients with cachexia

20. Anabolic Therapies Progressive resistance training (PRT) Dietary supplements Anabolic hormones

21. Progressive Resistance Training

22. Can progressive resistance training reverse rheumatoid cachexia? A Phase II Trial Marcora et al.Journal of Rheumatology (2005) 32(6):1031-1039

23. Intense Progressive Resistance Training

24. Very Intense!!!

25. Exercise Dose

26. Training Progression * P < 0.01

27. Results: Body Composition FM = Fat Mass; LM = Lean Mass. Significance was tested by ANCOVA on follow-up scores using baseline scores as covariate.

28. Objective Functional Capacity Tests Rickli & Jones, Senior Fitness Test Manual, Human Kinetics (2001)

29. 30sec sit-stand test (lower body strength) Leg extension (lower body strength) Dumbbell arm curls (30sec) (upper body strength) Hand grip strength (upper body strength) 8’ up-and-go (agility/dynamic balance) 6 min walk (aerobic endurance) 2-min step test (aerobic endurance) Chair sit-and-reach (lower body flexibility) Rickli & Jones, Senior Fitness Test Manual, Human Kinetics (2001)

30. Results: Muscle Strength Significance was tested by ANCOVA on follow-up scores using baseline scores as covariate.

31. Significant decrease (-0.25 HAQ score) in disability (P = 0.01) by ANCOVA r = -0.50, P = 0.03

32. Can 24 wks progressive resistance training reverse cachexia in rheumatoid arthritis patients? A RCT Lemmey et al.,Arthritis & Rheum(2009) 61:1726-34

33. Exercise Dose

34. Effects of 24 wks high intensity PRT on body composition in RA patients

35. Effects of 24 wks high intensity PRT on body composition in RA patients Lemmey et al., Arthritis & Rheum (2009) 61:1726-34

36. Effects of 24 wks high intensity PRT on physical function in RA patients * p<0.05, ** p<0.01, *** p<0.001 (group x time interaction). Line represents “healthy control” values (gender and age weighted)

37. Values are the mean ± SD. P values are for group x time interaction. Effect size was calculated as eta squared (η2), with thresholds for small, moderate, large and very large effects set at .01, .08, .26 and .50 respectively. Muscle IGF values (mIGF) are for PRT group (n=9) and control group (n=5), whilst serum IGF (sIGF) values are for PRT group (n=13) and control group (n=15). Lemmey et al., Arthritis & Rheum (2009) 61:1726-34

38. ** Fig. 3. Skeletal muscle IGF-І and IGFBP-3 levels (normalized for total protein content) for 5 healthy controls and 7 HD patients. Values are mean ± SD. **, p < 0.001 from healthy controls. Macdonald et al., Clin Physiol Functional Imaging (2005) 25:113-18

39. Pharmacological Nutrition

40. Nutritional Treatment of Rheumatoid Cachexia Number of nutrition intervention trials [either randomized controlled trials (RCTs) or observational trials (OTs)] in patients with chronic diseases (Akner and Cederholm, 2001)

41. Randomised Controlled Trial of Juven in RA Patients Oral mixture of amino acids:Arginine = 14 g/dayGlutamine = 14 g/dayβ-hydroxy-β-methylbutyrate(HMB) = 3 g/day What is Juven? Marcora et al., Clinical Nutrition (2005) 24(3): 442-454

42. Randomised Controlled Trial of Juven in RA Patients • 40 RA patients were randomly assigned to either Juven (n = 20) or “Placebo” (n = 20) • Placebo = a nitrogen and calorie balanced mix of 11 g of alanine, 1.75 g of glutamic acid, 6.10 g of glycine, and 4.22 g of serine • Both subjects and researchers were unaware of allocation until analysis (double blind) • Subjects were tested at baseline and after 12 weeks of oral supplementation • 36 subjects completed the study

43. Changes in Appendicular Muscle Mass (Main Factor Time P < 0.05) Data presented as Mean ± SEM

44. Randomised Controlled Trial of Juven in RA Patients Non significant group x time interaction; P = 0.74, η2 = 0.00 # Significant main effect for time; P = 0.02, η2 = 0.16

45. Changes in Lower Body Function (Main Factor Time P < 0.05) Data presented as Mean ± SEM

46. Anabolic Hormones

47. Anabolic/Androgenic Steroids Tengstrand et al. (2002)

48. Anabolic Steroids in RA: Women (Bird et al., 1987) • Single-blind, randomised, parallel, controlled trial • 24 female RA patients received 50 mg of nandrolone decanoate every third week for 2 years • 23 female RA patients received only standard medical treatment • Patients assessed at month 0, 6, 12, 18, 24 • Body composition by neutron activation analysis and whole-body counting • Main focus osteoporosis, no effect • No effect on disease activity • Striking improvement in anemia • Side effects were hoarseness, slight facial hair growth and occasionally breast enlargement

49. Anabolic Steroids in RA: Women (Bird et al., 1987) Equivalent to 3 kg of FFM. Body mass did not change * P < 0.01

50. Johansen et al., JAMA, 1999 * * 6 months 6 months