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Drugs & Aging

, Volume 35, Issue 8, pp 719–734 | Cite as

Pharmacological Interventions to Improve Muscle Mass, Muscle Strength and Physical Performance in Older People: An Umbrella Review of Systematic Reviews and Meta-analyses

  • Anton De Spiegeleer
  • David Beckwée
  • Ivan Bautmans
  • Mirko Petrovic
  • the Sarcopenia Guidelines Development group of the Belgian Society of Gerontology and Geriatrics (BSGG)
Systematic Review

Abstract

Background

Sarcopenia, defined as the pathological decline in muscle mass, muscle strength and physical performance with aging, has become one of the geriatric giants because of its increasing prevalence and devastating health effects. The Belgian Society of Gerontology and Geriatrics (BSGG) is currently developing evidence-based guidelines for the prevention and therapy of sarcopenia for use in broad clinical practice. This systematic review summarizes the results of the Working Group on Pharmacology.

Objective

Our objective was to provide an evidence-based overview of the possible pharmacological interventions for sarcopenia with a focus on interventions that have already been studied in systematic reviews or meta-analyses.

Methods

We conducted a systematic umbrella review. Using the electronic databases PubMed and Web of Science, we identified systematic reviews and meta-analyses that assessed the effect of pharmacological interventions on criteria for sarcopenia in subjects aged ≥ 65 years. Study selection, quality assessment and data extraction were performed by two independent reviewers.

Results

We identified seven systematic reviews or meta-analyses, encompassing ten pharmacological interventions: vitamin D, combined estrogen–progesterone, dehydroepiandrosterone, growth hormone, growth hormone-releasing hormone, combined testosterone–growth hormone, insulin-like growth factor-1, pioglitazone, testosterone and angiotensin-converting enzyme inhibitors. Importantly, very few systematic reviews or meta-analyses clearly mentioned baseline sarcopenia status. Therefore, our recommendations are generalised to older people, without specifying whether the muscle effect is more effective in healthy, pre-sarcopenic or sarcopenic older people. Vitamin D had a significant effect on muscle strength and physical performance, especially in women with low baseline values (< 25 nmol/l). Adverse events were rare. Testosterone had a strong effect on muscle mass and a modest to minimal effect on muscle strength and physical performance, respectively, when supplementing men with low serum levels (< 200–300 ng/dl). The adverse events were rare and mild. Insufficient evidence was available to recommend other pharmacological interventions.

Conclusion

Only vitamin D, especially in older women, and testosterone in older men with clinical muscle weakness and low testosterone serum levels can be justified in daily clinical practice to improve muscle mass, muscle strength and/or physical performance.

Notes

Acknowledgements

The Sarcopenia Guideline Development Group of the BSGG includes the following members: Bautmans I, Beaudart C, Beckwée D, Beyer I, Bruyère O, De Breucker S, De Cock A-M, Delaere A, de Saint-Hubert M, De Spiegeleer A, Gielen E, Perkisas S, Vandewoude M.

Compliance with Ethical Standards

Funding

No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

Anton De Spiegeleer, David Beckwée, Ivan Bautmans and Mirko Petrovic have no conflicts of interest that are directly relevant to the content of this review.

Supplementary material

40266_2018_566_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 12 kb)

References

  1. 1.
    von Haehling S, Ebner N, dos Santos MR, Springer J, Anker AD. Muscle wasting and cachexia in heart failure: mechanisms and therapies. Nat Rev Cardiol. 2017;14(6):323–41.CrossRefGoogle Scholar
  2. 2.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. Sarcopenia: European consensus on definition and diagnosis. Age Ageing. 2010;39(4):412–23.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Visser M, Schaap LA. Consequences of sarcopenia. Clin Geriatr Med. 2011;27(3):387–99.CrossRefPubMedGoogle Scholar
  4. 4.
    Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull. 2010;95(1):139–59.CrossRefPubMedGoogle Scholar
  5. 5.
    Urano T, Inoue S. Recent genetic discoveries in osteoporosis, sarcopenia and obesity. Endocr J. 2015;62(6):475–84.CrossRefPubMedGoogle Scholar
  6. 6.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Shea BJ, Grimshaw JM, Wells GA, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Austin TM, Richter RR, Sebelski CA. Introduction to the GRADE approach for guideline development: considerations for physical therapist practice. Phys Ther. 2014;94(11):1652–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Anagnostis P, Dimopoulou C, Karras S, Lambrinoudaki I, Goulis DG. Sarcopenia in post-menopausal women: Is there any role for vitamin D? Maturitas. 2015;82(1):56–64.CrossRefPubMedGoogle Scholar
  11. 11.
    Borst SE. Interventions for sarcopenia and muscle weakness in older people. Age Ageing. 2004;33(6):548–55.CrossRefPubMedGoogle Scholar
  12. 12.
    O’Connell MD, Tajar A, Roberts SA, Wu FC. Do androgens play any role in the physical frailty of ageing men? Int JAndrol. 2011;34(3):195–211.CrossRefGoogle Scholar
  13. 13.
    Ottenbacher KJ, Ottenbacher ME, Ottenbacher AJ, Acha AA, Ostir GV. Androgen treatment and muscle strength in elderly men: a meta-analysis. J Am Geriatr Soc. 2006;54(11):1666–73.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Poggiogalle E, Migliaccio S, Lenzi A, Donini LM. Treatment of body composition changes in obese and overweight older adults: insight into the phenotype of sarcopenic obesity. Endocrine. 2014;47(3):699–716.CrossRefPubMedGoogle Scholar
  15. 15.
    Beaudart C, Dawson A, Shaw SC, Harvey NC, Kanis JA, Binkley N, et al. Nutrition and physical activity in the prevention and treatment of sarcopenia: systematic review. Osteoporos Int. 2017;28(6):1817–33.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Zhou LS, Xu LJ, Wang XQ, Huang YH, Xiao Q. Effect of angiotensin-converting enzyme inhibitors on physical function in elderly subjects: a systematic review and meta-analysis. Drugs Aging. 2015;32(9):727–35.CrossRefPubMedGoogle Scholar
  17. 17.
    Vasquez-Morales A, Wanden-Berghe C, Sanz-Valero J. Exercise and nutritional supplements; effects of combined use in people over 65 years; a systematic review. Nutr Hosp. 2013;28(4):1077–84.PubMedGoogle Scholar
  18. 18.
    Ceglia L, Niramitmahapanya S, Morais MD, Rivas DA, Harris SS, Bischoff-Ferrari H, et al. A randomized study on the effect of vitamin D-3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. J Clin Endocrinol Metab. 2013;98(12):E1927–35.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chanet A, Salles J, Guillet C, Giraudet C, Berry A, Patrac V, et al. Vitamin D supplementation restores the blunted muscle protein synthesis response in deficient old rats through an impact on ectopic fat deposition. J Nutr Biochem. 2017;46:30–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Rosendahl-Riise H, Spielau U, Ranhoff AH, Gudbrandsen OA, Dierkes J. Vitamin D supplementation and its influence on muscle strength and mobility in community-dwelling older persons: a systematic review and meta-analysis. J Hum Nutr Diet. 2017;30(1):3–15.CrossRefPubMedGoogle Scholar
  21. 21.
    Avenell A, Mak JCS, O’Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;(4):CD000227.Google Scholar
  22. 22.
    Dawson-Hughes B. Vitamin D and muscle function. J Steroid Biochem Mol Biol. 2017;173:313–6.CrossRefPubMedGoogle Scholar
  23. 23.
    Zhang MZ, Zhao LJ, Zhou Y, Badr R, Watson P, Ye A, et al. SNP rs11185644 of RXRA genes identified for dose-response variability to vitamin D3 supplementation: a randomized clinical trial. Sci Rep. 2017;7:40593.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Takiar R, Lutsey PL, Zhao D, Guallar E, Schneider ALC, Grams ME, et al. The associations of 25-hydroxyvitamin D levels, vitamin D binding protein gene polymorphisms, and race with risk of incident fracture-related hospitalization: Twenty-year follow-up in a bi-ethnic cohort (the ARIC Study). Bone. 2015;78:94–101.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Greising SM, Baltgalvis KA, Lowe DA, Warren GL. Hormone therapy and skeletal muscle strength: a meta-analysis. J Gerontol A Biol Sci Med Sci. 2009;64(10):1071–81.CrossRefPubMedGoogle Scholar
  26. 26.
    Michael YL, Gold R, Manson JE, Keast EM, Cochrane BB, Woods NF, et al. Hormone therapy and physical function change among older women in the Women’s Health Initiative: a randomized controlled trial. Menopause. 2010;17(2):295–302.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Baker WL, Karan S, Kenny AM. Effect of dehydroepiandrosterone on muscle strength and physical function in older adults: a systematic review. J Am Geriatr Soc. 2011;59(6):997–1002.CrossRefPubMedGoogle Scholar
  28. 28.
    Gotherstrom G, Elbornsson M, Stibrant-Sunnerhagen K, Bengtsson BA, Johannsson G, Svensson J. Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement. Eur J Endocrinol. 2010;163(2):207–15.CrossRefPubMedGoogle Scholar
  29. 29.
    White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, et al. Effects of an oral growth hormone secretagogue in older adults. J Clin Endocrinol Metab. 2009;94(4):1198–206.CrossRefPubMedGoogle Scholar
  30. 30.
    Veldhuis JD, Patrie JT, Frick K, Weltman JY, Weltman A. Sustained growth hormone (GH) and insulin-like growth factor I responses to prolonged high-dose twice-daily GH-releasing hormone stimulation in middle-aged and older men. J Clin Endocrinol Metab. 2004;89(12):6325–30.CrossRefPubMedGoogle Scholar
  31. 31.
    Veldhuis JD, Patrie JM, Frick K, Weltman JY, Weltman AL. Administration of recombinant human GHRH-1,44-amide for 3 months reduces abdominal visceral fat mass and increases physical performance measures in postmenopausal women. Eur J Endocrinol. 2005;153(5):669–77.CrossRefPubMedGoogle Scholar
  32. 32.
    Marsh AP, Shea MK, Locke RMV, Miller ME, Isom S, Miller GD, et al. Resistance training and pioglitazone lead to improvements in muscle power during voluntary weight loss in older adults. J Gerontol A Biol Sci Med Sci. 2013;68(7):828–36.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Yokota T, Kinugawa S, Hirabayashi K, Suga T, Takada S, Omokawa M, et al. Pioglitazone improves whole-body aerobic capacity and skeletal muscle energy metabolism in patients with metabolic syndrome. J Diabetes Investig. 2017;8(4):535–41.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–24.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Storer TW, Basaria S, Traustadottir T, Harman SM, Pencina K, Li ZY, et al. Effects of testosterone supplementation for 3 Years on muscle performance and physical function in older men. J Clin Endocrinol Metab. 2017;102(2):583–93.PubMedGoogle Scholar
  36. 36.
    Traish AM, Haider A, Haider KS, Doros G, Saad F. Long-term testosterone therapy improves cardiometabolic function and reduces risk of cardiovascular disease in men with hypogonadism: a real-life observational registry study setting comparing treated and untreated (control) groups. J Cardiovasc Pharmacol Ther. 2017;22(5):414–33.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Elagizi A, Kohler TS, Lavie CJ. Testosterone and cardiovascular health. Mayo Clin Proc. 2018;93(1):83–100.CrossRefPubMedGoogle Scholar
  38. 38.
    De Spiegeleer A, Petrovic M, Boeckxstaens P, Van den Noortgate N. Treating sarcopenia in clinical practice: where are we now? Acta Clin Belg. 2016;71(4):197–205.CrossRefPubMedGoogle Scholar
  39. 39.
    Sattler FR, Castaneda-Sceppa C, Binder EF, Schroeder ET, Wang Y, Bhasin S, et al. Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab. 2009;94(6):1991–2001.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Giannoulis MG, Sonksen PH, Umpleby M, Breen L, Pentecost C, Whyte M, et al. The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. J Clin Endocrinol Metab. 2006;91(2):477–84.CrossRefPubMedGoogle Scholar
  41. 41.
    Shrikrishna D, Tanner RJ, Lee JY, Natanek A, Lewis A, Murphy PB, et al. A randomized controlled trial of angiotensin-converting enzyme inhibition for skeletal muscle dysfunction in COPD. Chest. 2014;146(4):932–40.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Spira D, Walston J, Buchmann N, Nikolov J, Demuth I, Steinhagen-Thiessen E, et al. Angiotensin-converting enzyme inhibitors and parameters of sarcopenia: relation to muscle mass, strength and function: data from the Berlin Aging Study-II (BASE-II). Drugs Aging. 2016;33(11):829–37.CrossRefPubMedGoogle Scholar
  43. 43.
    Band MM, Sumukadas D, Struthers AD, Avenell A, Donnan PT, Kemp PR, et al. Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial. Trials. 2018;19(1):6.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Sumukadas D, Band M, Miller S, Cvoro V, Witham M, Struthers A, et al. Do ACE inhibitors improve the response to exercise training in functionally impaired older adults? A randomized controlled trial. J Gerontol A Biol Sci Med Sci. 2014;69(6):736–43.CrossRefPubMedGoogle Scholar
  45. 45.
    Bhasin S, Woodhouse L, Casaburi R, Singh AB, Mac RP, Lee M, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2005;90:678–88.CrossRefPubMedGoogle Scholar
  46. 46.
    Srinivas-Shankar U, Roberts SA, Connolly MJ, O’Connell MDL, Adams JE, Oldham JA, et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab. 2010;95:639–50.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Anton De Spiegeleer
    • 1
    • 6
    • 7
  • David Beckwée
    • 2
    • 3
    • 4
    • 5
    • 7
  • Ivan Bautmans
    • 3
    • 5
  • Mirko Petrovic
    • 1
    • 7
  • the Sarcopenia Guidelines Development group of the Belgian Society of Gerontology and Geriatrics (BSGG)
  1. 1.Section of Geriatrics, Department of Internal MedicineGhent UniversityGhentBelgium
  2. 2.Rehabilitation Sciences Research DepartmentVrije Universiteit BrusselBrusselsBelgium
  3. 3.Frailty in Ageing Research DepartmentVrije Universiteit BrusselBrusselsBelgium
  4. 4.Department of Rehabilitation Sciences and PhysiotherapyUniversity of AntwerpAntwerpBelgium
  5. 5.Department of Geriatric PhysiotherapySOMT University of PhysiotherapyAmersfoortThe Netherlands
  6. 6.VIB Inflammation Research Center, Unit for Molecular Immunology and InflammationGhent UniversityGhentBelgium
  7. 7.Working Group on Pharmacology of the Belgian Society of Gerontology and Geriatrics (BSGG)LovendegemBelgium

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