Current and Future Pharmacologic Treatment of Sarcopenia
Section snippets
Testosterone
Testosterone levels gradually decline in elderly men at a rate of 1% per year. Hypogonadism occurs in approximately 20% of men older than 60 years and 50% of men older than 80 years.2 Epidemiologic studies support a relationship between low levels of testosterone in elderly men and loss of muscle mass, strength, and function.3, 4
Currently, supraphysiologic doses of testosterone are known to dramatically increase muscle mass and strength in young subjects performing resistance training. However,
Cardiovascular drugs angiotensin II-converting enzyme inhibitors
Angiotensin II-converting enzyme (ACE) inhibitors improve the vital prognostic of patients with congestive heart failure, and can also reduce their functional decline. This beneficial effect is attributable to the cardiovascular actions but may also be related to the direct effect of ACE inhibitors on the skeletal muscle tissue.15, 102, 103, 104, 105 The activation of the renin-angiotensin-aldosterone system may be involved in the progress of sarcopenia, and growing evidence from basic and
Cytokine Inhibitors
The age-related inflammation process is supposed to play a crucial role in the development of sarcopenia through increasing myofibrillar protein degradation and decreasing protein synthesis. Anti-inflammatory drugs may delay its onset and progression. New drugs are currently being tested, mainly in the context of cachexia. Cytokine inhibitors, such as thalidomide, increase weight and lean tissue anabolism in patients with AIDS.156 In a model of cardiac cachexia, anti-TNF treatment attenuated
Creatine
Creatine supplementation increases energy storage through increasing intramuscular phosphocreatin.171 It may enable increased physical working capacity and resistance training, which stimulate muscle mass synthesis.172 The benefit of creatine on exercise performances has been reported repeatedly in young adults, and creatine was recently proposed to be a potential medication for the prevention and management of sarcopenia.1 However, few clinical trials in older people of creatine
Summary
Sarcopenia is a major cause of frailty and disability in older persons.193, 194 Relevant new pharmacologic drugs for sarcopenia will have a dramatic impact on improving the health and quality of life for elderly patients, reducing the associated comorbidity and disability and stabilizing rising health care costs. However, further clinical research on their effects on muscle physiology is needed before these new rising therapeutic can be recommended. The long-term safety and side effects must be
References (194)
- et al.
Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men
Metabolism
(1997) - et al.
Predictors of skeletal muscle mass in elderly men and women
Mech Ageing Dev
(1999) - et al.
Testosterone and leptin in older African-American men: relationship to age, strength, function, and season
Metabolism
(2000) - et al.
Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives
J Nutr Health Aging
(2008) - et al.
Validated treatments and therapeutics prospectives regarding pharmacological products for sarcopenia
J Nutr Health Aging
(2009) - et al.
Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women
Am J Clin Nutr
(2009) Testosterone and the aging male: to treat or not to treat?
Maturitas
(2010)- et al.
Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs)
Drug Discov Today
(2007) - et al.
Advances in understanding and treating cardiac cachexia: highlights from the 5th Cachexia Conference
Int J Cardiol
(2010) - et al.
Postmenopausal HRT and tibolone in relation to muscle strength and body composition
Maturitas
(2007)
Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial
Lancet
Muscle strength and tibolone: a randomised, double-blind, placebo-controlled trial
BJOG
Effects of tibolone on body composition in postmenopausal women: a 1-year follow up study
Maturitas
Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults
Metabolism
Skeletal muscle accretion and turnover in lean and obese (ob/ob) mice
Metabolism
The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action
Mol Aspects Med
Vitamin d redux
J Am Med Dir Assoc
Vitamin d deficiency/insufficiency practice patterns in a veterans health administration long-term care population: a retrospective analysis
J Am Med Dir Assoc
Vitamin D deficiency, muscle function, and falls in elderly people
Am J Clin Nutr
The rapid effects of 1,25-dihydroxyvitamin D3 require the vitamin D receptor and influence 24-hydroxylase activity: studies in human skin fibroblasts bearing vitamin D receptor mutations
J Biol Chem
Antagonism of myostatin enhances muscle regeneration during sarcopenia
Mol Ther
Nutritional recommendations for the management of sarcopenia
J Am Med Dir Assoc
Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade for prostate cancer
BJU Int
Effects of testosterone supplementation in the aging male
J Clin Endocrinol Metab
Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study
J Am Geriatr Soc
Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism
J Clin Endocrinol Metab
Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial
J Clin Endocrinol Metab
A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency
J Clin Endocrinol Metab
Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels
J Gerontol A Biol Sci Med Sci
Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status
J Gerontol A Biol Sci Med Sci
Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial
JAMA
Androgen treatment and muscle strength in elderly men: a meta-analysis
J Am Geriatr Soc
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
Dehydroepiandrosterone combined with exercise improves muscle strength and physical function in frail older women
J Am Geriatr Soc
Adverse events associated with testosterone administration
N Engl J Med
Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations
J Androl
Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline
J Clin Endocrinol Metab
Discovery of potent and muscle selective androgen receptor modulators through scaffold modifications
J Med Chem
Developing novel therapeutic approaches to frailty
Curr Pharm Des
Impaired growth hormone secretion in the adult population: relation to age and adiposity
J Clin Invest
Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men
J Clin Endocrinol Metab
Effect of growth hormone and resistance exercise on muscle growth and strength in older men
Am J Physiol
GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men
J Clin Endocrinol Metab
Growth hormone administration and exercise effects on muscle fiber type and diameter in moderately frail older people
J Am Geriatr Soc
Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women
J Clin Endocrinol Metab
Effects of growth hormone and insulin-like growth factor-1 on postoperative muscle and substrate metabolism
J Nutr Metab
Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein synthesis in healthy subjects over 60 years old
J Clin Endocrinol Metab
Effect of recombinant human growth hormone in elderly osteoporotic women
Clin Endocrinol (Oxf)
Testosterone and growth hormone improve body composition and muscle performance in older men
J Clin Endocrinol Metab
Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial
JAMA
Cited by (70)
Effects of losartan and exercise on muscle mass and exercise endurance of old mice
2022, Experimental GerontologySARC-F for Screening of Sarcopenia Among Older Adults: A Meta-analysis of Screening Test Accuracy
2018, Journal of the American Medical Directors AssociationCitation Excerpt :In addition, previous reports have noted that those diagnosed with sarcopenia using SARC-F are strongly associated with declined physical performance, quality of life, and death23 and hospitalization.28 The fact that positive sarcopenia screened using SARC-F is associated with clinically important outcomes also suggests the effectiveness of SARC-F. Treatment for sarcopenia includes resistance exercises, protein intake,29–31 and drug therapy to improve sarcopenia symptoms.32,33 Because sarcopenia is treatable,34 it is important to make an early diagnosis and rapidly implement treatment measures for sarcopenia; thus, SARC-F is useful for accomplishing this goal.
Sarcopenia
2017, Clinics in Geriatric MedicineFrailty, sarcopenia and diabetic kidney disease: where do we stand?
2023, International Urology and Nephrology