Sarcopenia: An Overview

C H R I S F O N T I M A Y O R M S - I I I M E R C E R U N I V E R S I T Y S C H O O L O F M E D I C I N E D R . R A H I M I – R T R M E D I C A L G R O U P , S A V A N N A H , G A 9 / 1 6 / 2 0 1 1

Sarcopenia

       20 years old “The age-associated loss of skeletal muscle mass and function” Cachexia – disease-related loss of body mass Muscle mass decreases by approximately 6% per decade in the average person beginning at age 45 Prevelance estimations are 5-13% of 60-70 year olds and 11-50% in population older than 80 Estimated direct health care cost attributable to sarcopenia in the U.S. in 2000 was $1.5 billion Diagnosis and treatment is not a standard part of the geriatric care in the U.S. as it is in Europe  No clear consensus on definition or diagnosis

Sarcopenia

     No reliable markers to distinguish true age-specific sarcopenia from other forms of muscle wasting (ie cachexia) Muscle wasting in older patients is almost always a combined effect of aging and disease Data has shown that muscle mass is not necessarily linear with muscle function Health ABC Study – muscle function is a better predictor of adverse outcomes than muscle mass Combination of both variables is helpful in studies

Mechanisms of Saropenia

    Atrophy and loss of skeletal muscle, mainly type II fibers Increased type I fibers  decreased strength increase endurance BUT Imbalance between protein synthesis and degradation rates  Positive/negative nitrogen balance Still unknown whether sarcopenia in elderly is an inevitable result of aging or due to a combination of illness, poor nutrition, inactivity, etc.

Etiologic Factors

        Inactivity Increased muscle fat Insulin resistance Loss of alpha motor neurons Decreased protein intake Increased IL-6 Loss of estrogen or testosterone Decreased growth hormone secretion

Diagnostic Criteria

    The European Society of Parenteral and Enteral Nutrition Special Interest Groups   Low muscle mass – percentage of muscle mass > 2 SDs below the mean in individuals aged 18-39 in the National Health and Nutrition Examination Survey III Cohort Walking speed <0.8 m/s in the 4-meter walk test or reduced performance in any functional test used to assess the geriatric population The European Working Group on Sarcopenia in Older People  Low muscle mass   Low muscle strength, eg, grip strength Low physical performance, eg, gait speed The International Working Group on Sarcopenia   Gait speed < 1m/s Objectively measured low muscle mass Measurement techniques   Dual-energy X-ray absorptiometry (DXA) Bioelectric impedance analysis (BIA)

Consequences of Sarcopenia

 Loss of functional status   New Mexico Elder Health Survey    Appendicular skeletal muscle mass (ASMM) estimated using a prediction equation (weight, height, hip circumference, grip strength, gender) Sarcopenia – ASMM/height² <7.26 for males and <5.45 for females Sarcopenia was significantly associated with a three to four-fold increase risk of self-reported physical disability National Health and Nutrition Examination Survey   Sarcopenia defined by the ratio of skeletal muscle mass by bioelectrical impedance divided by total body mass Sarcopenic participants reported an increased need for assistance with activities of daily living

Consequences of Sarcopenia

 Loss of functional status  Other epidemiologic studies note no association  Recent cross sectional study  109 men and women over the age of 60  Sarcopenia measured by Dual-emission X-ray absorptiometry (DXA) was not associated with self-reported functional limitations  EPIDOS study  Women above the age of 75  Extrapolated data showed no association between sarcopenia and decline in activities of daily living

Consequences of Sarcopenia

 Loss of functional status  Only one study examined CHANGES in body composition and its relationship with self-reported loss of daily function in the elderly  97 women (71.4) and 62 men (71.6)  DXA analysis and report of disability level at baseline, 2 years, 5.5 years  Participants with loss of ASMM (cut-off at median change in muscle mass) had a 2.15-fold increased risk of having a worsening disability compared to those whose ASMM remained stable  Further research needed due to differing results of studies

Consequences of Sarcopenia

 Fall Risk    Not much data on relationship between muscle mass in old age and risk of falls (2 major studies, retrospective, 12 months) New Mexico, 883 elderly, sarcopenic Hispanic and Non Hispanic white males and females with mean age of 74  22% of males and 31% of females reported a fall in the past year  After adjustment for confounding factors, the odds ratio for falls in males was statistically significant but not in females MINOS study – 796 males aged 50 to 85    25.4% reported falls in the past year After adjustment for confounding factors, the odds ratio per SD lower of relative appendicular muscle mass (RAMM) was 1.31

Men in the highest tertile for RAMM were less likely to report falls in the previous year than those in the lower quartile for RAMM

Consequences of Sarcopenia

 Fall Risk   Problem with the 2 studies being retrospective  Cannot exclude muscle mass has declined as a result of the fall Warrants prospective studies on the relationship between loss of muscle mass and fall risk

Consequences of Sarcopenia

 Mortality   1396 men and women aged 70 years and older  After confounding adjustments, low arm muscle area (≤21.4 cm² for men and ≤21.6 cm² for women) was associated with an 8 year mortality risk ( hazard ratio (HR)= 1.95) 957 community-dwelling Japanese men and women aged 65 to 102 years old  Low arm muscle area (<23.5 cm²) was associated with a higher mortality risk (HR=2.03) compared to high muscle area (≥33.4 cm²)  236 people died before the 2 year follow up

Consequences of Sarcopenia

 Mortality   4107 British men aged 60 to 79 years old  Low mid arm muscle circumference was associated with an increased risk of mortality during a 6-year follow up Many more large studies demonstrating that low upper body muscle mass is associated with an increased risk of mortality in elderly men and women

Consequences of Sarcopenia

 Mortality  Recently, large epidemiologic studies have been using more accurate measures of skeletal muscle mass  Health, Aging and Body composition study  2292 well functioning men and women aged 70 to 79      Leg skeletal muscle mass measured with DXA and mid-thigh muscle cross-sectional area from CT scan Confounding factors were adjusted for Low mid-thigh muscle area was associated with increased mortality risk for men (per SD of 28.1 cm² lower muscle area the HR was 1.26) This risk not found in women (HR=0.94) Mean follow up was 4.9 years in which 286 people died

Consequences of Sarcopenia

 Mortality  InChianti study  934 Italian men and women aged 65 or older  Muscle cross-sectional area of the calf with quantitative CT scan  After adjustment for confounders, no increased risk of mortality for low muscle mass  Muscle density of calf not related to mortality risk  715 French men and women aged 50 to 85 years  Baseline appendicular skeletal muscle mass was not associated with increased mortality when adjusted for confounding factors

Consequences of Sarcopenia

 Mortality  Framingham Heart Study and MINOS study  Prospective studies that examined the CHANGE in muscle mass over time and its relationship with mortality risk  Both showed that accelerated muscle mass loss is a risk factor for mortality in the elderly   Heterogeneity in the literature Further research is warranted

Pharmacologic Treatment

 Hormonal Approach  Testosterone       Increases the rate of muscle protein synthesis and # of muscle satellite cells In hypogonadal elderly men, has been shown to increase muscle mass and strength and to decrease fat mass BUT inconclusive results from studies evaluating effectiveness in muscle strength and functionality in community-dwelling populations A 2006 meta-analysis of 11 studies suggested a moderate increase in muscle strength Healthy men aged 60 to 80 with low testosterone  Testosterone replacement therapy over 6 months showed increases in lean muscle mass, but no improvement in strength and function Large clinical trials are necessary

Pharmacologic Treatment

 Hormonal Approach  Growth hormone (GH)  Promotes muscle growth via insulin-like growth factor I (IGF-I)  30% of men older than 60 years are GH deficient  In elderly men, many clinical trials show no additional benefit of GH in combination with exercise or testosterone therapy  Possibly due to small sample size, lack of pulsatile pattern of GH administration, high incidence of side effects  However, other studies report that a few months of GH therapy significantly increases lower extremity muscle strength and mass in healthy, elderly men and women  Further research needed

Pharmacologic Therapy

 Hormonal Approach  Estrogen  Some evidence links estrogen replacement to muscle mass and strength  Few clinical trials included older women  5 clinical trials assessed the effect of estrogens on muscle strength in women  3 reported statistically significant improvement in muscle strength, 2 studies were negative

Pharmacologic Treatment

 Hormonal Approach  Vitamin D     Hypovitaminosis D has a high prevelance in the elderly population Proximal muscle weakness is a clinical symptom of Vit. D deficiency Nutritional recommendations for sarcopenia are to measure levels and provide supplementation if less than 100 nmol/L Several randomized controlled trials have reported Vit. D supplementation improves muscle strength   In people aged 65 and above, 800 IU of Vit. D3 significantly improves lower extremity strength and function by 4% to 11% and body sway by 28% after 2 to 12 months of therapy A recent meta-analysis reported that 700-1000 IU/day reduces fall risk by 19% in the elderly

Pharmacologic Treatment

 Hormonal Approach  Myostatin Inhibitors  Myostatin decreases protein synthesis leading to decreased muscle cell synthesis  Follistatin – myostatin-binding protein, recombinant Abs against myostatin, activin type IIB receptor (ActRIIB-Fc) - soluble myostatin decoy receptor  Animal models show promise, however experts report muscle tissue may be more susceptible to injury in mice with myostatin deficiency  A randomized, double-blind, phase I study on healthy post menopausal women demonstrated a 2.4-2.6% increase in muscle mass after 15 days of treatment with ActRIIB-Fc

Pharmacologic Treatment

 Statins  In a longitudinal study performed on community dwelling elderly adults, statin therapy was associated with declines in muscle strength and increased risk of falls   However, this was not confirmed by other authors There is a consensus that statins increase appendicular lean muscle mass, especially after resistance training  Small tissue injury  hypertrophy local release of growth factors  muscle  Further studies are needed to assess the effect of statins on muscle strength and functionality

Pharmacologic Treatment

 Creatine    Increases energy storage via increasing intramuscular phosphocreatine Benefits on exercise performance in young adults are well documented Few trials on the elderly population  Mixed results on increases in muscle mass and strength  Physical Activity  Partially reverses the age-related declines in muscle mass and dysfunction

Summary

    Sarcopenia is a possible major cause of frailty and disability in the elderly population Fresh research topic that needs increased attention and awareness Further research will improve care and treatment to help lower health care costs related to sarcopenia The hope is for a consensus on sarcopenia  part of clinical practice routine

References

 Rolland, Yves (editor). Sarcopenia. Clinics in Geriatric Medicine, August 2011; 27 (3); 341-482.