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Effect of 10 Days of Bed Rest on Skeletal Muscle in Healthy Older Adults
To the Editor: Older adults are more likely to be hospitalized and are at risk for functional decline during hospitalization. Bed rest may contribute to this functional compromise. We examined the effect of 10 days of bed rest in healthy older men and women on skeletal muscle protein synthesis, nitrogen balance, lean tissue mass, and lower extremity strength.
Methods
Twelve healthy older adults who were moderately active (mean [SD] age, 67 [5] years; 50% women) were recruited from advertisements and compensated for their participation. They remained in bed continuously for 10 days, except for toileting, and they consumed a eucaloric diet providing the recommended dietary allowance for protein (0.8 g/kg of protein per day). Measurements before and after bed rest included the fractional muscle protein synthesis rate over 24 hours, lean body mass by dual-energy x-ray absorptiometry (DEXA, Hologic Inc, Waltham, Mass), and unilateral knee extension strength (Cybex Strength Systems, Ronkonkoma, NY). Urinary nitrogen balance was determined before and during the bed rest period. Prophylactic measures were performed to prevent deep vein thrombosis, and ultrasound examination results were negative for all participants at the conclusion of the bed rest. One participant was excluded from all analyses due to insufficient protein intake; an additional participant was excluded from the DEXA analysis because a DEXA scan was not administered before bed rest, and another participant's fractional synthesis rate measurement was excluded because of a technical error.
Values for muscle protein synthesis, DEXA, and knee extension strength before and after bed rest were compared by paired t tests. Nitrogen balance data were analyzed with repeated measures analysis of variance and post hoc Tukey test. A change in the mean (SD) fractional synthesis rate of 0.034% (0.019%) per hour (2-tailed  = .05) would result in a power of 99.9% with 12 participants. However, when power was calculated with the actual changes for each parameter and the number of participants assessed, the following values were obtained: fractional synthetic rate, 77%; whole body lean mass, 90%; leg lean mass, 94%; strength, 97%; and nitrogen balance, 70%. Analyses were performed with Excel 2004 (Microsoft Corp, Redmond, Wash) and SPSS version 12.0 (SPSS Inc, Chicago, Ill). The institutional review board at each site approved this study, and each participant signed a written informed consent.
Results
Comparing values after bed rest with before bed rest values, there was a significant decrease in muscle protein synthesis (–0.027% per hour; 95% confidence interval [CI], –0.007 to –0.047% per hour; % change, –30%; 95% CI, –7% to –54%; P = .02), whole body lean mass (–1.50 kg; 95% CI, –0.62 to –2.48 kg; P = .004), lower extremity lean mass (–0.95 kg; 95% CI, –0.42 to –1.48 kg; P = .003), and strength (–19 Newton meters per second; 95% CI; –11 to –30 Newton meters per second; % change, –15.6%; 95% CI, –8.0% to –23.1%; P = .001; Table). Total mean nitrogen balance remained negative throughout the study (including before bed rest) but was significantly lower during the last half of the bed rest period compared with before bed rest (–30 mg/kg per day; 95% CI, –7 to –32 mg/kg per day vs –15 mg/kg per day; 95% CI, –3 to –27 mg/kg per day; P = .02; Figure). Total body fat did not change significantly (–0.07 kg; 95% CI; –0.67 to 0.53 kg; % change, –0.3%; 95% CI; –2.3 to 1.8). No differences between sexes were found.
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Table. Effects of 10 Days of Bed Rest in Older Adults
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Figure. Daily Nitrogen Balance (n=11)
Squares with error bars represent means and 95% confidence intervals for the time period. *Significantly different from days 1 through 4 and days 5 through 8 before bed rest (repeated measures analysis of variance with post hoc Tukey test, P = .02).
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Comment
In this group of healthy older adults, there was a large loss of skeletal muscle as a result of bed rest, particularly from the lower extremities. Participants experienced a greater lean tissue loss in 10 days than did young individuals after 28 days,1 whereas the decline in protein synthesis and strength was similar to that of younger participants after 14 days.2 Protein undernutrition is common in hospitalized older adults3; the participants in this study were in negative nitrogen balance even before bed rest despite being on a diet with the recommended dietary allowance for protein. Their nitrogen balance declined further during bed rest.
The results of this study cannot be directly extrapolated to chronically ill or frail elderly persons. However, the pronounced effect of bed rest alone on skeletal muscle mass and function suggests that this factor combined with the physiological stress and other deleterious factors associated with hospitalization4 may result in a more substantial loss of muscle size and function for many older adults during hospitalization. Further studies are needed to characterize other key components (eg, nutritional compromise, inflammation) compromising muscle function, as well as interventions to prevent or ameliorate the functional decline that frequently occurs in this patient population.
Drs Wolfe and Ferrando were affiliated with the University of Texas Medical Branch, Galveston, at the time of the study.
Author Contributions: Dr Kortebein had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Conception and design: Ferrando, Wolfe, Evans.
Acquisition of data: Kortebein, Ferrando, Lombeida, Evans.
Analysis and interpretation of data: Kortebein, Ferrando, Lombeida, Wolfe, Evans.
Drafting of the manuscript: Kortebein.
Critical revision of the manuscript for important intellectual content: Kortebein, Ferrando, Lombeida, Wolfe, Evans.
Statistical analysis: Kortebein, Ferrando, Wolfe, Evans.
Obtaining funding: Ferrando, Wolfe, Evans.
Administrative, technical, or material support: Kortebein, Ferrando, Lombeida, Evans.
Supervision: Ferrando, Wolfe, Evans.
Financial Disclosures: None reported.
Funding/Support: The work for this research letter was funded by grant PO1AG023591 from the National Institute on Aging (Evans). The studies were conducted in the General Clinical Research Center at the University of Arkansas for Medical Sciences and the University of Texas Medical Branch at Galveston, and funded by grant MO1 RR14288 (University of Arkansas Medical Sciences), and MO1 RR 00073 (University of Texas Medical Branch) from the National Center for Research Resources.
Role of the Sponsor: These organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Acknowledgment: We thank Douglas Paddon-Jones, PhD, Ola Ronsen, MD, PhD, and T. Brock Symons, PhD, of the University of Texas Medical Branch, Galveston, for their significant contributions toward the completion of this study, including data collection and analysis, as well as review of the manuscript. These individuals received compensation.
Patrick Kortebein, MD;
Arny Ferrando, PhD;
Juan Lombeida, MD;
Robert Wolfe, PhD
University of Arkansas for Medical Sciences
William J. Evans, PhD
evanswilliamj{at}uams.edu
Central Arkansas Veterans Healthcare System
Little Rock
1. Paddon-Jones D, Sheffield-Moore M, Urban RJ, et al. Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. J Clin Endocrinol Metab. 2004;89:4351-4358.
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2. Ferrando AA, Tipton KD, Bamman MM, Wolfe RR. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J Appl Physiol. 1997;82:807-810.
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3. Sullivan DH, Sun S, Walls RC. Protein-energy undernutrition among elderly hospitalized patients: a prospective study. JAMA. 1999;281:2013-2019.
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4. Hoenig HM, Rubinstein LZ. Hospital-associated deconditioning and dysfunction. J Am Geriatr Soc. 1991;39:220-222.
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Letters Section Editor: Robert M. Golub, MD, Senior Editor.
JAMA. 2007;297:1772-1774.
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