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00005768-201101000-0001900005768_2011_43_146_loehr_musculoskeletal_1miscellaneous-article< 147_0_32_14 >Medicine & Science in Sports & Exercise©2011The American College of Sports MedicineVolume 43(1)January 2011pp 146-156Musculoskeletal Adaptations to Training with the Advanced Resistive Exercise Device[APPLIED SCIENCES]LOEHR, JAMES A.1; LEE, STUART M. C.1; ENGLISH, KIRK L.2; SIBONGA, JEAN3; SMITH, SCOTT M.4; SPIERING, BARRY A.1; HAGAN, R. DONALD4†1Wyle Integrated Science and Engineering Group, Houston, TX; 2JES Tech, Houston, TX; 3Universities Space Research Association, Houston, TX; and 4NASA Johnson Space Center, Houston, TXAddress for correspondence: James A. Loehr, M.S., Space Physiology and Countermeasures, NASA Johnson Space Center, 2101 NASA Parkway, Mail code: SK3, Houston, TX 77058; E-mail:†Deceased.Submitted for publication October 2009.Accepted for publication April 2010.ABSTRACTResistance exercise has been used as a means to prevent the musculoskeletal losses associated with spaceflight. Therefore, the National Aeronautics and Space Administration designed the Advanced Resistive Exercise Device (ARED) to replace the initial device flown on the International Space Station. The ARED uses vacuum cylinders and inertial flywheels to simulate, in the absence of gravity, the constant mass and inertia, respectively, of free weight (FW) exercise.Purpose: To compare the musculoskeletal effects of resistance exercise training using the ARED with the effects of training with FW.Methods: Previously untrained, ambulatory subjects exercised using one of two modalities: FW (6 men and 3 women) or ARED (8 men and 3 women). Subjects performed squat, heel raise, and dead lift exercises 3 d·wk−1 for 16 wk. Squat, heel raise, and dead lift strength (one-repetition maximum; using FW and ARED), bone mineral density (via dual-energy x-ray absorptiometry), and vertical jump were assessed before, during, and after training. Muscle mass (via magnetic resonance imaging) and bone morphology (via quantitative computed tomography) were measured before and after training. Bone biomarkers and circulating hormones were measured before training and after 4, 8, and 16 wk.Results: Muscle strength, muscle volume, vertical jump height, and lumbar spine bone mineral density (via dual-energy x-ray absorptiometry and quantitative computed tomography) significantly increased (P ≤ 0.05) in both groups. There were no significant differences between groups in any of the dependent variables at any time.Conclusions: After 16 wk of training, ARED exercise resulted in musculoskeletal effects that were not significantly different from the effects of training with FW. Because FW training mitigates bed rest-induced deconditioning, the ARED may be an effective countermeasure for spaceflight-induced deconditioning and should be validated during spaceflight.Decreased muscle function and loss of bone strength during long-duration spaceflight may jeopardize crew health and mission success by impairing or limiting work performance or by increasing the risk of muscle injury or bone fracture. During bed rest, a spaceflight analog, high-intensity resistance exercise protects against musculoskeletal deconditioning (6,5,12,27). Therefore, the National Aeronautics and Space Administration (NASA) deployed the interim Resistive Exercise Device (iRED) in 2001 as an exercise countermeasure during long-duration stays aboard the International Space Station (ISS). Despite the availability of the iRED, results from long-duration ISS missions (≥4 months) indicate that astronauts continue to lose muscle mass, muscle strength, and bone mineral density (BMD) (16,31).Several factors limit the effectiveness of the iRED as a countermeasure to spaceflight-induced musculoskeletal deconditioning. First, the peak resistance is limited to 136 kg (300 lb) (26); this is less than the resistance shown to be effective in previous bed rest studies (5,6,27). Further, considering that body mass will not contribute to overall resistance in spaceflight, a 75-kg astronaut who performed a squat (SQ) with the iRED's peak resistance on the ISS would experience a load roughly equivalent to the resistance from performing a SQ with only 60 kg of load in normal gravity (20). Second, during the eccentric portion of the movement, the force is only ∼70% of the corresponding concentric force (26), and a lack of eccentric resistance may compromise strength gains because of a suboptimal intensity (9). Finally, the iRED provides a variable resistance in which force increases as the cable is extended farther from the iRED. During closed-chain exercises (i.e., SQ, heel raise (HR), and dead lift (DL)), the iRED may be providing insufficient resistance at the bottom of the movement, where the muscles are most active (11), and greater resistance at the top, where the muscles are working less owing to an increased mechanical advantage (4).To address the limitations of the iRED, NASA developed the Advanced Resistive Exercise Device (ARED), in the hope that its improved functionality would more completely protect the musculoskeletal system during long-duration spaceflight. Specifically, the ARED uses vacuum cylinders to provide a concentric resistance up to 272 kg (600 lb), an eccentric-concentric ratio of ∼90%, and a constant force throughout the range of motion. In addition, inertial flywheels were integrated into the resistance path of each vacuum cylinder to simulate the inertial characteristics of free weight (FW) exercise, an effective method to protect against muscle atrophy and bone loss during bed rest (27).The purpose of this study was to compare the musculoskeletal adaptations to 16 wk of resistance exercise training with the ARED to training with FW in healthy, untrained, ambulatory men and women. First, we hypothesized that 16 wk of training with the ARED or with FW would result in significant increases in muscle strength, muscle volume, lean tissue mass, vertical jump (VJ) height, and BMD. Second, we hypothesized FW would increase muscle strength, muscle volume, lean tissue mass, and BMD to a greater extent than ARED because of the differences in inertial characteristics of the ARED flywheels and FW. We further hypothesized that there would be a difference between the groups for markers of bone formation and resorption and for blood concentrations of anabolic and catabolic hormones.METHODSSubjects.Twenty-two volunteers (mean ± SD; age = 34 ± 6 yr, body mass = 77.1 ± 12.1 kg, height = 171 ± 9 cm), 16 men and 6 women, were recruited by the Human Test Subject Facility at NASA Johnson Space Center to participate in this study. The ratio of men to women was chosen specifically to mimic the distribution of men and women in the astronaut corps (15). Before they were enrolled in the study, all subjects passed a modified Air Force Class III physical examination, which included a comprehensive evaluation to exclude subjects with metabolic, musculoskeletal, or cardiovascular disease, soft tissue or joint injuries, and lumbar spine and hip BMD less than 2 SD below that of the healthy population mean measured by a dual-energy x-ray absorptiometry (DXA). Testing protocols were reviewed and approved by the NASA Johnson Space Center Committee for the Protection of Human Subjects. Subjects received written and verbal explanations of the study procedures and provided written informed consent before participating. Two subjects withdrew from the study before completing all the training and were not replaced. One subject had scheduling conflicts that did not allow adherence to the prescribed training schedule, and the other withdrew because of a musculoskeletal injury unrelated to the study.The subject screening, selection criteria, and dietary controls were similar to those used in a previous study from our laboratory (26). Subjects had not participated in a resistance training program for at least 6 months before entering the study and performed only the prescribed resistance exercise protocol during the study. They were instructed to maintain their prestudy aerobic exercise habits (intensity, frequency, and duration) and not to initiate any new exercise programs during the study. A similar number of subjects (FW n = 6 and ARED n = 8) in both groups participated in various types of light to moderate aerobic exercise (i.e., jogging, walking, swimming) approximately 1-2 d·wk−1 for the duration of the study. Subjects were instructed to maintain their dietary habits for the duration of the study and to not take any nutritional supplements that might affect muscle performance, lean tissue mass, or bone metabolism.Experimental design and procedures.The total length of the study was 24 wk. It was composed of 6 wk of pretraining tests, 16 wk of training, and 2 wk of posttraining tests (Fig. 1). Subjects were not assigned randomly because a planned NASA bed rest study required the only available ARED unit. The first subjects to be selected were assigned to the ARED training group to ensure that all testing and training were completed before the ARED was needed for the planned bed rest study. The rest of the subjects were assigned to the FW training group after the ARED training subjects had completed the study.FIGURE 1-Timeline of the study.Resistance exercise training protocol.Each group performed the parallel SQ, HR, and DL exercises (the primary lower body exercises prescribed during spaceflight) 3 d·wk−1 for 16 wk. The level of resistance used during training for each group was based on a percentage of the pretraining and midtraining one-repetition maximum (1-RM) using the exercise hardware (FW or ARED) corresponding to their group assignment. A periodized training protocol was used, in which the resistance varied in a predetermined fashion within each week and every subsequent week (2) (Fig. 2). The protocol was derived from the astronaut in-flight resistive exercise prescription, which was developed by the Astronaut Strength Conditioning and Rehabilitation specialists responsible for designing astronaut exercise protocols. The first exercise day (day 1) of each week was considered the heavy resistance day, day 2 was the light resistance day (10% less resistance than day 1), and day 3 was a moderate resistance day (5% less resistance than day 1). For example, a heavy resistance day in which training was performed with loads equivalent to 80% 1-RM would be followed by training with 70% 1-RM for the light day and training with 75% 1-RM for the moderate day. Subjects performed the same number of sets and repetitions within each week, while the number of sets and repetitions changed each week to correspond to the given intensity. The exercise prescription included several warm-up sets performed before the training sets (highest resistance) during each session. Each subject was required to complete at least 90% of the total number of training sessions.FIGURE 2-Exercise intensity and volume across the training study by week. Within a week, training intensity is represented by percentage 1-RM for the heavy day of training. Training resistance in the first 8 wk was determined based on pretraining 1-RM measurements. Midtraining 1-RM strength was measured during week 9 and was used to prescribe the training intensity for the remainder of the study.Exercise hardware.ARED training and testing were performed using a version of the NASA-designed device (NASA Johnson Space Center, Houston, TX; Fig. 3A) identical to the one constructed for use on ISS. The ARED was designed to mimic two components of FW exercise: 1) constant resistance, provided by two vacuum cylinders; and 2) the inertial component of moving a constant mass, simulated by two flywheels within each cylinder's resistance path (Fig. 3B). ARED bar exercises are "semi-free form" exercises; lateral motion follows a fixed path with the ARED, similar to a smith machine, but unlike a smith machine, the ARED allows fore-aft motion (Fig. 4).FIGURE 3-A, The ARED as it was used in this study. B, The resistance was primarily provided by two vacuum cylinders, and forces due to inertia that are experienced during FW exercises were simulated using a flywheel assembly.FIGURE 4-Demonstration of SQ performed using the ARED. Lines have been drawn to demarcate the yoke and upright support of the ARED, and the angle between them throughout the range of motion, illustrating the fore-aft movement and the semi-free form motion of ARED exercise.Air is evacuated from inside the cylinders to create a vacuum, and resistance is created when the pistons inside the cylinders are pulled away from the top of the vacuum-sealed cylinders. As the bar is lifted away from the platform, the vacuum inside the cylinders resists against the motion of the piston, trying to pull the piston back to the starting position. Therefore, concentric resistance is created as the subject pulls against the vacuum, and eccentric resistance is created as the subject resists against the vacuum pulling the piston back to the starting position. Because the vacuum is constant, the amount of resistance is adjusted by changing the length of the lever arm through which the piston is pulled, thereby increasing or decreasing mechanical advantage. To ensure accurate resistance, a weekly four-point static calibration between 0 and 272 kg (600 lb) was performed using a calibrated measurement tool and procedure designed by NASA for in-flight ARED calibration. In addition, a monthly seven-point static calibration using a load cell was performed between 0 and 114 kg (250 lb) to validate a greater number of resistances within the potential range of prescribed values. Resistance never varied more than ±1.7 kg at any calibration point throughout the study.Testing and training for the FW SQ, HR, and DL were performed using a standard Olympic bar and weights. A lighter Olympic training bar (6.8 kg, 15 lb) was used for smaller individuals whose warm-up resistance was less than 20.5 kg (45 lb). The SQ exercise was performed using a half rack (York Barbell Company, York, PA), and the HR was performed using a standard Smith machine (Bigger, Faster, Stronger 30052; Salt Lake City, UT). Because the lowest setting for the ARED bar height for the DL was 2 cm higher than the height of the Olympic bar with standard Olympic plates, two dense foam pads were placed beneath the plates during FW DL exercise to ensure identical starting positions on both devices.1-RM testing.Each subject completed six 1-RM testing sessions during the pretraining period, two during the midtraining period, and two during the posttraining period (Fig. 1). During the pretraining period, three 1-RM tests were conducted using the ARED and three using FW; all three 1-RM tests on a given device were performed consecutively before testing with the other device. The first 1-RM session for each modality was used to familiarize each subject with the hardware and testing procedures as well as to establish a preliminary 1-RM. The pretraining 1-RM scores were defined as the highest resistance lifted during the subsequent two 1-RM test sessions. All six sessions were separated by at least 5-7 d to avoid a training effect, fatigue, and muscle soreness. The FW and ARED midtraining and posttraining 1-RM sessions were conducted during 1-wk periods and were separated by a minimum of 3 d. The order of devices used for the 1-RM testing was randomized for each subject at each time point (pretraining, midtraining, and posttraining).Tests to obtain 1-RM were conducted using a progression of resistance from low warm-up sets to maximal efforts. The first two sets consisted of eight repetitions at 50% and 60% of 1-RM, respectively, followed by a set of five repetitions at 70% 1-RM and a set of three repetitions at 80% 1-RM. Subsequent sets of one repetition were performed at 90% and 100%, and until the subject could not lift the resistance through the desired range of motion using proper technique. Approximately 2-3 min of rest was given between each set. A 1-RM session was terminated if the subject failed on two consecutive attempts to lift a given resistance or if their technique was poor. Certified Strength and Conditioning Specialists evaluated the technique and form of each subject according to National Strength and Conditioning Association guidelines and oversaw all testing and training sessions. Values for the initial 1-RM session for each device were approximated on the basis of subject feedback and performance. The values for the remaining 1-RM test sessions were based on the 1-RM achieved during the previous test session.During the familiarization session, the depth and height of the SQ and HR, respectively, were established and recorded using a linear encoder (Ergotest Technology, Langesund, Norway) and customized software program (LabVIEW 7.2; National Instruments, Austin, TX). The appropriate SQ depth was achieved when the midline of the thigh was parallel to the floor, and HR height was determined as the maximum height achieved during the performance of the 80% 1-RM value. During all subsequent 1-RM tests, the linear encoder and software were used to verify that the subject achieved the appropriate range of motion by generating an audible cue to indicate that the appropriate depth or height had been reached. The DL was considered successful if the subject was able to lift the bar from the floor to the upright position using proper technique. A pilot study conducted in our laboratory revealed three FW 1-RM sessions were needed to obtain an intraclass correlation coefficient (ICC) ≥ 0.90. In the current study, the reliability of FW and ARED 1-RM testing for the SQ, HR, and DL was between 4% and 6%.VJ.Three countermovement VJ with a minimum of 30 s of rest between jumps were performed in the pretraining, midtraining, and posttraining periods on the same day as, but before, the first FW 1-RM testing session. Subjects were instructed on proper jumping technique before each session and performed three or four practice jumps before performing the test. VJ height, determined using a Vertec (Perform Better, Cranston, RI), was defined as the maximum height achieved during the three repetitions. Using similar methods, Moir et al. (22) reported that these tests can be performed with a precision of 2.4%.Magnetic resonance imaging.Muscle volumes of the calf and thigh were determined before and after training using a Signa Horizon LX 1.5T MRI System (General Electric, Piscataway, NJ) at a local hospital (Clear Lake Regional Medical Center, Webster, TX). The posttraining magnetic resonance imaging (MRI) was performed in the week after 1-RM measurement to avoid potential fluid shifts resulting from performing two 1-RM measures in the same week. A hospital MRI technician acquired the desired images under the supervision of a member of the research staff. Subjects wore standard medical scrubs and removed all metal (such as jewelry) before the technician positioned the subject on the MRI table for scanning. To control for the effects of fluid shifts on these data, subjects were recumbent for a minimum of 15 min before data acquisition.The subject's feet were positioned in a holder to minimize movement during image acquisition and to ensure repeatable positioning. The imaged portion of the limb was suspended, whereas the nonimaged portion was supported with foam. Each scan was "landmarked" at the base of the patella, and thirty-two 1.0-cm slices were obtained for both the thigh and calf muscles, using an echo time of 14 ms and a repetition time of 800 ms. The order for thigh and calf measurements was maintained across imaging sessions. A phantom was used to periodically determine pixel size stability and showed no change during the study. Using the same method, we have reported a test-retest reliability of 2.3% (26).For each muscle region, the outlined area (pixels) was plotted against position (mm). After appropriate adjustments to compare identical regions, volume was obtained by adding the number of pixels under each area curve and converting to cubic centimeters. Typically, this precluded using the entire scanned region because of slight positioning errors between repeat scans during the study (26).Quantitative computed tomographyQuantitative computed tomography (QCT) scanning of the hip and spine was performed before and after training using a Lightspeed Ultra 8-slice CT scanner (General Electric) at a local hospital (Clear Lake Regional Medical Center). A trained and experienced hospital technician acquired the desired images under the supervision of a member of the research staff. The subject wore standard medical scrubs and removed all metal (such as jewelry) before the technician positioned the subject in the CT scanner. The volumetric spine CT scan was performed first. A phantom was placed under the subject's lower back and was scanned simultaneously to calibrate the CT Hounsfield units to equivalent concentrations of calcium hydroxyapatite. As part of the scanning protocol, an initial lateral-view scout scan was acquired to determine the location of the L1 and L2 vertebrae. The actual L1-L2 scan was then acquired, using 5 mm above the L1 superior end plate and 5 mm below the L2 inferior end plate as the outer limits of the scan region. The slice thickness was 2.5 mm.The subject was then repositioned for the hip (femur) scan. The phantom was placed under the patient in the scan region so that the head end of the phantom aligned with the iliac crest of the subject. A scout scan was acquired to define the hip scanning volume. The hip scan limits were set at 1 cm superior to the superior aspect of the femoral head and at 5 mm inferior to the inferior aspect of the lesser trochanter. The hip scan was acquired using a slice thickness of 2.5 mm. Femoral neck, trochanter, total femur, and spine volumetric BMD (vBMD) were obtained using methods described previously (16). Li et al. (21) have reported a precision of 4.5%, 0.6%, 0.8%, and 2.0%, respectively, for these measurements. Posttraining QCT measures were performed in the week after 1-RM measurement to avoid scheduling conflicts.DXA.Pretraining and posttraining BMD (g·cm−2) was measured using DXA for each of three body scanning sites: whole body, spine, and hip. To ensure the reliability of the DXA measurements, all pretraining and posttraining scans were conducted and analyzed by the same operator. Measurements were obtained in triplicate for each site using a fan-beam x-ray densitometer (Discovery; Hologic, Inc., Bedford, MA). All measures of areal BMD (aBMD) were obtained using previously reported techniques with a precision of 1% for the whole body, 1.4% for the lumbar spine, and 1.5% for the femoral neck (27). Whole-body lean mass and leg lean mass were calculated using previously published methods with a precision of 0.9% and 1.3%, respectively (27). DXA measures were performed before any strength measures to minimize any effects of fluid shifts.Bone and muscle biomarkers.Urine samples were collected as separate voids into individual bottles during a period of 24 h. The volume of each was determined, and a 24-h pool was prepared. After total volume and pH measurements were made, aliquots were removed, processed, and frozen at −70°C until batch analysis. Urine samples were analyzed for collagen cross-links using commercially available kits (Pyrilinks and Pyrilinks-D (Quidel, Inc., Santa Clara, CA) or Osteomark ELISA Kit (Ostex International, Inc., Seattle, WA)). Serum and urinary calcium were determined by atomic absorption spectrophotometry. Urinary creatinine and phosphorus were determined spectrophotometrically. Urinary 3-methyl histidine (3-MH) was analyzed on a Hitachi L-8800 Amino Acid Analyzer (Hitachi Instruments Incorporated, Danbury, CT). Biochemical tests were completed using previously published methods (28,29,35).Fasting (>10 h) blood samples were collected in the morning before any exercise for that week. Samples were stored at −70°C and assayed after all subjects had completed the study. Circulating bone- and calcium-related factors (such as intact parathyroid hormone (PTH) and vitamin D metabolites) were assessed in serum. Bone-specific serum alkaline phosphatase (BSAP) and osteocalcin, which are markers of bone formation, were also measured. All biochemical tests were completed using previously published methods (28,29,35). Serum and urinary cortisol (DiaSorin, Stillwater, MN) and insulin-like growth factor (IGF-1; Diagnostic Systems Laboratories, Webster, TX) were analyzed by radioimmunoassay. Growth hormone and testosterone (both free testosterone and total testosterone) were also analyzed by radioimmunoassay (Diagnostic Products Corp., Los Angeles, CA).Statistical analyses.A power analysis was performed to determine the required number of subjects to achieve statistical significance based on expected increases in muscle strength, the primary dependent variable of interest. Assuming that the mean increase in strength would be similar to that observed in the previous training study in our laboratory (26) and that all assumptions of the test were met, eight subjects per group were needed to detect a difference between training groups with an α of 0.05 and a power of 0.80. To model the distribution of men and women in the astronaut corps (15), three additional female subjects were included in each study group. All data were analyzed using a two-way repeated-measures ANOVA. The Tukey post hoc analysis was performed when the ANOVA revealed significant differences. The criterion for statistical significance was set a priori at P ≤ 0.05. All data are presented as the mean ± SE, unless otherwise noted.RESULTSExercise training.There were no statistically significant differences between groups concerning height, body mass, or age, and training had no effect on body mass in either group (Table 1). Overall subject compliance across the 16 wk of training for the FW and ARED groups was 97% and 98% of the prescribed exercise sessions, respectively. If a subject was unavailable for exercise training as prescribed, a makeup session was scheduled in most cases. In the event a full week of training was missed, the training schedule was altered to include up to 4 d·wk−1 of training immediately before and/or after a missed week of training; all others were considered missed sessions. The groups did not differ significantly in the percentage of exercise prescription completed, repetitions completed per workout, or peak resistance lifted during the training period (Table 2).TABLE 1. Age, height, and body weight (mean ± SE).TABLE 2. Percentage of overall prescription completed, repetitions completed per workout, and peak load lifted during the training period (mean ± SE).Muscle strength.FW SQ strength increased during training in both groups (Fig. 5), and a significant group × time interaction occurred. In the FW group, FW SQ strength increased from pretraining to midtraining (31.9% ± 4.9%), midtraining to posttraining (12.9% ± 1.9%), and pretraining to posttraining (48.9% ± 6.1%). In the ARED group, FW SQ strength increased only from pretraining to midtraining (28.2% ± 4.3%) and from pretraining to posttraining (31.2% ± 3.8%). However, FW SQ strength was not significantly different between groups at any time point. Similarly, ARED SQ strength increased in both groups during training (Fig. 5), and a significant group × time interaction occurred. In the FW group, ARED SQ strength increased from pretraining to midtraining (28.6% ± 4.5%), midtraining to posttraining (9.7% ± 1.9%), and pretraining to posttraining (41.1% ± 5.3%). In the ARED group, ARED SQ strength increased only from pretraining to midtraining (20.2 ± 2.9%) and from pretraining to posttraining (26.3% ± 3.0%). However, there was no significant difference between groups at any time point for ARED SQ strength.FIGURE 5-SQ, HR, and DL 1-RM strength (mean ± SE) of the FW and ARED training groups during FW and ARED testing at pretraining, midtraining, and posttraining. *Significantly greater than at pretraining. †Significantly greater than at midtraining.FW HR strength increased in both the ARED and FW groups, but there was no group × time interaction. FW HR strength (Fig. 5) increased from pretraining to midtraining (ARED = 14.2% ± 2.4%, FW = 7.9% ± 2.0%) and from pretraining to posttraining (ARED = 18.0% ± 1.6%, FW = 12.3% ± 2.4%). ARED HR strength also increased in both groups, with a significant group × time interaction. The ARED training group increased ARED HR strength from pretraining to midtraining (22.3% ± 2.7%), midtraining to posttraining (8.4% ± 2.6%), and pretraining to posttraining (32.7% ± 4.6%), whereas the FW training group increased ARED HR strength from midtraining to posttraining (11.3% ± 2.5%) and from pretraining to posttraining (13.8% ± 4.2%). However, no significant difference occurred between groups in ARED HR strength at any time.There was a significant main effect of time for FW DL strength but no group × time interaction. Both groups increased FW DL strength (Fig. 5), measured using the FW hardware, from pretraining to midtraining (ARED = 13.1% ± 2.1%, FW = 13.0% ± 2.7%), from midtraining to posttraining (ARED = 9.1% ± 2.6%, FW = 9.0% ± 2.1%), and from pretraining to posttraining (ARED = 23.2% ± 2.8%, FW = 23.3% ± 4.4%). When testing was conducted with the ARED, both groups increased in ARED DL strength from pretraining to midtraining (ARED = 15.1% ± 3.3%, FW = 11.0% ± 3.0%) and from pretraining to posttraining (ARED = 20.0% ± 3.0%, FW = 18.1% ± 3.7%).VJ height.VJ height increased in both groups, and there was a significant group × time interaction (Fig. 6). The FW training group increased in VJ height from pretraining to midtraining (11.5% ± 2.1%) and from pretraining to posttraining (14.3% ± 2.7%); the ARED training group increased from pretraining to posttraining (8.4% ± 2.1%) only. However, there was no significant difference between groups at any time point for VJ height.FIGURE 6. VJ height (mean ± SE) of the FW and ARED training groups pretraining, midtraining, and posttraining. *Significantly different from pretraining.MRI.Thigh muscle volume (Fig. 7) increased in both groups from pretraining to posttraining (ARED = 7.1% ± 1.2%, FW = 9.8% ± 0.9%). Lower leg muscle volume increased from pretraining to posttraining in the FW group (FW = 3.0% ± 1.1%, P ≤ 0.01) and tended to increase (P = 0.09) in the ARED group (ARED = 2.1% ± 0.7%). There were no significant differences between groups for thigh or lower leg muscle volume.FIGURE 7-Volume of thigh and lower leg muscles (mean ± SE) of the FW and ARED training groups pretraining and posttraining. *Significantly greater than pretraining.Lean tissue mass.Whole-body lean mass (Table 3) increased significantly in both groups from pretraining to midtraining (ARED = 2.4% ± 0.5%, FW = 2.5% ± 0.6%) and from pretraining to posttraining (ARED = 2.6% ± 0.7%, FW = 2.5% ± 0.7%), and leg lean mass increased significantly from pretraining to midtraining (ARED = 3.2% ± 0.7%, FW = 3.6% ± 0.9%) and from pretraining to posttraining (ARED = 4.8% ± 0.7%, FW = 3.9% ± 1.1%). There were no significant differences between groups for either measure.TABLE 3. Whole-body and leg lean mass (mean ± SE) pretraining, midtraining, and posttraining.QCT.Lumbar spine trabecular vBMD increased in both groups from pretraining to posttraining (ARED = 12.3% ± 3.1%, FW = 8.9% ± 2.4%; Table 4), and there was no difference between groups. Trabecular vBMD of the total femur, femoral neck, and trochanter did not change significantly from the pretraining period in either group.TABLE 4. Trabecular vBMD (mean ± SE) before and after 16 wk of training.BMD.Both groups showed an increase in lumbar spine aBMD from pretraining to posttraining (Table 5). A group × time interaction occurred for greater trochanteric aBMD. In the FW group, greater trochanter aBMD increased from pretraining to midtraining and tended to increase from pretraining to posttraining (P = 0.07), but no significant difference occurred in the ARED group. Training had no effect on total hip or femoral neck BMD. There was no significant difference between groups at any time point for any of the BMD variables.TABLE 5. aBMD (mean ± SE) before, during, and after 16 wk of training.Bone and muscle biomarkers.A main effect of training occurred in IGF-1, serum cortisol, PTH, BSAP, osteocalcin, N-telopeptide (NTX; expressed either as per day or per creatinine), and helical peptide (per day or per creatinine; Tables 6 and 7); however, post hoc analysis was unable to detect specific pairwise differences. No significant group × time interaction occurred for any of the biochemical markers. Data for growth hormone are not reported because approximately two-thirds of the data points were below the lowest standard on the kit (0.1 ng·mL−1). Similarly, data for free and total testosterone are not reported for the female subjects.TABLE 6. Bone and muscle biomarkers (mean ± SE) in blood serum.TABLE 7. Bone and muscle biomarkers (mean ± SE) in urine.DISCUSSIONHigh-intensity resistance exercise attenuates bed rest-induced musculoskeletal deconditioning (6,5,12,27) and has been recommended as a countermeasure for use by astronauts in microgravity (3). The iRED, NASA's first-generation resistance exercise hardware on the ISS, fails to maintain muscle strength and BMD during long-duration spaceflight (16,31). The ARED was designed to address several of the key limitations of the iRED (such as peak resistance, eccentric-to-concentric force ratio, and inertial forces) with the intent of improving overall countermeasure effectiveness. Although some measures had large disparities in percent change between ARED and FW training at various time points, the primary finding of the present study was that after 16 wk, ARED training resulted in adaptations that were not statistically different from those resulting from FW training.Muscle strength and power.When evaluating the effect of two different exercise devices on muscle strength and power, the principle of training specificity indicates that strength gains should be less when training and testing are performed using different exercise devices (13). Pipes (24) evaluated two different strength training devices and reported large increases in strength when testing and training were performed on the same hardware, but they reported little to no change in strength when tested with the other system. Because we were evaluating two different devices, we speculated that we might find differences in strength gains between ARED- and FW-trained groups when testing was performed using the other modality. Interestingly, we found no statistical difference between ARED and FW training regardless of which device was used for testing. These results suggest that ARED training mimics FW enough to elicit similar training adaptations in muscle strength and power.Although both groups increased muscle strength and power, some device-dependent differences occurred during resistance exercise training. Specifically, the FW group improved FW and ARED SQ strength at a greater rate from midtraining to posttraining than the ARED group, and the FW group increased VJ height (an indicator of lower body power) at a greater rate than the ARED group. Given that the exercise prescription (resistance, volume, frequency, and choice of exercises) for the two groups was virtually identical (Table 2), differences in strength and power adaptations may be due to subtle differences between the exercise hardware. Because the ARED provides constant resistance throughout the range of motion and an eccentric-to-concentric force of approximately 90% (unpublished NASA engineering analysis), we speculate that differences in adaptation rate were due to variations in inertial resistance characteristics and/or exercise kinematics.Subtle device-dependent differences in inertial characteristics may have a sizeable impact on muscle strength and power. Rapidly decelerating a mass before the concentric motion occurs activates the stretch reflex, resulting in greater peak accelerations, greater peak forces (8,23), and a stronger concentric action (30). The ARED flywheels were designed to mimic the inertia of FW up to 91 kg (200 lb). Approximately 41% of all ARED exercises were performed at resistances greater than 91 kg (200 lb), potentially providing lower forces at heavier resistances compared with FW. Over time, the reduced forces might affect chronic strength and power adaptations to training.Although no direct measures were obtained in this study, anecdotal evidence indicates that biomechanical differences exist between devices. During SQ, ARED subjects reported that they felt as if the ARED bar was "forcing them forward," and test operators reported a corresponding increase in hip flexion during the ARED SQ. Increased forward torso lean has been associated with reduced forces at the knee (14,34), resulting in reduced forces imparted to the thigh musculature and a reduced training stimulus (10). During HR, the ARED restricted only lateral movements, thus requiring subjects to balance the resistance in the sagittal plane. Exercising while attempting to maintain balance results in an increased effort to maintain stability, reducing force production (1,7) and potentially resulting in device-specific adaptations. In contrast, DL form did not seem to differ between devices, and this may explain the lack of statistical difference between the training groups.BMD.Long-duration spaceflight reduces aBMD (18,19,26) and vBMD, with the decrease in vBMD occurring more in trabecular than in cortical bone (16,17,32). With limited previous information describing the effect of resistance exercise on vBMD, our results indicate that as little as 16 wk of FW or ARED training can increase lumbar spine trabecular vBMD. These results agree with the aBMD results in the current study and a previous investigation from our laboratory (26). Although no changes in hip BMD were seen after training, also previously observed (26), this does not preclude the possibility that ARED resistance exercise could mitigate BMD loss in a microgravity environment. Shackelford et al. (27) maintained total hip aBMD using high-intensity resistance exercise after 17 wk of bed rest. In addition, our study might have been too short to detect changes in hip BMD because 6-12 months of resistance training seems to be necessary to detect changes in hip aBMD (25,33).Spaceflight.Spaceflight imposes considerable obstacles to developing in-flight exercise hardware. First, exercise hardware must be vibration-isolated because vibrations due to exercise resonate throughout the ISS, potentially resulting in damage and a reduced life span of the vehicle (e.g., the vibrations can extend to the long, protruding solar panels and impart substantial torque on their attachments). Second, exercise hardware must require minimal-to-no external electrical power because power is in limited supply during spaceflight. Third, exercise hardware must provide a complement of exercises to sufficiently load all major muscle groups and joints, especially the lower body and spine. Finally, exercise hardware must be reliable and easily maintainable for a 15-yr period with minimal need to provide replacement parts. For these reasons, designing an exercise device to mimic the resistance characteristics of FW (i.e., providing high levels of resistance, constant force, an eccentric-to-concentric force close to 100%, and an inertial component) while adhering to the constraints imposed by spaceflight was a considerable challenge.The current study demonstrates an increase in muscle strength, muscle size, and BMD after 16 wk of training in ambulatory subjects. However, these results must be treated with caution when extending them to spaceflight because increasing muscle strength, muscle volume, and BMD in ambulatory subjects does not translate directly to an ability to prevent loss during unloading. Schneider et al. (26) reported that iRED training increased muscle strength and size in ambulatory subjects, with no change in BMD. However, astronauts continue to experience measurable decreases in muscle strength, muscle mass, and BMD after long-duration spaceflight, despite using the iRED (16,31). With this limitation in mind, our data indicate that the ARED has a greater likelihood than the iRED of being a successful countermeasure device on the ISS because the resistance characteristics during ARED exercise closely resemble those demonstrated to provide effective protection against muscle atrophy and bone loss during bed rest (27). Future data from crewmembers participating in spaceflight missions will allow us to test this hypothesis.CONCLUSIONSThe ARED was designed to address the limitations of the iRED and serve as the next generation of in-flight resistance exercise hardware. We evaluated the musculoskeletal adaptations to 16 wk of training using the ARED and compared these results with those obtained when training with FW. In ambulatory subjects, ARED training resulted in increases similar to those with FW training for all of the variables measured, the only exceptions being a greater rate of increase in SQ strength from midtraining to posttraining and a greater rate of increase in VJ height in the FW group. These device-dependent differences might relate to the inability of the ARED flywheels to mimic inertial characteristics of FW throughout the full range of resistances, or they could relate to differences in the biomechanics of exercise between the two devices. Given these findings, and considering the effectiveness of FW training at mitigating bed rest-induced deconditioning, we expect that ARED training will be a more effective countermeasure than iRED training against musculoskeletal deconditioning during spaceflight.Funding for this work was provided by the Exercise Countermeasures Project at NASA Johnson Space Center.The authors thank the subjects for their enthusiastic participation in this training study; Jason Bentley, Roxanne Nash, and Mark Leach for their assistance with exercise training and testing; Scott A. Smith, Mary Jane Maddocks, and Dr. Harlan Evans for their contributions to MRI and DXA data collection; Dr. Alan Feiveson for his support of the statistical analyses; and Meghan Everett and Dr. Carwyn Sharp for their review of this article.The results of the present study do not constitute endorsement by the American College of Sports Medicine.REFERENCES1. Anderson KG, Behm DG. Maintenance of EMG activity and loss of force output with instability. J Strength Cond Res. 2004;18(3):637-40. [CrossRef] [Full Text] [Medline Link] [Context Link]2. Baechle TR, Earle RW, Wathen D. Resistance training. In: Baechle TR, Earle RW, editors. Essentials of Strength Training and Conditioning. 2nd ed. Champaign (IL): Human Kinetics; 2002. p. 407-11. [Context Link]3. Baldwin KM, White TP, Arnaud SB, et al. Musculoskeletal adaptations to weightlessness and development of effective countermeasures. Med Sci Sports Exerc. 1996;28(10):1247-53. [CrossRef] [Full Text] [Medline Link] [Context Link]4. Bamman MM, Caruso JF. Resistance exercise countermeasures for space flight: implications of training specificity. J Strength Cond Res. 2000;14(1):45-9. [CrossRef] [Full Text] [Medline Link] [Context Link]5. Bamman MM, Clarke MS, Feeback DL, et al. Impact of resistance exercise during bed rest on skeletal muscle sarcopenia and myosin isoform distribution. J Appl Physiol. 1998;84(1):157-63. [Medline Link] [Context Link]6. Bamman MM, Hunter GR, Stevens BR, Guilliams ME, Greenisen MC. Resistance exercise prevents plantar flexor deconditioning during bed rest. Med Sci Sports Exerc. 1997;29(11):1462-8. [CrossRef] [Full Text] [Medline Link] [Context Link]7. Behm DG, Anderson K, Curnew RS. Muscle force and activation under stable and unstable conditions. J Strength Cond Res. 2002;16(3):416-22. [CrossRef] [Full Text] [Medline Link] [Context Link]8. Bojsen-Moller J, Magnusson SP, Rasmussen LR, Kjaer M, Aagaard P. Muscle performance during maximal isometric and dynamic contractions is influenced by the stiffness of the tendinous structures. J Appl Physiol. 2005;99(3):986-94. [CrossRef] [Medline Link] [Context Link]9. Dudley GA, Tesch PA, Miller BJ, Buchanan P. Importance of eccentric actions in performance adaptations to resistance training. Aviat Space Environ Med. 1991;62(6):543-50. [Medline Link] [Context Link]10. Escamilla RF, Fleisig GS, Lowry TM, Barrentine SW, Andrews JR. A three-dimensional biomechanical analysis of the squat during varying stance widths. Med Sci Sports Exerc. 2001;33(6):984-98. [CrossRef] [Full Text] [Medline Link] [Context Link]11. Escamilla RF, Fleisig GS, Zheng N, Barrentine SW, Wilk KE, Andrews JR. Biomechanics of the knee during closed kinetic chain and open kinetic chain exercises. Med Sci Sports Exerc. 1998;30(4):556-69. [CrossRef] [Full Text] [Medline Link] [Context Link]12. Ferrando AA, Tipton KD, Bamman MM, Wolfe RR. Resistance exercise maintains skeletal muscle protein synthesis during bed rest. J Appl Physiol. 1997;82(3):807-10. [Medline Link] [Context Link]13. Fleck SJ, Kraemer WJ. Types of strength training. In: Fleck SJ, Kraemer WJ, editors. Designing Resistance Training Programs. 2nd ed. Champaign (IL): Human Kinetics; 1997. p. 38. [Context Link]14. Fry AC, Smith JC, Schilling BK. Effect of knee position on hip and knee torques during the barbell squat. J Strength Cond Res. 2003;17(4):629-33. [CrossRef] [Full Text] [Medline Link] [Context Link]15. Harm DL, Jennings RT, Meck JV, et al. Invited review: gender issues related to spaceflight: a NASA perspective. J Appl Physiol. 2001;91(5):2374-83. [Medline Link] [Context Link]16. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A. Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res. 2004;19(6):1006-12. [CrossRef] [Medline Link] [Context Link]17. Lang TF, Leblanc AD, Evans HJ, Lu Y. Adaptation of the proximal femur to skeletal reloading after long-duration spaceflight. J Bone Miner Res. 2006;21(8):1224-30. [CrossRef] [Medline Link] [Context Link]18. LeBlanc A, Lin C, Shackelford L, et al. Muscle volume, MRI relaxation times (T2), and body composition after spaceflight. J Appl Physiol. 2000;89(6):2158-64. [Medline Link] [Context Link]19. LeBlanc A, Schneider V, Shackelford L, et al. Bone mineral and lean tissue loss after long duration space flight. J Musculoskelet Neuronal Interact. 2000;1(2):157-60. [Medline Link] [Context Link]20. Lee SM, Cobb K, Loehr JA, Nguyen D, Schneider SM. Foot-ground reaction force during resistive exercise in parabolic flight. Aviat Space Environ Med. 2004;75(5):405-12. [Medline Link] [Context Link]21. Li W, Sode M, Saeed I, Lang T. Automated registration of hip and spine for longitudinal QCT studies: integration with 3D densitometric and structural analysis. Bone. 2006;38(2):273-9. [CrossRef] [Medline Link] [Context Link]22. Moir G, Button C, Glaister M, Stone MH. Influence of familiarization on the reliability of vertical jump and acceleration sprinting performance in physically active men. J Strength Cond Res. 2004;18(2):276-80. [Context Link]23. Newton RU, Murphy AJ, Humphries BJ, Wilson GJ, Kraemer WJ, Hakkinen K. Influence of load and stretch shortening cycle on the kinematics, kinetics and muscle activation that occurs during explosive upper-body movements. Eur J Appl Physiol Occup Physiol. 1997;75(4):333-42. [CrossRef] [Medline Link] [Context Link]24. Pipes TV. Variable resistance versus constant resistance strength training in adult males. Eur J Appl Physiol Occup Physiol. 1978;39(1):27-35. [CrossRef] [Medline Link] [Context Link]25. Ryan AS, Ivey FM, Hurlbut DE, et al. Regional bone mineral density after resistive training in young and older men and women. Scand J Med Sci Sports. 2004;14(1):16-23. [Context Link]26. Schneider SM, Amonette WE, Blazine K, et al. Training with the International Space Station interim resistive exercise device. Med Sci Sports Exerc. 2003;35(11):1935-45. [CrossRef] [Full Text] [Medline Link] [Context Link]27. Shackelford LC, LeBlanc AD, Driscoll TB, et al. Resistance exercise as a countermeasure to disuse-induced bone loss. J Appl Physiol. 2004;97(1):119-29. [CrossRef] [Medline Link] [Context Link]28. Smith SM, Wastney ME, O'Brien KO, et al. Bone markers, calcium metabolism, and calcium kinetics during extended-duration space flight on the MIR space station. J Bone Miner Res. 2005;20(2):208-18. [Context Link]29. Smith SM, Zwart SR, Block G, Rice BL, Davis-Street JE. The nutritional status of astronauts is altered after long-term space flight aboard the International Space Station. J Nutr. 2005;135(3):437-43. [Medline Link] [Context Link]30. Takarada Y, Hirano Y, Ishige Y, Ishii N. Stretch-induced enhancement of mechanical power output in human multijoint exercise with countermovement. J Appl Physiol. 1997;83(5):1749-55. [Medline Link] [Context Link]31. Trappe S, Costill D, Gallagher P, et al. Exercise in space: human skeletal muscle after 6 months aboard the International Space Station. J Appl Physiol. 2009;106(4):1159-68. [CrossRef] [Medline Link] [Context Link]32. Vico L, Collet P, Guignandon A, et al. Effects of long-term microgravity exposure on cancellous and cortical weight-bearing bones of cosmonauts. Lancet. 2000;355(9215):1607-11. [CrossRef] [Full Text] [Medline Link] [Context Link]33. Winters-Stone KM, Snow CM. Site-specific response of bone to exercise in premenopausal women. Bone. 2006;39(6):1203-9. [Context Link]34. Wretenberg P, Feng Y, Arborelius UP. High- and low-bar squatting techniques during weight-training. Med Sci Sports Exerc. 1996;28(2):218-24. [CrossRef] [Full Text] [Medline Link] [Context Link]35. Zwart SR, Hargens AR, Lee SM, et al. Lower body negative pressure treadmill exercise as a countermeasure for bed rest-induced bone loss in female identical twins. Bone. 2007;40(2):529-37. 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C.; ENGLISH, KIRK L.; SIBONGA, JEAN; SMITH, SCOTT M.; SPIERING, BARRY A.; HAGAN, R. DONALDApplied Sciences143