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Interlimb Muscle and Fat Comparisons in Persons With Lower-Limb Amputation
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Interlimb Muscle and Fat Comparisons in Persons With Lower-Limb Amputation Vanessa D. Sherk, MS, Michael G. Bemben, PhD, Debra A. Bemben, PhD ABSTRACT. Sherk VD, Bemben MG, Bemben DA. Interlimb muscle and fat comparisons in persons with lower-limb amputation. Arch Phys Med Rehabil 2010;91:1077-81. Objectives: To investigate differences in muscle and fat tissue between amputated and intact limbs in subjects with transfemoral and transtibial amputations and to determine the effect of amputation level on limb differences. We hypothesized that the amputated limb would have a higher relative amount of fat than the intact limb, and transfemoral amputees would have greater limb differences in muscle size than transtibial amputees. Design: Cross-sectional, repeated-measures design. Setting: Laboratory. Participants: Subjects included persons with unilateral transfemoral (TF) (n⫽5) and transtibial (TT) (n⫽7) amputations and age- and sex-matched nonamputation controls (n⫽12). Interventions: Not applicable. Main Outcome Measures: Muscle cross-sectional areas and fat cross-sectional areas of the end of residual limbs were compared with similar cross-sectional sites of the intact limb by using peripheral quantitative computed tomography scans. Thigh and lower-leg fat mass (FM) and bone-free lean body mass were measured by dual-energy x-ray absorptiometry. Results: There was a 93% to 117% difference between limbs in muscle cross-sectional areas for TF and TT. TT had a between-limb difference of 39% for fat cross-sectional areas. Thigh bone-free lean body masses and FM were significantly (P⬍.05) lower for the amputated limb for both TF and TT. Thigh percent fat was significantly (P⬍.05) higher in the amputated thigh for TF and TT, but limb differences were greater in TF. Conclusions: Muscle atrophy was prevalent in the residual limb with larger relative amounts of fat in the thighs, especially in TF subjects. Key Words: Amputation; Rehabilitation. © 2010 by the American Congress of Rehabilitation Medicine USCLE RECRUITMENT strategies for gait and joint M stabilization change after amputation, and studies have reported differences in thigh strength and circumference be-
and the degree of change may depend on the level of amputation and the residual limb length.4,8 Soft-tissue composition of an amputated limb may be important for the control of a prosthesis, but little data exist that quantify muscle and fat composition changes after TF and TT amputation.7-9 Furthermore, studies investigating muscle atrophy after TT amputation have focused on the thigh musculature,7,9 rather than the end of the residual limb, where prosthesis fit, comfort, and ability to end weight bear are affected. A developing trend in socket fit research is the use of finite element modeling for predicting pressure-sensitive and tolerant areas to improve socket design and prevent deep-tissue injuries.10 Assumptions of soft-tissue structural properties used for prediction may be oversimplified, depending on the variability in relative lean and fat tissue amounts and distribution. Thus, the effectiveness of modeling and fitting techniques may be improved if soft-tissue characteristics are better quantified. Quantifying soft-tissue changes after amputation is important for assessing the effectiveness of rehabilitation programs for improved ability to transfer, ambulate on varied terrain (stairs, inclines, declines, uneven terrain), and maintain balance. Also, patients wishing to engage in recreational or occupational activities requiring high levels of mobility can benefit from effective and specific training programs that maintain or increase lean tissue in the amputated limb. Exercise interventions during bed rest have been effective at reducing muscle and strength losses11-13; thus, early intervention may translate to improved functional outcomes in new patients with amputation. Previous methods of investigating atrophy in amputated limbs have included computed tomography scanning, MRI, ultrasound, photography, and simple circumference measures. pQCT allows for easy quantification of muscle and fat crosssectional areas, uses far less radiation than a traditional computed tomography scanner, and is less expensive than MRI. DXA can be used for estimating whole-body and appendicular body composition.14 These methods can also be used for tracking muscular changes after unloading or interventions. The purpose of this cross-sectional study was to examine leg lean and FM distribution in persons with TF and TT amputations and to compare amputation groups with nonamputation
1-3
tween amputated and nonamputated limbs.4-6 Strength losses and muscle atrophy in patients with amputation are interrelated,6,7
List of Abbreviations ANOVA CTF
From the Bone Density Research Laboratory, Department of Health and Exercise Science, University of Oklahoma, Norman, OK. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Debra A. Bemben, PhD, Dept of Health and Exercise Science, University of Oklahoma, Norman, 1401 Asp Ave, Norman, OK 73109, e-mail: [email protected]. 0003-9993/10/9107-00052$36.00/0 doi:10.1016/j.apmr.2010.04.008
CTT DXA FM MCSA MRI pQCT TF TT
analysis of variance control group for transfemoral amputation group control group for transtibial amputation group dual-energy x-ray absorptiometry fat mass muscle cross-sectional area magnetic resonance imaging peripheral quantitative computed tomography transfemoral transtibial
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controls by using DXA and pQCT. It was hypothesized that the amputated limb would have higher relative amounts of fat than the intact limb, and TF subjects would have greater limb differences in muscle size than TT subjects. Also, interlimb differences in amputation groups would be greater than interlimb differences in control groups. METHODS Study Design This study is a cross-sectional, repeated-measures design comparing absolute and relative amounts of bone-free lean and fat tissue, and muscle and fat areas in the lower limbs of persons with unilateral TF and TT amputations. Furthermore, persons without amputations were tested as control participants, primarily to show interlimb variations in soft tissue not attributable to amputation. Thigh muscle volume and area data from previous amputee studies7,8 resulted in large effect sizes, creating a sample size need of 4 to achieve significant differences between limbs with 80% power. Participants Men and premenopausal women between the ages of 18 and 64 years with unilateral TF (n⫽5) and TT (n⫽7) amputations who had been ambulatory with a prosthesis for at least 6 months participated in the study. Two age- (⫾1 year) and sex-matched nonamputation control groups (CTF and CTT) were tested. Subjects weighing more than 136kg and having transfemoral amputations with less than 50% of their femur remaining on the residual limb, bilateral amputations, or disarticulation amputations were excluded from participating. This study was approved by the University of Oklahoma Institutional Review Board for Human Subjects. Participants in the amputation groups self-reported the date and reason for their amputation, the hours per day wearing a prosthesis, the time lapse between the amputation and the first definitive prosthesis, and the average ambulation distance per day. Height and weight were measured while wearing the prosthesis. The prosthesis was weighed alone to calculate the weight of the participant. The femur lengths were measured for TF and CTF participants and were measured from the greater trochanter to the end of the residual limb (amputated side) or to the lateral epicondyle (intact side). The tibia lengths were measured for TT and CTT participants and were measured from the medial tibial plateau to the end of the residual limb or to the medial malleolus. Soft-Tissue Measurements The MCSA and fat cross-sectional area were measured by pQCT by using an XCT 3000 with software version 6.00.a Crosssectional scans were of a single 2.2-mm-thick slice on each limb with an image voxel (3-dimensional pixel) size of 0.4mm. For participants with an amputation, the residual limb was scanned at 5% of the residual limb length superior to the distal end of the limb. The intact limb was scanned at the same absolute crosssectional location as shown in figure 1. CTF had each midthigh scanned, and CTT had each calf scanned. Threshold-driven softtissue analyses within the Stratec software were used to separate bone-free lean tissue, fat tissue, and bone tissue to quantify muscle and fat areas. The F03F05 noise filter was used when determining MCSA and fat cross-sectional area on shanks. The F01F06U01 noise filter was used to determine the MCSA and fat crosssectional area on the thighs. All pQCT scans were performed by the same technician. Body composition variables (body fat percent, FM, bonefree lean body mass of the total body and lower limbs) were Arch Phys Med Rehabil Vol 91, July 2010
Fig 1. The pQCT scan sites for the intact and amputated limbs. NOTE. Figure is not drawn to scale.
measured by using DXAb from total body scans. Custom regions of interest were created to separate the upper and lower legs for TT and CTT participants and to partition the upper legs for TF and CTF participants for comparing residual limb tissue composition. All scans were performed and analyzed by a single technician. Statistical Analysis Data are reported as mean ⫾ SD. Statistical analysis was performed by using SPSS for Windows version 17.0.c For purposes of comparing control participants with amputation participants, control subjects had the same leg as their amputation match assigned as the “amputated” side. The percent difference between limbs was calculated with the following equation: % difference ⫽ ([intact side ⫺ amputation side]/ [intact side ⫹ amputation side]/2) ⫻ 100. Significant group effects for percent differences between limbs (residual, intact) were determined by 1-way ANOVA. Thigh bone-free lean body mass and FM, leg fat percent, the MCSA, and the fat cross-sectional area for TF versus CTF and for TT versus CTT were compared by using a 2 ⫻ 2 (limb, group) mixed-factorial, repeated-measures ANOVA. Thigh percent fat values were also compared between TT and TF, and shank bone-free lean body mass and FM amounts were compared between TT and CTT. Effect sizes for mixed-factorial, repeated-measures ANOVAs are reported as partial eta squared, and effect sizes for 1-way ANOVAs are reported as eta squared. F ratios and between- and within-measure degrees of freedom are denoted as Fbetween and Fwithin, respectively. The level of significance was set at P less than .05. RESULTS Table 1 shows participant characteristics. Subjects ranged in age from 23.2 to 62.9 years. There were no significant differences in whole-body composition characteristics between groups. Table 2 shows results of the soft-tissue analyses from pQCT (MCSA and fat cross-sectional area) and DXA (bonefree lean body mass and FM). MCSA values were significantly lower (F1,12⫽28.7–30.0, p2⫽.71; F1,8⫽ 62.5– 68.9, p2⫽.89 – .90, P⬍.01) on the amputated limb for TF and TT groups, and
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MUSCLE LOSS AFTER AMPUTATION, Sherk Table 1: Participant Characteristics Group Variable
TT (n⫽7)
CTT (n⫽7)
TF (n⫽5)
CTF (n⫽5)
Age (y) Height (cm) Weight (kg) BFLBM (kg) FM (kg) Body fat % Years postamputation Age at amputation (y)
43.4⫾15.8 171.9⫾7.8 88.1⫾17.1 56.1⫾9.5 30.4⫾11.3 33.5⫾9.1 14.7⫾17.5 28.6⫾13.8
42.9⫾15.6 171.4⫾4.6 74.5⫾18.8 52.4⫾11.3 18.9⫾12.9 24.2⫾12.0 NA NA
38.5⫾10.6 175.9⫾9.8 79.7⫾13.9 50.9⫾10.2 25.6⫾5.7 32.4⫾5.7 19.7⫾11.1 18.8⫾8.9
39.0⫾11.0 167.4⫾6.9 74.4⫾13.3 54.5⫾14.4 19.3⫾11.4 25.5⫾15.2 NA NA
NOTE. Values are mean ⫾ SD. There were no significant group differences (P⬎.05). Abbreviations: BFLBM, bone-free lean body mass; NA, not applicable.
the amputated limb values were lower (P⬍.01) than controls. There were no significant limb or interaction effects for the fat cross-sectional area. DXA-based soft-tissue amounts were lower (F1,12⫽10.3–207.2, p2⫽.46–.95; F1,8⫽25.0–92.9, p2⫽ .76 –.92, P⬍.01) for the amputated limb. There were also significant limb ⫻ group interaction effects for thigh bone-free lean body mass (F1,12⫽38.0, p2⫽.70; F1,8⫽82.3, p2⫽.91, P⬍.01) and FM (F1,12⫽6.4, p2⫽.35; F1,8⫽19.0, p2⫽.70, P⬍.05) for TT versus CTT and for TF versus CTF, with limb effects only existing in the amputation groups. Relative limb differences in MCSA in TF and TT groups were 117.6%⫾22.2% and 104.4%⫾32.6%, respectively, meaning that the MCSA of the intact limbs was more than 2-fold greater than the amputated limb for both amputation groups. These differences were significantly (F1,8⫽131.8, 2⫽.94; F1,12⫽64.6, 2⫽.84, P⬍.01) greater than the relative limb differences in their respective control groups (2.0%⫾7.1% and ⫺1.9%⫾8.7% for CTF and CTT participants, respectively). Percent differences in MCSA were not significantly different between amputation groups. Limb differences in the fat cross-sectional area in the TT amputees (39.3%⫾41.9%) were significantly greater (F1,12⫽5.2, 2⫽.30,
P⬍.05) than relative limb differences in CTT (2.0%⫾11.3%). There were no significant differences in relative limb difference in the fat cross-sectional area between amputation groups (TF: 4.4%⫾18.0%). Figure 2 shows the leg fat percentage values based on the DXA analysis. Lower-leg differences obviously were not computed for the TF group. For thigh percent fat, there was a significant limb ⫻ group interaction (F1,12⫽6.9, p2⫽.37, P⬍.05) effect between TT versus CTT, with limb effects occurring only in TT. A significant limb and limb ⫻ group interaction effect existed for TF versus TT and TF versus CTF (F1,10⫽16.8 –39.2, p2⫽.63–.80; F1,8⫽16.8 –19.2, p2⫽.68 – .71, respectively, P⬍.01); limb effects were greater in TF. There were no significant effects for calf percent fat. DISCUSSION To our knowledge, this is the first study that has quantified leg composition at the end of the residual limb. The MCSA was smaller, and relative FM was higher in the amputated limb compared with the intact limb. Qualitatively, pQCT analyses showed that the ends of residual limbs had noticeable amounts of intermuscular fatty tissue. Although the mean percent dif-
Table 2: Soft-Tissue Variables by Limb and Group Group Variable
MCSA (mm2)储 Intact Residual FCSA (mm2)储 Intact Residual Thigh BFLBM (kg) Intact Residual Thigh FM (kg) Intact Residual Calf BFLBM (kg) Intact Residual Calf FM (kg) Intact Residual
TT (n⫽7)
CTT (n⫽7)
TF (n⫽5)
CTF (n⫽5)
5320.4⫾1869.6 1621.3⫾710.6*†
5675.9⫾974.9 5637.1⫾1307.9
17,122.8⫾5448.0 4818.9⫾2811.9*†
17,028.3⫾5199.5 17,326.4⫾5060.0
2502.9⫾1111.4 1862.9⫾1397.4
1795.0⫾840.1 1812.7⫾979.0
9109.4⫾4069.2 8447.0⫾2950.4
7514.9⫾6523.2 7361.1⫾5800.8
6.57⫾0.74 5.85⫾0.80*†§
5.66⫾1.30 5.68⫾1.35
7.37⫾1.88 3.41⫾1.14*†
6.43⫾1.59 6.32⫾1.80
4.18⫾1.38 3.93⫾1.30*‡§
2.68⫾1.38 2.65⫾1.38
4.18⫾1.64 2.49⫾0.93*†
2.83⫾1.92 2.71⫾1.65
2.35⫾0.33 0.82⫾0.34*†
2.12⫾0.39 2.12⫾0.47
NA NA
NA NA
0.93⫾0.17 0.37⫾0.18*†
0.64⫾0.29 0.65⫾0.35
NA NA
NA NA
NOTE. Values are mean ⫾ SD. Abbreviations: BFLBM, bone-free lean body mass; FCSA, fat cross-sectional area. *P⬍.01, significant limb effect; †P⬍.01; ‡P⬍.05, significant limb ⫻ group interaction effect versus respective control group; §P⬍.01, significant limb ⫻ group interaction effect with TF. 储Calf MCSA and FCSA for TT and CTT and thigh MCSA and FCSA for TF and CTF.
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Fig 2. Thigh and calf percent fat values (mean ⴞ SD) for amputated and intact limbs for each amputation group. For control participants, the same leg (right or left) that was amputated from their age- and sex-matched amputation participant was assigned as the “amputated” limb. *P<.01, significant limb effect; †P<.01; ††P<.05, significant limb ⴛ group interaction effect with the control group. ‡ P<.01, significant limb and limb ⴛ group interaction effect with TF. Abbreviations: Amp, amputated.
ference in the fat cross-sectional area between limbs for the TT group was much greater than for the TF group, the lack of significance was likely caused by the large between-subject variability and the small sample size. It is unclear if these results were true adaptations of changes after amputation or if they were caused by characteristics of the muscle flap, but based on the work of Jaegers et al8 and Schmalz et al,9 these changes were largely caused by muscle atrophy. Our results showing lower thigh bone-free lean body mass in the TT group complements previous studies using other methods. Renstrom et al7 found that muscle fiber size in the vastus lateralis of limbs amputated below the knee was less than that of the intact limb. The amputated limb had a greater proportion of type IIb fibers, and the intact limb had a greater proportion of type IIa fibers. The MCSA was most severely reduced in the quadriceps. The reduction of the whole thigh circumference was less than the reduction of the muscle area, suggesting an increase in relative amounts of FM. Schmalz et al9 found that TT had 15% to 30% lower MCSA and muscle thickness of the quadriceps but not hamstrings on the amputated limb when using ultrasound. This study, however, was unable to detect whether fatty infiltration occurred. A study by Isakov et al4 reported that thigh circumference of the amputated limb was smaller in transtibial subjects, but this study also did not assess the composition of the thighs. The importance of this was shown by the lack of significance in strength difference when subjects were divided based on differences in thigh circumferences. For all subjects, the concentric strength of the quadriceps and hamstrings in the amputated limb ranged from 40% to 60% of the intact limb. Eccentric quadriceps strength was weaker in those with shorter residual tibia, and shorter residual tibia had weaker hamstrings. Muscle atrophy after amputation results from a combination of bed rest, changes in gait strategy, and a loss of ability to strongly contract the distal muscles of a residual limb. Therefore, our results can also be compared with bed rest and unilateral unloading studies. Bed rest studies have reported rapid declines in lean tissue mass. Lean tissue losses have been shown to occur more quickly in plantarflexors than in the quadriceps or hamstrings, and lean tissue loss rates are more Arch Phys Med Rehabil Vol 91, July 2010
similar between quadriceps and hamstrings.15 Sixty days of bed rest caused 21% to 29% losses in thigh and calf muscle volume, which coincided with large decreases in strength.13 Rittweger and Felsenberg16 found that 90 days of bed rest resulted in a 22.5% decrease in calf MCSA, which was reduced to a 5% loss by 14 days of recovery. Hospital bed rest is often a result of trauma, including amputation procedures, resulting in increased cortisol levels. Padden-Jones et al17 artificially elevated cortisol levels in subjects on bed rest for 28 days, resulting in a 1.3-kg loss in leg lean mass. Losses were found to be a result of decreased protein synthesis. All of our subjects wore prosthetics, and there was a wide range of time since amputation. Therefore, although bed rest certainly contributed to muscular atrophy after amputation, there was probably a period of hypertrophy, in at least the intact limb, after returning to an ambulatory state. Unilateral loss of muscular contractions leading to muscle atrophy has been shown in spinal cord injury and stroke patients. The first 6 months after spinal cord injury has led to MCSA losses of 12% to 24% in the thigh and calf muscles.18 Changes (10%) in the MCSA as assessed by MRI between 6 weeks and 4.5 months after a spinal cord injury were not significant in a study by Gorgey and Dudley,19 likely because of the large variability and the small sample size. Intramuscular fat, however, largely increased (26%).19 Jorgensen and Jacobsen20 reported that after 1 year poststroke, subjects lost 3% of lean mass and gained 9% FM in the paretic leg, whereas they gained 2% lean mass and 6% FM in the nonparetic leg. Lean mass losses were greater in subjects who did not walk by 2 months poststroke.20 A cross-sectional study21 of stroke patients with a large variation in time since stroke found that after stroke the plegic thigh had, on average, approximately 75% to 83% of the volume as the nonplegic side depending on age. These reported differences are smaller than muscle and fat differences in our amputees. However, these studies tested a shorter duration of unilateral loading and may be more comparable to changes that occur early after amputation. Study Limitations There are several limitations to this study. Our amputation group sample sizes were small, so although many of our effect sizes were large and our power was high for our significant findings, our results may not be fully generalizable to all patients with amputation. Because we only measured pQCT at a single site on the residual limb, we do not know about the uniformity of muscle and fat differences along the residual limb. Also, because this was a cross-sectional design, we cannot truly consider the intact limb a control because there were likely periods of muscular atrophy from bed rest and hypertrophy from subsequent reambulation. Exercise interventions during bed rest have been shown to be effective for preserving muscle mass.11-13 We were not involved in the specific rehabilitation programs of our subjects, meaning that differences in rehabilitation within our subjects may have affected our results. Therefore, although it can be assumed that there was significant atrophy and changes in fat distribution on the amputated limb, we can only speculate about the time course of soft-tissue composition changes. Longitudinal studies that control for rehabilitation and limb-reloading strategies are needed to determine the potentially unique time course of muscle atrophy after amputation. CONCLUSIONS Muscle losses in the thigh muscles of TF and TT amputated limbs were evident. Also, there were large amounts of inter-
MUSCLE LOSS AFTER AMPUTATION, Sherk
muscular adipose tissue at the end of residual limbs. Studies are needed to determine the uniformity of muscle and fat changes in the distal segments of residual limbs.
12.
Acknowledgments: We thank Hanger Prosthetics and Orthotics, Inc and Kyle Sherk, CPO, for assistance with subject recruitment. References 1. Centomo H, Amarantini D, Martin L, Prince F. Differences in the coordination of agonist and antagonist muscle groups in belowknee amputee and able-bodied children during dynamic exercise. J Electromyography Kinesiol 2008;18:487-94. 2. Sadeghi H, Allard P, Duhaime M. Muscle power compensatory mechanisms in below-knee amputee gait. Am J Phys Med Rehabil 2001;80:25-32. 3. Perry J. Amputee gait. In: Smith DG, Michael JW, Bowker JH, editors. Atlas of amputations and limb deficiencies: surgical, prosthetic, and rehabilitation principles. Rosemont: American Academy of Orthopaedic Surgeons; 2004. p 367-84. 4. Isakov E, Burger H, Gregoric M, Marincek C. Stump length as related to atrophy and strength of the thigh muscles in trans-tibial amputees. Prosthetics Orthotics Int 1996;20:96-100. 5. Zachariah SG, Saxena R, Fergason JR, Sanders JE. Shape and volume change in the transtibial residuum over the short term: preliminary investigation of six subjects. J Rehabil Res Dev 2004;41:683-94. 6. Renstrom P, Grimby G, Larsson E. Thigh muscle strength in below-knee amputees. Scand J Rehabil Med 1983;9:163-73. 7. Renstrom P, Grimby G, Morelli B, Palmertz B. Thigh muscle atrophy in below-knee amputees. Scand J Rehabil Med 1983;9: 150-62. 8. Jaegers SM, Arendzen JH, de Jongh HJ. Changes in hip muscles after above-knee amputation. Clin Orthop Relat Res 1995; Oct(319):276-84. 9. Schmalz T, Blumentritt S, Reimers CD. Selective thigh muscle atrophy in trans-tibial amputees: an ultrasonographic study. Arch Orthop Trauma Surg 2001;121:307-12. 10. Portnoy S, Yarnitzky G, Yizhar Z, et al. Real-time patient-specific finite element analysis of internal stresses in the soft tissues of a residual limb: a new tool for prosthetic fitting. Ann Biomed Eng 2007;35:120-35. 11. Belavy DL, Miokovic T, Armbrecht G, Rittweger J, Felsenberg D. Resistive vibration exercise reduces lower limb muscle atrophy
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during 56-day bed-rest. J Musculoskelet Neuronal Interact 2009;9:225-35. Rittweger J, Frost HM, Schiessl H, et al. Muscle atrophy and bone loss after 90 days’ bed rest and the effects of flywheel resistive exercise and pamidronate: results from the LTBR study. Bone 2005;36:1019-29. Trappe TA, Burd NA, Louis ES, Lee GA, Trappe SW. Influence of concurrent exercise or nutrition countermeasures on thigh and calf muscle size and function during 60 days of bed rest in women. Acta Physiol 2007;191:147-59. Kim J, Wang Z, Heymsfield SB, Baumgartner RN, Gallagher D. Total-body skeletal muscle mass: estimation by a new dual-energy X-ray absorptiometry method. Am J Clin Nutr 2002;76:378-83. Belavy DL, Miokovic T, Armbrecht G, Richardson CA, Rittweger J, Felsenberg D. Differential atrophy of the lower-limb musculature during prolonged bed-rest. Eur J Appl Physiol 2009;107:489-99. Rittweger J, Felsenberg D. Recovery of muscle atrophy and bone loss from 90 days bed rest: results from a one-year follow-up. Bone 2009;44:214-24. Padden-Jones D, Sheffield-Moore M, Cree MG, et al. Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. J Clin Endocrinol Metabol 2006;91:4836-41. Castro MJ, Apple DF, Hillegass EA, Dudley GA. Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury. Eur J Appl Physiol 1999;80: 373-8. Gorgey AS, Dudley GA. Skeletal muscle atrophy and increased intramuscular fat after incomplete spinal cord injury. Spinal Cord 2007;45:304-9. Jorgensen L, Jacobsen BK. Changes in muscle mass, fat mass, and bone mineral content in the legs after stroke: a 1 year prospective study. Bone 2001;28:655-9. Metoki N, Sato Y, Satoh K, Okumura K, Iwamoto J. Muscular atrophy in the hemiplegic thigh in patients after stroke. Am J Phys Med Rehabil 2003;82:862-5.
Suppliers a. Stratec Medizintechnik GmbH, Durlacher Straße 35, Pforzheim, 75172 Germany. b. Lunar Prodigy enCORE software version 10.50.086; GE Medical Systems, 3030 Ohmeda Dr, Madison, WI 53718. c. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.
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ORIGINAL ARTICLE
Interlimb Muscle and Fat Comparisons in Persons With Lower-Limb Amputation Vanessa D. Sherk, MS, Michael G. Bemben, PhD, Debra A. Bemben, PhD ABSTRACT. Sherk VD, Bemben MG, Bemben DA. Interlimb muscle and fat comparisons in persons with lower-limb amputation. Arch Phys Med Rehabil 2010;91:1077-81. Objectives: To investigate differences in muscle and fat tissue between amputated and intact limbs in subjects with transfemoral and transtibial amputations and to determine the effect of amputation level on limb differences. We hypothesized that the amputated limb would have a higher relative amount of fat than the intact limb, and transfemoral amputees would have greater limb differences in muscle size than transtibial amputees. Design: Cross-sectional, repeated-measures design. Setting: Laboratory. Participants: Subjects included persons with unilateral transfemoral (TF) (n⫽5) and transtibial (TT) (n⫽7) amputations and age- and sex-matched nonamputation controls (n⫽12). Interventions: Not applicable. Main Outcome Measures: Muscle cross-sectional areas and fat cross-sectional areas of the end of residual limbs were compared with similar cross-sectional sites of the intact limb by using peripheral quantitative computed tomography scans. Thigh and lower-leg fat mass (FM) and bone-free lean body mass were measured by dual-energy x-ray absorptiometry. Results: There was a 93% to 117% difference between limbs in muscle cross-sectional areas for TF and TT. TT had a between-limb difference of 39% for fat cross-sectional areas. Thigh bone-free lean body masses and FM were significantly (P⬍.05) lower for the amputated limb for both TF and TT. Thigh percent fat was significantly (P⬍.05) higher in the amputated thigh for TF and TT, but limb differences were greater in TF. Conclusions: Muscle atrophy was prevalent in the residual limb with larger relative amounts of fat in the thighs, especially in TF subjects. Key Words: Amputation; Rehabilitation. © 2010 by the American Congress of Rehabilitation Medicine USCLE RECRUITMENT strategies for gait and joint M stabilization change after amputation, and studies have reported differences in thigh strength and circumference be-
and the degree of change may depend on the level of amputation and the residual limb length.4,8 Soft-tissue composition of an amputated limb may be important for the control of a prosthesis, but little data exist that quantify muscle and fat composition changes after TF and TT amputation.7-9 Furthermore, studies investigating muscle atrophy after TT amputation have focused on the thigh musculature,7,9 rather than the end of the residual limb, where prosthesis fit, comfort, and ability to end weight bear are affected. A developing trend in socket fit research is the use of finite element modeling for predicting pressure-sensitive and tolerant areas to improve socket design and prevent deep-tissue injuries.10 Assumptions of soft-tissue structural properties used for prediction may be oversimplified, depending on the variability in relative lean and fat tissue amounts and distribution. Thus, the effectiveness of modeling and fitting techniques may be improved if soft-tissue characteristics are better quantified. Quantifying soft-tissue changes after amputation is important for assessing the effectiveness of rehabilitation programs for improved ability to transfer, ambulate on varied terrain (stairs, inclines, declines, uneven terrain), and maintain balance. Also, patients wishing to engage in recreational or occupational activities requiring high levels of mobility can benefit from effective and specific training programs that maintain or increase lean tissue in the amputated limb. Exercise interventions during bed rest have been effective at reducing muscle and strength losses11-13; thus, early intervention may translate to improved functional outcomes in new patients with amputation. Previous methods of investigating atrophy in amputated limbs have included computed tomography scanning, MRI, ultrasound, photography, and simple circumference measures. pQCT allows for easy quantification of muscle and fat crosssectional areas, uses far less radiation than a traditional computed tomography scanner, and is less expensive than MRI. DXA can be used for estimating whole-body and appendicular body composition.14 These methods can also be used for tracking muscular changes after unloading or interventions. The purpose of this cross-sectional study was to examine leg lean and FM distribution in persons with TF and TT amputations and to compare amputation groups with nonamputation
1-3
tween amputated and nonamputated limbs.4-6 Strength losses and muscle atrophy in patients with amputation are interrelated,6,7
List of Abbreviations ANOVA CTF
From the Bone Density Research Laboratory, Department of Health and Exercise Science, University of Oklahoma, Norman, OK. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Debra A. Bemben, PhD, Dept of Health and Exercise Science, University of Oklahoma, Norman, 1401 Asp Ave, Norman, OK 73109, e-mail: [email protected]. 0003-9993/10/9107-00052$36.00/0 doi:10.1016/j.apmr.2010.04.008
CTT DXA FM MCSA MRI pQCT TF TT
analysis of variance control group for transfemoral amputation group control group for transtibial amputation group dual-energy x-ray absorptiometry fat mass muscle cross-sectional area magnetic resonance imaging peripheral quantitative computed tomography transfemoral transtibial
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controls by using DXA and pQCT. It was hypothesized that the amputated limb would have higher relative amounts of fat than the intact limb, and TF subjects would have greater limb differences in muscle size than TT subjects. Also, interlimb differences in amputation groups would be greater than interlimb differences in control groups. METHODS Study Design This study is a cross-sectional, repeated-measures design comparing absolute and relative amounts of bone-free lean and fat tissue, and muscle and fat areas in the lower limbs of persons with unilateral TF and TT amputations. Furthermore, persons without amputations were tested as control participants, primarily to show interlimb variations in soft tissue not attributable to amputation. Thigh muscle volume and area data from previous amputee studies7,8 resulted in large effect sizes, creating a sample size need of 4 to achieve significant differences between limbs with 80% power. Participants Men and premenopausal women between the ages of 18 and 64 years with unilateral TF (n⫽5) and TT (n⫽7) amputations who had been ambulatory with a prosthesis for at least 6 months participated in the study. Two age- (⫾1 year) and sex-matched nonamputation control groups (CTF and CTT) were tested. Subjects weighing more than 136kg and having transfemoral amputations with less than 50% of their femur remaining on the residual limb, bilateral amputations, or disarticulation amputations were excluded from participating. This study was approved by the University of Oklahoma Institutional Review Board for Human Subjects. Participants in the amputation groups self-reported the date and reason for their amputation, the hours per day wearing a prosthesis, the time lapse between the amputation and the first definitive prosthesis, and the average ambulation distance per day. Height and weight were measured while wearing the prosthesis. The prosthesis was weighed alone to calculate the weight of the participant. The femur lengths were measured for TF and CTF participants and were measured from the greater trochanter to the end of the residual limb (amputated side) or to the lateral epicondyle (intact side). The tibia lengths were measured for TT and CTT participants and were measured from the medial tibial plateau to the end of the residual limb or to the medial malleolus. Soft-Tissue Measurements The MCSA and fat cross-sectional area were measured by pQCT by using an XCT 3000 with software version 6.00.a Crosssectional scans were of a single 2.2-mm-thick slice on each limb with an image voxel (3-dimensional pixel) size of 0.4mm. For participants with an amputation, the residual limb was scanned at 5% of the residual limb length superior to the distal end of the limb. The intact limb was scanned at the same absolute crosssectional location as shown in figure 1. CTF had each midthigh scanned, and CTT had each calf scanned. Threshold-driven softtissue analyses within the Stratec software were used to separate bone-free lean tissue, fat tissue, and bone tissue to quantify muscle and fat areas. The F03F05 noise filter was used when determining MCSA and fat cross-sectional area on shanks. The F01F06U01 noise filter was used to determine the MCSA and fat crosssectional area on the thighs. All pQCT scans were performed by the same technician. Body composition variables (body fat percent, FM, bonefree lean body mass of the total body and lower limbs) were Arch Phys Med Rehabil Vol 91, July 2010
Fig 1. The pQCT scan sites for the intact and amputated limbs. NOTE. Figure is not drawn to scale.
measured by using DXAb from total body scans. Custom regions of interest were created to separate the upper and lower legs for TT and CTT participants and to partition the upper legs for TF and CTF participants for comparing residual limb tissue composition. All scans were performed and analyzed by a single technician. Statistical Analysis Data are reported as mean ⫾ SD. Statistical analysis was performed by using SPSS for Windows version 17.0.c For purposes of comparing control participants with amputation participants, control subjects had the same leg as their amputation match assigned as the “amputated” side. The percent difference between limbs was calculated with the following equation: % difference ⫽ ([intact side ⫺ amputation side]/ [intact side ⫹ amputation side]/2) ⫻ 100. Significant group effects for percent differences between limbs (residual, intact) were determined by 1-way ANOVA. Thigh bone-free lean body mass and FM, leg fat percent, the MCSA, and the fat cross-sectional area for TF versus CTF and for TT versus CTT were compared by using a 2 ⫻ 2 (limb, group) mixed-factorial, repeated-measures ANOVA. Thigh percent fat values were also compared between TT and TF, and shank bone-free lean body mass and FM amounts were compared between TT and CTT. Effect sizes for mixed-factorial, repeated-measures ANOVAs are reported as partial eta squared, and effect sizes for 1-way ANOVAs are reported as eta squared. F ratios and between- and within-measure degrees of freedom are denoted as Fbetween and Fwithin, respectively. The level of significance was set at P less than .05. RESULTS Table 1 shows participant characteristics. Subjects ranged in age from 23.2 to 62.9 years. There were no significant differences in whole-body composition characteristics between groups. Table 2 shows results of the soft-tissue analyses from pQCT (MCSA and fat cross-sectional area) and DXA (bonefree lean body mass and FM). MCSA values were significantly lower (F1,12⫽28.7–30.0, p2⫽.71; F1,8⫽ 62.5– 68.9, p2⫽.89 – .90, P⬍.01) on the amputated limb for TF and TT groups, and
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MUSCLE LOSS AFTER AMPUTATION, Sherk Table 1: Participant Characteristics Group Variable
TT (n⫽7)
CTT (n⫽7)
TF (n⫽5)
CTF (n⫽5)
Age (y) Height (cm) Weight (kg) BFLBM (kg) FM (kg) Body fat % Years postamputation Age at amputation (y)
43.4⫾15.8 171.9⫾7.8 88.1⫾17.1 56.1⫾9.5 30.4⫾11.3 33.5⫾9.1 14.7⫾17.5 28.6⫾13.8
42.9⫾15.6 171.4⫾4.6 74.5⫾18.8 52.4⫾11.3 18.9⫾12.9 24.2⫾12.0 NA NA
38.5⫾10.6 175.9⫾9.8 79.7⫾13.9 50.9⫾10.2 25.6⫾5.7 32.4⫾5.7 19.7⫾11.1 18.8⫾8.9
39.0⫾11.0 167.4⫾6.9 74.4⫾13.3 54.5⫾14.4 19.3⫾11.4 25.5⫾15.2 NA NA
NOTE. Values are mean ⫾ SD. There were no significant group differences (P⬎.05). Abbreviations: BFLBM, bone-free lean body mass; NA, not applicable.
the amputated limb values were lower (P⬍.01) than controls. There were no significant limb or interaction effects for the fat cross-sectional area. DXA-based soft-tissue amounts were lower (F1,12⫽10.3–207.2, p2⫽.46–.95; F1,8⫽25.0–92.9, p2⫽ .76 –.92, P⬍.01) for the amputated limb. There were also significant limb ⫻ group interaction effects for thigh bone-free lean body mass (F1,12⫽38.0, p2⫽.70; F1,8⫽82.3, p2⫽.91, P⬍.01) and FM (F1,12⫽6.4, p2⫽.35; F1,8⫽19.0, p2⫽.70, P⬍.05) for TT versus CTT and for TF versus CTF, with limb effects only existing in the amputation groups. Relative limb differences in MCSA in TF and TT groups were 117.6%⫾22.2% and 104.4%⫾32.6%, respectively, meaning that the MCSA of the intact limbs was more than 2-fold greater than the amputated limb for both amputation groups. These differences were significantly (F1,8⫽131.8, 2⫽.94; F1,12⫽64.6, 2⫽.84, P⬍.01) greater than the relative limb differences in their respective control groups (2.0%⫾7.1% and ⫺1.9%⫾8.7% for CTF and CTT participants, respectively). Percent differences in MCSA were not significantly different between amputation groups. Limb differences in the fat cross-sectional area in the TT amputees (39.3%⫾41.9%) were significantly greater (F1,12⫽5.2, 2⫽.30,
P⬍.05) than relative limb differences in CTT (2.0%⫾11.3%). There were no significant differences in relative limb difference in the fat cross-sectional area between amputation groups (TF: 4.4%⫾18.0%). Figure 2 shows the leg fat percentage values based on the DXA analysis. Lower-leg differences obviously were not computed for the TF group. For thigh percent fat, there was a significant limb ⫻ group interaction (F1,12⫽6.9, p2⫽.37, P⬍.05) effect between TT versus CTT, with limb effects occurring only in TT. A significant limb and limb ⫻ group interaction effect existed for TF versus TT and TF versus CTF (F1,10⫽16.8 –39.2, p2⫽.63–.80; F1,8⫽16.8 –19.2, p2⫽.68 – .71, respectively, P⬍.01); limb effects were greater in TF. There were no significant effects for calf percent fat. DISCUSSION To our knowledge, this is the first study that has quantified leg composition at the end of the residual limb. The MCSA was smaller, and relative FM was higher in the amputated limb compared with the intact limb. Qualitatively, pQCT analyses showed that the ends of residual limbs had noticeable amounts of intermuscular fatty tissue. Although the mean percent dif-
Table 2: Soft-Tissue Variables by Limb and Group Group Variable
MCSA (mm2)储 Intact Residual FCSA (mm2)储 Intact Residual Thigh BFLBM (kg) Intact Residual Thigh FM (kg) Intact Residual Calf BFLBM (kg) Intact Residual Calf FM (kg) Intact Residual
TT (n⫽7)
CTT (n⫽7)
TF (n⫽5)
CTF (n⫽5)
5320.4⫾1869.6 1621.3⫾710.6*†
5675.9⫾974.9 5637.1⫾1307.9
17,122.8⫾5448.0 4818.9⫾2811.9*†
17,028.3⫾5199.5 17,326.4⫾5060.0
2502.9⫾1111.4 1862.9⫾1397.4
1795.0⫾840.1 1812.7⫾979.0
9109.4⫾4069.2 8447.0⫾2950.4
7514.9⫾6523.2 7361.1⫾5800.8
6.57⫾0.74 5.85⫾0.80*†§
5.66⫾1.30 5.68⫾1.35
7.37⫾1.88 3.41⫾1.14*†
6.43⫾1.59 6.32⫾1.80
4.18⫾1.38 3.93⫾1.30*‡§
2.68⫾1.38 2.65⫾1.38
4.18⫾1.64 2.49⫾0.93*†
2.83⫾1.92 2.71⫾1.65
2.35⫾0.33 0.82⫾0.34*†
2.12⫾0.39 2.12⫾0.47
NA NA
NA NA
0.93⫾0.17 0.37⫾0.18*†
0.64⫾0.29 0.65⫾0.35
NA NA
NA NA
NOTE. Values are mean ⫾ SD. Abbreviations: BFLBM, bone-free lean body mass; FCSA, fat cross-sectional area. *P⬍.01, significant limb effect; †P⬍.01; ‡P⬍.05, significant limb ⫻ group interaction effect versus respective control group; §P⬍.01, significant limb ⫻ group interaction effect with TF. 储Calf MCSA and FCSA for TT and CTT and thigh MCSA and FCSA for TF and CTF.
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Fig 2. Thigh and calf percent fat values (mean ⴞ SD) for amputated and intact limbs for each amputation group. For control participants, the same leg (right or left) that was amputated from their age- and sex-matched amputation participant was assigned as the “amputated” limb. *P<.01, significant limb effect; †P<.01; ††P<.05, significant limb ⴛ group interaction effect with the control group. ‡ P<.01, significant limb and limb ⴛ group interaction effect with TF. Abbreviations: Amp, amputated.
ference in the fat cross-sectional area between limbs for the TT group was much greater than for the TF group, the lack of significance was likely caused by the large between-subject variability and the small sample size. It is unclear if these results were true adaptations of changes after amputation or if they were caused by characteristics of the muscle flap, but based on the work of Jaegers et al8 and Schmalz et al,9 these changes were largely caused by muscle atrophy. Our results showing lower thigh bone-free lean body mass in the TT group complements previous studies using other methods. Renstrom et al7 found that muscle fiber size in the vastus lateralis of limbs amputated below the knee was less than that of the intact limb. The amputated limb had a greater proportion of type IIb fibers, and the intact limb had a greater proportion of type IIa fibers. The MCSA was most severely reduced in the quadriceps. The reduction of the whole thigh circumference was less than the reduction of the muscle area, suggesting an increase in relative amounts of FM. Schmalz et al9 found that TT had 15% to 30% lower MCSA and muscle thickness of the quadriceps but not hamstrings on the amputated limb when using ultrasound. This study, however, was unable to detect whether fatty infiltration occurred. A study by Isakov et al4 reported that thigh circumference of the amputated limb was smaller in transtibial subjects, but this study also did not assess the composition of the thighs. The importance of this was shown by the lack of significance in strength difference when subjects were divided based on differences in thigh circumferences. For all subjects, the concentric strength of the quadriceps and hamstrings in the amputated limb ranged from 40% to 60% of the intact limb. Eccentric quadriceps strength was weaker in those with shorter residual tibia, and shorter residual tibia had weaker hamstrings. Muscle atrophy after amputation results from a combination of bed rest, changes in gait strategy, and a loss of ability to strongly contract the distal muscles of a residual limb. Therefore, our results can also be compared with bed rest and unilateral unloading studies. Bed rest studies have reported rapid declines in lean tissue mass. Lean tissue losses have been shown to occur more quickly in plantarflexors than in the quadriceps or hamstrings, and lean tissue loss rates are more Arch Phys Med Rehabil Vol 91, July 2010
similar between quadriceps and hamstrings.15 Sixty days of bed rest caused 21% to 29% losses in thigh and calf muscle volume, which coincided with large decreases in strength.13 Rittweger and Felsenberg16 found that 90 days of bed rest resulted in a 22.5% decrease in calf MCSA, which was reduced to a 5% loss by 14 days of recovery. Hospital bed rest is often a result of trauma, including amputation procedures, resulting in increased cortisol levels. Padden-Jones et al17 artificially elevated cortisol levels in subjects on bed rest for 28 days, resulting in a 1.3-kg loss in leg lean mass. Losses were found to be a result of decreased protein synthesis. All of our subjects wore prosthetics, and there was a wide range of time since amputation. Therefore, although bed rest certainly contributed to muscular atrophy after amputation, there was probably a period of hypertrophy, in at least the intact limb, after returning to an ambulatory state. Unilateral loss of muscular contractions leading to muscle atrophy has been shown in spinal cord injury and stroke patients. The first 6 months after spinal cord injury has led to MCSA losses of 12% to 24% in the thigh and calf muscles.18 Changes (10%) in the MCSA as assessed by MRI between 6 weeks and 4.5 months after a spinal cord injury were not significant in a study by Gorgey and Dudley,19 likely because of the large variability and the small sample size. Intramuscular fat, however, largely increased (26%).19 Jorgensen and Jacobsen20 reported that after 1 year poststroke, subjects lost 3% of lean mass and gained 9% FM in the paretic leg, whereas they gained 2% lean mass and 6% FM in the nonparetic leg. Lean mass losses were greater in subjects who did not walk by 2 months poststroke.20 A cross-sectional study21 of stroke patients with a large variation in time since stroke found that after stroke the plegic thigh had, on average, approximately 75% to 83% of the volume as the nonplegic side depending on age. These reported differences are smaller than muscle and fat differences in our amputees. However, these studies tested a shorter duration of unilateral loading and may be more comparable to changes that occur early after amputation. Study Limitations There are several limitations to this study. Our amputation group sample sizes were small, so although many of our effect sizes were large and our power was high for our significant findings, our results may not be fully generalizable to all patients with amputation. Because we only measured pQCT at a single site on the residual limb, we do not know about the uniformity of muscle and fat differences along the residual limb. Also, because this was a cross-sectional design, we cannot truly consider the intact limb a control because there were likely periods of muscular atrophy from bed rest and hypertrophy from subsequent reambulation. Exercise interventions during bed rest have been shown to be effective for preserving muscle mass.11-13 We were not involved in the specific rehabilitation programs of our subjects, meaning that differences in rehabilitation within our subjects may have affected our results. Therefore, although it can be assumed that there was significant atrophy and changes in fat distribution on the amputated limb, we can only speculate about the time course of soft-tissue composition changes. Longitudinal studies that control for rehabilitation and limb-reloading strategies are needed to determine the potentially unique time course of muscle atrophy after amputation. CONCLUSIONS Muscle losses in the thigh muscles of TF and TT amputated limbs were evident. Also, there were large amounts of inter-
MUSCLE LOSS AFTER AMPUTATION, Sherk
muscular adipose tissue at the end of residual limbs. Studies are needed to determine the uniformity of muscle and fat changes in the distal segments of residual limbs.
12.
Acknowledgments: We thank Hanger Prosthetics and Orthotics, Inc and Kyle Sherk, CPO, for assistance with subject recruitment. References 1. Centomo H, Amarantini D, Martin L, Prince F. Differences in the coordination of agonist and antagonist muscle groups in belowknee amputee and able-bodied children during dynamic exercise. J Electromyography Kinesiol 2008;18:487-94. 2. Sadeghi H, Allard P, Duhaime M. Muscle power compensatory mechanisms in below-knee amputee gait. Am J Phys Med Rehabil 2001;80:25-32. 3. Perry J. Amputee gait. In: Smith DG, Michael JW, Bowker JH, editors. Atlas of amputations and limb deficiencies: surgical, prosthetic, and rehabilitation principles. Rosemont: American Academy of Orthopaedic Surgeons; 2004. p 367-84. 4. Isakov E, Burger H, Gregoric M, Marincek C. Stump length as related to atrophy and strength of the thigh muscles in trans-tibial amputees. Prosthetics Orthotics Int 1996;20:96-100. 5. Zachariah SG, Saxena R, Fergason JR, Sanders JE. Shape and volume change in the transtibial residuum over the short term: preliminary investigation of six subjects. J Rehabil Res Dev 2004;41:683-94. 6. Renstrom P, Grimby G, Larsson E. Thigh muscle strength in below-knee amputees. Scand J Rehabil Med 1983;9:163-73. 7. Renstrom P, Grimby G, Morelli B, Palmertz B. Thigh muscle atrophy in below-knee amputees. Scand J Rehabil Med 1983;9: 150-62. 8. Jaegers SM, Arendzen JH, de Jongh HJ. Changes in hip muscles after above-knee amputation. Clin Orthop Relat Res 1995; Oct(319):276-84. 9. Schmalz T, Blumentritt S, Reimers CD. Selective thigh muscle atrophy in trans-tibial amputees: an ultrasonographic study. Arch Orthop Trauma Surg 2001;121:307-12. 10. Portnoy S, Yarnitzky G, Yizhar Z, et al. Real-time patient-specific finite element analysis of internal stresses in the soft tissues of a residual limb: a new tool for prosthetic fitting. Ann Biomed Eng 2007;35:120-35. 11. Belavy DL, Miokovic T, Armbrecht G, Rittweger J, Felsenberg D. Resistive vibration exercise reduces lower limb muscle atrophy
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Suppliers a. Stratec Medizintechnik GmbH, Durlacher Straße 35, Pforzheim, 75172 Germany. b. Lunar Prodigy enCORE software version 10.50.086; GE Medical Systems, 3030 Ohmeda Dr, Madison, WI 53718. c. SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL 60606.
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