电刺激：它能在脊髓损伤增加肌肉力量和个人骨质疏松？

Electrical Stimulation:Can It Increase Muscle Strength and Reverse Osteopenia in Spinal Cord Injured Individuals?Marc Be´langer,PhD,Richard B.Stein,DPhil,Garry D.Wheeler,PhD,Tessa Gordon,PhD,Bernard Leduc,MDABSTRACT.Be´langer M,Stein RB,Wheeler GD,Gordon T,Leduc B.Electrical stimulation:can it increase muscle strength and reverse osteopenia in spinal cord injured individu-als?Arch Phys Med Rehabil2000;81:1090-8.Objective:To study the extent to which atrophy of muscle and progressive weakening of the long bones after spinal cord injury(SCI)can be reversed by functional electrical stimulation (FES)and resistance training.Design:A within-subject,contralateral limb,and matching design.Setting:Research laboratories in university settings. Participants:Fourteen patients with SCI(C5to T5)and14 control subjects volunteered for this study.Interventions:The left quadriceps were stimulated to con-tract against an isokinetic load(resisted)while the right quadriceps contracted against gravity(unresisted)for1hour a day,5days a week,for24weeks.Main Outcome Measures:Bone mineral density(BMD)of the distal femur,proximal tibia,and mid-tibia obtained by dual energy x-ray absorptiometry,and torque(strength). Results:Initially,the BMD of SCI subjects was lower than that of controls.After training,the distal femur and proximal tibia had recovered nearly30%of the bone lost,compared with the controls.There was no difference in the mid-tibia or between the sides at any level.There was a large strength gain, with the rate of increase being substantially greater on the resisted side.Conclusion:Osteopenia of the distal femur and proximal tibia and the loss of strength of the quadriceps can be partly reversed by regular FES-assisted training.Key Words:Electric stimulation;Resistance training;Bone density;Osteopenia;Osteoporosis;Spinal cord injuries;Reha-bilitation.௠2000by the American Congress of Rehabilitation Medi-cine and the American Academy of Physical Medicine and RehabilitationS PINAL CORD INJURY(SCI)commonly results in the loss of voluntary control of the limbs.Even when partial motor control remains,a frequent outcome is relative inactivity and disuse of the limbs.Gradually,the leg muscles atrophy,1-8and the long bones weaken,as a result of a rapid and severe loss of bone mineral density(BMD)in the paralyzed limbs(osteope-nia).9-16Electrical stimulation can reverse the muscle weakness, although the extent of the reversal differs markedly in different studies.Most studies using electrical stimulation of muscle show little or no change in bone density.10,17-20Because of bone weakness,persons with SCI have an increased risk for fractures as a result of mild trauma,such as when transferring to or from a wheelchair.9,12,21The incidence of long-bone fractures has been reported to be between1%and6%,and it is likely underestimated because numerous cases are either untreated or unreported at SCI centers.9,22Similarly,Nottage22reported an incidence rate of6.7%,with complication rates as high as20% to40%with open or closed treatment of extremity fractures. Strengthening muscle with electrical stimulation can further increase the risk,unless the bones are also strengthened.While it has been shown that mechanical stress is important in bone formation and remodeling,23,24no study has documented the level of physical training needed for a positive effect on BMD.25 Pettersson and colleagues26reported that a group with a high level of physical activity(Ϸ10hours a week)showed higher BMD for total body and numerous sites compared with a reference group with a low level of physical activity(3or fewer hours a week).Ayalon and associates27have also reported that in postmeno-pausal women exercise for50minutes three times per week for 5months resulted in a3.8%gain of bone density of the distal radius.Interestingly,de Bruin and colleagues28have reported no or insignificant loss of trabecular bone in subjects with SCI during thefirst25weeks after injury simply with weight bearing by standing and treadmill walking.It is not known whether this could be maintained over longer periods of time and,more important,whether atrophic changes that have occurred can be reversed substantially by electrical stimulation. The purpose of our investigation was twofold:(1)to deter-mine if functional electrical stimulation(FES)training,which loads the muscles and bones,can slow or reverse osteopenia in patients with spinal cord lesion;and(2)to study whether the amount of loading(through progressive increases of isokinetic loading)has any effect on the strengthening of stimulated muscle.The reasons for wanting to increase the muscle strength were also twofold:(1)to increase the stress and loading on the bone(Doyle and colleagues29have reported a strong relation between muscle weight and BMD);and(2)to increase the strength of the quadriceps muscles for FES-assisted standing and walking.METHODSSubjectsSubjects were recruited from regions near the research institutions in Edmonton and Montre´al.All subjects with SCI were screened to exclude those who:(1)were on medications or had a medical condition that could interfere with bone forma-tion,(2)had lesions of the quadriceps motoneurons that rendered stimulation ineffective,(3)could not tolerate the stimulation(ie,because of pain),or(4)had other medicalFrom the De´partement de Kinanthropologie,Universite´du Que´bec a`Montre´al (Be´langer),and the Institut de re´adaptation de Montre´al(Leduc),Montreal,Quebec; and the Division of Neuroscience(Stein,Gordon)and the Rick Hansen Centre (Wheeler),University of Alberta,Edmonton,Alberta.Submitted November17,1999.Accepted in revised form January12,2000. Supported in part by the Medical Research Council of Canada and the Neuroscience Network of the Centres of Excellence.Dr.Be´langer was partly supported by the Fonds de recherche en sante´du Que´bec.The authors have chosen not to select a disclosure statement.Reprint requests to Marc Be´langer,De´partement de Kinanthropologie,Universite´du Que´bec a`Montre´al,C.P.8888,succursale,Centre-Ville,Montre´al,Que´bec,Canada H3C3P8.0003-9993/00/8108-5943$3.00/0doi:10.1053/apmr.2000.71701090Arch Phys Med Rehabil Vol81,August2000problems (eg,previous cardiac problems,newly formed decubi-tus ulcers)that would put their health at risk by taking part inthe study.Subjects were informed of the risks and signed a consent form before starting training,as had been approved by human ethics committees at the Universities of Que ´bec and of Alberta.After the initial screening,the BMD of each subject was evaluated using dual energy x-ray absorptiometry (DEXA)techniques.a,b Subjects were excluded if a fracture of either the femur or tibia was detected in this evaluation.The DEXA technique was used because of its availability,reproducibility,and good overall accuracy (5%to 8%)and precision (Ͻ2%)for a number of sites.30The accuracy and precision of the DEXA equipment that was used was well within these values.Charac-teristics of the SCI subjects who participated in this study are presented in table 1.Fourteen age-and sex-matched control subjects with no known neurologic lesions were also tested to compare bone density.Initial EvaluationsBefore starting the training program and on a weekly basis thereafter,the thigh circumference and quadriceps muscle strength and endurance for each limb were evaluated in the laboratory.The circumference was measured 15cm proximal to the superior patellar margin to test for gross changes in the bulk of the thighs.A skinfold measurement was also obtained from the 15-cm mark for the last 3subjects (subjects 1,8,and 11).Evoked muscle torques were measured over a range of 90°(ie,90°of flexion to full extension)using a Cybex isodynamom-eter c set at 30°/sec.The Cybex manual recommends this setting for knee torque measurements,but more important,the risk of fracture is less than with isometric testing.Because this isodynamometer did not automatically correct for gravity,this correction was performed offline on all the Cybex data.This was done by subtracting the torque generated by the weight of the limb and lever arm of the apparatus for the angles of knee extension where measurements were obtained.31Strength and endurance were tested with a 40-Hz train lasting 2seconds,repeated every 5seconds for 4minutes.32The stimulus consisted of rectangular pulses of 0.5-msec duration and sufficient amplitude to produce a maximal twitch response.For the most part,the testing was done using the samemultiweek electrodes d,e and the same placement (see below)as for the training sessions.In several cases,gel-and saline-coated electrodes were used during testing with no appreciable differ-ences in the results.The signal from the Cybex was digitized at 166Hz and stored on computer using Axotape 2.fTraining and ComplianceTraining was conducted in the laboratory 5days per week for 24weeks,and consisted of stimulating both quadriceps muscles with the same parameters.The stimulation,300-µsec rectangu-lar pulses delivered at 25Hz with a 5-sec on/5-sec off duty cycle,was applied with an isolated stimulator g through multi-week electrodes.The electrodes were placed at 5cm and 15cm proximal to the superior patellar margin.These sites were chosen because they were easily accessible and repeatable,but more important,they were relatively close to the motor point,thereby requiring less stimulation current to produce a smooth contraction.The stimulation amplitude was adjusted (0to 150mA)to produce a contraction that could be maintained for the duration of the stimulus.The stimulus intensity was increased if the leg began to drop more than 15°during the stimulation.A within-subject,contralateral limb design was used to evaluate the effects of resistance during training.On the right side,the stimulated quadriceps muscles extended against no resistance other than gravity (unresisted),while on the left side the limb extended against an added resistance (resisted).An isokinetic leg extension/flexion device (either Hydragym h or Cybex c )was used to apply this load.Subjects trained for 1hour per day or until a fatigue criterion (less than 30°of extension from 90°in the unloaded limb)was met.The resistance on the loaded limb was increased when full extension could be produced for 15minutes or more at a set load.Resistance was added either by changing the damping on the Hydragym apparatus (eg,going from level 1to level 2on a 6-level scale)or by decreasing the set velocity on the Cybex by 5°/sec intervals (eg,going from 30°/sec to 25°/sec).The training program was set up to try to initially increase the strength so that the subject could stand when assisted with FES.Based on studies by Kralj and Bajd,33standing requires that the knee extensors be able to generate a torque of more than 50Nm.More important,the training with low resistance for 24weeksTable 1:Description of SubjectsSubjectGenderAge (yrs)Mass (kg)Height (cm)Level of Lesion*Type of Lesion*Cause of LesionYears Postlesion1M 32.973.3172.7C5C MVA 7.52M 40.966.7182.9C6I MVA 233F 28.750.7160T6C MVA 44M 41.684120C6C MVA 2.35M 39.765.3185.4T2C MVA146F 34.645.4162.6C6C Gun shot 17.87M 28.668.5168C6C MVA 12.48M 35.469.3172.7C5I Fall 12.59M 36.473.3185.4C6C MVA 1810F 24.348.5167.6C6C MVA 6.711M 25.757.8177.8C6C MVA 6.512M 23.360177.8T3C MVA 6.213M 28.082180C7C MVA 1.214M32.985179T5C MVA1.8SCI (mean ϮSD)32.4Ϯ5.966.4Ϯ12.3170.9Ϯ16.19.6Ϯ6.6Control (mean ϮSD)33.5Ϯ6.375.4Ϯ14.5174.5Ϯ10.8Abbreviations:MVA,motor vehicle accident;SD,standard deviation.*Level and completeness (C ϭcomplete,I ϭincomplete)of the lesion was based on the American Spinal Cord Injury Association (ASIA)scale.On the Frankel scale,all spinal cord injury (SCI)subjects were between A and C.1091REVERSAL OF OSTEOPENIA IN SCI INDIVIDUALS,Be ´langerArch Phys Med Rehabil Vol 81,August 2000was designed to increase endurance.This type of training should allow SCI subjects to stand or walk with FES for long periods.Most of the subjects who embarked on the training program continued until the end of the24-week period.The compliance, measured as the attendance of subjects for the sessions,was remarkably high,ranging from65%to99%,with a mean and standard deviation(SD)of93.4%Ϯ5.6%.The average is equivalent to missing only8of120sessions.Data and Statistical AnalysisAfinal BMD evaluation was performed on completion of the training program and compared with the initial evaluation. Areas from1.44cm2to12.6cm2were used to measure the BMD for the distal femur,proximal tibia,and mid-tibia.Analysis of variance(ANOV A)was used to determine the differences between the control and SCI subjects for the three areas of interest before and after FES training.Tukey tests were used to determine significant changes.To study the strength and endurance,three peak torque values were averaged for every30-second interval over the4-minute fatigue test.The peak torque was measured from a stable portion of the signal,between100msec and300msec(ie,the initial overshoot or superimposed spasms were omitted).Be-cause the test lasted4minutes,the last average occurred after the3.5-minute mark.The initial(maximal)values were used to determine strength gains.Thefinal values were normalized with respect to the initial values to indicate the changes in thefatigability(index of enduranceϭ100%ϫtorque values at 3.5min/torque values at0min)of the muscle as training progressed.In some cases,it was possible to generate a muscle twitch in the quadriceps muscle right from the onset of training using a1-msec rectangular pulse and the same electrode placement as previously outlined.It was then possible to measure the contraction time from the recorded torque curve (ie,from the onset of torque change to the peak torque value), thereby yielding an indication of the changes in muscle characteristics.Regressions were used to determine rates of change in both torque and endurance using either linear or nonlinear least-mean squares algorithms.A repeated-measures ANOV A was used to compare initial andfinal strengths for both limbs.RESULTSBone DensityThe mean(Ϯstandard error)for the bone density of the control and SCI subjects(before training)are illustrated in figure1.The pretraining BMD values of the SCI subjects for all three regions were lower than those of age-and sex-matched control subjects.BMD loss was approximately the same at all three sites,with the declines ranging from25.8%to44.4%.The same order in density was also seen between the regions in both SCI and control individuals(mid-tibiaϾdistal femurϾproxi-mal tibia,pϽ.05).There was no statistical difference between the left(resisted)and right(unresisted)sides in the SCI subjects (pϾ.05).Figure2shows the BMD for the three regions for each subject with respect to the time after the spinal cord lesion.The data werefitted with the exponential equation yϭbeϪax, yielding yϭ.71ϫeϪ.06x(correlation coefficient[R]ϭ.68)for distal femur(fig2A),yϭ.64ϫeϪ.08x(Rϭ.70)for the proximal tibia(fig2B),and yϭ1.37ϫeϪ.03x(Rϭ.75)for mid-tibia(fig2C).The time constants for decay(␶ϭ1/a)were relatively similar for the3regions(between13and33yrs),with the only significant difference being between proximal tibia and mid-tibia(pϽ.05);the relative changes for all3regions are plotted infigure2D.Because of the long time constant,bone loss in these regions is relatively small,less than10%after1 year.After10years,the bone density had decayed by about half for the distal femur(43.2%)and proximal tibia(54.6%),but only about a quarter for mid-tibia(24.1%).The data were also fitted with the exponential equation yϭcϩbeϪax,but either c was not significantly different from0,or thefit improved by less than1%.Thus,bone density will decay to almost zero with sufficient time.Training increased BMD significantly,but the type of training had no effect,ie,there was no difference between the resisted(left)and unresisted(right)sides.Because there was no side difference before training and the type of training had no effect(no left-right difference),the data were collapsed to simply examine regional changes.There was a significant increase in the BMD of the distal femur(.082g/cm2)and proximal tibia(.052g/cm2),but not in the mid-tibia(.001 g/cm2)(fig3A).The difference between distal femur and proximal tibia was not significant,but the changes in BMD for both were significantly different from that of the mid-tibia (pϽ.05).When expressed as a percentage of the control values,these changes amount to11.1%,9.7%,and0.0%for the distal femur,proximal tibia,and mid-tibia,respectively(fig 3B).More important,these values represent a recovery of the BMD lost after SCI of28.7%for distal femur and28.0%for proximal tibia.In contrast,the mid-tibia showed no recovery. Interestingly,there was no correlation between the initial BMD and the BMD change with training(fig4A).The BMD change was weakly correlated with the years since SCI(fig4B). The linear regression line(yϭ.01-.006x;Rϭ.30)is also shown infigure4B,with the95%confidence intervals.The confidence intervals indicate that no significant gain was seen when training began more than13.5years after SCI.Unfortu-nately,these subjects tended to have the lowest bone densities (fig2),and thus the greatest need forimprovement.Fig1.Absolute bone mineral density(BMD)for control(᭿)and for the left(ᮀ)and right(8)sides of subjects with SCI before training. The three regions are statistically different from each other,both for the control and SCI subjects(p F.05).The lower bone densities in the SCI subjects are also significantly different from control subjects in all three regions(indicated by the asterisk above the bars).The BMD expressed as a percentage of control values are indicated at the bottom of the bars.1092REVERSAL OF OSTEOPENIA IN SCI INDIVIDUALS,Be´langer Arch Phys Med Rehabil Vol81,August2000Muscle ForceFigure 5illustrates the left knee torques generated by subject 3at the beginning and after 24weeks of FES.The torque generated by FES increased by 40Nm in this subject by the end of training.The maximal torque could sometimes be even larger (by about 25Nm),if a spasm was triggered on top of the contraction (see the difference between the dashed and dotted lines after the time indicated by the single-ended arrow,fig 5).In this example,the spasm could easily be discerned because there was a delay in its onset.However,in other cases,the increase in torque was much smoother,making it harder to detect.In addition to the large increase in amplitude,the torque could also be maintained for the duration of the tetanic stimulation (ie,2sec).At the onset of training,there was extreme weakness and the torque decayed rapidly despite continued stimulation (ie,the contraction was not strong enough for the limb to keep pushing against the dynamometer).The increase in torque with training for all subjects is shown in figure 6.For clarity,only the regression lines and the 95%confidence intervals are plotted.Clearly,FES training increases strength dramatically,even after the extra torque produced by the occasional spasms (fig 5)was excluded.The data were fitted with parabolas,which had values of y ϭ98.1ϩ8.1x Ϫ.09x 2(R ϭ.57,resisted)and y ϭ95.6ϩ4.5x Ϫ.06x 2(R ϭ.54,unresisted).Thus,the initial strength gain was substantially faster on the legs that worked against resistance (8.1%per week)compared with the unresisted side (4.5%per week).The rate of increase in strength did slow down with time and appeared to be approaching asymptotic values by 24weeks.These values represented gains of nearly 75%(unresisted)and 150%(resisted).The torque gain as a function of the initial torque values is presented in figure 7.There was no significant trend for either the resisted or unresisted side,which indicates that the absolute increase is independent of the starting torque value (fig 7A).However,the relative increase will then be much greater for subjects with low initial strength (fig 7B).If the change in torque ⌬y ϭc,a constant,then ⌬y/y ϭc/y.The curves fitted to this equation have values of c equal to 4809(R ϭ.78,resisted)and 2995(R ϭ.90,unresisted).An index of fatigability was calculated for each week of training,but the fatigability did not change significantly for either the resisted or the unresisted legs.Thus,the endurance did not improve.This was corroborated by measuringtheFig 2.Bone mineral density (BMD)of the (A)distal femur,(B)proximal tibial,and (C)mid-tibia for controls (symbols having means ؎standarderror at years n ϭ0)and for subjects with SCI as a function of time after the SCI.The other points represent the pooled data for the right and left side for each of the 12SCI subjects.(D)The BMD for the 3regions are expressed as a percentage of the initial values obtained from the regression equations for the SCI subjects.1093REVERSAL OF OSTEOPENIA IN SCI INDIVIDUALS,Be ´langerArch Phys Med Rehabil Vol 81,August 2000contraction time of the muscle twitch.Again,no significant change was observed over the 24-week training period.Some individuals showed greater muscle definition and an apparent increase in muscle size,but the limb girth of the whole population did not change significantly over the training period on either the resisted or the unresisted sides.Finally,the skinfold measurements from 3of the subjects were also inconclusive.DISCUSSIONThis study demonstrates that 1hour of daily FES training can substantially reverse the loss of bone density after SCI.Likewise,FES produced a dramatic increase in muscle strength that depends on the type of training applied (resisted vs unresisted).These changes occurred without a significant change in fatigability or limb size,as measured by the thigh girth.Bone DensityAfter SCI,there is a large and continuing loss of BMD 10(fig 2).However,our data show that nearly 30%of the lost BMD can be recovered in the distal femur and proximal tibia with FES training.Previous studies,using similar FES techniques that produce mechanical stress and loading of bone,were largely unsuccessful.Leeds 17and BeDell 19and their colleagues found no change in BMD after FES-assisted cycling training.Rodgers and associates 10showed a decrease in the rate of bone loss in the proximal tibia after knee extension training,but were unable to demonstrate any reversal of osteopenia.Recently,Mohr and colleagues 20showed a 10%increase in proximal tibial BMD after 1year of FES-assisted cycling training.The difference between our study and the previous ones may lie in the amount of training and loading.For example,Hangartner and associates 18had subjects train 3times per week with 2sets of 30contractions and 1set of 60repetitions,for a total of approximately 360contractions per week.In our study,subjects trained for up to 1hour per day at a rate of 12contractions per minute,which totals 720contractions per day.Moreover,subjects trained 4times per week and were tested once (12contractions/min for 4min),for a total of 2928contractions per week.This is more than 8times the amount of training and loading as in the study by Hangartner et al.18Our data certainly support the ‘‘mechanostat theory’’of Frost,34which claims that bone will only respond to certain levels of loading.Induced strains must be both above a lower threshold and below an upper threshold level for bone to have an adaptive response.35Why is it that individuals who have a lot of muscle spasms do not maintain high level of BMD?We showed previously 32that even SCI subjects with spasms generate on average only about 20%as much electromyography over a 24-hour period as control subjects.Perhaps the number of spasms or the intensity of the resulting contractions are not sufficient to stimulate osteogenesis.Another possible explanation for the discrepancies with some previous studies may be the skeletal regions being evaluated.Several groups 17,19measured BMD changes intheFig 3.Change in bone mineral density (BMD)(mean ؎standard error)as a result of (A)training in absolute units (g/cm 2)and (B)as a percentage of the values in control subjects.The asterisks indicate significant differences at p F.05.femoral neck,in Ward’s triangle (a triangular radiolucency formed between the primary trabecular patterns within the femoral neck),and in the trochanter,although loading was applied mainly lower in the legs by FES cycling exercises.Bloomfield and colleagues 36also reported no change in BMD in the femoral neck,distal femur,and proximal tibia for the group as a whole.However,in a subset of subjects,the FES cycle ergometry training increased the BMD in the distal femur.Similarly,Mohr and associates 20observed an increase in the proximal tibia BMD,but not in the femoral neck and lumbar spine,which suggests site-specific changes.Our results support this notion of site-specificity,because BMD increased in thedistal femur and proximal tibia but not in the mid-tibia.The regional effects are likely the result of the specificity of the loading,because the FES knee-extension exercise used in this study produced much greater loading around the knee joint (distal femur and proximal tibia)than in the tibial shaft (mid-tibia).Along with this loading,contraction of the quadri-ceps muscles and movements of the knee joint could increase local blood flow and augment the circulation of material necessary for bone formation in the distal femur and proximal tibia.37In contrast,the mid-tibia would not benefit from such local increases in circulation.Why did the BMD not increase more in the leg that worked against resistance?One explanation may be the duration of the stimulation and the setting of the isokinetic device.The quadriceps were stimulated for 5seconds,while the Cybex was set at 30°/sec.Thus,after approximately 3seconds,the knee joint would be fully extended and the muscles would then contract isometrically for about 2seconds.The unresisted leg would contract more quickly and have a somewhat longer isometric period.Of course,the speed of the Cybex could have been reduced to 18°/sec,thereby eliminating this isometric contraction on the resisted side but not on the unresisted side,because it was free to move.However,this would have placed the subjects at greater risk of fracture,particularly at the onset of training,because reducing the speed has the effect of increasing the resistance.Both sides had the weight of the leg as an initial load,so the differences between the two may not have been great enough to influence bone formation or loss.Another possible explanation for the lack of difference between the sides may be cross-training effects.Vuori and colleagues 38reported that unilateral leg presses in young women without SCI produced a small but systematic increase in BMD in the contralateral limb.Several studies have demonstrated varied level of bone loss for different regions of the body including the lumbar spinal,theFig 5.Curves of the torques atthe beginning (solid line )and end (dashed and dotted lines )of the 24-week training period.The downward-pointing arrow shows the onset of a spasm in one of the first contractions of the last recording session.The double-ended arrow at the bot-tom of the graph indicates the region where the torque mea-surements were taken (ie,avoiding the initial overshoot and the spasm).The small ver-tical lines represent the stimuli (ie,40Hz for 2sec).It should be noted that a 0-Nm torque is recorded when the muscle contraction is not strong enough to move the leg at the set speed of the isokinetic dy-namometer (eg,the torque trace at the beginning of train-ing is null beyond500msec).Fig 6.Increase in strength in the resisted (solid lines )and unresisted limbs (dashed lines )as a function of the duration of training.The thick lines represent the regression lines,the thin lines give the 95%confidence intervals.1095REVERSAL OF OSTEOPENIA IN SCI INDIVIDUALS,Be ´langerArch Phys Med Rehabil Vol 81,August 2000。