Limb Unloading Research Articles

Recovery of lower limb function following 6 weeks of non-weight bearing

Skeletal muscle weakness and atrophy occur following an extended period of decreased use, including space flight and limb unloading. It is also likely that affected muscles will be susceptible to a re-loading injury when they begin return to earth or weight bearing. However, there is a paucity of literature evaluating the response of human unloaded muscle to exercise and return to activity. The purpose of this pilot study was to evaluate the soreness, function and strength response of muscle to re-loading in seven patients who were non-weight bearing for 6 weeks, compared to five healthy subjects. Function improved significantly over time for the patients but was still less than the healthy subjects over 12 weeks of physiotherapy. Concentric quadriceps muscle strength increased significantly over time for the patients. There was considerable variability in the patients’ reports of muscle soreness but there were no significant changes over time or between groups.

MULTIDIRECTIONAL PROTECTIVE STEPPING FOR BALANCE RECOVERY IN YOUNG AND OLDER ADULTS.

PURPOSE/HYPOTHESIS: Lateral instability of postural balance has been associated with increased risk for falls in the elderly. During forward-backward induce stepping older adults have demonstrated difficulties with lateral balance control. These observations suggest that older individuals might have specific problems with maintaining balance through protective stepping in the lateral direction. The purpose of this study was to quantify the stepping characteristics of young and older adults to different directions of postural disturbance of standing balance. NUMBER OF SUBJECTS: The study included 91 healthy adults (36 young, mean age 23.3 years 2.8; 55 older, mean age of 74.1 years 6.8). MATERIALS/METHODS: Subjects wore a safety harness and stood with each foot on a force platform. Six cables were attached at different points to a waist-belt and to a motor-driven puller at the opposite end. From a stationary standing posture, subjects received 60 randomly applied waist-pull trials in 12 different directions oriented at 30 intervals around the subjects body. Kinematic and kinetic data were collected. A two way ANOVA assessed between group differences in stepping behavior in relation to pulling direction. RESULTS: Differences in step efficiency between the groups (p<0.001) indicated that younger subjects needed only one step to recover their balance in 90% of the trials whereas older adults used multiple steps in 57% of the trials. Post-hoc analyses of groups by directions showed that the younger subjects step efficiency was not affected by direction; however, older adults exhibited increased multiple stepping as the perturbations became more lateral (p<0.001). Different stepping strategies were observed during lateral and diagonal pulls: passively unloaded limb stepping; and passively loaded limb side stepping. Older adults tended to use unloaded limb stepping more often (69% of trials) than the young (56% of trials) (p<0.076) where 75 inter-limb collisions involving 26 older subjects occurred versus only 4 collisions for 2 younger subjects. There were no differences between groups or disturbance directions for step onset time. CONCLUSIONS: Older adults had more difficulty recovering their balance through stepping when the postural challenges became more lateral as evidenced by an increase in multiple steps and limb collisions. Older subjects also tended to initiate stepping more often with the limb that was passively unloaded by the waist-pull, and had multiple inter-limb collisions indicating a different and potentially riskier stepping strategy than younger subjects. CLINICAL RELEVANCE: The results supported the hypothesis that older subjects may be particularly vulnerable to lateral instability during protective stepping and other balance functions. These findings suggest that clinicians more systematically examine older adults protective stepping strategies, utilize interventions that address directional vulnerability and include performance outcomes such as step efficiency and frequency of limb collisions. Supported by NIA #RO1 AG16780

A method for the automatic characterization of bone architecture in 3D mice microtomographic images

We developed an automatic method to characterize mice bone architecture from three-dimensional (3D) microtomographic images. The distal metaphyses of the femur of mice were imaged using 3D synchrotron radiation microtomography at the European Synchrotron Radiation Facility (ID19) with a voxel size of 6.65 μm. Within each reconstructed volume, a region of interest was defined and trabecular and cortical bones were automatically separated. Then, 3D morphologic and topologic model-independent parameters quantifying the 3D bone architecture were computed in both regions. The technique was applied to study the response of the C57BL/6J@Ico strain of mice submitted to a model of bone loss by hind limb unloading produced by tail-suspension.

Neural adaptations with chronic activity patterns in able-bodied humans.

The purpose of this article is to review the neural adaptations that occur in able-bodied humans with alterations in chronic patterns of physical activity. The adaptations are categorized as those related to cortical maps, motor command, descending drive, muscle activation, motor units, and sensory feedback. We focused on the adaptations that occur with such activities as strength training, limb immobilization, and limb unloading. For these types of interventions, the adaptations are widely distributed throughout the nervous system, but those changes that are observed with strength training are often not the converse of those found with reduced-use protocols.

Can stabilizing features of rapid triggered stepping reactions be modulated to meet environmental constraints?

This study examined whether the stabilizing features of rapid triggered compensatory stepping reactions can be modulated to accommodate an environmental constraint, in the form of an obstacle placed in front of the subject. The compensatory stepping reactions were evoked, in 11 healthy young adults, by unpredictable multidirectional platform translation; the forward-step reactions evoked by large backward translations were analyzed. Clearance of the obstacle required a doubling of the usual (no obstacle) swing duration and therein presented significant challenges to both anteroposterior (a-p) and lateral stability, yet the central nervous system (CNS) was able to decelerate and stabilize the body's center of mass (COM) without taking additional steps. Findings that the response was modulated successfully without prior practice or exposure to the perturbation suggest that the CNS automatically incorporates exteroceptive information into the control of compensatory stepping. Control of a-p stability appeared primarily to involve an increase in forward step distance. Surprisingly, the control of lateral stability involved both an anticipatory postural adjustment (APA) and lateral step placement. By including a much larger APA prior to foot-lift (137% increase in amplitude and 50% increase in duration versus no-obstacle trials), the COM was propelled to a more stable position prior to swing phase. This was achieved with minimal (32 ms) delay in foot-lift, due, in part, to more rapid initiation and execution of limb unloading. In contrast to previous findings that APAs are commonly absent or severely reduced during compensatory stepping, the present results demonstrate that large APAs can be incorporated into these reactions when demanded by task conditions. However, these large APAs were still insufficient to counter the increased tendency of the COM to fall during the prolonged swing phase. The fact that the APA was included at all may indicate a hybrid control, in which predictive control (via APA) is used to reduce the anticipated lateral instability, and reactive control of the final foot placement, governed by sensory discharge related to the actual COM motion, provides any additional stabilization required.

Rat Hindlimb Unloading by Tail Suspension Reduces Osteoblast Differentiation, Induces IL-6 Secretion, and Increases Bone Resorption in Ex Vivo Cultures

In this research we utilized tail-suspended rats as an in vivo model for bone loss studies in order to investigate the effects of the tail suspension on the structure of the suspended bones and in ex vivo cultures the activities of trabecular osteoblasts, marrow-derived osteogenic cells, and osteoclasts obtained from treated animals, compared with untreated controls. After a 5-day hind limb unloading, trabecular thinning was already evidenced in the tibial primary spongiosa. In the secondary spongiosa, the bone formation activity was reduced whereas osteoclastic parameters were not yet altered. Bone marrow-derived osteogenic cells and differentiated osteoblasts from enzymatic digestion of posterior limb trabecular bone were prepared from 5 day tail-suspended rats and from normally loaded rats as controls. Cell morphology, alkaline phosphatase (ALPH) activity, production of mineral matrix, osteocalcin, and IL-6 secretion were evaluated in both cell populations. Tail suspension reduced the osteogenic potential of stromal marrow cells and of already differentiated osteoblasts. In fact, ALP positive colonies were significantly reduced in number and were smaller in size compared with controls and bone nodules formed in permissive conditions were also significantly fewer and smaller, whereas in cultures of cells from control conditions, large mineralizing nodules were formed. Osteocalcin secretion was not affected by unloading. Finally, IL-6 concentration was increased in marrow-derived cells from treated rats compared with controls. Primary cultures of osteoclasts were obtained from the nonadherent fraction of the bone marrow of the same animals. The number of TRAP positive cells in culture from tail-suspended rats was significantly increased, as well as bone resorption activity, measured as resorbed surfaces of a suitable synthetic hydroxyapatite, compared with controls. These data clearly suggest that skeletal unloading not only reduces the osteogenic potential of osteoblastic cells but induces an increased osteoclastogenesis and osteoclast activity in ex vivo cultures. They also indicate for the first time that a possible mediator responsible for the increased osteoclastogenesis could be represented by the IL-6 whose secretion by bone marrow cells was significantly enhanced by unloading.

Effect of single-limb inertial loading on bilateral reaching: interlimb interactions.

This study employed the paradigm of asymmetric limb loading during bilateral arm reaching to examine the motor system's ability to independently organize the discrete movement of both upper limbs to equidistant targets when one of the limbs is loaded under specific timing constraints. The loading procedure involved attaching two different Velcro strapped weights to the right wrist, thus increasing the right arm's mass by 25% (1 kg) and 50% (2 kg). Movements were captured by a high-speed digital camera (240 Hz), while electromyographic (EMG) activity of selected elbow and shoulder muscles of both limbs was recorded (1,000 Hz) simultaneously. The results revealed that the mechanisms used by the system to compensate for unilateral limb loading were as follows: First, addition of an inertial load resulted in an increased movement time and concomitant decrease in peak velocity of both the upper arm and forearm of only the loaded limb and was scaled to the added weight. Second, for the EMG parameters, adjustments to the inertial load were primarily characterized by an increase in burst duration of all muscles, with load-specific changes in activity and onset time: the elbow antagonist (biceps) demonstrated a decrease in activity with the 50% load, and the elbow agonist (triceps) had an earlier onset with the 25% load. Concomitant adjustments on the unloaded limb consisted primarily of an increase in burst duration of the shoulder and elbow agonists (pectoralis and triceps), an earlier triceps onset solely with the 25% load, and a decrease in activity of the biceps solely with the 50% load. Third, with the exception of biceps activity, the amplitude of EMG activity was invariant across changes in load for both the loaded and unloaded limb. This lack of modulation in activity may have been related to the inability of performers to meet the time constraint of simultaneous bilateral limb arrival to the end targets. This inability can be the result of an active strategy selection process to safeguard the actions against interference or alternatively it could simply be a consequence of the biomechanical properties of the system in relation to task constraints. These issues are discussed in the light of the present findings and those of previous studies.

Medio-lateral balance adjustments preceding reflexive limb withdrawal are modified by postural demands

We have recently observed medio-lateral balance adjustments (BA) preceding reflexive stepping elicited by noxious stimulation. While task specific modulation is evident for BA prior to voluntary leg movement, it is unclear whether rapid BA reactions (prior to ‘reflexive’ stepping) represent a generic response to evoked limb withdrawal or can be modified to suit task-conditions. This study was designed to establish whether the CNS is able to modify rapid onset latency BAs to match task conditions. Reflexive stepping was evoked by applying a noxious stimulus (50 ms stimulus train, 1 ms pulses, 300 Hz, 4×perceptual threshold) to the plantar surface of the either the left or right foot. Task conditions were varied prior to stimulation by having subjects maintain one of three different static positions: (1) lean left (70% body weight (BW) on left), (2) neutral (50% BW both sides), (3) lean right (70% BW on right). BAs were denoted by centre-of-pressure (CoP) excursions towards the swing foot after the onset of noxious stimulation (average onset latency of 128 ms). There was a significant increase in frequency of occurrence and a significant increase in magnitude of CoP shift when the stimulation was applied to a loaded limb (leaning with 70% BW on the stimulated foot) as compared to an unloaded limb (30%BW). In addition, 78% of loaded trials featured steps taken with the unstimulated foot, which delayed removal of the stimulated foot. Collectively, the results indicate modifiability of the very rapid onset balance adjustments that precede the onset of limb withdrawal revealing complex control of balance exists even over very brief latencies.

Expression of heat shock protein 72 in atrophied rat skeletal muscles

Changes in the expression of heat shock protein 72 (HSP72) in response to atrophic-inducing perturbations of muscle involving chronic mechanical unloading and denervation were determined. Adult male Wistar rats were assigned randomly to a sedentary cage control (CON), hind limb unloading (HU, via tail suspension), HU plus tenotomy (HU + TEN), HU plus denervation (HU + DEN), or HU + TEN + DEN group. Tenotomy and DEN involved cutting the Achilles tendon and removing a segment of the sciatic nerve, respectively. After 5 days, HSP72 levels in the soleus of the HU + DEN and HU + TEN + DEN groups were 42 (P < 0.05) and 53% (P < 0.01) less than CON, respectively. Soleus weight decreased in both groups. Heat shock protein 72 levels in the plantaris of the HU + TEN, HU + DEN, and HU + TEN + DEN groups were 31, 25, and 30% lower than CON, respectively (P < 0.05). Plantaris weight decreased in the HU + DEN and HU + TEN + DEN, but not in the HU + TEN group. Hind limb unloading alone had little effect on the HSP72 level in either muscle. Reduced levels of HSP72 were associated with a decreased soleus (r=0.62, P < 0.01) and plantaris (r=0.78, P < 0.001) weight. These results indicate that the levels of HSP72 in both a slow and a fast rat plantarflexor are responsive to a chronic decrease in the levels of loading and/or activation and suggest that the neuromuscular activity level and the presence of innervation of a muscle are important factors that induce HSP72 expression.

EFFECTS OF ACTUAL AND SIMULATED MICROGRAVITY ON CARDIAC MASS AND FUNCTION IN THE RAT

The purpose of this study was to test the hypothesis that exposure to actual or simulated microgravity induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: Preflight (PF, n = 12); Flight (FL, n = 7); Flight Cage Simulation (SIM, n = 6), and Vivarium Control (VIV, n = 7). Animals in the FL group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the simulated microgravity study were subdivided into three groups: Control (CON, n = 20); 7 day hindlimb unloaded (7HU, n = 10); and 28 day unloaded (28HU, n = 19). In a subset of CON (n = 7) and 28HU (n = 6) rats, a catheter was advanced into the left ventricle to measure the rate of rise in ventricular pressure (+dP/dt) during standing as an estimate of cardiac contractility. After completion of their respective treatments, hearts were removed and weighed. Animals in the PF group were sacrificed 24 hr prior to launch while the FL group was sacrificed 11- 17 hr after landing. The SM and VIV groups were sacrificed 48 and 96 hr after the FL group, respectively. Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- .03 g; FL 1.32 +/- 0.02 g; SIM 1.28 +/- 0.04 g; VIV 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hin~limb unloading (CON 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on myocardial contractility (CON 8055 +/- 385 mmHg/sec; 28HU 8545 +/- 755 mmHg/sec). These data suggest that cardiac atrophy does not occur following short-term exposure to microgravity, and that neither short- nor long-term simulated microgravity alter cardiac mass or function.

Myosin heavy chain isoform expression following reduced neuromuscular activity: potential regulatory mechanisms.

In this review, the adaptations in myosin heavy chain (MHC) isoform expression induced by chronic reductions in neuromuscular activity (including electrical activation and load bearing) of the intact neuromuscular unit are summarized and evaluated. Several different animal models and human clinical conditions of reduced neuromuscular activity are categorized based on the manner and extent to which they alter the levels of electrical activation and load bearing, resulting in three main categories of reduced activity. These are: 1) reduced activation and load bearing (including spinal cord injury, spinal cord transection, and limb immobilization with the muscle in a shortened position); 2) reduced loading (including spaceflight, hindlimb unloading, bed rest, and unilateral limb unloading); and 3) inactivity (including spinal cord isolation and blockage of motoneuron action potential conduction by tetrodotoxin). All of the models discussed resulted in increased expression of fast MHC isoforms at the protein and/or mRNA levels in slow and fast muscles (with the possible exception of unilateral limb unloading in humans). However, the specific fast MHC isoforms that are induced (usually the MHC-IIx isoform in slow muscle and the MHC-IIb isoform in fast muscle) and the degree and rate of adaptation are dependent upon the animal species and the specific model or condition that is being studied. Recent studies designed to elucidate the mechanisms by which electrical activation and load bearing alter expression of MHC isoforms at the cellular and genetic levels are also reviewed. Two main mechanisms have been proposed, the myogenin:MyoD and calcineurin:NF-AT pathways. Collectively, the data suggest that the regulation of MHC isoform expression involves a complex interaction of multiple control mechanisms including the myogenin:MyoD and calcineurin:NF-AT pathways; however, other intracellular signaling pathways are likely to contribute.

Mechanical signaling in the development of postmenopausal osteoporosis.

Estrogen deficiency results in increased bone turnover and net bone loss in rats as well as humans. The respective roles of bone turnover and mechanical strain in mediating estrogen deficiency-induced cancellous bone loss were investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in long bones. However, cancellous bone was preferentially lost in the metaphysis, a site that experiences low strain energy during normal physical activity. No bone loss was observed in the epiphysis, a site experiencing higher strain energy, despite a similar increase in bone turnover. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased or decreased in long bones of ovariectomized rats by treadmill exercise or functional unloading, respectively. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing weight bearing accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in unloaded limbs and prevented bone loss in the loaded limbs. These results suggest that estrogen alters the mechanosensory (mechanostat) set point for skeletal adaptation, effectively reducing the minimum strain energy levels at which bone is added. Additionally, these studies suggest that physical activity as well as endocrine status play an important role in maintenance of the female skeleton during aging.

Parathyroid hormone and mechanical usage have a synergistic effect in rat tibial diaphyseal cortical bone.

Previous reports showed that bone mass and architecture only partially recovered by remobilization (RM) after immobilization (IM)-induced osteopenia, and that parathyroid hormone (PTH) had an anabolic effect on the skeleton. The aim of this study was to determine whether low doses of PTH could restore IM-induced cortical bone loss and whether a combination of PTH plus loading (RM) treatment would be more effective than the PTH in unloaded (IM) limbs. One hundred and sixty 6-month-old rats were divided into aging and IM groups. The right hindlimb of the rat was immobilized by elastic bandage for 18 weeks, and then groups of rats were either kept IM or RM and treated with 30 microgram or 80 microgram of hPTH(1-38)/kg/day for 2, 10, and 20 weeks. Fluorescent-labeled, undecalcified cross-sections of right tibial shafts were studied. We found that RM for 20 weeks after 18 weeks of IM only partially recovered IM-induced muscle weight loss and PTH had no effect on muscle weight in either IM or RM limbs; that RM for 20 weeks after 18 weeks of IM partially restored some minimal cortical width by stimulating periosteal and endocortical bone formation and decreasing endocortical resorption; that PTH treatment of IM limbs completely restored IM-induced cortical bone loss and added extra bone by stimulating bone formation indices on all bone surfaces and depressing bone resorption on endocortical surface; that PTH treatment of RM limbs produced similar anabolic effects as in IM limbs with 30 microgram/kg/day dose but the 80 microgram/kg/day dose-treated limbs had a higher periosteal bone formation rate, which created a larger cross-sectional area, more cortical bone area, and a thicker cortex than the same dose treated IM limbs; and that PTH 80 microgram/kg/day treatment produced more anabolic effect than the 30 microgram/kg/day in both IM and RM limbs. We concluded that reloading the hindlimb by RM after long-term IM could not recover the cortical bone mass. PTH at employed doses was able to completely restore IM-induced cortical bone loss, and this effect was independent of mechanical stimulation. However, when PTH was combined with mechanical loading (RM), a synergistic anabolic effect on periosteal bone formation occurred which increased the cross sectional area that can increase bone strength.

Skeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I.

Skeletal unloading decreases bone formation and osteoblast number in vivo and decreases the number and proliferation of bone marrow osteoprogenitor (BMOp) cells in vitro. We tested the ability of parathyroid hormone (PTH) to stimulate BMOp cells in vivo by treating Sprague Dawley rats (n = 32) with intermittent PTH(1-34) (1 h/day at 8 microg/100 g of body weight), or with vehicle via osmotic minipumps during 7 days of normal weight bearing or hind limb unloading. Marrow cells were flushed from the femur and cultured at the same initial density for up to 21 days. PTH treatment of normally loaded rats caused a 2.5-fold increase in the number of BMOp cells, with similar increases in alkaline phosphatase (ALP) activity and mineralization, compared with cultures from vehicle-treated rats. PTH treatment of hind limb unloaded rats failed to stimulate BMOp cell number, ALP activity, or mineralization. Hind limb unloading had no significant effect on PTH receptor mRNA or protein levels in the tibia. Direct in vitro PTH challenge of BMOp cells isolated from normally loaded bone failed to stimulate their proliferation and inhibited their differentiation, suggesting that the in vivo anabolic effect of intermittent PTH on BMOp cells was mediated indirectly by a PTH-induced factor. We hypothesize that this factor is insulin-like growth factor-I (IGF-I), which stimulated the in vitro proliferation and differentiation of BMOp cells isolated from normally loaded bone, but not from unloaded bone. These results suggest that IGF-I mediates the ability of PTH to stimulate BMOp cell proliferation in normally loaded bone, and that BMOp cells in unloaded bone are resistant to the anabolic effect of intermittent PTH therapy due to their resistance to IGF-I.

The effect of unloading on protein synthesis in human skeletal muscle.

Atrophy of skeletal muscle is observed in response to immobilization and lack of weight-bearing. The aim of this study was to investigate the effect of immobilization on muscle protein synthesis and associated biochemical parameters in skeletal muscle of healthy volunteers employing a standardized model of lower limb unloading. One leg was unloaded for 10 days, and percutaneous muscle biopsies were taken before and at the end of the unloading period. The capacity for protein synthesis, as reflected by the concentration of RNA, decreased by 16% (P < 0.05) although the fractional synthesis rate (FSR) of protein was not significantly changed after 10 days of unloading. Furthermore there was an increase in the concentration of the free branched chain amino acids in muscle by 48% (P < 0.05).

Effects of microgravity on muscle and cerebral cortex: A suggested interaction

The “slow” antigravity muscle adductor longus was studied in rats after 14 days of spaceflight (SF). The techniques employed included standard methods for light microscopy, neural cell adhesion molecule (N-CAM) immunocytochemistry and electron microscopy. Light and electron microscopy revealed myofiber atrophy, segmental necrosis and regenerative myofibers. Regenerative myofibers were N-CAM immunoreactive (N-CAM-IR). The neuromuscular junctions showed axon terminals with a decrease or absence of synaptic vesicles, degenerative changes, vacant axonal spaces and changes suggestive of axonal sprouting. No alterations of muscle spindles was seen either by light or electron microscopy. These observations suggest that muscle regeneration and denervation and synaptic remodeling at the level of the neuromuscular junction may take place during spaceflight. In a separate study, GABA immunoreactivity (GABA-IR) was evaluated at the level of the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension (“simulated” microgravity). A reduction in number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-IR terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system after spaceflight and hindlimb suspension it is suggested that after limb unloading there are alterations of afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the changes observed in GABA immunoreactivity of cells and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

Body Weight Support Treadmill Gait Training in the Subacute Recovery Phase of Incomplete Spinal Cord Injury

Objectives: A pilot study was conducted on five patients with an incomplete spinal cord injury (iSCI) using a body weight support treadmill training (BWSTT) gait strat egy within the subacute phase of recovery. The objectives of this project were to de fine appropriate candidates, identify treatment parameters, select impairment and dis ability outcome measures, and solicit consumer input in preparation for a clinical efficacy trial.Methods: Five patients with injuries ranging from C2 lesion to T10 lesion con sented to participate and were within 2 months post injury. A commercially available mechanical suspension frame straddled a motorized treadmill, and a modified climber's harness was used for support. All participants were nonambulatory on entry into the study. The BWSTT intervention, consisting of 36 1-hour sessions over a 3-month period, was conducted by physical therapists and was customized to the patient's abil ities. Evaluations were conducted at baseline, at 6 weeks, and at the 12-week post- test interval. Clinical impairment measures included muscle strength, sensation, mus cle tone, perceived exertion, and treadmill training endurance. Gait analysis provided dynamic quantification of kinematic and surface electromyography (EMG) of five mus cles of the right lower limb on all participants on the BWS treadmill and three of the five patients during overground walking. A disability outcome measure was used to grade the level of ambulation function. A consumer team member conducted feed back interviews with participants to obtain their input to this research direction.Results: Lower limb unloading varied from 26 percent to 83 percent of body weight. All participants completed the 12-week training program and four individu als eventually progressed to overground walking. The fifth participant, who had the most severe motor impairments, did not achieve functional overground walking with out the aid of bilateral knee-ankle-foot orthoses. Improvements were evident in the clinical measures of strength, endurance, and percent BWS in four patients. Positive changes were recorded in temporal-spatial, joint motion, and EMG gait measures matching increased ambulation function in four of the five patients. Gait analysischanges in one patient were highlighted to illustrate dynamic measures of motor re covery. Consumer input and feedback from patients and therapists were positive and included suggestions for improvements.Conclusions: A multicenter randomized controlled trial is advocated to evaluate the efficacy of a BWSTT gait strategy in the subacute recovery phase of iSCI. This pilot work resulted in specific recommendations in the selection of candidates, the training and evaluation parameters, and the potential value of consumer input for fu ture research. Key Words: Incomplete spinal cord injury—Rehabilitation—Weight- supported treadmill gait training—Consumer input.

The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats.

A 14-day orbital spaceflight was performed using ovariectomized Fisher 344 rats to determine the combined effects of estrogen deficiency and near weightlessness on tibia radial bone growth and cancellous bone turnover. Twelve ovariectomized rats with established cancellous osteopenia were flown aboard the space shuttle Columbia (STS-62). Thirty ovariectomized rats were housed on earth as ground controls: 12 in animal enclosure modules, 12 in vivarium cages, and 6 killed the day of launch for baseline measurements. An additional 18 ovary-intact rats were housed in vivarium cages as ground controls: 8 rats were killed as baseline controls and the remaining 10 rats were killed 14 days later. Ovariectomy increased periosteal bone formation at the tibia-fibula synostosis; cancellous bone resorption and formation in the secondary spongiosa of the proximal tibial metaphysis; and messenger RNA (mRNA) levels for the prepro-alpha2(1) subunit of type 1 collagen, osteocalcin, transforming growth factor-beta, and insulin-like growth factor I in the contralateral proximal tibial metaphysis and for the collagen subunit in periosteum pooled from tibiae and femora and decreased cancellous bone area. Compared to ovariectomized weight-bearing rats, the flight group experienced decreases in periosteal bone formation, collagen subunit mRNA levels, and cancellous bone area. The flight rats had a small decrease in the cancellous mineral apposition rate, but no change in the calculated bone formation rate. Also, spaceflight had no effect on cancellous osteoblast and osteoclast perimeters or on mRNA levels for bone matrix proteins and signaling peptides. On the other hand, spaceflight resulted in an increase in bone resorption, as ascertained from the diminished retention of a preflight fluorochrome label. This latter finding suggests that osteoclast activity was increased. In a follow-up ground-based experiment, unilateral sciatic neurotomy of ovariectomized rats resulted in cancellous bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

Biomechanical abnormalities of post-polio patients and the implications for orthotic management

Muscle weakness resulting from the combined effects of acute and late motor neuron pathology is the basic cause of post-polio dysfunction. Through their normal sensation and moter control, post-polio patients minimize their disability by useful substitutions. Orthoses are needed only when these substitutions either are inadequate or result in muscle or joint overuse. The areas most commonly showing late disability are the lower extremities, shoulders and low-back. In the lower extremities, the major muscle groups are the hip extensors and abductors, the knee extensors (quadriceps), ankle plantar flexors and dorsi flexors. Each group has a specific function which relates to one of the basic tasks of walking, weight acceptance, single limb support and swing. To determine orthotic needs, polio gait deviations representing useful substitutions must be differentiated from symptomatic dysfunction. Weight acceptance utilizes the quadriceps, hip extensors and hip abductors to establish a stable limb and provide shock absorbing mechanics. Substitutions to preserve weight bearing stability include sacrifice of normal shock absorbing knee flexion for quadriceps weakness, backward or lateral trunk lean for hip extensor and abductor weakness. Knee pain, excessive hyperextension and flexion contractures are indications for orthotic assistance with a KAFO. Orthotic designs relate to the type of knee joint (off-set, free, locked) and completeness of the AFO component. Low-back pain from hip substitutions or over use of the hip muscles requires a walking aid. Single limb support is the period when the limb and body advance over the supporting foot. The key muscle group is the soleus-gastrocnemius complex. Swing involves lifting and advancing the unloaded limb. While all three joints flex simultaneously, the hip flexors and ankle dorsi flexors are the critical muscles. A drop foot from ankle dorsiflexor weakness is the common disability. Excessive hip flexion is the usual substitution. An orthosis which assists dorsiflexion without obstructing loading response plantar flexion is the most functional design.

Changes in muscle function in response to 10 days of lower limb unloading in humans

Force-generating capacity and electromyographic (EMG) activity of the knee extensor muscles were studied before and after short-term (10 d) unilateral lower limb unloading and during 4 days of recovery. Ten healthy males used crutches to prevent one of their lower limbs from weight-bearing while maintaining joint mobility as well as daily ambulatory activities. Knee extensor torque and quadriceps rectified EMG during maximal voluntary isometric contraction (MVC) was measured repeatedly before and after the intervention. Also, EMG at a fixed submaximal level (100 Nm; 30-45% MVC) and maximal angular velocity (AVmax), during unresisted knee extension, were assessed. Maximum torque decreased (P < 0.05) by 13 +/- 8% in response to unloading while maximum EMG activity did not change after unloading or during recovery (P = 0.35). Submaximum EMG increased (P < 0.05) by 25 +/- 16% after unloading. Maximum and submaximum torque/EMG ratio decreased (P < 0.05) after unloading. AVmax decreased (P < 0.05) by 9 +/- 8% after unloading. The post value, however, was not different from that of the weight-bearing limb. Torque, EMG and AVmax were recovered (P > 0.05) after 4 days of resumed weight-bearing. The pronounced decrease and the rapid recovery in maximum torque appears not to be attributed to a change in muscle mass alone. Because the findings of unchanged maximum EMG and increased EMG at a submaximal force level suggest no change in neural drive, we propose that unspecific tissue factors in part impair muscle function in response to short-term loss of weight-bearing activity. Results also indicate that recovery in muscle function after short-term unloading seems to be completed in a time span shorter than the period of preceding inactivity.