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At least 73 records · Page 4

The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.

NASA Discipline Musculoskeletal↗

Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading

Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.

Review, Academic↗

Skeletal unloading inhibits the in vitro proliferation and differentiation of rat osteoprogenitor cells

Loss of weight bearing in the growing rat decreases bone formation, osteoblast numbers, and bone maturation in unloaded bones. These responses suggest an impairment of osteoblast proliferation and differentiation. To test this assumption, we assessed the effects of skeletal unloading using an in vitro model of osteoprogenitor cell differentiation. Rats were hindlimb elevated for 0 (control), 2, or 5 days, after which their tibial bone marrow stromal cells (BMSCs) were harvested and cultured. Five days of hindlimb elevation led to significant decreases in proliferation, alkaline phosphatase (AP) enzyme activity, and mineralization of BMSC cultures. Differentiation of BMSCs was analyzed by quantitative competitive polymerase chain reaction of cDNA after 10, 15, 20, and 28 days of culture. cDNA pools were analyzed for the expression of c-fos (an index of proliferation), AP (an index of early osteoblast differentiation), and osteocalcin (a marker of late differentiation). BMSCs from 5-day unloaded rats expressed 50% less c-fos, 61% more AP, and 35% less osteocalcin mRNA compared with controls. These data demonstrate that cultured osteoprogenitor cells retain a memory of their in vivo loading history and indicate that skeletal unloading inhibits proliferation and differentiation of osteoprogenitor cells in vitro.

NASA Discipline Musculoskeletal↗

Resistance exercise prevents plantar flexor deconditioning during bed rest

Because resistance exercise (REX) and unloading induce opposing neuromuscular adaptations, we tested the efficacy of REX against the effects of 14 d of bed rest unloading (BRU) on the plantar flexor muscle group. Sixteen men were randomly assigned to no exercise (NOE, N = 8) or REX (N = 8). REX performed 5 sets x 6-10 repetitions to failure of constant resistance concentric/eccentric plantar flexion every other day during BRU. One-repetition maximum (1RM) strength was tested on the training device. The angle-specific torque-velocity relationship across 5 velocities (0, 0.52, 1.05, 1.75, and 2.97 rad.s-1) and the full range-of-motion power-velocity relationship were assessed on a dynamometer. Torque-position analyses identified strength changes at shortened, neutral, and stretched muscle lengths. Concentric and eccentric contractile work were measured across ten repetitions at 1.05 rad.s-1. Maximal neural activation was measured by surface electromyography (EMG). 1RM decreased 9% in NOE and improved 11% in REX (P < 0.05). Concentric (0.52 and 1.05 rad.s-1), eccentric (0.52 and 2.97 rad.s-1), and isometric angle-specific torques decreased (P < 0.05) in NOE, averaging 18%, 17%, and 13%, respectively. Power dropped (P < 0.05) in NOE at three eccentric (21%) and two concentric (14%) velocities. REX protected angle-specific torque and average power at all velocities. Concentric and eccentric strength decreased at stretched (16%) and neutral (17%) muscle lengths (P < 0.05) in NOE while REX maintained or improved strength at all joint positions. Concentric (15%) and eccentric (11%) contractile work fell in NOE (P < 0.05) but not in REX. Maximal plantar flexor EMG did not change in either group. In summary, constant resistance concentric/eccentric REX completely prevented plantar flexor performance deconditioning induced by BRU. The reported benefits of REX should prove useful in prescribing exercise for astronauts in microgravity and for patients susceptible to functional decline during bed- or chair-bound hospital stays.

NASA Discipline Musculoskeletal↗

Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting

The role of apoptosis in the elimination of myonuclei during hindlimb unloading-induced atrophy and the inhibition of apoptosis in the prevention of muscle atrophy were examined. The number of nuclei demonstrating double-stranded DNA fragmentation seen by terminal deoxynucleotidyl transferase (TDT) histochemical staining, an indicator of apoptosis, was significantly increased after 14 days of suspension. Double staining with TDT and antilaminin immunohistochemistry revealed that some TDT-positive nuclei were within the fiber lamina and were most likely myonuclei. The number of fibers containing morphologically abnormal nuclei was also significantly greater in suspended compared with control rats. Combined treatment with growth hormone and insulin-like growth factor I (GH/ IGF-I) and resistance exercise attenuated the increase in TDT-positive nuclei (approximately 26%, P > 0.05) and significantly decreased the number of fibers with morphologically abnormal nuclei. The data suggest that 1) "programmed nuclear death" contributes to the elimination of myonuclei and/or satellite cells from atrophying fibers, and 2) GH/IGF-I administration plus muscle loading ameliorates the apoptosis associated with hindlimb unloading.

Non-NASA Center↗

Effects of static fingertip loading on carpal tunnel pressure

The purpose of this study was to explore the relationship between carpal tunnel pressure and fingertip force during a simple pressing task. Carpal tunnel pressure was measured in 15 healthy volunteers by means of a saline-filled catheter inserted percutaneously into the carpal tunnel of the nondominant hand. The subjects pressed on a load cell with the tip of the index finger and with 0, 6, 9, and 12 N of force. The task was repeated in 10 wrist postures: neutral; 10 and 20 degrees of ulnar deviation; 10 degrees of radial deviation; and 15, 30, and 45 degrees of both flexion and extension. Fingertip loading significantly increased carpal tunnel pressure for all wrist angles (p = 0.0001). Post hoc analyses identified significant increase (p < 0.05) in carpal tunnel pressure between unloaded (0 N) and all loaded conditions, as well as between the 6 and 12 N load conditions. This study demonstrates that the process whereby fingertip loading elevates carpal tunnel pressure is independent of wrist posture and that relatively small fingertip loads have a large effect on carpal tunnel pressure. It also reveals the response characteristics of carpal tunnel pressure to fingertip loading, which is one step in understanding the relationship between sustained grip and pinch activities and the aggravation or development of median neuropathy at the wrist.

NASA Center ARC↗

Prediction of human gait parameters from temporal measures of foot-ground contact

Investigation of the influence of human physical activity on bone functional adaptation requires long-term histories of gait-related ground reaction force (GRF). Towards a simpler portable GRF measurement, we hypothesized that: 1) the reciprocal of foot-ground contact time (1/tc); or 2) the reciprocal of stride-period-normalized contact time (T/tc) predict peak vertical and horizontal GRF, loading rates, and horizontal speed during gait. GRF data were collected from 24 subjects while they walked and ran at a variety of speeds. Linear regression and ANCOVA determined the dependence of gait parameters on 1/tc and T/tc, and prediction SE. All parameters were significantly correlated to 1/tc and T/tc. The closest pooled relationship existed between peak running vertical GRF and T/tc (r2 = 0.896; SE = 3.6%) and improved with subject-specific regression (r2 = 0.970; SE = 2.2%). We conclude that temporal measures can predict force parameters of gait and may represent an alternative to direct GRF measurements for determining daily histories of habitual lower limb loading quantities necessary to quantify a bone remodeling stimulus.

NASA Center ARC↗

Vulnerability to dysfunction and muscle injury after unloading

OBJECTIVE: To test whether unloading increases vulnerability to eccentric exercise-induced dysfunction and muscle injury. DESIGN: Before-after trial. SETTING: General community. PATIENTS OR OTHER PARTICIPANTS: Two women and 5 men (73 +/- 3kg [mean +/- SE]) who were active college students but were not trained in lower body resistance exercise volunteered. INTERVENTION: Five weeks of unilateral lower limb suspension (ULLS), which has been shown to decrease strength and size of the unloaded, left, but not load-bearing, right quadriceps femoris muscle group (QF) by 20% and 14%, respectively; performance of 10 sets of ten eccentric actions with each QF immediately after the ULLS strength tests with a load equivalent to 65% of the post-ULLS eccentric 1-repetition maximum. MAIN OUTCOME MEASURE(S): Concentric and eccentric 1-repetition maximum for the left, unloaded and the right, load-bearing QF measured immediately after ULLS and 1,4,7,9, and 11 days later; cross-sectional area and spin-spin relaxation time (T2) of each QF as determined by magnetic resonance imaging and measured the last day of ULLS and 3 days later. RESULTS: The mean load used for eccentric exercise was 23 +/- 2 and 30 +/- 3kg for the left, unloaded and right, load-bearing QF, respectively. The concentric and eccentric 1-repetition maximum for the unloaded and already weakened left QF was further decreased by 18% (p = .000) and 27% (p = .000), respectively, 1 day after eccentric exercise. Strength did not return to post-ULLS levels until 7 days of recovery. The right, load-bearing QF showed a 4% decrease (p = .002) in the eccentric 1-repetition maximum 1 day after eccentric exercise. The left, unloaded QF showed an increase in T2 (p = .002) in 18% of its cross-sectional area 3 days after the eccentric exercise, thus indicating muscle injury. The right, load-bearing QF showed no elevation in T2 (p = .280). CONCLUSION: Unloading increases vulnerability to eccentric exercise-induced dysfunction and muscle injury, even at relatively light loads.

NASA Program Space Physiology and Countermeasures↗

Haptic cues for orientation and postural control in sighted and blind individuals

Haptic cues from fingertip contact with a stable surface attenuate body sway in subjects even when the contact forces are too small to provide physical support of the body. We investigated how haptic cues derived from contact of a cane with a stationary surface at low force levels aids postural control in sighted and congenitally blind individuals. Five sighted (eyes closed) and five congenitally blind subjects maintained a tandem Romberg stance in five conditions: (1) no cane; (2,3) touch contact (< 2 N of applied force) while holding the cane in a vertical or slanted orientation; and (4,5) force contact (as much force as desired) in the vertical and slanted orientations. Touch contact of a cane at force levels below those necessary to provide significant physical stabilization was as effective as force contact in reducing postural sway in all subjects, compared to the no-cane condition. A slanted cane was far more effective in reducing postural sway than was a perpendicular cane. Cane use also decreased head displacement of sighted subjects far more than that of blind subjects. These results suggest that head movement control is linked to postural control through gaze stabilization reflexes in sighted subjects; such reflexes are absent in congenitally blind individuals and may account for their higher levels of head displacement.

NASA Discipline Neuroscience↗

Synergistic ablation does not affect atrophy or altered myosin heavy chain expression in the non-weight bearing soleus muscle

The purpose of this study was to investigate whether the soleus muscle undergoes atrophy and alterations in myosin heavy chain (MHC) composition during non-weight bearing in the absence of synergists. Thirty-two female rats were randomly assigned to four groups: control (C), synergistic ablation (ABL) of the gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb suspension (HLS), or a combination of synergistic ablation and hindlimb suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non-weight bearing decreased mixed and myofibrillar protein contents and Type I MHC 49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS animals. Similarly, when compared to C rats, mixed and myofibrillar protein contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed. Collectively, these data indicate that the loss of muscle protein and Type I MHC, and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur independently of the presence of synergists during non-weight bearing. Furthermore, these results confirm the contention that soleus mass and MHC expression are highly sensitive to alterations in mechanical load.

NASA Center ARC↗

Hindlimb suspension diminishes femoral cross-sectional growth in the rat

Growth, functional adaptation, and torsional strength were examined in the femora of 39-day-old male Sprague-Dawley rats subjected to hindlimb suspension for 0, 1, 2, 3, or 4 weeks and were compared with measurements for age-matched control animals. Our goal was to understand the effect of reduced loading on the normal age-related changes in femoral properties during growth. The control animals exhibited growth-related increases in all geometric and torsional properties of the femur. The mean body mass and femoral length of the hindlimb-suspended rats were similar to those of the controls throughout the experiment. Over 4 weeks, the femoral cross-sectional and torsional measurements from the hindlimb-suspended rats demonstrated increases in comparison with the basal values (+33% cross-sectional area, +64% polar moment of inertia, +67% ultimate torque, and +181% torsional rigidity), but the age-matched controls showed significantly greater growth-related increases (+71% cross-sectional area, +136% polar moment of inertia, +127% ultimate torque, and +367% torsional rigidity). The differences in femoral structural strength between the hindlimb-suspended animals and the age-matched controls were attributable to differences in altered cross-sectional geometry.

NASA Discipline Musculoskeletal↗

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Non-NASA Center↗

Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage

Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

NASA Discipline Musculoskeletal↗

Skeletal unloading induces resistance to insulin-like growth factor I

In previous studies with a hindlimb elevation model, we demonstrated that skeletal unloading transiently inhibits bone formation. This effect is limited to the unloaded bones (the normally loaded humerus does not cease growing), suggesting that local factors are of prime importance. IGF-I is one such factor; it is produced in bone and stimulates bone formation. To determine the impact of skeletal unloading on IGF-I production and function, we assessed the mRNA levels of IGF-I and its receptor (IGF-IR) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation. The mRNA levels for IGF-I and IGF-IR rose during hindlimb elevation, returning toward control values during recovery. This was accompanied by a 77% increase in IGF-I levels in the bone, peaking at day 10 of unloading. Changes in IGF binding protein levels were not observed. Infusion of IGF-I (200 micrograms/day) during 1 week of hindlimb elevation doubled the increase in bone mass of the control animals but failed to reverse the cessation of bone growth in the hindlimb-elevated animals. We conclude that skeletal unloading induces resistance to IGF-I, which may result secondarily in increased local production of IGF-I.

NASA Center ARC↗

Temporal changes in sarcomere lesions of rat adductor longus muscles during hindlimb reloading

Focal sarcomere disruptions were previously observed in adductor longus muscles of rats flown approximately two weeks aboard the Cosmos 1887 and 2044 biosatellite flights. These lesions, characterized by breakage and loss of myofilaments and Z-line streaming, resembled damage induced by unaccustomed exercise that includes eccentric contractions in which muscles lengthen as they develop tension. We hypothesized that sarcomere lesions in atrophied muscles of space flow rats were not produced in microgravity by muscle unloading but resulted from muscle reloading upon re-exposure to terrestrial gravity. To test this hypothesis, we examined temporal changes in sarcomere integrity of adductor longus muscles from rats subjected to 12.5 days of hindlimb suspension unloading and subsequent reloading by return to vivarium cages for 0, 6, 12, or 48 hours of normal weightbearing. Our ultrastructural observations suggested that muscle unloading (0 h reloading) induced myofibril misalignment associated with myofiber atrophy. Muscle reloading for 6 hours induced focal sarcomere lesions in which cross striations were abnormally widened. Such lesions were electron lucent due to extensive myofilament loss. Lesions in reloaded muscles showed rapid restructuring. By 12 hours of reloading, lesions were moderately stained foci and by 48 hours darkly stained foci in which the pattern of cross striations was indistinct at the light and electron microscopic levels. These lesions were spanned by Z-line-like electron dense filamentous material. Our findings suggest a new role for Z-line streaming in lesion restructuring: rather than an antecedent to damage, this type of Z-line streaming may be indicative of rapid, early sarcomere repair.

Non-NASA Center↗

Alterations in skeletal muscle related to impaired physical mobility: an empirical model

The objective of this investigation was to study impaired physical mobility and the resulting skeletal muscle atrophy. An animal model was used to study morphological adaptations of the soleus and plantaris muscles to decreased loading induced by hindlimb suspension of an adult rat for 7, 14, and 28 consecutive days. Alterations in weight, skeletal muscle growth, and changes in fiber type composition were studied in synergistic plantar flexors of the rat hindlimb. Body weight and the soleus muscle mass to body mass ratio demonstrated significant progressive atrophy over th 28-day experimental period with the most significant changes occurring in the first 7 days of hindlimb suspension. Hindlimb suspension produced atrophy of Type I and Type IIa muscle fibers as demonstrated by significant decreases in fiber cross-sectional area (micron 2). These latter changes account for the loss of contractile force production reported in the rat following hindlimb unloading. When compared to traditional models of hindlimb suspension and immobilization, the ISC model produces a less severe atrophy while maintaining animal mobility and health. We conclude that it is the preferred animal model to address nursing questions of impaired physical mobility.

Non-NASA Center↗

Decomposition of superimposed ground reaction forces into left and right force profiles

The process of collecting ground reaction force data by mounting a forceplate beneath a treadmill belt has the advantage that numerous walking trials can be analyzed without the problem of subjects 'targeting' their footsteps. However, a potential problem is that the measured forces represent a summation of bilateral force profiles during the double support phase of walking. To address this issue, an algorithm is described for decomposing superimposed ground reaction force data into individual left and right profiles. It is based on an examination of the side-to-side oscillations of the measured center of pressure (CoP). Whenever the measured CoP exceeds a certain threshold, it is assumed that the person is being supported by a single limb, and the measured GRF data reflect the forces under that limb. Conversely, when the measured CoP indicates that both feet are on the treadmill, it is assumed that the location of the individual CoP under each foot is given by wL2 and wR2. These quantities reflect the greatest excursion of the measured CoP towards the left and right sides of the forceplate, respectively. With this assumption, individual GRF profiles can be calculated by means of solving two simultaneous equations--one describing the equilibrium of forces in the vertical direction, and one describing the equilibrium of moments about an antero-posterior axis of the forceplate. The algorithm describing this procedure is simple enough to be implemented on a spreadsheet and yields estimates for average force, impulse, peak force and stance time that are typically within 3% of the true values.

Non-NASA Center↗