叩击式骨应力刺激仪预防废用性骨质疏松的实验研究

目的通过建立一种新的废用性骨质疏松山羊模型,观察叩击式骨应力刺激仪预防废用性骨质疏松的效果。方法4月龄山羊18只,随机分组:①对照组,②废用组,③治疗组。废用组和治疗组切断右侧坐骨神经。治疗组术后运用叩击式骨应力刺激仪进行治疗,叩击力为100N,频率为3Hz。每天3次,每次60min,每次间隔3h。治疗2～4个月后分别检测和分析山羊右侧胫骨骨密度、组织学及生物力学的变化。结果同对照组和治疗组相比,废用组胫骨的骨密度值及生物力学性能明显下降(P0.01);而治疗组与对照组也有差别(P0.05)。表现为:对照组治疗组废用组。组织病理学检查提示:HE染色见废用组骨小梁较对照组和治疗组明显减少、变细。Masson染色结果表明废用组骨基质矿化不良,骨基质中矿物成分较对照组和治疗组明显减少。结论切除山羊一侧坐骨神经可以建立起废用性骨质疏松模型。叩击式骨应力刺激仪对废用性骨质疏松有明显的防治效果。     

Gender influences neuromuscular adaptations to muscle unloading

Muscle unloading results in decreased strength. This is partly attributed to reduced neural activation. This study examined whether men and women experienced different adaptations to muscle unloading. Ten men (21.4 ± 0.8 years; mean ± SE) and ten women (20.9 ± 0.2 years) were subjected to 1 week of muscle unloading. Muscle function was quantified during knee extensions before, and following unloading. Electromyography (EMG) was assessed during maximal isometric contractions before, and after unloading. Results showed greater (P < 0.05) unloading-induced decrement in muscle performance in women than men. The loss of peak torque was significantly correlated (r = 0.69) with the decline in EMG consequent to unloading, and women displayed significantly larger reductions in EMG. These findings indicate that: (1) women are more affected by muscle unloading than men, and (2) gender-related differences in strength declines are associated with similar disparities in the nervous system’s capacity to maximally stimulate muscle.     

Reversibility of nontraumatic disuse osteoporosis during its active phase

The potential for the recovery of bone lost during the active phase of disuse osteoporosis, both in the diaphyseal compacta and metaphyseal spongiosa was tested in young adult and old Beagle dogs. Immobilization for up to 60 weeks was achieved by placing the forelimb in a spica cast and remobilization by removing it. Bone volume was estimated in the third metacarpus, radius, ulna and humerus at the mid-diaphysis and at the level of distal metaphyseal spongiosa in both forelimbs by radiography and histomorphometry.

Measurements carried out on animals remobilized showed considerable recovery of the original bone loss. In both age groups, the residual deficits increased, however, with the duration of immobilization and were similar in the metaphyseal spongiosa and in the diaphyseal compacta. The old dogs which began the study with 10% less bone than the younger dogs, showed smaller proportional losses than the younger dogs but greater residual deficits, most evident in the diaphysis. In both age groups the distal, weight-bearing bones tended to show greater losses and also greater recovery both in diaphyseal compacta and the metaphyseal spongiosa. Thus, 28 weeks after cast removal following 32 weeks of immobilization the following findings were noted: In the third metacarpal diaphyseal compacta in the younger dogs, a 53.6% loss (mostly from the periosteal envelope) decreased to 16.3% (a 70% recovery) while in the older dogs a 37.6% loss (mostly from the endosteal envelope) decreased to 23% (a 40% recovery). In metacarpal metaphyseal spongiosa in young adult dogs, a 50% loss reduced to 16.8% (a 66% recovery) while in the older dogs a 47% loss reduced to 19% (a 60% recovery).

These observations apply only to the effect of remobilization on recovery of bone loss incurred during the active phase of disuse osteoporosis. The same potential for recovery may not exist later in the inactive phase of established disuse osteoporosis. The permanent losses, however, could be prevented by appropriate measures taken during the active phase of osteoporosis.     

Interplay among the changes of muscle strength,cross-sectional area and maximal explosive power: theory and facts

A model has recently been proposed to predict the changes of mechanical power ( ) during a maximal explosive effort (such as a standing high jump off both feet) following an adaptation (e.g. training/de-training). The model is based on the assumption that, all other things being equal (ceteris paribus), the predicted changes in depend on the measured changes of muscle force (F) or cross-sectional area (CSA) only. It follows that, if the measured changes in are not equal to those predicted by the model, factors other than a change in F (or CSA) must be responsible for this difference. The model does not allow the determination of factors specifically involved in the adaptation process but it helps in discriminating whether an adaptation has taken place at a local level (when the observed changes in F would be attributed to factors other than the observed changes in CSA, e.g. co-contractions, fibre type modifications...), or at a central level (when the observed changes in would be attributed to other factors than the observed changes in F, e.g. co-ordination of multiple joints and muscle groups...), or in both regions. In this paper the model has been applied to data reported in the literature on disuse (BR, bed rest), de-conditioning (SF, space flight), strength training (ST) and de-training (DT). The results of these calculations have confirmed previous observations on the determinants of the adaptation process and further suggest: (1) that training for one specific motor task (e.g. ST) could affect the performance of a second task (e.g. a maximal explosive jump) but that, as soon as the trained motor task is terminated (DT), this ability is re-gained; and (2) that neuromuscular impairment in disuse (BR) is closer to de-training than to the de-conditioning brought about by weightlessness (SF). Electronic Publication     

Immobilization osteoporosis: a review

Bone mass is not only subject to systemic hormonal homeostatic mechanisms, but also to local mechanical influences. The importance of the mechanical balance of bone has been more recently stressed by the research on the effect of weightlessness on bone, and by the introduction of the concept of mechanostat in the pathogenesis of osteoporotic conditions. Immobilization osteoporosis has clinical (fractures, sometimes hypercalcemia, urinary lithiasis) and radiological features. Immobilization has an effect on bone modeling and remodeling, through an increased activation of remodeling loci, and a decrease of the osteoblastic stimulus. This leads directly to a local reduction in bone mass, the increased activation multiplying the effect of the deficit in bone formation. The prevention is based on exercise if the load is applied intermittently for a daily period. It seems also that muscle weight is an important determinant of bone mass. There is a potential for recovery during the active early phase of immobilization osteoporosis that may disappear in the subsequent late (about six months) inactive phase. Permanent losses could be prevented by appropriate measures, pharmacology or exercises, applied during the first months of immobilization. No recovery has been demonstrated after the inactive phase has been reached, whatever the treatment. The cumulative effect of repeated periods of immobilization remains hypothetical.     

Effect of disuse on the ultrastructure of the achilles tendon in rats

Summary We examined the influence exerted, through disuse of the hindlimb, on the collagen fibres of the achilles tendon in rats. With disuse the body mass decreased by 28%, and the mass of soleus muscle decreased by 20%. A decrease in the surface area and diameter was observed in the experimental group when compared to the control group. A histogram of the collagen fibres showed a decrease of the thick fibres in the experimental group. The maximum surface area of collagen fibres in the experimental group was seen to be only 43% of that of the control group. These results showed a decrease in the thickness of the collagen fibres of the achilles tendon through disuse. This seemed to suggest that resistance to tension is decreased by disuse.     

Hypo-activity induced skeletal muscle atrophy and potential nutritional interventions: A review

Periods of hypo-activity result in profound changes in skeletal muscle morphology and strength. This review primarily addresses the differential impact of de-training, bed-rest, limb immobilisation and unilateral lower limb suspension on muscle morphology, strength and fatigability. The degree of muscle atrophy differs depending on the hypo-activity model and the muscles in question, with the leg and postural muscles being the most susceptible to atrophy. Hypo-activity also results in the dramatic loss of strength that often surpasses the loss of muscle mass, and consequently, the nervous system and contractile properties adapt to adjust for this excessive loss of strength. In addition, the degree of muscle strength loss is different depending on the hypo-activity model, with immobilisation appearing to have a greater impact on strength than unloaded models. There is a step-wise difference in the magnitude of muscle loss so that, even after accounting for differential durations of interventions immobilisation ≥ unilateral lower limb suspension ≥ bed-rest ≥ de-training. Muscle fatigability varies between hypo-activity models but the results are equivocal and this may be due to task-specific adaptations. This review also addresses potential nutritional interventions for attenuating hypo-activity induced muscle atrophy and strength declines, in the absence of exercise. Essential amino acid supplementation stands as a strong candidate but other supplements are good contenders for attenuating hypo-activity induced atrophy and strength losses. Several potential nutritional supplements are highlighted that could be used to combat muscle atrophy but extensive research is needed to determine the most effective.     

The activation of apoptosis factor in hindlimb unloading-induced muscle atrophy under normal and low-temperature environmental conditions

In order to identify the apoptosis-induced factors and apoptosis pathway in hindlimb unloading muscle atrophy, the reciprocal relationships between caspase-3 activation and factors related to mitochondria, other organelle pathways, oxidative stress and nitric oxide were investigated. Male Wistar rats were divided into four groups, two groups of hindlimb-unloaded rats were maintained under normal (25 degrees C) and low-temperature (10 degrees C) environmental conditions for a 3-week experimental period, plus two corresponding control groups. Active caspase-3-containing myofibers were observed in the hindlimb-unloaded rats in normal and low-temperature environments, but not in the control rats. In these caspase-3-containing fibers, DNA fragmentation, dystrophin breakdown, increased immunolabeling of mu-calpain, decreased cytochrome c, cathepsin-D effusion from the lysosomes and increased lipid peroxidation were observed, while no changes in active caspase-12, eNOS or nNOS immunolabeling were seen. Furthermore, although caspase-3 activation was observed in type-I fibers, caspase-12 labeling was observed in fibers of the hybrid type. These results show that the apoptosis observed in hindlimb unloading-induced muscle atrophy is caused by activation of the caspase cascade via the lysosome pathway. Moreover, the results suggest that caspase-12 does not activate caspase-3 due to differences in the cell differentiation or the apoptosis-inducing stimulation.     

Continuous Loss of Bone During Chronic Immobilization: A Monozygotic Twin Study

Acute immobilization is associated with rapid loss of bone. Prevailing opinion, based on population cross-sectional data, assumes that bone mass stabilizes thereafter. In order to address whole-body and regional skeletal mass in long-term immobilization, monozygotic twins were studied, one of each twin pair having chronic spinal cord injury (SCI) of a duration ranging from 3 to 26 years. The research design consisted of the co-twin control method using 8 pairs of identical male twins (mean ± SD age, 40 ± 10 years; range 25–58 years), one of each set with SCI. The twins were compared by paired t-tests for total and regional bone mineral content (BMC) and bone mineral density (BMD) measured by dual-energy X-ray absorptiometry. Linear regression analyses were performed to determine the associations of age or duration of injury with the differences between twin pairs for total and regional skeletal bone values. In the SCI twins, total-body BMC was significantly reduced (22%± 9%, p<0.001), with the predominant sites of reduction for BMC and BMD being the legs (42%± 14% 35%± 10%, p<0.0001), and pelvis (50%± 10% and 29%± 9%, p<0.0001). Duration of SCI, not age, was found to be linearly related to the degree of leg bone loss in SCI twins (BMC: r ²= 0.60, p<0.05; BMD: r ²= 0.70, p<0.01). Our findings suggest that pelvic and leg bone mass continues to decline throughout the chronic phase of immobilization in the individual with SCI, and this bone loss appears to be independent of age. Received: 28 September 1998 / Accepted: 28 December 1998     

Skeletal muscle atrophy during short-term disuse: Implications for age-related sarcopenia

Situations such as the recovery from injury and illness can lead to enforced periods of muscle disuse or unloading. Such circumstances lead to rapid skeletal muscle atrophy, loss of functional strength and a multitude of related negative health consequences. The elderly population is particularly vulnerable to the acute challenges of muscle disuse atrophy. Any loss of skeletal muscle mass must be underpinned by a chronic imbalance between muscle protein synthesis and breakdown rates. It is recognized that muscle atrophy during prolonged (>10 days) disuse is brought about primarily by declines in post-absorptive and post-prandial muscle protein synthesis rates, without a clear contribution from changes in muscle protein breakdown. Few data are available on the impact of short-term disuse (<10 days) on muscle protein turnover in humans. However, indirect evidence indicates that considerable muscle atrophy occurs during this early phase, and is likely attributed to a rapid increase in muscle protein breakdown accompanied by the characteristic decline in muscle protein synthesis. Short-term disuse atrophy is of particular relevance in the development of sarcopenia, as it has been suggested that successive short periods of muscle disuse, due to sickness or injury, accumulate throughout an individual's lifespan and contributes considerably to the net muscle loss observed with aging. Research is warranted to elucidate the physiological and molecular basis for rapid muscle loss during short periods of disuse. Such mechanistic insight will allow the characterization of nutritional, exercise and/or pharmacological interventions to prevent or attenuate muscle loss during periods of disuse and therefore aid in the treatment of age-related sarcopenia.