아프면 움직이지 마세요(immobilization)의 재앙에 관한 논문 - 임나라

[문형철]

immobilization은 "아프니까 움직이지 마세요"라는 내면의 말로 시작하고, 어리석은 의사의 말로 재확인된다.

rest와 avoid aggravation이라는 그럴듯한 치료법으로 포장되면서..

재앙은 거기서 시작된다.

움직이지 않은 관절은 약해지고, 굳어지고(유착), 근육-인대-건은 가늘어지고, 움직임을 잃어버린다(proprioception).

약해지고, 굳어지고, 움직임을 잃어버린 관절을 직립보행하면서 사용할 수밖에 없는 인체는 다시 통증이 유발된다.

다시 움직이지 않는다. 그리고 관절은 더욱더 기능을 잃어버린다.

재앙은 이렇게 "악화의 사이클"로 순환한다.

의사는 무엇을 해야할까?

panic bird....

Changes in musculoskeletal structure and function with prol.doc

Recovery of muscle atrophy and bone loss from 90 days bed r.pdf

resting injured limbs delays recovery. review.pdf

Changes in musculoskeletal structure and function with prolonged bed rest

ISSN: 0195-9131

Accession: 00005768-199702000-00006

Author(s):	BLOOMFIELD, SUSAN A. Section Editor(s): Convertino, Victor A. Writing Group Chair
Issue:	Volume 29(2), February 1997, pp 197-206
Publication Type:	[Basic Sciences: Symposium: Physiological Effects of Bed Rest and Restricted Physical Activity: an Update]
Publisher:	ⓒ Williams & Wilkins 1997. All Rights Reserved.
Institution(s):	Department of Health & Kinesiology, Texas A&M University, College Station, TX 77843-4243 Submitted for publication February 1995. Accepted for publication December 1995. Address for correspondence: Susan A. Bloomfield, Ph.D., Department of Health & Kinesiology, Texas A&M University, College Station, TX 77843-4243. E-mail: sbloom@acs.tamu.edu

Keywords: IMMOBILIZATION, MUSCLE ATROPHY, OSTEOPENIA, MICROGRAVITY, SPINAL CORD INJURY, DECONDITIONING, WEIGHTLESSNESS

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Outline

• ABSTRACT
• HUMAN MODELS OF MUSCULOSKELETAL DISUSE
• CHANGES IN MUSCLE MASS AND FUNCTION WITH BED REST
• CHANGES IN BONE MASS AND CALCIUM METABOLISM WITH BED REST
• PREVENTING BED REST-INDUCED LOSS OF MUSCLE AND BONE
• SUMMARY: PRACTICAL IMPLICATIONS AND FUTURE RESEARCH
• REFERENCES

Graphics

• Figure 1-A spectrum ...
• Figure 2-Unilateral ...
• Figure 3-Magnetic re...
• Figure 4-Change in m...
• Table 1
• Figure 5-Change in i...
• Figure 6-Ultrastruct...
• Figure 7-Alterations...
• Table 2
• Figure 8-Alterations...
• Figure 9-Decrements ...
• Figure 10-Time cours...
• Table 3

ABSTRACT

Prolonged bed rest produces profound changes in muscle and bone, particularly of the lower limb. This review first addresses the various models used by researchers to study disuse-induced changes in muscle and bone as observed during prolonged bed rest in humans. 

- 오랜 침상안정은 특히 하지의 근육과 뼈에 깊은 변화를 초래함. 

Dramatic change in muscle mass occurs within 4-6 wk of bed rest, accompanied by decreases of 6 to 40% in muscle strength. Immobilization studies in humans suggest that most of this lost muscle mass and strength can be regained with appropriate resistance training within several weeks after a period of disuse. Significant decrements in bone mineral density of the lumbar spine, femoral neck, and calcaneus observed in able-bodied men after bed rest are not fully reversed after 6 months of normal weightbearing activity. 

- 4-6주의 침상안정내에 근육질량에 드라마틱한 변화가 발생함.근육힘은 6-40% 감소를 동반함. 

- 인체에서 고정 결과에 대한 탐구는 근육질양의 감소, 근력의 감소가 근육사용중단 후 몇주간의 적절한 재훈련을 통해 다시 원상회복할 수 있음에 관한 것!

- 심각한 요추, 경추, 종골 뼈의 밀도감소는 6개월간의 체중부하 운동에도 정상회복하기 힘듬. 

Importantly, the lost bone mass is not regained for some weeks or months after muscle mass and strength have returned to normal, further contributing to the risk of fracture. Those who enter a period of bed rest with subnormal muscle and bone mass, especially the elderly, are likely to incur additional risk of injury upon reambulation. Practical implications for exercise professionals working with individuals confined to bed rest are discussed.

- 중요하게, 잃어버린 뼈질량은 근육질량과 근력회복 후  몇주 또는 몇개월동안에도 회복하지 못함. 

- 노인들은 특히 더 회복하기 힘듬. 

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The human musculoskeletal system has evolved to support the body in an upright, erect posture. The antigravity muscles of the lower back, abdomen, thighs, and lower legs are especially critical to the maintenance of posture and balance. Architecture of cortical and cancellous bone in the axial and appendicular skeleton is adapted to the specific patterns of mechanical loading provided by muscle contraction and by the longitudinal compression of gravity (10).

- 인체 근골격계 시스템은 선자세에서 인체지지를 이끌어냄. 

- 허리, 복부, 대퇴, 하지의 항중력 근육은 자세와 균형을 유지하는데 중요한 역할을 함. 

Muscle and bone tissue start adapting to the decreased loading of bed rest within a matter of days. Key elements of bed rest contributing to changes in the musculoskeletal system are 1) the lack of usual weightbearing forces(i.e., longitudinal compression) acting on bones of the lower limb in the vertical position and 2) the decrease in number and/or magnitude (i.e., intensity) of muscle contractions, especially in the postural musculature. 

- 근육과 뼈조직은 며칠내에 침상안정의 감소된 부하에 적응하기 시작함. 침상안정의 가장 중요한 요소는 근골격계 시스템에서 1)체중부하 힘의 부족 2) 근수측의 강도, 양, 횟수의 감소

This review starts with a brief discussion of the various research models used to study responses to disuse, each of which offers certain advantages and disadvantages in understanding changes seen with bed rest. Data from these various models will then be used to illustrate the magnitude and time course of alterations in muscle and/or bone with disuse and following prolonged(>5 d) bed rest. The focus will be on data obtained from studies of human subjects completed within the last 15 years; mention will be made of animal data only sparingly, primarily to address the mechanisms for alterations in musculoskeletal structure and function.

- 이 논문은 근골격계 사용중단에 반응하는 것에 대한 토의임. 

- 오랜 침상안정(5일 이상)과 함게 근육, 뼈의 변화과정에 대한 토의

HUMAN MODELS OF MUSCULOSKELETAL DISUSE^

Simply reducing normal activity levels represents the first element in a“spectrum of disuse” (Fig. 1). Decrements in muscle mass and strength have been documented in trained humans undergoing detraining, for example (9,24). Similarly, reductions in weekly weight-bearing exercise time result in a loss of bone mass in both men and women (36). More dramatic changes occur with prolonged bed rest or spaceflight, particularly in bone. These conditions result in removal of longitudinal compression forces on bone usually experienced in the upright posture in normal gravity. Muscle contraction is still possible although limited during bed rest unless deliberate exercise (isometric contractions, supine cycling) is undertaken. The muscular force required for producing movement, however, is very much diminished once ground reaction forces are removed. Adding head-down tilt to the bed rest model more effectively mimics the fluid shifts experienced in microgravity (48); whether head-down tilt is important for modeling muscle and bone response to microgravity remains to be established.

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Figure 1-A spectrum of disuse ranging from a minimal reduction of usual activity levels to the extreme immobilization of spinal cord injury; all these models have been used to investigate disuse deconditioning.

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Casting of a limb provides a more rigid immobilization and has been used most extensively with animal models; it will produce more rapid decrements in muscle mass and bone mass than does bed rest alone. The extreme on this“spectrum of disuse” is represented by the individual with chronic spinal cord injury; muscle and bone in the paralyzed limb is perfectly immobilized. Although muscle tension is low, there remains some measurable muscle EMG activity unless the lower motor neuron is injured (32). As valuable as information is from this clinical population, we must be cautious about extrapolating these results to able-bodied bed-rested individuals because other pathologies unique to spinal cord injury may magnify effects of the decreased load-bearing.

An intriguing alternative model for studying effects of unweighting of a limb in humans was first developed by Tesch et al. (54). This unilateral lower limb suspension method provides a model that allows for freely moveable joints but removes loadbearing (Fig. 2), similar to hindlimb suspension in rats. A sling suspends one lower leg and the contralateral shoe has an elevated sole to allow for a relaxed position of the unloaded limb. The subject is able to ambulate with crutches. This model provides a viable alternative to labor- and cost-intensive bed rest studies, at least for the study of muscle and bone in the unloaded limb. A similar disuse model for the upper limb has been developed which requires casting of the arm and suspension of the cast in a sling (37).

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Figure 2-Unilateral lower limb suspension. Reprinted with permission from reference 2. Berg, H. E., G. A. Dudley, T. Haggmark, H. Ohlsen, and P. A. Tesch. Effects of lower limb unloading on skeletal muscle mass and function in humans. J. Appl. Physiol. 70:1882-1885, 1991.

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It is important to note that even rigidly immobilizing a limb by casting does not truly induce “disuse” in muscle. The immobilized muscle is not electrically quiescent (32). Even with the absence of all voluntary contraction, electromyographic activity in both lower and upper motor neurons is essentially normal. Therefore, with immobilization and bed rest models, we are really speaking of “decreased use,” since these muscles receive some neural input and are still capable of isometric contraction. Throughout this review I will refer to “disuse” in this context.

CHANGES IN MUSCLE MASS AND FUNCTION WITH BED REST^

Data from early bed rest studies revealed a variable but significant increase in urinary nitrogen excretion by the fifth day of bed rest. Deitrick et al. (11) studied four healthy young males subjected not only to bed rest but also to lower body immobilization with waist-to-toe casts. Urinary nitrogen excretion peaked in the second week of bed rest at 20-43% above baseline. These data reflect the increased protein degradation of immobilization documented in numerous animal models. This negative nitrogen balance is an early marker for the dramatic muscle atrophy that will occur in even the most robust individual if bed rest is prolonged.

In more recent studies, 4 wk of unilateral lower limb suspension resulted in a 7% decrease in muscle cross-sectional area (CSA) at mid-thigh, with no change noted in the contralateral limb muscle CSA (2). In MRI images of the legs of one subject, the 14% decrease in CSA in the unloaded left leg, as compared to the CSA of the weight-bearing right leg, can be visualized easily (Fig. 3). Muscle biopsy data confirm‎ this atrophy, with an average 14% decrease in fiber CSA after 6 wk of limb suspension (19). Much of this decrease in muscle mass is a result of a two-fold greater atrophy of the knee extensors than the knee flexors. Interestingly, the rectus femoris shows no change in CSA after 6 wk of unloading. Suspension and casting of the arm for a brief 9 d produces a 4% decrease in forearm muscle CSA (37).

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Figure 3-Magnetic resonance images of left and right legs at midthigh of a subject pre- and post-five weeks of unilateral lower limb suspension; images were taken immediately after performance of 5 sets of 10 concentric knee extensions. The muscle cross-sectional area of the unloaded left leg (which appears on the right of each image) is smaller than the cross-sectional area for the contralateral weightbearing leg. The left, unweighted quadriceps femoris in the “post” image also shows a greater exercise-induced shift in signal intensity (appears lighter), indicating greater muscle involvement after disuse. Photographs courtesy of G.A. Dudley and L. Ploutz-Snyder.

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Similar changes in muscle CSA have been observed following bed rest. Muscle CSA at mid-thigh decreases by 8% after 30 d of head-down tilt bed rest (8). Similar atrophy (-12%) is observed in plantar flexors after 35 d of horizontal bed rest; no significant change is noted in dorsiflexor muscle groups (27). Muscle biopsy data from subjects after head-down tilt bed rest reveal a 7.5% decrease in slow-twitch fiber CSA and a 14.7% decrease in fast-twitch fiber CSA; these decreases in fiber area are more pronounced in the vastus lateralis than in the soleus (21). Much of the animal data suggest that slow-twitch fiber populations experience a greater relative atrophy with immobilization than do fast-twitch fibers (32), but these results in human subjects (21) clearly do not agree because the human fast-twitch fibers were preferentially affected in at least two different muscle groups. More prolonged bed rest is clearly capable of inducing loss of muscle mass in predominantly fast-twitch muscle; 119 d of bed rest produces a 21% decrement in muscle volume of the ankle flexors (29). Interestingly, volume of intrinsic lower back muscles, important in postural control, decreases by only 9% after prolonged bed rest (29).

The contrast between results from human studies and those in animal models may be explained if fiber cross-sectional area at baseline is an important determinant of the magnitude of atrophy (21). Slow-twitch fibers in rat muscle are typically the largest before immobilization, whereas in human muscle the fast-twitch fibers are larger before bed rest begins. Perhaps the larger fibers experience the greater relative decrease in daily loading during bed rest and therefore atrophy relatively more. Which fiber type population is more dramatically affected in humans with disuse has important implications for the development of specific rehabilitative strategies to be recommended after a prolonged period of detraining or bed rest; confirm‎atory studies are needed.

The magnitude and time course of changes in human muscle morphology with relative disuse are summarized in Figure 4. Clearly, with increasing duration of bed rest (8,21,27,29), casting (22,34,49), or limb suspension (2,19,37), progressively greater decrements in muscle mass are observed, whether measured as fiber CSA, limb volume, or muscle CSA from computed tomography or MRI images. Ethical issues limit the duration of bed rest studies; whether these decreases in muscle mass would continue with longer than 6 months of bed rest is unknown. Extensors of the leg are affected to a greater degree than leg flexors, as illustrated in data on plantar flexors as compared with dorsiflexors of the lower leg after 35 d of bed rest (27). These changes are quantitatively similar to those with 6 wk of lower-limb suspension.

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Figure 4-Change in measures of muscle mass seen with increasing duration of unilateral lower limb suspension, limb casting, and bed rest. FT = fast-twitch muscle; ST = slow-twitch muscle; VL = vastus lateralis; TB = triceps brachii; SOL = soleus; PF = plantar flexors; DF = dorsiflexors; CSA = cross-sectional area. Data from references: 2. Berg, H. E., G. A. Dudley, T. Haggmark, H. Ohlsen, and P. A. Tesch. Effects lower limb unloading on skeletal muscle mass and function in humans. J. Appl. Physiol. 70:1882-1885, 1991; 8. Convertino, V. A., D. F. Doerr, K. L. Mathes, S. L. Stein, and P. Buchanan. Changes in volume, muscle compartment, and compliance of the lower extremities in man following 30 days of exposure to simulated microgravity.Aviat. Space Environ. Med. 60:653-658, 1989; 19. Hather, B. M., G. R. Adams, P. A. Tesch, and G. A. Dudley. Skeletal muscle responses to lower limb suspension in humans. J. Appl. Physiol. 72:1493-1498, 1992; 21. Hikida, R. S., P. D. Gollnick, G. A. Dudley, V. A. Convertino, and P. Buchanan. Structural and metabolic characteristics of human skeletal muscle following 30 days of simulated microgravity.Aviat. Space Environ. Med. 60:664-670, 1989; 22. Ingemann-Hansen, T. and J. Halkjær-Kristensen. Computerized tomographic determination of human thigh components: the effects of immobilization in plaster and subsequent physical training. Scand. J. Rehab. Med. 12:27-31, 1980; 27. Leblanc, A., P. Gogia, V. Schneider, J. Krebs, E. Schonfeld, and H. Evans. Calf muscle area and strength changes after five weeks of horizontal bed rest. Am. J. Sports Med. 16:624-629, 1988; 29. Leblanc, A. D., V. S. Schneider, H. J. Evans, C. Pientok, R. Rowe, and E. Spector. Regional changes in muscle mass following 17 weeks of bed rest. J. Appl. Physiol. 73:2172-2178, 1992; 34. MacDougall, J. D., G. C. B. Elder, D. G. Sale, J. R. Moroz, and J. R. Sutton. Effects of strength training and immobilization on human muscle fibers. Eur. J. Appl. Physiol. 43:25-34, 1980; 37. Miles, M. P., P. M. Clarkson, M. Bean, K. Ambach, J. Mulroy, and K. Vincent. Muscle function at the wrist following 9 d of immobilization and suspension.Med. Sci. Sports Exerc. 26:615-623, 1994; 47. Sale, D. G., A. J. McComas, J. D. MacDougall, and A. R. M. Upton. Neuromuscular adaptation in human thenar muscles following strength training and immobilization. J. Appl. Physiol. 53:419-424, 1982.

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With decreases in muscle mass and cross-sectional area, one expects to see a change in muscle strength of the affected limbs. Thirty days of bed rest produce an 18-20% decrease in peak torque of knee extensors and a nonsignificant 6% decrease in knee flexor strength during both eccentric and concentric contraction (12). Within 30 d after the end of bed rest, strength recovers to within 92% of pre-bed rest levels, which provides encouraging evidence that these decrements in muscle strength can be reversed within a reasonable amount of time (12).

Data from a number of American and Soviet bed rest studies demonstrate a dose-response relationship between the duration of bed rest and the resulting decrements in muscle strength (Table 1). Extensor muscle groups experience greater decreases in strength than do the corresponding flexor muscles; strength losses in lower limb muscles are greater than those in the upper limb musculature. With bed rest of less than 60 d duration, elbow flexors and the forearm muscles experience little loss of strength; if bed rest is prolonged beyond 60 d, however, decrements in strength of these arm muscles become evident. More restrictive immobilization and unweighting of the upper arm produces significant decrements in wrist flexor and wrist extensor strength after only 9 d (37).

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TABLE 1. Change in maximal muscle strength with disuse.

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Can we attribute any of these changes in muscle strength to a reduction in muscle electrical activity? Changes in EMG activity occur in rat gastrocnemius muscle immobilized in casts for 28 d in neutral, shortened, or lengthened positions ((13), Fig. 5). After 28 d of immobilization, EMG activity decreases by 50% in the shortened but not the neutral-length muscle. However, both the shortened and neutral-length muscles experience a similar degree of atrophy as measured by muscle wet weight. Hence, there does not appear to be a consistent relationship between neural activity in the muscle and the relative decrement in muscle mass.

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Figure 5-Change in integrated electromyograms (EMG) and muscle mass in rat gastrocnemius muscle after 28 d of immobilization of the hindlimb in various positions producing neutral, lengthened, or shortened muscle length. Redrawn from data in reference 13. Fournier, M., R. R. Roy, H. Perham, C. P. Simard, and V. R. Edgerton. Is limb immobilization a model of muscle disuse? Exp. Neurol. 80:147-156, 1983.

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There is evidence for a decrease in the electrical efficiency of muscle following relatively brief exposure to muscle unloading. In humans, ankle extensors exhibit an increased ratio of EMG activity to unit of force produced after seven days of spaceflight, as compared to values obtained pre-flight for static and isokinetic contractions (25). These results imply an increase in the neural activity required to elicit the same muscular force output after a period of unloading. This altered electrical efficiency may be related to changes in motor unit recruitment with disuse. Five weeks of cast immobilization produces a 57% decrease in maximal voluntary contraction force in human thenar muscle accompanied a concurrent 29% decrease in the estimated number of functioning motor units and a 45% decrease in reflex potentiation in the immobilized muscle (47). These results provide evidence for decreased motoneuron excitability and an impairment of the ability to activate motor units during maximal contractions as mechanisms for the decrements in muscle strength after a period of disuse. These decrements in neuromuscular function are completely reversed with 18 wk of strength training (47).

The effect of neuromuscular changes on balance and locomotor ability after a period of bed rest may be an important concern. Russian researchers have documented increased postural sway, changes in gait, and impaired kinesthetic sense in cosmonauts during the first 2 d after returning from space (6,44). These factors, in combination with increased fatigability and decreased muscular strength, constitute a familiar-looking constellation of factors contributing to increased risk of falling in the elderly (56). Research documenting changes in balance or gait with prolonged bed rest in the normal gravity of earth would be of great value to the many elderly who experience prolonged or repeated periods of bed rest as well as to their caretakers. Factors contributing to falling and subsequent debilitating bone fractures and soft tissue injury must be minimized in this population.

Relatively few data are available regarding changes in muscle endurance with disuse. After 4 wk of lower-limb suspension, average peak torques produced during repeated knee extensions are 17% lower than before the unloading period. Importantly, this reduced ability to maintain force output is not fully reversed after 7 wk of weight-bearing recovery (54). Factors contributing to muscle endurance may require a longer recovery time than those contributing to muscle mass and strength. Decrements in skeletal muscle oxidative enzyme activities in both the vastus lateralis and soleus have been demonstrated (21) after 30 d of bed rest. Enzymes critical to both beta-oxidation ([beta]-hydroxyacyl-CoA dehydrogenase) and the TCA cycle(citrate synthase) are affected. Concurrently, maximal blood flow in the calf after an ischemic challenge decreases 38% (8). Clearly, there are deficits in both O₂ delivery and utilization in skeletal muscle after a period of disuse imposed by bed rest.

Muscle biopsies from bed-rested subjects reveal a number of ultrastructural changes (Fig. 6). Abnormalities observed in soleus muscle include Z-line streaming, myofibrillar protein disorganization, cellular edema, and occasional mitochondria in the extracellular space, suggesting a disruption of the muscle sarcolemma (21). It is unknown how quickly or to what extent these ultrastructural changes reverse upon remobilization.

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Figure 6-Ultrastructural changes in soleus muscle biopsy taken from a healthy male after 30 d of bed rest, illustrating Z-line streaming and myofibrillar protein disorganization. Magnification: 9, 180X. Photomicrograph courtesy of R. S. Hikida.

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CHANGES IN BONE MASS AND CALCIUM METABOLISM WITH BED REST^

The rate of structural change in bone lags behind that seen in muscle during a period of bed rest or unweighting, in part because of the slow turnover of bone tissue. However, a dramatic increase in both urine and fecal calcium is routinely observed within 1 wk of the onset of bed rest, reflecting an evolving negative calcium balance. Twenty wk of bed rest in healthy young males results in a 60% increase in urine calcium, which peaks between the 5th and 7th week (50). An increase in fecal calcium loss eventually accounts for 50% of the negative calcium balance observed after the eighth week of bed rest. This increase in fecal calcium suggests a reduction in intestinal calcium absorption, which has been verified with calcium balance studies in bed-rested humans. True calcium absorption gradually decreases from 31 to 24% of dietary intake over 17 wk of horizontal bed rest (31).

Increasing calcium intake to 1000 mg·d^-1 can reduce but does not normalize the negative calcium balance (35). Results from a recent study indicate that treatment with a bisphosphonate (an anti-resorptive pharmacological agent) coupled with exercise reduces the negative calcium balance by up to 80% during prolonged (360-d) bed rest (17). Intestinal calcium absorption is regulated by 1,25-dihydroxyvitamin D (1,25-D) and therefore indirectly by parathyroid hormone (PTH); the latter stimulates conversion of biologically inactive 25-hydroxyvitamin D to 1,25-D in the kidney. Increases (39) or no change (31,46) in serum PTH concurrent with a negative calcium balance are observed during bed rest in healthy men; serum 1,25-D decreases (31,57) or does not change (46). On the other hand, patients with acute spinal cord injury and functionally complete immobilization of the affected limbs have consistently low PTH and 1,25-D serum levels (3,43,52,58) and presumably reduced intestinal calcium absorption. Immobilization-induced decreases in intestinal calcium absorption have been demonstrated in rats (62).

The bed rest-induced decrease in intestinal absorption cannot alone account for the large increases observed in urinary calcium. That this hypercalciuria derives from bone calcium has been confirmed with more recent measurements of changes in bone mineral density (by pQCT and dual energy x-ray absorptiometry) and biochemical markers of bone resorption after periods of bed rest. In lumbar disc disease patients bed rest combined with traction results in a rapid loss of bone mineral density (-1%·wk^-1) in lumbar vertebrae (26). Strict bed rest in healthy male volunteers (19-52 yr in age) produces significant decrements in bone mineral density in the lumbar spine (-4%), femoral neck (-4%), tibia (-2%), and most notably in the calcaneus (-10%) over 4 months, whereas no significant change occurs in the radius ((28), Fig. 7). This reflects comparable findings of large decreases in calcaneal bone mineral content, but little loss of bone mass in the upper limb, with the unloading of spaceflight (60). The bones of the lower limbs, normally exposed to frequent longitudinal compressive loading with weightbearing in 1 g, experience the largest decrease in daily loading events with bed rest or microgravity, whereas use of the upper limb usually is increased during spaceflight to maneuver within the shuttle compartments and to perform work tasks. Biochemical markers of bone resorption such as serum pyridinoline, deoxypyridinoline, and hydroxyproline increase significantly after only 4 d of head-down tilt bed rest (33).

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Figure 7-Alterations in bone mineral density (BMD), expressed as% change from baseline, during 4 months of bed rest and 6 months of reambulation in able-bodied young men. Redrawn from data in reference 28. LeBlanc, A. D., V. S. Schneider, H. J. Evans, D. A. Engelbretson, and J. M. Krebs. Bone mineral loss and recovery after 17 weeks of bed rest. J. Bone Miner. Res. 5:843-850, 1990.

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Histomorphometric analysis of bone derived from biopsy samples is the only direct means of determining whether changes in bone mineral density with disuse result from increased resorption of bone, or from decreased formation of new bone, or from both. A collaborative study between French and Russian investigators provides unique biopsy data on the effect of 120 d of bed rest on cancellous bone in 20 healthy males ((59),Table 2). No significant change was found in formation of nonmineralized bone matrix, but subsequent mineralization of newly formed bone matrix appeared to be impaired. Simultaneously, a 51% increase in bone resorption surface was observed, reflecting an increase in the activity of bone resorbing cells. Interestingly, bone volume in these iliac crest biopsies did not change even in the face of these alterations in bone cell activities, although some changes noted in architecture of cancellous bone could reduce bone strength without a significant loss of bone mass (41).

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TABLE 2. Change in histomorphometric measures of cancellous bone mass, bone formation, bone resorption in iliac crest biopsies from able-bodied men following 120 d of head-down tilt bed rest.

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Bone biopsies are normally obtained from the iliac crest (a nonweightbearing bone) for ethical reasons because of the increased risk of fracture at or near the biopsy site for up to 6 wk after the biopsy. It is possible that the proximal tibia, a site sensitive to changes in weightbearing, does experience a net loss of cancellous bone volume in individuals confined to bed rest. Primates restricted to a chair for 6 months exhibit up to a 31% decrease in bone mineral density of the proximal tibia (64), with evidence of increased resorption and decreased formation in both cancellous and cortical bone at this site (63). In addition, bone mineral density does decrease during 4 months of bed rest at several other anatomical sites in the lower limb (Fig. 7). Whether these decrements in bone mass in healthy subjects are self limiting with longer exposure to bed rest or the unloading of microgravity is unknown.

These findings in able-bodied subjects contrast with those findings in patients with spinal cord injury, in whom iliac crest cancellous bone volume decreases by 33% in the first 6 months after the injury (38). In this case, a 70% increase in bone resorption occurs concurrent with a significant decrease in bone formation; once these two processes stabilize, bone mass reaches a new equilibrium with no further losses (Fig. 8). The maximal calciuria observed in this type of patient is two to four times greater than in able-bodied men subjected to bed rest; disrupted calcium metabolism can persist for at least 12 months post-injury (3,7). These data suggest that some factor unique to patients with spinal cord injury accentuates the changes in bone cell activities noted in ablebodied men with prolonged bed rest. For example, changes in bone blood flow after spinal cord injury may produce alterations in tissue pH that favor resorptive activity (5). Perhaps the more complete immobilization of paralysis, with the attendant decrease in muscle tone, accelerates the changes in bone cell activities noted in the bed-rested men.

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Figure 8-Alterations in calcium balance and indices of bone formation (osteoid volume), bone resorption (resorption surfaces), and bone mass (trabecular bone volume) in individuals with spinal cord injury, an extreme form of immobilization. After the transitional period, bone resorption has returned to baseline; bone formation and bone mass stabilized at 30% below baseline. Used with permission from reference 1. Arnaud, S. B. Effects of inactivity on bone. In: Inactivity: Physiological Effects, H. Sandler and J. Vernikos (Eds.). Orlando, FL: Academic Press, Inc., 1986, pp. 49-76.

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The largest decrements in bone mineral density in spinal cord-injured patients occur in the paralyzed lower limb. Bone density of the femoral neck and proximal tibia in individuals with chronic spinal cord injury averages 65% and 45%, respectively, of values for able-bodied controls (4). By contrast, density of the lumbar spine, which is below the level of the injury and connected to paralyzed muscle, remains within normal range. Continued load-bearing on the spine while seated in a wheelchair may provide a sufficient loading stimulus to maintain bone mass at this site. Changes in bone mass with prolonged bed rest, exposure to microgravity, and following SCI are summarized in Figure 9.

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Figure 9-Decrements in trabecular bone volume (TBV), determined from iliac crest biopsies, and bone mineral density at various sites observed after bed rest, exposure to microgravity, or spinal cord injury. Data fromreferences: 4 Biering-Sørensen, F., H. H. Bohr, and O. P. Schaadt. Longitudinal study of bone mineral content in the lumbar spine, the forearm and the lower extremities after spinal cord injury.Eur. J. Clin. Invest. 20:330-335, 1990; 28. Leblanc, A. D., V. S. Schneider, H. J. Evans, D. A. Engelbretson, and J. M. Krebs. Bone mineral loss and recovery after 17 weeks of bed rest. J. Bone Miner. Res. 5:843-850, 1990; 30. Leblanc, A., V. Schneider, J. Krebs, H. Evans S. Jhingran, and P. Johnson. Spinal bone mineral after 5 weeks of bed rest. Calcif. Tissue Int. 41:259-261, 1987; 38 Minaire, P., P. Meunier, C. Edouard, J. Bemard, P. Courpron, and J. Bourret. Quantitative histological data on disuse osteoporosis: comparison with biological data. Calcif. Tissue Res. 17:57-73, 1974; 51. Schneider, V. S. and J. McDonald. Skeletal calcium homeostasis and countermeasures to prevent disuse osteoporosis. Calcif. Tissue Int. 36:S151-S154, 1984; 53. Stupakov, G. P., V. S. Kazaykin, A. O. Kozlovsky, and V. V. Korolev. Eval‎uation of changes in human axial skeletal bone structures during long-term spaceflights. Kosm. Biol. Aviakosm. Med. 18:33-39, 1984; 59. Vico, L., D. Chappard, C. Alexandre, et al. Effects of a 120-day period of bed rest on bone mass and bone cell activities in man: attempts at countermeasure. Bone Miner. 2:383-394, 1987.

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Recovery of bone mass after immobilization is usually very much slower than the rate at which it is lost. Cancellous bone mass lost in beagle dogs whose hindlimb was immobilized by casting for 12 wk was gradually regained within 12 wk of normal weightbearing activity. With longer periods of casting, the dogs' hindlimb bone mass did not return to normal even after 28 wk of remobilization((23) Fig. 10). These residual deficits of bone mass after remobilization were larger in older dogs subjected to the same protocol(23). This observation implies some dysfunction in the function of osteoblasts(bone-forming cells) in aging animals; similar deficits have been demonstrated in aging human osteoblasts (42). A residual deficit in bone mineral density of the calcaneus has been observed in American astronauts 5 yr after exposure to microgravity (55). The loss of density at lumbar spine and femoral neck is seemingly unaffected by a full 6 months of normal weightbearing activity ((28),Fig. 7).

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Figure 10-Time course of changes in cancellous bone mass in the third metaphysis of young (1-3 yr old) beagle dogs during immobilization and remobilization. If the immobilization period is 12 wk or less, bone mass is regained in full after 12 wk of remobilization; with longer periods of immobilization, some residual deficit in bone mass remains even after 28 wk of remobilization. Redrawn from data in reference 23. Jaworski, Z. F. G. and H. K. Uhthoff. Reversibility of nontraumatic disuse osteoporosis during its active phase. Bone 7:431-439, 1986.

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It is doubtful that these changes in bone mass in bed-rested subjects will have any immediate impact on functional capacity, as do the decrements in muscle strength and endurance. Of more concern is the individual's increased risk of bone fracture if a significant amount of bone has been lost, particularly upon resumption of normal activities after a period of bed rest or immobilization. For each bony site there is some critical bone density value that constitutes a “fracture threshold;” i.e., bone at densities below this threshold is very susceptible to fracture with minimal trauma (45). It is highly probable that during a period of bed rest the age-related bone loss we all experience might be temporarily accelerated, resulting in a more precipitous decline in bone mass over time and an earlier arrival at the fracture-threshold bone density specific to any one bony site.

Reductions in bone mass after a period of bed rest, coupled with decrements in muscle strength and possible alterations in balance and gait, significantly increase the risk of bone fracture with even minor falls. Hip fractures in elderly individuals can be life threatening; mortality in the first year after a hip fracture, usually from complications of prolonged immobility, is as high as 15-20% (61). For those who survive, decreased mobility detracts significantly from functional capacity and general quality of life.

PREVENTING BED REST-INDUCED LOSS OF MUSCLE AND BONE^

Evidence is encouraging that if muscle atrophy during prolonged bed rest can be minimized subsequent bone loss might be significantly diminished. Zeman et al. (65) tested the effectiveness of clenbuterol, a[beta]₂-agonist, in preventing the muscle and bone loss seen with various disuse treatments in young rats. This pharmacological treatment effectively prevented up to one-third of the decrement in tibial bone mass seen in control denervated rats. This normalizing effect on bone mass was abolished in those rats whose triceps surae were ablated, suggesting that the beneficial effect of the clenbuterol treatments depended upon its prevention of muscle atrophy. Further, there was an impressive correlation between the degree of normalization of bone mass with the degree of normalization of muscle mass with clenbuterol treatments in the various disuse models tested.

Researchers and therapists should aggressively expand our knowledge base regarding the usefulness of active muscle contraction and appropriate pharmacological treatments during prolonged bed rest in attenuating loss of muscle mass and strength and perhaps bone mass as well. Intensive supine cycling and isokinetic exercise training performed during a period of bed rest appears to attenuate or prevent, respectively, the muscle atrophy and loss of muscle strength typically seen with disuse (16,18). Studies investigating the effectiveness of exercise training during bed rest or spaceflight in minimizing bone loss of the lower limb have, unfortunately, been less successful (40,50).

SUMMARY: PRACTICAL IMPLICATIONS AND FUTURE RESEARCH^

There are many practical implications of these findings of musculoskeletal changes with bed rest for exercise professionals to consider when working with bed rested individuals (Table 3). Clearly, the highest priority should be avoidance of prolonged immobility; periods of bed rest mandated by medical conditions must be limited to as short a duration as possible. In many cases, bed rest deconditioning can exacerbate pre-existing conditions; for example, the severe osteopenia in hip fracture patients almost certainly is worsened during the prolonged immobilization during recovery (20). During remobilization, selective training of those muscle groups most seriously affected by relative disuse should be emphasized, using a very gradual, progressive overload program. Given the slower time course of recovery of bone mass relative to muscle mass, one should be aware of the increased risk of fracture in individuals remobilizing after prolonged bed rest. The imbalance between muscle and bone strength will be greatest at that time point when muscle mass and strength has returned to normal but before bone mass has been restored. These concerns are magnified in elderly individuals who may enter a period of bed rest with little bone or muscle mass to spare.

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TABLE 3. Guidelines for exercise professionals working with severely detrained or bedrested individuals.

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Last, more work is needed to define what mechanisms account for these musculoskeletal changes, particularly in bone, in human subjects experiencing prolonged bed rest. Does the reduced mechanical loading of bone during bed rest affect some critical local regulator of bone cell activity? What is the optimal mode, duration, and intensity of exercise training that bed rest patients can use to minimize these changes in musculoskeletal structure and function? Few data are available on middle-aged and female subjects and virtually none on elderly subjects. The time course and potential for full recovery of muscular strength and endurance, and of bone mass and strength, in bed-rested subjects remains to be defined and should be a high research priority.

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1: J Fam Pract. 2004 Sep;53(9):706-12. Links

Comment in:

J Bone Joint Surg Am. 2005 May;87(5):1167.

Resting injured limbs delays recovery: a systematic review.

Nash CE, Mickan SM, Del Mar CB, Glasziou PP.

Centre for General Practice, University of Queensland, Herston, Queensland, Australia.

OBJECTIVES: Rest is commonly used as primary treatment, rather than just palliation, for injured limbs. We searched the literature for evidence of benefit or harm from immobilization or mobilization of acute limb injury in adults. DATA SOURCES: We systematically searched for and retrieved randomized controlled trials (RCTs) of mobilization or rest for treatment of acute limb injuries, in Medline (1966-2002), EMBASE, Web of Science, and the Cochrane library, in all languages. REVIEW METHODS: We examined patient-centered outcomes (pain, swelling, and cost), functional outcomes (range of motion, days lost from work) and complications of treatment. RESULTS: Forty-nine trials of immobilization for soft tissue injuries and fractures of both upper and lower limbs were identified (3366 patients). All studies reported either no difference between rest and early mobilization protocols, or found in favor of early mobilization. Reported benefits of mobilization included earlier return to work; decreased pain, swelling, and stiffness; and a greater preserved range of joint motion. Early mobilization caused no increased complications, deformity or residual symptoms. CONCLUSIONS: We should not assume any benefit for immobilization after acute upper or lower limb injuries in adults. Rest appears to be overused as a treatment. More trials are needed to identify optimal programs for early mobilization.

1: Bone. 2009 Feb;44(2):214-24. Epub 2008 Oct 31. Links

Recovery of muscle atrophy and bone loss from 90 days bed rest: results from a one-year follow-up.

Rittweger J, Felsenberg D.

Institute for Biomedical Research into Human Movement and Health, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK. j.rittweger@mmu.ac.uk

Earlier studies found the recovery of bone loss after clinical immobilization to be incomplete. It has been argued that this is due to the human skeleton's inability to accrue bone mass once peak bone mass has been attained. However, recent studies suggest that bone losses can fully recover when complete functional rehabilitation is achieved. Accordingly, we hypothesized that bone losses by experimental bed rest would recover within one-year of follow-up. Twenty-five men (mean age 32 years, SD 4.2) were randomly assigned to either bed rest only (Ctrl), resistive flywheel exercise (FW), or to a group receiving 60 mg. i.v pamidronate prior to bed rest (Pam). Calf muscle cross sectional area and bone mineral content of the tibia was measured by peripheral quantitative computed tomography. Calcium, PTH and alkaline phosphatase blood levels were assessed along with urinary desoxypyridinoline excretion. Physical activity was assessed by the Freiburg questionnaire. In Pam and FW, diaphyseal bone losses were completely recovered at a 180-day follow-up, and there was even a small surplus after 1 year (p=0.016). Epiphyseal bone losses were largely, although not completely recovered after 1 year, when they still amounted to -0.6% (SD 1.3%, p=0.034, averaged over all groups). Bone formation and resorption markers had returned to baseline values at this time. However, epiphyseal recovery may still have been on-going, and fitting an exponential model yielded full recovery of the epiphysis within 2 years. Importantly, recovery of calf muscle cross-section and resumption of impact sport activities seemed to precede bone recovery, and bone accrual was closely matching the prior losses on an individual basis. No relationship was found between the epiphyseal BMC deficit at one-year follow-up and the participants' age. Results demonstrate recovery of bed rest induced bone losses in healthy adults. The initial re-accrual rate was remarkably high and is comparable to the accrual of bone mass during the pubertal growth spurt. This and the fact that the recovery of bone appeared to be tightly regulated, and generally followed neuromuscular recovery underline the adult skeleton's capability to adapt to mechanical stimuli.

1: Med Sci Sports Exerc. 1997 Feb;29(2):197-206. Links

Changes in musculoskeletal structure and function with prolonged bed rest.

Bloomfield SA.

Department of Health & Kinesiology, Texas A & M University, College Station 77843-4243, USA. sbloom@acs.tamu.edu

Prolonged bed rest produces profound changes in muscle and bone, particularly of the lower limb. This review first addresses the various models used by researchers to study disuse-induced changes in muscle and bone as observed during prolonged bed rest in humans. Dramatic change in muscle mass occurs within 4-6 wk of bed rest, accompanied by decreases of 6 to 40% in muscle strength. Immobilization studies in humans suggest that most of this lost muscle mass and strength can be regained with appropriate resistance training within several weeks after a period of disuse. Significant decrements in bone mineral density of the lumbar spine, femoral neck, and calcaneus observed in able-bodied men after bed rest are not fully reversed after 6 months of normal weightbearing activity. Importantly, the lost bone mass is not regained for some weeks or months after muscle mass and strength have returned to normal, further contributing to the risk of fracture. Those who enter a period of bed rest with subnormal muscle and bone mass, especially the elderly, are likely to incur additional risk of injury upon reambulation. Practical implications for exercise professionals working with individuals confined to bed rest are discussed.

[박수홍]

읽기 immobilization의 재앙

[여인호]

읽기