complications DOUGL\S K. DITTMIER, MID, FRCPC ROBERT TEASELL, ID, FRCPC SUMMARY Prolonged bed rest and immobilization inevitably lead to complications. Such complications are much easier to prevent than to treat. Musculoskeletal complications ED RES I AND) IMMNOBILIZ.ATION * mental disorders (catatonia, hysterical include loss of muscle strength D are time-honoured treat- paralysis); and and endurance, contractures and D ments for managing trau- * loss of sensation: discomfort does not soft tissue changes, disuse ma and acute and chronic dictate change of position. osteoporosis, and degenerative illnesses. Although bed rest joint disease. Cardiovascular and immobilization often benefit the Chronically ill, disabled, and geriatric complications include an acutely affected part of the body, when increased heart rate, decreased people are particularly at risk.2 These peo- cardiac reserve, orthostatic prolonged, they often harm the rest of the ple already have little or no reserve physi- hypotension, and venous body. Only within the last four decades ologic function, and any additional thromboembolism. have clinicians become aware of the difficulties created by immobilization harmful effects of bed rest and inactivity result in functional losses. Table 1 lists mus- RESUME and the beneficial effects of activity.' culoskeletal and cardiovascular complica- L'immobilisation et le repos Problems arising from immobilization can tions of bed rest and immobilization. au lit prolong6 engendrent complicate a primary disease or trauma inevitablement des complications and might actually become greater prob- Musculoskeletal complications qui sont beaucoup plus faciles a lems than the primary disorder. Muscle weakness and atrophy. The prevenir qu'a guerir. Parmi Complications of immobilization are most obvious effect of prolonged immobi- les complications musculo- much easier to prevent than to treat. lization is loss of muscle strength and squelettiques, notons la perte NMany types of immobilizations can lead to endurance. A muscle at complete rest de force et d'endurance musculaire, les contractures et complications: loses 1O0% to 15% of its strength each les changements tissulaires, * enforced bed rest (illness or convales- week. Nearly half of normal strength is I'osteoporose due a l'inactivite cence); lost within 3 to 5 weeks of immobilization. et l'arthropathie degenerative. * paralysis; Patients immobilized in bed and astro- Quant aux complications * immobilizations of body parts with nauts3; in zero gravity (Figure 1) find the cardiovasculaires, on y retrouve braces, casts, or corsets; first muscles to become weak and atroph- une acceleration du rythme * joint stiffness and pain with protective ic are those of the lower extremities and cardiaque, une diminution limitations of motion; trunk that normally resist gravity.' The de la reserve cardiaque, antigravity muscles are reported to expe- I'hypertension orthostatique et Dr Dittmer and Dr Teasell are on staff in the rience greater loss of strength than other la thromboembolie veineuse. Department of Physical ledicine and Rehabilitation skeletal muscles with inactivity and a Can m San 1993;39:1428-1437. at the University of Jlestern Ontario in London, Ont. greater proportional loss of muscular
1428 (anadian Family Physician VOL 39 J1ne 1993
torque.6 Postural and locomotive muscles spastic (eg, stroke) paralysis or in patients lose their tension-generating capacity. whose limbs are immobilized by splinting, Generalized muscle weakness hampers the degree ofmuscle atrophy is less, gener- people in the activities of daily living, work, ally around 30% to 40%. Combined mus- climbing stairs, and even walking. Local cle atrophy, decreased strength, and muscle weakness results from local immobi- limited endurance leads to poor coordina- lization when fractured bones or injured tion of the movements of the extremities joints are set in casts (Figure 2).7,8 LeBlanc et and could affect the patient's ability to al' demonstrated changes in muscle atro- perform the activities of daily living. phy and strength after immobilization among nine male volunteers given absolute Contractures and soft tissue horizontal bed rest. They used magnetic changes. Contractures, defined as fixed resonance imaging to calculate muscle area deformities of joints as a consequence of and a Cybex II dynamometer to measure immobilization, occur because of the strength. The muscle area of the plantar dynamic nature of connective tissue and flexors (gastrocnemius and soleus) muscle in the body. Connective tissue is decreased 12% and strength decreased constantly being removed, replaced, and 26%; dorsiflexion muscle area and strength reorganized and can be seen to go through were not significantly decreased. These a series ofphases during healing. " In areas results have implications for patients with of frequent movement, loose areolar con- severe orthopedic and neurologic disorders nective tissue develops. In areas of little or and for persons who are voluntarily inac- no motion, collagen eventually is laid tive (many of the elderly). down as a dense mesh of sheets. Collagen Unfortunately the rate of recovery fibres maintain their length if frequently from disuse weakness is slower than the stretched but shorten if immobilized. rate of loss. Disuse weakness is reversed at Ligament complexes are affected bio- a rate of only 6% per week using submax- mechanically, biochemically, and mor- imal exercise (65% to 750% of maximum).8 phologically by immobilization, and Muscle strength can be maintained with- these changes occur in both bony liga- out loss or gain with daily muscle contrac- ment insertions and the ligament sub- tions of 20% or more of maximal tension stance itself i2,13 Hence, after trauma to for several seconds each day.' Functional the soft tissue and bone, it is important to electrical stimulation and biofeedback realize that immobilization in a cast with training can increase or maintain muscu- non-weight-bearing status (eg, a lower lar strength in those muscles with less than limb fracture) can lead to changes that antigravity strength. are difficult to reverse later. Experiments Complete rest will also result in with animals have shown that, after decreased endurance through a reduc- 8 weeks of immobilization in whole body tion in muscle strength, metabolic casts, knee ligament stiffness, maximum activity,"° and circulation. Decreased load at failure, and energy absorption endurance levels that cause a sense of before failure decreased to 69%, 610%, fatigue and reduce patient motivation set and 68% of normal, respectively, and Table 1. Potential up a vicious circle of greater inactivity that the ligaments had not returned to complications of and (both as a contributing factor to and normal even 1 year later.' 14 immobilization a result of) further fatigue. Immobilization can cause fibrofatty Muscle atrophy is defined as loss of infiltration in joints that can mature into MUSCULOSKELETAL muscle mass. It might account for a strong adhesions within the joints and * Decreased muscle strength decrease in muscle strength and might destroy cartilage. In periarticular and atrophy endurance. Normal muscles at rest can connective tissue, increased cross-link- * Decreased endurance lose half their bulk after only 2 months.8 * Contracture age between existing collagen and new * Osteoporosis During flaccid paralysis (ie, peripheral type I collagen that has been abnormal- nerve injury) a totally denervated muscle ly deposited within the matrix con- (ARDIOVASCULAR can lose as much as 95% of its bulk. With tributes to contracture rather than to the * Increased heart rate irreversible denervation, muscle fibres synthesis of a new type of collagen. 16 * Decreased cardiac reserve undergo permanent degeneration and are Shortening collagen fibres can restrict * Orthostatic hypotension replaced by fat and connective tissue. In movement significantly even within * Venous thromboembolism
Canadian Family Physician VOL 39: June 1993 1429
F~gure 2..Patient t .
1 week. If a joint has to be immobilized, changes during a variety of muscle degener-
Jarvinen et al'7 suggest that immobiliz- ative and inflammatory disorders; soft tissue ing the gastrocnemius muscle-tendon disorders, such as scleroderma or burns; unit in a lengthened position causes less and joint degenerative or inflammatory dis- muscle atrophy and less decrease in ten- orders. Contractures are most commonly sile properties than immobilizing in a seen in individuals with joint diseases or shortened position. paralysis of a muscle group or in elderly Many factors contribute to contractures. individuals who are frail, cognitively Denervated muscle (with no opposition to impaired, or very passive. Muscles that cross antagonistic muscle) or spasticity (where two joints, such as the hamstring or back either flexor or extensor muscle are muscles, tensor muscles of fascia lata, rectus favoured) can lead to dynamic muscle muscle of the thigh, gastrocnemius muscles, imbalance. Improper bed positioning can and biceps muscles, are particularly at risk result in deformities, particularly in joints of of shortening during immobilization.I the lower extremities. Adaptive shortening Contractures limit positioning, making of soft tissues when the limb is held in a bathing and transfers difficult; increase shortened position (eg, in a cast) might the risk of pressure sores; are often painful; occur. Sometimes contractures arise from and sometimes prevent ambulation and the disease itself, such as intrinsic muscle lengthen hospital stays. For instance, a hip
1430 Canadian Family Physician VOL 39 June 1993
flexion contracture shortens stride, used.'8" 9 Functional braces or hinged casts increases lumbar lordosis, causes the ham- have also helped to avoid "cast disease." string muscle to shorten resulting in a flex- Work by Sarmiento and Latta2" has shown ion contracture, and leads to increased that, after initial stabilization and forma- energy consumption while moving.' tion of early callus, joints associated with Treatment of contractures emphasizes the fracture can be mobilized if properly prevention. Varying the positions ofimmo- braced to prevent rotation. Eriksson2' first bile joints regularly, performing active or promoted cast bracing following knee liga- passive range-of-motion exercises twice ment repair to decrease muscle atrophy daily, and using resting splints for joints and obtain a quicker return of motion. that tend to maintain an undesirable posi- Continuous passive motion has also tion help prevent contractures. Abundant been used to diminish the effects of immo- evidence appears to show that early active bilization after surgery by enhancing reab- mobilization after initial stabilization is sorption of the hemarthrosis; decreasing beneficial. Achilles tendon ruptures and adhesions, pain, thrombophlebitis, and ankle sprains seem to recover with greater muscle atrophy; and improving cartilage strength and sooner (allowing earlier nutrition, range of motion, and collagen return to work) when early functional orientation and strength. Yet continuous activities are permitted than when casts are passive motion alone showed no significant
Canadian Family Physician VOL 39 June 1993 1431
advantages over active therapy after knee Osteoporosis can lead to fractures of the ligament reconstructions.22Joints should be spinal vertebrae, femur, and distal radius. immobilized in the neutral position so Repeated anterior fractures of the spinal opposing muscles are at equal length vertebrae result in a dorsal kyphosis and and tension.23-26' chronic back pain. But osteopenia some- Established contractures are treated times is undetected for years. Routine radi- with passive range of motion and terminal ographs do not demonstrate osteoporosis stretch for 20 to 30 seconds. Prolonged until 40% of bone density is lost. stretch can be provided manually or through traction devices applied at low Degenerative joint disease. Exper- tension after heating the tissues involved imental immobilization of animals has to 40° to 45°C. Progressive dynamic resulted in severe degenerative joint splinting can be used in specific cases. changes.3'3 Researchers now believe that Contraindications to aggressive manage- both the contracted capsule and joint ment of immobilized or contracted joints immobilization in a fixed position cause include osteoporosis, heterotopic ossifica- prolonged compression of the cartilage tion, acute arthritis, ligamentous instabili- contact sites and their subsequent degen- ty, new fractures, insensate areas, and an eration.1 These findings have not been inability to communicate pain. If contrac- correlated with human subjects. The ear- tures are significantly impeding function lier work of Salter et al36 on damaged rab- and do not respond to conservative man- bit cartilage showed that continuous agement, surgery might be required. After passive motion had a beneficial biologic contractures are overcome, the factors that effect on the healing of full thickness caused them will remain and a preventive defects in articular cartilage. maintenance program is a necessity. Finally, one randomized, clinical trial of bed rest treatment for mechanical low Disuse osteoporosis. Like connective back pain without neuromotor deficits tissue, bone is a dynamic tissue. A constant showed convincingly that the sooner equilibrium is maintained between bone patients were up and moving around formation and resorption. Bone morphol- (ie, after 2 days' rest rather than 7 days') ogy and density depend on forces that act the fewer days ofwork they missed. No dif- upon the bone,27'281 such as the direct ferences in other functional, physiologic, pulling action of tendons and weight bear- or perceived outcomes were noted.3' Bed ing. Astronauts in weightless environments rest to allow an underlying lesion to heal suffer profound loss of bone mass despite by avoiding biomechanical strain clearly is rigorous physical activity, Immobilization being challenged as a useful way to treat leads to bone mass loss in association with musculoskeletal injury. hypercalciuria and negative calcium bal- ance.29 Loss is generally greater with lower Cardiovascular complications motor neuron flaccid lesions than with Cardiovascular complications of immobiiza- upper motor neuron spastic lesions. tion include an increased heart rate, Experimental studies demonstrate decreased cardiac reserve, orthostatic that increased bone resorption accounts hypotension, and venous thromboembolism. for loss of bone mass28,30-33 even though the parathyroid hormone is not sup- Increased heart rate and decreased pressed. Both cortical and trabecular cardiac reserve. Heart rate increases bone are lost, trabecular bone predomi- (generally to more than 80 beats/min) fol- nantly. 3 Trabecular bone is found in the lowing immobilization, probably due to spine, femur, and wrist, making these increased sympathetic nervous system areas susceptible to fractures after trau- activity. During bed rest, the resting pulse ma. Bone loss during long-term immobi- rate speeds up one beat each minute every lization tends to occur in stages: first, 2 days.38 Because the increased heart rate rapid bone loss; second, beginning at results in less diastolic filling time and a 12 weeks, slower but more prolonged shortened systolic ejection time, the heart bone loss; until third, stabilization at is less capable of responding to metabolic 4000 to 70%/o of original mass. demands above the basal level. Shorter
1432 Canadian lamily Plvsiciall \'0l,(i9:.7tlie 1993
diastolic time reduces coronary blood flow Venous thromboembolism. Venous and decreases the oxygen available to car- thromboembolism is due primarily to diac muscle. Cardiac output, stroke vol- venous stasis and to a lesser degree to ume, and left ventricular function decline increased blood coagulability (two of the overall.)18 41 Physical exertion can then three factors in Virchow's triad). Stasis lead to tachycardia and angina in predis- occurs in the legs following decreased posed individuals and work capacity is contraction of the gastrocnemius and reduced. In a classic study by Saltin et al,42 soleus muscles. Most deep venous 24 male college students were subjected to thrombi occur in the calf and mainly 20 days of bed rest. Results showed a originate in the soleus sinus. Researchers 27% decrease in maximal °2 uptake, believe that 80% of the clots lyse before 25% decrease in stroke volume, 15% to reaching the level of the knee. Patients 26% increase in cardiac output, and a with proven deep venous thrombi involv- 20% increase in heart rate. ing the popliteal or more proximal leg To reverse the effects of bed rest and veins have a 50% chance of developing build endurance, patients should exercise pulmonary emboli.44 Mortality from to between 50% and 70% of maximal untreated pulmonary embolism is oxygen consumption, or 65% to 75% of 20% to 35%.4 Organization and resolu- maximal heart rate. Maximal heart rate tion of a deep venous thrombosis occurs (beats/min) can be calculated as 210 - (age within 7 to 10 days. Length of bed rest is in years 0.65). This formula is justified directly related to frequency of deep when, apart from deconditioning, the venous thrombosis.46 patient has no evident heart disease. Most patients who develop deep TFarget heart rates can be achieved using venous thrombosis fail to demonstrate any treadmill or bicycle ergometer (Figure 3) clinical signs. Venous collaterals are gener- training, or arm ergometry (Figure 4) for ally so well developed that the thrombi patients with lower limb injury or disease. must be quite extensive to clog the veins or cause vessel wall inflammation. Clinical Orthostatic hypotension. Orthostatic signs of deep venous thrombosis tend to be hypotension is believed to occur when the unreliable. These include pain and ten- cardiovascular system does not adapt nor- derness, swelling, venous distention, pal- mally to an upright posture. It occurs lor, cyanosis, redness, or a positive after 3 weeks of bed rest (earlier for the Homans' sign. More than 50% of patients elderly) because of excessive pooling of who have clinical signs of deep venous blood in the lower extremities and a thrombosis have no evidence of it on decrease in circulating blood volume. venography.47 Clinical diagnosis is both This, along with a rapid heart rate, results nonsensitive and nonspecific, and it is in diminished diastolic ventricular filling important to verify clinical suspicions with and a decline in cerebral perfusion.39'43 diagnostic tests such as Doppler ultra- The circulatory system is unable to sonography, impedance plethysmography, restore a stable pulse and blood pressure and contrast venography. Each test has level. Generally, orthostatic hypotension specific advantages and disadvantages; is characterized by a pulse rate increase of contrast venography is the gold standard. more than 20 beats/min and a 70% or The clinical picture of pulmonary more decrease in pulse pressure with thromboembolism is both nonspecific and venous pooling in the legs. poorly sensitive. Symptoms of pulmonary Treatment of orthostatic hypotension emboli include dyspnea, tachypnea, involves leg exercises, early mobilization tachycardia, pleuritic chest pain, cough, and ambulation, and elastic stockings. hemoptysis, or a pleural rub or effusion.48 In cases of prolonged bed rest, a tilt Less specific signs include fever, confusion, table with graduated increase in the wheezing, and arrhythmia. Severe cases standing posture might be necessary. might lead to pulmonary consolidation or Reconditioning the cardiovascular system atelectasis, right heart failure, and even generally takes longer than decondition- cardiovascular collapse with hypotension. ing. Reconditioning appears to take even The key diagnostic test is a lung scan for longer for elderly patients. ventilation and perfusion. Generally, a
Canadian Family Phy.sician VOL '3) June 1993 1435
mismatch is present with parts of the lung 7. MacDougallJD, Elder GCB, Sale DG, appearing adequately ventilated but not MorozJR, SuttonJR. Effects of strength training adequately perfused. Arterial blood gases and immobilization of human muscle fibres. could show a fall in the arterial oxygen EurJ7 Appl Physiol 1980;43:25-34. level and no change in the arterial carbon 8. Muller EA. Influence of training and of inactivity dioxide level. An electrocardiogram can on muscle strength. Arch Phys Mfed Rehabil 1970; rule out myocardial infarction. 51:449-62. Treating venous thromboembolism 9. LeBlanc A, Gogia P, Schneider V, KrebsJ, involves decreasing venous stasis by such Schonfeld E, Evans H. Calf muscle area and physiotherapy as leg exercises, leg eleva- strength changes after five weeks of horizontal tion, elastic stockings, early ambulation, bed rest. Am ] Sports Aled 1988; 16:6,624-9. and mechanical compression. Methods 10. MacDougallJD, Ward GR, Sale DG, to decrease blood coagulability include SuttonJR. Biochemical adaptation of human dextran, antiplatelet drugs such as skeletal muscle to heavy resistance trainiing and acetylsalicylic acid, and anticoagulants immobilization. 7 Appl Physiol 1977;43:700-3. such as warfarin and heparin. 11. Van der MeulenJCH. Present state of Prophylactic methods that effectively knowledge on processes of healing in collagen prevent venous thromboembolism structures. Intff Sports Aled 1982;3:4-8. include low-dose heparin, intermittent 12. Akeson WH, Amiel D, Abel MF, Garfin SR, pneumatic compression, oral anticoagu- Woo SLY. Effects of immobilization on joints. lants, and dextran. Heparin has Clin Orthop 1987;219:28-37. significantly decreased deep venous 13. W'Valsh S, Frank C, Hart D. Immobilization thrombosis in many trials and is required alters cell metabolism in an immature ligament. only in low doses because it does not Clin Orthop 1992;277:277-88. amplify the coagulation cascade seen 14. Noyes FR, Torvik PJ, Hyde W\'B. Biomechanics with established venous thrombi. of ligament failure. II. An analysis of Treatment should continue until the immobilization, exercise and reconditioning patient is ambulatory. D effects in primates. 7 Bone_Joint Surg Am 1974; 56A: 1406-18. Requests for reprints to: Dr Douglas K. 15. Zarins B. Soft tissue injury and repair - Dittmer, Victonra Hospital, 800 Commissioners Rd E, biomechanical aspects. Int] Sports Med 1982;3:9-1 1. London, ON N6A 4G5 16. Amiel D, Akeson WH, Harwood FL, Mlechanic GL. The effect of immobilization on References the types of collagen synthesized in periarticular 1. Halar EM, Bell K. Rehabilitations' relationship connective tissue. Connect Tissue Res 1980;8:27-32. to inactivity. In: Kottke FJ, LehmannJF, editors. 17.Jarvinen MJ, Einola SA, Virtanen EO. Effect of Krusen's handbook ofphysical medicine and rehabilitation. the position of immobilization upon the teinsile 4th ed. Philadelphia: WB Saunders Co, properties of the rat gastrocnemius muscle. 1990:1113-39. Arch Phys MIed Rehabil 1992;73:253-7. 2. Bonner CD. Rehabilitation instead of bedrest? 18. Brooks SC, Potter BT, RaineyJB. Treatment Geriatrics 1969;24: 109-18. for partial tears of the lateral ligament of the 3. Herbison GJ, TalbotJM. Muscle atrophy during ankle: a prospective trial. BMJ 1981;282:606-7. space flight: research needs and opportunities. 19. Enwemeka CS, Spielholz NI, Nelson AJ. Physiologist 1985;28:520-4. The effect of early functional activities on 4. Riley DA, Ellis S. Research on the adaptation of experimentally tenotomized Achilles tendons in skeletal muscle to hypogravity: past and future rats. Am ]7 Phys Mied Rehabil 1988;67(6):264-9. directions. Adv Space Res 1983;3(9):191-7. 20. Sarmiento A, Latta LL. Closedfunctional treatment 5. Thorton WVE, RummelJA. Muscular offractures. New York: Springer-Verlag, 1981. deconditioning and its prevention in spaceflight. 21. Eriksson E. Sports injuries of the knee Proceedings of the Skylab Life Sciences ligaments: their diagnosis, treatment, Symposium. J Am Space Agency TVIX rehabilitation, and presentation. Alled Sci Sports 1974;58154:403-16. Exerc 1976;8: 133-44. 6. Gogia PP, Schneider VS, LeBlanc AD, KrebsJ, 22. Rosen MA,Jackson DW, Atwell EA. Kasson C, Pientok C. Bedrest effect on extremity The efficacy of continuous passive motion in the muscle torque in healthy men. Arch Phys Mlfed rehabilitation of anterior cruciate ligament Rehabil 1 988;69: 1030-2. reconstructions. Am]f Sports Med 1 992;20: 122-7.
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23. Spector SA, Simard CP, Fournier M, 39. Holmgren A, Mossfeldt F, Sjostrand T, Sternlicht E, Edgerton VR. Architectural Strom G. Effect of training on work capacity, alterations of rat hind-limb skeletal muscle total hemoglobin, blood volume, heart volume immobilized at different lengths. Exp Neurol and pulse rate in recumbent and upright 1982;76:94-1 10. positions. Acta Physiol Scand 1960;50:73-83. 24. Spence WA, Vallbona C, Carter RE. 40. Taylor HL, Henschel A, ProzekJ, Keys A. Physiologic concepts of immobilization. Arch Phys Effects of bedrest on cardiovascular function and Med Rehabil 1965;46:89- 100. work performance. JAppl Psychol 1949;2:223-9. 25. Stolov WC, Fry LR, Riddel WM, Weilepp TGJr. 41. Taylor HL. The effects of rest in bed and of Adhesive forces between muscle fibres and exercise on cardiovascular function. Circulation connective tissue in normal and denervated rat 1968;38: 1016-7. skeletal muscle. Arch Phys Med Rehabil 1973; 42. Saltin B, Blomqvist G, MitchellJH, 54:208-13. Johnson RL, Wildenthal K, Chapman CB. 26. Stremel RW, Convertino VA, GreenleafJE, Response to exercise after bed rest and after Bernauer EM. Response to maximal exercise training - a longitudinal study of adaptive after bedrest [abstract]. Fed Proc 1974;33:327. changes in oxygen transport and body 27. Ede MC, Burr RG. Circadian rhythm of composition. Circulation 1968;38(Suppl 7): 1-78. urinary calcium excretion during immobilization. 43. Chobanian AV, Lillie RD, Tercyak A, Aerosp Med 1973;44:495-8. Blevins P. The metabolic and hemodynamic 28. UhthoffHK,Jaworski ZFG. Bone loss in effects of prolonged bedrest in normal subjects. response to long-term immobilization. J BoneJoint Circulation 1974;49:551-9. Surg Br 1978;60B:420-9. 44. HirshJ, Hull R. Natural history and clinical 29. Issekutz B, BlizzardJJ, Birkhead NC, features of venous thrombosis. In: Colman RW, Rodahl M. Effect of prolonged bedrest on urinary HirshJ, Marder VJ, Salzman EW, editors. calcium output. 7 Appl Physiol 1966;21:1013-20. Hemostasis and thrombosis: basic principles and 30. Enneking WF, Horowitz M. The intraarticular clinical practice. Philadelphia:JB Lippincott, effects of immobilization on the human knee. 1982:831-43. Bonejoint SurgAm 1972;54A: 973-83. 45. Tibbutt DA, Chesterman CN. Pulmonary 31. Heaney RP. Radiocalcium metabolism in disuse embolism: current therapeutic concepts. osteoporosis in man. Am j Med 1962;33: 188-200. Drugs 1976;11: 161-92. 32. Landry M, Fleisch H. The influence of 46. Micheli LJ. Thromboembolic complications of immobilization on bone formation as evaluated cast immobilization for injuries of the lower by osseous incorporation of tetracyclines. extremities. Clin Orthop 1975;108:191-5. J Bone Joint Surg Br 1964;46B:764-7 1. 47. Hull R, HirshJ, Sackett DL. Cost effectiveness 33. Young DR, Niklowitz WJ, Brown RJ,Jee WS. of clinical diagnosis, venography, and non- Immobilization-associated osteoporosis in invasive testing in patients with symptomatic deep primates. Bone 1986;7:109-17. vein thrombosis. NEngl] Med 1981 ;304: 1561-7. 34. Carr CE, Genant HK, Young DR. 48. Bell WR, Simon TL, Demets DL. The clinical Comparison ofvertebral and peripheral mineral features of submassive and massive pulmonary losses in disuse osteoporbsis in monkeys. Radiology emboli. Am]Med 1977;62:355-60. 1980; 134:525-9. 35. Finsterbush A, Friedman B. Early changes in immobilized rabbit's knee joint: a light and electron microscopic study. Clin Orthop 1973;92:305-19. 36. Salter RB, Simmonds DF, Malcolm BW. The biological effect of continuous motion on the healing of full thickness defects in articular cartilage. 7 BoneJoint Surg Am 1980;62A: 1232-51. 37. Deyo RA, Diehl AK, Rosenthal M. How many days of bed rest for acute low back pain? J/Engl_JMed 1986;315:1064-70. 38. Halar EM, Bell KR. Contracture and other deleterious effects of immobility. In: DeLisaJA, editor. Rehabilitation medicine, principle and practices. Philadelphia:JB Lippincott, 1988:448-62.