SUMMARYProlonged bed rest andimmobilization inevitably leadto complications. Suchcomplications are much easierto prevent than to treat.Musculoskeletal complicationsinclude loss of muscle strengthand endurance, contractures andsoft tissue changes, disuseosteoporosis, and degenerativejoint disease. Cardiovascularcomplications include anincreased heart rate, decreasedcardiac reserve, orthostatichypotension, and venousthromboembolism.

RESUMEL'immobilisation et le reposau lit prolong6 engendrentinevitablement des complicationsqui sont beaucoup plus faciles aprevenir qu'a guerir. Parmiles complications musculo-squelettiques, notons la pertede force et d'endurancemusculaire, les contractures etles changements tissulaires,I'osteoporose due a l'inactiviteet l'arthropathie degenerative.Quant aux complicationscardiovasculaires, on y retrouveune acceleration du rythmecardiaque, une diminutionde la reserve cardiaque,I'hypertension orthostatique etla thromboembolie veineuse.

Can m San 1993;39:1428-1437.

Complications of

Immobilization and

Part 1: Musculoskeletal and cardiovascularcomplications

DOUGL\S K. DITTMIER, MID, FRCPCROBERT TEASELL, ID, FRCPC

ED RES I AND) IMMNOBILIZ.ATION

D are time-honoured treat-D ments for managing trau-

ma and acute and chronicillnesses. Although bed rest

and immobilization often benefit theacutely affected part of the body, whenprolonged, they often harm the rest of thebody. Only within the last four decadeshave clinicians become aware of theharmful effects of bed rest and inactivityand the beneficial effects of activity.'Problems arising from immobilization cancomplicate a primary disease or traumaand might actually become greater prob-lems than the primary disorder.

Complications of immobilization aremuch easier to prevent than to treat.NMany types of immobilizations can lead tocomplications:* enforced bed rest (illness or convales-

cence);* paralysis;* immobilizations of body parts with

braces, casts, or corsets;* joint stiffness and pain with protective

limitations of motion;

Dr Dittmer and Dr Teasell are on staff in theDepartment ofPhysical ledicine and Rehabilitationat the University of Jlestern Ontario in London, Ont.

* mental disorders (catatonia, hystericalparalysis); and

* loss of sensation: discomfort does notdictate change of position.

Chronically ill, disabled, and geriatricpeople are particularly at risk.2 These peo-ple already have little or no reserve physi-ologic function, and any additionaldifficulties created by immobilizationresult in functional losses. Table 1 lists mus-culoskeletal and cardiovascular complica-tions of bed rest and immobilization.

Musculoskeletal complicationsMuscle weakness and atrophy. Themost obvious effect ofprolonged immobi-lization is loss of muscle strength andendurance. A muscle at complete restloses 1O0% to 15% of its strength eachweek. Nearly half of normal strength islost within 3 to 5 weeks of immobilization.Patients immobilized in bed and astro-nauts3; in zero gravity (Figure 1) find thefirst muscles to become weak and atroph-ic are those of the lower extremities andtrunk that normally resist gravity.' Theantigravity muscles are reported to expe-rience greater loss of strength than otherskeletal muscles with inactivity and agreater proportional loss of muscular

1428 (anadian Family Physician VOL 39 J1ne 1993

torque.6 Postural and locomotive muscleslose their tension-generating capacity.

Generalized muscle weakness hamperspeople in the activities of daily living, work,climbing stairs, and even walking. Localmuscle weakness results from local immobi-lization when fractured bones or injuredjoints are set in casts (Figure 2).7,8 LeBlanc etal' demonstrated changes in muscle atro-phy and strength after immobilizationamong nine male volunteers given absolutehorizontal bed rest. They used magneticresonance imaging to calculate muscle areaand a Cybex II dynamometer to measurestrength. The muscle area of the plantarflexors (gastrocnemius and soleus)decreased 12% and strength decreased26%; dorsiflexion muscle area and strengthwere not significantly decreased. Theseresults have implications for patients withsevere orthopedic and neurologic disordersand for persons who are voluntarily inac-tive (many of the elderly).

Unfortunately the rate of recoveryfrom disuse weakness is slower than therate of loss. Disuse weakness is reversed ata rate of only 6% per week using submax-imal exercise (65% to 750% ofmaximum).8Muscle strength can be maintained with-out loss or gain with daily muscle contrac-tions of 20% or more of maximal tensionfor several seconds each day.' Functionalelectrical stimulation and biofeedbacktraining can increase or maintain muscu-lar strength in those muscles with less thanantigravity strength.

Complete rest will also result indecreased endurance through a reduc-tion in muscle strength, metabolicactivity,"° and circulation. Decreasedendurance levels that cause a sense offatigue and reduce patient motivation setup a vicious circle of greater inactivityand (both as a contributing factor to anda result of) further fatigue.

Muscle atrophy is defined as loss ofmuscle mass. It might account for adecrease in muscle strength andendurance. Normal muscles at rest canlose half their bulk after only 2 months.8During flaccid paralysis (ie, peripheralnerve injury) a totally denervated musclecan lose as much as 95% of its bulk. Withirreversible denervation, muscle fibresundergo permanent degeneration and arereplaced by fat and connective tissue. In

spastic (eg, stroke) paralysis or in patientswhose limbs are immobilized by splinting,the degree ofmuscle atrophy is less, gener-ally around 30% to 40%. Combined mus-cle atrophy, decreased strength, andlimited endurance leads to poor coordina-tion of the movements of the extremitiesand could affect the patient's ability toperform the activities of daily living.

Contractures and soft tissuechanges. Contractures, defined as fixeddeformities of joints as a consequence ofimmobilization, occur because of thedynamic nature of connective tissue andmuscle in the body. Connective tissue isconstantly being removed, replaced, andreorganized and can be seen to go througha series ofphases during healing." In areasof frequent movement, loose areolar con-nective tissue develops. In areas of little orno motion, collagen eventually is laiddown as a dense mesh of sheets. Collagenfibres maintain their length if frequentlystretched but shorten if immobilized.

Ligament complexes are affected bio-mechanically, biochemically, and mor-phologically by immobilization, andthese changes occur in both bony liga-ment insertions and the ligament sub-stance itself i2,13 Hence, after trauma tothe soft tissue and bone, it is important torealize that immobilization in a cast withnon-weight-bearing status (eg, a lowerlimb fracture) can lead to changes thatare difficult to reverse later. Experimentswith animals have shown that, after8 weeks of immobilization in whole bodycasts, knee ligament stiffness, maximumload at failure, and energy absorptionbefore failure decreased to 69%, 610%,and 68% of normal, respectively, andthat the ligaments had not returned tonormal even 1 year later.' 14

Immobilization can cause fibrofattyinfiltration in joints that can mature intostrong adhesions within the joints andmight destroy cartilage. In periarticularconnective tissue, increased cross-link-age between existing collagen and newtype I collagen that has been abnormal-ly deposited within the matrix con-tributes to contracture rather than to thesynthesis of a new type of collagen. 16

Shortening collagen fibres can restrictmovement significantly even within

Canadian Family Physician VOL 39: June 1993 1429

Table 1. Potentialcomplications ofimmobilization

MUSCULOSKELETAL* Decreased muscle strength

and atrophy* Decreased endurance* Contracture* Osteoporosis

(ARDIOVASCULAR* Increased heart rate* Decreased cardiac reserve* Orthostatic hypotension* Venous thromboembolism

F~gure 2..Patient t .

1 week. If a joint has to be immobilized,Jarvinen et al'7 suggest that immobiliz-ing the gastrocnemius muscle-tendonunit in a lengthened position causes lessmuscle atrophy and less decrease in ten-sile properties than immobilizing in ashortened position.

Many factors contribute to contractures.Denervated muscle (with no opposition toantagonistic muscle) or spasticity (whereeither flexor or extensor muscle arefavoured) can lead to dynamic muscleimbalance. Improper bed positioning canresult in deformities, particularly in joints ofthe lower extremities. Adaptive shorteningof soft tissues when the limb is held in ashortened position (eg, in a cast) mightoccur. Sometimes contractures arise fromthe disease itself, such as intrinsic muscle

changes during a variety ofmuscle degener-ative and inflammatory disorders; soft tissuedisorders, such as scleroderma or burns;and joint degenerative or inflammatory dis-orders. Contractures are most commonlyseen in individuals with joint diseases orparalysis of a muscle group or in elderlyindividuals who are frail, cognitivelyimpaired, or very passive. Muscles that crosstwo joints, such as the hamstring or backmuscles, tensor muscles of fascia lata, rectusmuscle of the thigh, gastrocnemius muscles,and biceps muscles, are particularly at riskof shortening during immobilization.I

Contractures limit positioning, makingbathing and transfers difficult; increasethe risk ofpressure sores; are often painful;and sometimes prevent ambulation andlengthen hospital stays. For instance, a hip

1430 Canadian Family Physician VOL 39 June 1993

flexion contracture shortens stride,increases lumbar lordosis, causes the ham-string muscle to shorten resulting in a flex-ion contracture, and leads to increasedenergy consumption while moving.'

Treatment of contractures emphasizesprevention. Varying the positions ofimmo-bile joints regularly, performing active orpassive range-of-motion exercises twicedaily, and using resting splints for jointsthat tend to maintain an undesirable posi-tion help prevent contractures. Abundantevidence appears to show that early activemobilization after initial stabilization isbeneficial. Achilles tendon ruptures andankle sprains seem to recover with greaterstrength and sooner (allowing earlierreturn to work) when early functionalactivities are permitted than when casts are

used.'8" 9 Functional braces or hinged castshave also helped to avoid "cast disease."Work by Sarmiento and Latta2" has shownthat, after initial stabilization and forma-tion of early callus, joints associated withthe fracture can be mobilized if properlybraced to prevent rotation. Eriksson2' firstpromoted cast bracing following knee liga-ment repair to decrease muscle atrophyand obtain a quicker return of motion.

Continuous passive motion has alsobeen used to diminish the effects of immo-bilization after surgery by enhancing reab-sorption of the hemarthrosis; decreasingadhesions, pain, thrombophlebitis, andmuscle atrophy; and improving cartilagenutrition, range of motion, and collagenorientation and strength. Yet continuouspassive motion alone showed no significant

Canadian Family Physician VOL 39 June 1993 1431

advantages over active therapy after kneeligament reconstructions.22Joints should beimmobilized in the neutral position soopposing muscles are at equal lengthand tension.23-26'

Established contractures are treatedwith passive range of motion and terminalstretch for 20 to 30 seconds. Prolongedstretch can be provided manually orthrough traction devices applied at lowtension after heating the tissues involvedto 40° to 45°C. Progressive dynamicsplinting can be used in specific cases.Contraindications to aggressive manage-ment of immobilized or contracted jointsinclude osteoporosis, heterotopic ossifica-tion, acute arthritis, ligamentous instabili-ty, new fractures, insensate areas, and aninability to communicate pain. If contrac-tures are significantly impeding functionand do not respond to conservative man-agement, surgery might be required. Aftercontractures are overcome, the factors thatcaused them will remain and a preventivemaintenance program is a necessity.

Disuse osteoporosis. Like connectivetissue, bone is a dynamic tissue. A constantequilibrium is maintained between boneformation and resorption. Bone morphol-ogy and density depend on forces that actupon the bone,27'281 such as the directpulling action of tendons and weight bear-ing. Astronauts in weightless environmentssuffer profound loss of bone mass despiterigorous physical activity, Immobilizationleads to bone mass loss in association withhypercalciuria and negative calcium bal-ance.29 Loss is generally greater with lowermotor neuron flaccid lesions than withupper motor neuron spastic lesions.

Experimental studies demonstratethat increased bone resorption accountsfor loss of bone mass28,30-33 even thoughthe parathyroid hormone is not sup-pressed. Both cortical and trabecularbone are lost, trabecular bone predomi-nantly.3 Trabecular bone is found in thespine, femur, and wrist, making theseareas susceptible to fractures after trau-ma. Bone loss during long-term immobi-lization tends to occur in stages: first,rapid bone loss; second, beginning at12 weeks, slower but more prolongedbone loss; until third, stabilization at4000 to 70%/o of original mass.

Osteoporosis can lead to fractures ofthespinal vertebrae, femur, and distal radius.Repeated anterior fractures of the spinalvertebrae result in a dorsal kyphosis andchronic back pain. But osteopenia some-times is undetected for years. Routine radi-ographs do not demonstrate osteoporosisuntil 40% ofbone density is lost.

Degenerative joint disease. Exper-imental immobilization of animals hasresulted in severe degenerative jointchanges.3'3 Researchers now believe thatboth the contracted capsule and jointimmobilization in a fixed position causeprolonged compression of the cartilagecontact sites and their subsequent degen-eration.1 These findings have not beencorrelated with human subjects. The ear-lier work of Salter et al36 on damaged rab-bit cartilage showed that continuouspassive motion had a beneficial biologiceffect on the healing of full thicknessdefects in articular cartilage.

Finally, one randomized, clinical trialof bed rest treatment for mechanical lowback pain without neuromotor deficitsshowed convincingly that the soonerpatients were up and moving around(ie, after 2 days' rest rather than 7 days')the fewer days ofwork they missed. No dif-ferences in other functional, physiologic,or perceived outcomes were noted.3' Bedrest to allow an underlying lesion to healby avoiding biomechanical strain clearly isbeing challenged as a useful way to treatmusculoskeletal injury.

Cardiovascular complicationsCardiovascular complications ofimmobiiza-tion include an increased heart rate,decreased cardiac reserve, orthostatichypotension, and venous thromboembolism.

Increased heart rate and decreasedcardiac reserve. Heart rate increases(generally to more than 80 beats/min) fol-lowing immobilization, probably due toincreased sympathetic nervous systemactivity. During bed rest, the resting pulserate speeds up one beat each minute every2 days.38 Because the increased heart rateresults in less diastolic filling time and ashortened systolic ejection time, the heartis less capable of responding to metabolicdemands above the basal level. Shorter

1432 Canadian lamily Plvsiciall \'0l,(i9:.7tlie 1993

diastolic time reduces coronary blood flowand decreases the oxygen available to car-diac muscle. Cardiac output, stroke vol-ume, and left ventricular function declineoverall.)18 41 Physical exertion can thenlead to tachycardia and angina in predis-posed individuals and work capacity isreduced. In a classic study by Saltin et al,4224 male college students were subjected to20 days of bed rest. Results showed a27% decrease in maximal °2 uptake,25% decrease in stroke volume, 15% to26% increase in cardiac output, and a20% increase in heart rate.

To reverse the effects of bed rest andbuild endurance, patients should exerciseto between 50% and 70% of maximaloxygen consumption, or 65% to 75% ofmaximal heart rate. Maximal heart rate(beats/min) can be calculated as 210 - (agein years 0.65). This formula is justifiedwhen, apart from deconditioning, thepatient has no evident heart disease.TFarget heart rates can be achieved usingtreadmill or bicycle ergometer (Figure 3)training, or arm ergometry (Figure 4) forpatients with lower limb injury or disease.

Orthostatic hypotension. Orthostatichypotension is believed to occur when thecardiovascular system does not adapt nor-mally to an upright posture. It occursafter 3 weeks of bed rest (earlier for theelderly) because of excessive pooling ofblood in the lower extremities and adecrease in circulating blood volume.This, along with a rapid heart rate, resultsin diminished diastolic ventricular fillingand a decline in cerebral perfusion.39'43The circulatory system is unable torestore a stable pulse and blood pressurelevel. Generally, orthostatic hypotensionis characterized by a pulse rate increase ofmore than 20 beats/min and a 70% ormore decrease in pulse pressure withvenous pooling in the legs.

Treatment of orthostatic hypotensioninvolves leg exercises, early mobilizationand ambulation, and elastic stockings.In cases of prolonged bed rest, a tilttable with graduated increase in thestanding posture might be necessary.Reconditioning the cardiovascular systemgenerally takes longer than decondition-ing. Reconditioning appears to take evenlonger for elderly patients.

Venous thromboembolism. Venousthromboembolism is due primarily tovenous stasis and to a lesser degree toincreased blood coagulability (two of thethree factors in Virchow's triad). Stasisoccurs in the legs following decreasedcontraction of the gastrocnemius andsoleus muscles. Most deep venousthrombi occur in the calf and mainlyoriginate in the soleus sinus. Researchersbelieve that 80% of the clots lyse beforereaching the level of the knee. Patientswith proven deep venous thrombi involv-ing the popliteal or more proximal legveins have a 50% chance of developingpulmonary emboli.44 Mortality fromuntreated pulmonary embolism is20% to 35%.4 Organization and resolu-tion of a deep venous thrombosis occurswithin 7 to 10 days. Length of bed rest isdirectly related to frequency of deepvenous thrombosis.46

Most patients who develop deepvenous thrombosis fail to demonstrate anyclinical signs. Venous collaterals are gener-ally so well developed that the thrombimust be quite extensive to clog the veins orcause vessel wall inflammation. Clinicalsigns ofdeep venous thrombosis tend to beunreliable. These include pain and ten-derness, swelling, venous distention, pal-lor, cyanosis, redness, or a positiveHomans' sign. More than 50% of patientswho have clinical signs of deep venousthrombosis have no evidence of it onvenography.47 Clinical diagnosis is bothnonsensitive and nonspecific, and it isimportant to verify clinical suspicions withdiagnostic tests such as Doppler ultra-sonography, impedance plethysmography,and contrast venography. Each test hasspecific advantages and disadvantages;contrast venography is the gold standard.

The clinical picture of pulmonarythromboembolism is both nonspecific andpoorly sensitive. Symptoms of pulmonaryemboli include dyspnea, tachypnea,tachycardia, pleuritic chest pain, cough,hemoptysis, or a pleural rub or effusion.48Less specific signs include fever, confusion,wheezing, and arrhythmia. Severe casesmight lead to pulmonary consolidation oratelectasis, right heart failure, and evencardiovascular collapse with hypotension.The key diagnostic test is a lung scan forventilation and perfusion. Generally, a

Canadian Family Phy.sician VOL '3) June 1993 1435

mismatch is present with parts of the lungappearing adequately ventilated but notadequately perfused. Arterial blood gasescould show a fall in the arterial oxygenlevel and no change in the arterial carbondioxide level. An electrocardiogram canrule out myocardial infarction.

Treating venous thromboembolisminvolves decreasing venous stasis by suchphysiotherapy as leg exercises, leg eleva-tion, elastic stockings, early ambulation,and mechanical compression. Methodsto decrease blood coagulability includedextran, antiplatelet drugs such asacetylsalicylic acid, and anticoagulantssuch as warfarin and heparin.Prophylactic methods that effectivelyprevent venous thromboembolisminclude low-dose heparin, intermittentpneumatic compression, oral anticoagu-lants, and dextran. Heparin hassignificantly decreased deep venousthrombosis in many trials and is requiredonly in low doses because it does notamplify the coagulation cascade seenwith established venous thrombi.Treatment should continue until thepatient is ambulatory. D

Requests for reprints to: Dr Douglas K.Dittmer, Victonra Hospital, 800 Commissioners Rd E,London, ON N6A 4G5

References1. Halar EM, Bell K. Rehabilitations' relationshipto inactivity. In: Kottke FJ, LehmannJF, editors.Krusen's handbook ofphysical medicine and rehabilitation.4th ed. Philadelphia: WB Saunders Co,1990:1113-39.

2. Bonner CD. Rehabilitation instead of bedrest?Geriatrics 1969;24: 109-18.

3. Herbison GJ, TalbotJM. Muscle atrophy duringspace flight: research needs and opportunities.Physiologist 1985;28:520-4.

4. Riley DA, Ellis S. Research on the adaptation ofskeletal muscle to hypogravity: past and futuredirections. Adv Space Res 1983;3(9):191-7.

5. Thorton WVE, RummelJA. Musculardeconditioning and its prevention in spaceflight.Proceedings of the Skylab Life SciencesSymposium. J Am Space Agency TVIX1974;58154:403-16.

6. Gogia PP, Schneider VS, LeBlanc AD, KrebsJ,Kasson C, Pientok C. Bedrest effect on extremitymuscle torque in healthy men. Arch Phys MlfedRehabil 1 988;69: 1030-2.

7. MacDougallJD, Elder GCB, Sale DG,MorozJR, SuttonJR. Effects of strength trainingand immobilization of human muscle fibres.

EurJ7 Appl Physiol 1980;43:25-34.8. Muller EA. Influence of training and of inactivityon muscle strength. Arch Phys Mfed Rehabil 1970;51:449-62.

9. LeBlanc A, Gogia P, Schneider V, KrebsJ,Schonfeld E, Evans H. Calf muscle area and

strength changes after five weeks of horizontal

bed rest. Am ] Sports Aled 1988; 16:6,624-9.10. MacDougallJD, Ward GR, Sale DG,SuttonJR. Biochemical adaptation of humanskeletal muscle to heavy resistance trainiing andimmobilization. 7 Appl Physiol 1977;43:700-3.

11. Van der MeulenJCH. Present state of

knowledge on processes of healing in collagenstructures. Intff Sports Aled 1982;3:4-8.

12. Akeson WH, Amiel D, Abel MF, Garfin SR,Woo SLY. Effects of immobilization on joints.Clin Orthop 1987;219:28-37.

13. W'Valsh S, Frank C, Hart D. Immobilizationalters cell metabolism in an immature ligament.Clin Orthop 1992;277:277-88.

14. Noyes FR, Torvik PJ, Hyde W\'B. Biomechanicsof ligament failure. II. An analysis ofimmobilization, exercise and reconditioningeffects in primates. 7 Bone_Joint Surg Am 1974;56A: 1406-18.

15. Zarins B. Soft tissue injury and repair -

biomechanical aspects. Int] Sports Med 1982;3:9-1 1.16. Amiel D, Akeson WH, Harwood FL,Mlechanic GL. The effect of immobilization on

the types of collagen synthesized in periarticularconnective tissue. Connect Tissue Res 1980;8:27-32.

17.Jarvinen MJ, Einola SA, Virtanen EO. Effect ofthe position of immobilization upon the teinsileproperties of the rat gastrocnemius muscle.Arch Phys MIed Rehabil 1992;73:253-7.

18. Brooks SC, Potter BT, RaineyJB. Treatmentfor partial tears of the lateral ligament of theankle: a prospective trial. BMJ 1981;282:606-7.

19. Enwemeka CS, Spielholz NI, Nelson AJ.The effect of early functional activities onexperimentally tenotomized Achilles tendons inrats. Am ]7 Phys Mied Rehabil 1988;67(6):264-9.

20. Sarmiento A, Latta LL. Closedfunctional treatmentoffractures. New York: Springer-Verlag, 1981.

21. Eriksson E. Sports injuries of the kneeligaments: their diagnosis, treatment,rehabilitation, and presentation. Alled Sci SportsExerc 1976;8: 133-44.

22. Rosen MA,Jackson DW, Atwell EA.The efficacy of continuous passive motion in therehabilitation of anterior cruciate ligamentreconstructions. Am]f Sports Med 1 992;20: 122-7.

1436 Canadian Family Physician VOL 39: June 1993

23. Spector SA, Simard CP, Fournier M,Sternlicht E, Edgerton VR. Architecturalalterations of rat hind-limb skeletal muscleimmobilized at different lengths. Exp Neurol1982;76:94-1 10.

24. Spence WA, Vallbona C, Carter RE.Physiologic concepts of immobilization. Arch PhysMed Rehabil 1965;46:89- 100.

25. Stolov WC, Fry LR, Riddel WM, Weilepp TGJr.Adhesive forces between muscle fibres andconnective tissue in normal and denervated rat

skeletal muscle. Arch PhysMed Rehabil 1973;54:208-13.

26. Stremel RW, Convertino VA, GreenleafJE,Bernauer EM. Response to maximal exerciseafter bedrest [abstract]. Fed Proc 1974;33:327.

27. Ede MC, Burr RG. Circadian rhythm ofurinary calcium excretion during immobilization.Aerosp Med 1973;44:495-8.

28. UhthoffHK,Jaworski ZFG. Bone loss inresponse to long-term immobilization. J BoneJointSurg Br 1978;60B:420-9.

29. Issekutz B, BlizzardJJ, Birkhead NC,Rodahl M. Effect of prolonged bedrest on urinarycalcium output. 7 Appl Physiol 1966;21:1013-20.

30. Enneking WF, Horowitz M. The intraarticulareffects of immobilization on the human knee.Bonejoint SurgAm 1972;54A: 973-83.

31. Heaney RP. Radiocalcium metabolism in disuseosteoporosis in man. Amj Med 1962;33: 188-200.

32. Landry M, Fleisch H. The influence ofimmobilization on bone formation as evaluated

by osseous incorporation of tetracyclines.J Bone Joint Surg Br 1964;46B:764-7 1.

33. Young DR, Niklowitz WJ, Brown RJ,Jee WS.Immobilization-associated osteoporosis inprimates. Bone 1986;7:109-17.

34. Carr CE, Genant HK, Young DR.Comparison ofvertebral and peripheral mineral

losses in disuse osteoporbsis in monkeys. Radiology1980; 134:525-9.

35. Finsterbush A, Friedman B. Early changes in

immobilized rabbit's knee joint: a light andelectron microscopic study. Clin Orthop1973;92:305-19.

36. Salter RB, Simmonds DF, Malcolm BW.The biological effect of continuous motion on the

healing of full thickness defects in articularcartilage. 7 BoneJoint SurgAm 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 otherdeleterious effects of immobility. In: DeLisaJA,editor. Rehabilitation medicine, principle and practices.Philadelphia:JB Lippincott, 1988:448-62.

39. Holmgren A, Mossfeldt F, Sjostrand T,Strom G. Effect of training on work capacity,total hemoglobin, blood volume, heart volumeand pulse rate in recumbent and uprightpositions. Acta Physiol Scand 1960;50:73-83.

40. Taylor HL, Henschel A, ProzekJ, Keys A.

Effects of bedrest on cardiovascular function andwork performance. JAppl Psychol 1949;2:223-9.

41. Taylor HL. The effects of rest in bed and of

exercise on cardiovascular function. Circulation1968;38: 1016-7.

42. Saltin B, Blomqvist G, MitchellJH,Johnson RL, Wildenthal K, Chapman CB.Response to exercise after bed rest and aftertraining - a longitudinal study of adaptivechanges in oxygen transport and bodycomposition. Circulation 1968;38(Suppl 7): 1-78.

43. Chobanian AV, Lillie RD, Tercyak A,Blevins P. The metabolic and hemodynamiceffects ofprolonged bedrest in normal subjects.Circulation 1974;49:551-9.

44. HirshJ, Hull R. Natural history and clinicalfeatures of venous thrombosis. In: Colman RW,HirshJ, Marder VJ, Salzman EW, editors.Hemostasis and thrombosis: basic principles andclinical practice. Philadelphia:JB Lippincott,1982:831-43.

45. Tibbutt DA, Chesterman CN. Pulmonaryembolism: current therapeutic concepts.

Drugs 1976;11: 161-92.46. Micheli LJ. Thromboembolic complications of

cast immobilization for injuries of the lowerextremities. Clin Orthop 1975;108:191-5.

47. Hull R, HirshJ, Sackett DL. Cost effectivenessof clinical diagnosis, venography, and non-

invasive testing in patients with symptomatic deepvein thrombosis. NEngl] Med 1981 ;304: 1561-7.

48. Bell WR, Simon TL, Demets DL. The clinicalfeatures of submassive and massive pulmonaryemboli. Am]Med 1977;62:355-60.

Canadian Family Physician VOL 39: June 1993 1437