Copyright EMAP Publishing 2019 This article is not for distribution except for journal club use

Clinical Practice Keywords Atrophy/Disuse/Sarcopenia/ Contracture/Collagen/Achilles tendon Systems of life This article has been Bedrest double-blind peer reviewed In this article... ● Effects of prolonged bedrest on muscles, tendons, ligaments and cartilage ● Mechanisms of muscle disuse, weakness and atrophy ● Immobility-induced alteration of collagen structure in tendons and ligaments

Effects of bedrest 5: the muscles, joints and mobility

Key points Authors John Knight is senior lecturer in biomedical science; Yamni Nigam is professor Disused muscles in biomedical science; both at the College of Human Health and Science, Swansea lose mass and University. Aled Jones is reader in patient safety and healthcare quality, Cardiff University. strength, become weaker and Abstract This article – the fifth in a series exploring the harmful consequences of undergo atrophy bedrest on body and mind – describes how prolonged bedrest and immobility affect muscles and joints, two of the main components of the musculoskeletal system. The Sarcopenia is sixth and final article in the series will cover the skeletal system. associated with reductions in the Citation Knight J et al (2019) Effects of bedrest 5: the muscles, joints and mobility. size of muscle fibres Nursing Times [online]; 115: 4, 54-57.

Loss of muscle strength during edrest is often necessary to accompanied by a decline in skeletal prolonged bedrest recover from injury or disease muscle strength at a rate of around 12% a is also due to but prolonged immobility is det- week (Jiricka, 2009) or even up to 40% metabolic and Brimental to all major organs and within the first week of immobility (Topp neural changes human body systems. Muscles and joints et al, 2002). allow the body to move and carry out phys- In patients who have had a stroke, are Immobility can ical activities, and muscle weakness or joint paralysed or have limbs immobilised by a cause contractures stiffness resulting from immobility may splint, muscles atrophy with a loss in size severe enough to limit patients’ physical activity and reduce and mass of 30-40%. People with periph- restrict the range their quality of life. Prolonged bedrest often eral nerve injury that leads to flaccid paral- of movement in leads to reduced muscle mass and increased ysis can lose as much as 95% of lean muscle major joints risk of fracture. This fifth article in our six- mass in affected muscles, where fibres are part series explores how bedrest affects replaced by fat and connective tissue Exercise and muscles and joints, two components of the (Dittmer and Teasell, 1993). mobilisation, when musculoskeletal system. Effects on bones One study found that 72 hours of limb feasible, help avoid will be discussed in part 6. immobilisation could cause atrophy of muscle disuse and slow- and fast-twitch muscle fibres by 14% joint contractures Effects on muscles and 17% respectively (Lindboe and Platou, Due to its heavy demand for oxygen and 1984). The larger and better trained the glucose, muscle tissue is metabolically muscle, the faster the loss of strength and expensive for the body to build and main- the quicker the deconditioning (Jiricka, tain. Muscles rapidly undergo disuse 2009). Muscle fibre atrophy quickly leads atrophy and lose mass after only a short to a loss of strength and mass in the pos- period of immobility. The principle of ‘use tural muscles of the back, legs and arms. it or lose it’ applies perfectly to them. Among the first muscles to atrophy and weaken are those in the lower limbs, Atrophy and sarcopenia because they resist gravitational forces in Disuse of skeletal muscles rapidly leads to the upright position (Parry and Puthu- a loss of lean muscle mass (sarcopenia) as cheary, 2015). Extensor muscles (such as individual muscle groups atrophy. This is the quadriceps femoris), which have a

Nursing Times [online] April 2019 / Vol 115 Issue 4 54 www.nursingtimes.net Copyright EMAP Publishing 2019 This article is not for distribution except for journal club use Clinical Practice Systems of life prime role in posture, tend to atrophy drop in protein synthesis within muscle, dietary supplementation with amino acids more than flexor muscles (such as ham- which suggests that immobility not only and sucrose. They also demonstrated that strings). Backache and fatigue during con- causes muscle atrophy, but also reduces the simulating an increase in the levels of valescence are often due to disuse atrophy biosynthesis of new muscle tissue. plasma cortisol to mimic those seen in a of the underlying core muscle groups, Reduction in muscle strength is not hospital inpatient caused an increase in rather than the condition that necessitated only due to the physical loss of muscle muscle protein catabolism, which resulted bedrest. Postural and locomotive muscles fibres, but also to metabolic changes in muscle breakdown exceeding protein lose their tension-generating capacity, within muscle tissue. The primary source synthesis. while paraspinal and abdominal muscles of fuel for muscle contraction is glucose, become weak if not used. which is delivered to muscle fibres under Neurological changes the control of the hormone insulin. Glu- Bedrest-induced physiological changes in Slow- and fast-twitch fibres cose is then stored in the muscles in the neural control (see part 3) contribute to the Skeletal voluntary muscle consists of two form of an animal starch called glycogen deterioration of muscle strength and types of fibres: (VanPutte et al, 2017). endurance. In patients who are inactive, l Slow-twitch (type 1); Periods of immobility have been linked motor unit recruitment (the progressive l Fast-twitch (type 2). with decreased glycogen stores and a activation of a muscle by successive Slow-twitch muscle fibres contract reduced ability of muscle to mobilise fatty recruitment of contractile units) is dimin- slowly and produce large amounts of acids. Simultaneously, the activity of oxi- ished, as is the ability to activate all motor energy so they can keep moving for long dative enzymes within contractile muscle units during contractions. periods. They are rich in blood capillaries, fibres drops with disuse, leading to a Changes in electrical activity within mitochondria (the organelles that release reduction in the use of oxygen by muscle muscles and a loss of integrity of the neuro- energy) and myoglobin, a protein pigment tissue. This reduced oxidative capacity of muscular junction have also been reported similar to haemoglobin that binds to and mitochondria contributes to muscles following immobility (Blottner and releases oxygen during muscular contrac- tiring more easily in patients who are Salanova, 2015), potentially contributing to tion. These features make slow-twitch immobile. Furthermore, the detrimental the fatigue seen with muscle disuse. muscles resistant to fatigue (VanPutte et effects of bedrest on the cardiovascular al, 2017). Slow-twitch fibres are abundant and respiratory systems (see parts 1 and 2) Avoiding disuse weakness in the muscles of the neck and back, where result in reduced blood flow in, and oxygen A recent study showed that, during 60 days they help maintain posture while sitting or supply to, muscle tissue. of bedrest, participants who did three standing. They are also abundant in many minutes of light jumping exercises (con- muscles of the lower leg, such as the sisting of three series of 12 jumps repeated soleus, where they support endurance “The risk of contracture six or seven times a week) maintained leg activities such as long-distance running can be reduced through muscle strength, whereas control groups and cycling. good positioning and body (who did not take part in the exercise) lost Fast-twitch muscle fibres contract alignment in bed” around 40% of their leg muscle strength quickly but contain little myoglobin and (Kramer et al, 2017). fewer mitochondria. They are found at Similar results have been reported with high density in the muscles of the arms, Protein synthesis and catabolic the use of flywheel exercise machines to where they allow rapid movements. Fast- breakdown provide resistance training for patients twitch fibres are not able to generate a Muscle is a dynamic tissue that is broken confined to bed for 90 days; the exercise was steady supply of adenosine triphosphate down and rebuilt when required. Atrophy effective in reducing leg muscle atrophy (ATP) to power muscle contraction so, and sarcopenia associated with prolonged and exercising participants retained a although they contract more rapidly, they bedrest typically occur when there is an higher leg muscle mass than their non- also tire more quickly. imbalance between protein synthesis and exercising counterparts (Belavý et al, 2017). Long periods of immobility affect the the catabolic breakdown of muscle. The Clearly, not all patients confined to bed two types of muscle fibres differently. loss of lean muscle mass occurs primarily will be able to exercise, but Belavý et al Studies conflict as to whether one type through disuse, but many researchers (2017) highlight the importance of exercise atrophies faster than the other (Topp et al, have highlighted increases in the long- in maintaining lower limb strength in 2002; Kannus et al, 1998). The consensus term stress hormone cortisol during pro- those who are able and willing to do so. As today is that sarcopenia occurring as a longed bedrest – and cortisol is known to highlighted in part 1 of this series, main- result of immobility is associated with an stimulate the catabolic breakdown of taining muscle mass in the legs is particu- overall reduction in size in both slow- and muscle (see part 3). larly important: when these muscles con- fast-twitch fibres, with a slightly more Prolonged immobility has also been tract, they squeeze the veins of the legs, rapid loss in the fast-twitch type (Parry linked to an increased production of var- encouraging venous return to the heart, and Puthucheary, 2015). ious inflammatory mediators and dam- which helps prevent the pooling of blood aging superoxide anions, both of which in the legs, thereby reducing the risk of Metabolic changes are associated with reduced protein syn- venous stasis and clots. A small bedrest study of six men found that, thesis and increased muscle breakdown after 14 days of immobility, there was a sig- (Puthucheary et al, 2010). Remobilisation nificant decrease in their leg and whole- Fitts et al (2007) showed that the nega- On remobilisation, disuse weakness is typ- body lean muscle mass (Ferrando et al, tive effects of bedrest on human skeletal ically reversed at a rate of around 6% per 1996). This sarcopenia coincided with a 50% muscle fibres could be partially offset by week with exercise. It typically takes about

Nursing Times [online] April 2019 / Vol 115 Issue 4 55 www.nursingtimes.net Copyright EMAP Publishing 2019 This article is not for distribution except for journal club use Clinical Practice Systems of life

four weeks to recover from the disuse Fig 1. Accessory structures of the musculoskeletal system atrophy caused by immobility, which is slower than the recovery from direct muscle trauma (Halar, 1994). Loss of muscle mass and strength can have negative psychological effects on Tendon patients, contributing to fatigue and low (connects muscle to bone) Muscle mood. This may affect their motivation to undertake exercise and lead to a vicious cycle of immobility and inactivity. The significant loss of strength in the Bone major muscle groups involved in main- taining posture may partially explain why patients may be unsteady on their feet when they start to remobilise; it certainly Ligaments contributes to an increased risk of falls. (connect bone to bone) Effects on tendons, ligaments Cartilage and cartilage (reduces friction between bones) Tendons, ligaments and cartilage (Fig 1) require motion to stay healthy and will, therefore, deteriorate in patients who are confined to bed. Changes to their structure Bone and functioning start to become apparent after 4-6 days of immobility and can remain, even after normal activity has been resumed. Most of these changes appear to be due to the altered structure of collagen fibres. Tendons are stiff, cord-like structures development because of the shortening affected were the elbow, ankle, knee, hip connecting muscle to bone; 20 days of and weakening of the muscles. and shoulder (Clavet et al, 2008). A follow- bedrest reduces their stiffness and Contractures can develop over joints, up study in the same population showed increases their viscosity (Kubo et al, 2004), often when there is an imbalance in the that those who had developed joint which negatively affects the transmission strength of opposing muscle groups. If contractures had difficulties with mobility of energy from muscle to bone and reduces allowed to progress, a joint contracture three years later (Clavet et al, 2015). The the ability of muscle groups to produce may develop to involve muscles, tendons, authors concluded that joint contractures dynamic force. This may manifest as ligaments and internal structure of the could cause irreversible disability and increased weakness and exhaustion. joint capsule, resulting in a stiffening joint that identifying and treating them in the Ligaments are elastic structures con- that is increasingly limited in its range of ICU could prevent long-term functional necting bone to bone; their elasticity motion. A common example of joint con- limitations. allows joints to maintain mobility while tracture caused by immobilisation is con- Furthermore, during bedrest, opposing ensuring they are held together and not tracture of a knee that has been plastered folds of the synovial membrane (connec- easily dislocated. Articular cartilage is the to treat a fractured tibia. tive tissue that lines the inner surface of smooth, translucent or transparent tissue Joint contractures may begin to form the capsules of synovial joints) may come that covers the ends of bones where they within as little as eight hours of immobility into contact with each other and form come together to form joints; healthy car- (Corcoran, 1991). This may partially explain abnormal adhesions that further limit tilage allows bones to glide over each other the morning stiffness many people experi- joint movement (Trudel et al, 2003). with little friction. Ligaments and artic- ence after a night’s sleep. Most morning ular cartilage are both negatively affected stiffness is transient as, after activity is Alteration in collagen structure by prolonged immobility. resumed, the joint tissues are stretched The main component of tendons and liga- again and stiffness dissipates. However, ments is the fibroblast-derived protein col- Joint contracture 2-3 weeks of immobilisation will produce a lagen. In joints that frequently move, col- A contracture is a permanent shortening much more severe form of joint contracture. lagen fibres are in a loosely coiled of tissue – such as muscle, tendon or skin Immobility can cause contractures that arrangement that allows stretching and tissue – resulting from disuse, injury or are severe enough to restrict the range of normal activity. In a patient who is immo- disease. It can occur, for example, as a movement in major joints; this is one of bile, the collagen structure changes into a result of changes to the collagen composi- the most frequent complications associ- mass of shortened, straighter and more tion of tendons and ligaments caused by ated with prolonged bedrest. Among 155 densely packed fibres within one day. disuse. Although contractures are patients who stayed in an intensive care Within two or three weeks, this change in extremely common, their aetiology is still unit (ICU) for two weeks or more, over a collagen structure can compound a joint poorly understood (Wong et al, 2015). third developed a movement-limiting contracture. After two or three months of

PETER LAMB PETER Muscle atrophy plays a part in their joint contracture; the joints most often immobility, contracture and stiffness may

Nursing Times [online] April 2019 / Vol 115 Issue 4 56 www.nursingtimes.net Copyright EMAP Publishing 2019 This article is not for distribution except for journal club use Clinical Practice Systems of life

have become so severe that surgical correc- Fig 2. Foot drop contracture tion will be needed to restore the full mobility of the joint.

Foot drop contracture Peroneal nerve A common problem associated with pro- longed bedrest and immobility is foot drop contracture or deformity (Fig 2), which Normal foot results in the inability to place the heel in its correct position on the ground when Drop foot standing or sitting. This is usually caused contracture by entrapment of the common peroneal nerve at the neck of the fibula at the top of Inability to lift the the calf. front part of the Foot drop contracture is compounded foot off the by a lack of passive exercise stretching the ground ankle joint or by inadequate joint support, both of which reduce tension on the Achilles tendon and lead to its shortening (Lippincott Williams and Wilkins, 2006). Similarly, a lack of stretching of the gas- Conclusion Porth CM, Matfin G (eds) Pathophysiology: Concepts trocnemius muscle (one of the two major As discussed here and in previous articles of Altered Health States. Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams and Wilkins. muscles of the calf ) when the body is in this series, exercise and mobilisation, Kannus P et al (1985) Free mobilization and low- supine can lead to a tightening of the calf, when feasible, will help counteract the to high-intensity exercise in immobilization- thereby contributing to foot drop contrac- negative physical and psychological induced muscle atrophy. Journal of Applied ture (Amis, 2014). effects of prolonged bedrest. In particular, Physiology; 84: 4, 1418-1424. Kramer et al A (2017) How to prevent the Once the patient regains mobility, a they will help avoid muscle disuse weak- detrimental effects of two months of bed-rest on shortened Achilles tendon can result in the ness and joint contractures. NT muscle, bone and cardiovascular system: an RCT. toes pointing further forward than normal Scientific Reports; 7: 1, 13177. and make it difficult to place the foot in its References Kubo K et al (2004) Effects of 20 days of bed rest Amis J (2014) The gastrocnemius: a new paradigm on the viscoelastic properties of tendon structures usual position. This makes walking diffi- for the human foot and ankle. Foot and Ankle in lower limb muscles. British Journal of Sports cult and places undue strain on the Clinics; 19: 4: 637-647. Medicine; 38: 3, 324-330. Achilles tendon, causing pain and Belavý DL et al (2017) High-intensity flywheel Lindboe CF, Platou CS (1984) Effect of increasing the risk of tendon rupture. exercise and recovery of atrophy after 90 days immobilization of short duration on the muscle bed-rest. BMJ Open Sport and Exercise Medicine; fibre size. Clinical Physiology; 4: 2, 183-188. 3: 1, e000196. Lippincott Williams and Wilkins (2006) Avoiding contractures Blottner D, Salanova M (2015) The NeuroMuscular Professional Guide to Signs and Symptoms The risk of contracture can be reduced System: From Earth to Space Life Science: Baltimore, MD: Lippincott Williams and Wilkins. through appropriate positioning and body Neuromuscular Cell Signalling in Disuse and Parry SM, Puthucheary ZA (2015) The impact of Exercise. London: Springer International. extended bed rest on the musculoskeletal system alignment in bed. Moving each joint Clavet H et al (2015) Joint contractures in the in the critical care environment. Extreme through its full range of motion at least intensive care unit: quality of life and function Physiology and Medicine; 4, 16. once every eight hours, whether actively or 3.3 years after hospital discharge. Disability and Puthucheary Z et al (2010) Skeletal muscle passively, also appears to help prevent con- Rehabilitation; 37: 3, 207-213. dysfunction in critical care: wasting, weakness, and Clavet H et al (2008) Joint contracture following rehabilitation strategies. Critical Care Medicine; 38: tractures. Nursing staff can help by prolonged stay in the intensive care unit. Canadian (10 Suppl), S676-S682. checking and correcting a patient’s posi- Medical Association Journal; 178: 6, 691-697. Topp R et al (2002) The effect of bed rest and tion in bed as well as their posture while Corcoran PJ (1991) Use it or lose it – the hazards of potential of prehabilitation on patients in the sitting. A physiotherapist can undertake bedrest and inactivity. Western Journal of intensive care unit. American Association of Critical Medicine; 154: 5, 536-538. Care Nurses Clinical Issues; 13: 2, 263-276. passive joint mobilisation exercises, as can Dittmer DK, Teasell R (1993) Complications of Trudel G et al (2003) Localized and adaptive appropriately trained nurses or healthcare immobilisation and bed rest. Part 1: synoviocyte proliferation characteristics in rat knee assistants. musculoskeletal and cardiovascular complications. joint contractures secondary to immobility. Canadian Family Physician; 39: 1428-1437. Archives of Physical Medicine and Rehabilitation; Ferrando AA et al (1996) Prolonged bed rest 84: 9, 1350-1356. CLINICAL decreases skeletal muscle and whole body protein VanPutte CL et al (2017) Seeley’s Anatomy and SERIES Effects of bedrest series synthesis. American Journal of Physiology; 270: 4 Physiology. New York, NY: McGraw-Hill Education. Part 1: Introduction and cardiovascular Dec Pt 1, E627-E633. Wong K et al (2015) Noninflammatory joint system Bit.ly/NTBedrest1 Fitts RH et al (2007) The deleterious effects of contractures arising from immobility: animal bed rest on human skeletal muscle fibers are models to future treatments. BioMed Research Part 2: Respiratory system, haematological Jan exacerbated by hypercortisolemia and ameliorated International; 2015, 848290. system Bit.ly/NTBedrest2 by dietary supplementation. American Journal of Part 3: Gastrointestinal, endocrine and Feb Physiology: Cell Physiology; 293: 1, C313-C320. nervous systems Bit.ly/NTBedrest3 Halar EM (1994) Disuse syndrome: recognition and For more on this topic online Part 4: Renal, reproductive and immune Mar prevention. In: Hays RM et al (eds) Chronic Disease systems Bit.ly/NTBedrest4 and Disability: A Contemporary Rehabilitation l Anatomy and physiology of ageing Part 5: Muscles and joints Apr Approach to Medical Practice. New York, NY: 10: the musculoskeletal system Demos Publications. Part 6: Bones, skin and self-perception May Bit.ly/NTMusculoskeletalSOL Jiricka MK (2009) Activity tolerance and fatigue. In: PETER LAMB PETER

Nursing Times [online] April 2019 / Vol 115 Issue 4 57 www.nursingtimes.net