Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health→

Impact of sedentarism due to the COVID-19 home confinement on neuromuscular, cardiovascular and metabolic health: Physiological and pathophysiological implications and recommendations for physical and nutritional countermeasures

Marco Naricia, Giuseppe De Vitoa, Martino Franchib, Antonio Paolic, Tatiana Moroc, GiuseppeMarcolinc, Bruno Grassid, Giovanni Baldassarred, Lucrezia Zuccarellid, Gianni Bioloe, Filippo Giorgio di Girolamoe, Nicola Fiottie, Flemming Delaf,g, Paul Greenhaffh, and ConstantinosMaganarisi

a Department of Biomedical Sciences, CIR-MYO Myology Center, Neuromuscular Physiology Laboratory, University of Padova, Padua, Italy

b Department of Biomedical Sciences, Neuromuscular Physiology Laboratory, University of Padova, Padua, Italy

c Department of Biomedical Sciences, Nutrition and Exercise Physiology Laboratory, University of Padova, Padua, Italy

d Department of Medicine, University of Udine, Udine, Italy

e Department of Internal Medicine, University of Trieste, Ospedale di Cattinara, Trieste, Italy

f Xlab, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

g Department of Geriatrics, Bispebjerg-Frederiksberg University Hospital, Copenhagen, Denmark

hMRC Versus Arthritis Centre for Musculoskeletal Ageing Research, Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, National Institute for Health Research Nottingham Biomedical Research Centre, School of Life Sciences, The Medical School, University of Nottingham, Queen's Medical Centre, Nottingham, UK

i School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK

ABSTRACT

The COVID-19 pandemic is an unprecedented health crisis as entire populations have been asked to self-isolate and live in home-confinement for several weeks to months, which in itself represents a physiological challenge with significant health risks. This paper describes the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on evidence from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Data form these studies show that muscle wasting occurs rapidly, being detectable within two days of inactivity. This loss of muscle mass is associated with fibre denervation, neuromuscular junction damage and upregulation of protein breakdown, but is mostly explained by the suppression of muscle protein synthesis. Inactivity also affects glucose homeostasis as just few days of step reduction or bed rest, reduce insulin sensitivity, principally in muscle. Additionally, aerobic capacity is impaired at all levels of the O2 cascade, from the cardiovascular system, including peripheral circulation, to skeletal muscle oxidative function. Positive energy balance during physical inactivity is associated with fat deposition, associated with systemic inflammation and activation of antioxidant defences, exacerbating muscle loss. Importantly, these deleterious effects of inactivity can be diminished by routine exercise practice, but the exercise dose–response relationship is currently unknown. Nevertheless, low to medium-intensity high volume resistive exercise, easily implementable in home-settings, will have positive effects, particularly if combined with a 15–25% reduction in daily energy intake. This combined regimen seems ideal for preserving neuromuscular, metabolic and cardiovascular health.

Highlights•This paper describes the impact of sedentarism, caused by the COVID-19 home confinement on the neuromuscular, cardiovascular, metabolic and endocrine systems.•Just few days of sedentary lifestyle are sufficient to induce muscle loss, neuromuscular junction damage and fibre denervation, insulin resistance, decreased aerobic capacity, fat deposition and low-grade systemic inflammation.•Regular low/medium intensity high volume exercise, together with a 15-25% reduction in caloric intake are recommended for preserving neuromuscular, cardiovascular, metabolic and endocrine health.

KEYWORDS

COVID-19, sedentarism, neuromuscular system, cardiovascular system, glucose homeostasis, body composition, nutrition, exercise

CONTACT Correspondence: Marco Narici. E-mail: marco.narici@unipd.it

© 2020 European College of Sport Science

Introduction

The COVID-19 pandemic is posing a very serious challenge to our societies as entire populations have been asked to restrict their social interactions and in many countries even to self-isolate and live in home-confinement for several weeks to months. This period of restricted movement affects all citizens regardless of age, sex and ethnicity. It forces people, even the youngest and fittest, to become suddenly inactive and adopt sedentary behaviours.

This short position-point paper aims to explain the impact of sedentarism on the human body at the level of the muscular, cardiovascular, metabolic, endocrine and nervous systems and is based on knowledge derived from several models of inactivity, including bed rest, unilateral limb suspension, and step-reduction. Evidence is provided on the degree and speed of muscle atrophy we can expect when undergoing a period of complete inactivity caused by bed rest. Notably, muscle atrophy is a very fast phenomenon detectable after just two days of inactivity. The novel and concerning findings of muscle denervation and damage to the neuromuscular junction associated with inactivity are also discussed. The mechanisms of disuse muscle atrophy are also examined in terms of muscle protein metabolism and cellular signalling, highlighting the different temporal contributions of changes in muscle protein synthesis and degradation and how these processes differ between young and older populations and can impact on muscle mass restoration during recovery. Additionally the concept of anabolic resistance, in the context of inactivity and ageing, and its role in impairing the anabolic response to feeding and exercise is considered. This paper also critically addresses the impact of bed rest and of step-reduction on glucose metabolism and on the pivotal role of skeletal muscle in inactivity-induced insulin resistance. Evidence is provided that inactivity leads to a specific reduction in muscle insulin sensitivity without affecting that of the liver. The noteworthy observations that just few days of step-reduction can induce insulin resistance and that changes in insulin sensitivity precede muscle atrophy and changes in body composition are also brought to the reader’s attention. Bed-rest and step reduction also have a major impact on aerobic capacity, yielding remarkably similar losses in VO2max within two weeks of inactivity (bed rest)/reduced activity (∼7%). It is also noteworthy that the impairment of VO2max after this period of inactivity is twice as large in older (aged 60 years) compared to younger individuals. A decrease in VO2max is associated with an increased mortality rate. Fundamentally, the available data shows that few days/weeks of inactivity impair the O2 pathway at all levels, from the cardiovascular system, including peripheral circulation, to the oxidative function of skeletal muscles. This paper also examines the relevance of nutritional intake versus energy expenditure on lean muscle loss, body fat and systemic inflammation. In particular, the observations that excess fat deposition during physical inactivity is associated with greater muscle loss and greater activation of systemic inflammation and antioxidant defences are highlighted. The contribution of these mechanisms to long-term changes in body composition and to the development of cardiometabolic risk in healthy sedentary persons are also explained. The importance of reducing caloric intake to match the energy expenditure is emphasised in this paper, and recommendations are given for maintaining a normal number of meals/day per day, without snacking and with a long overnight fast. The role of fasting on inflammation and on the immune response are also addressed.

Finally, this paper provides recommendations for lifestyle, exercise and nutritional interventions to prevent loss of muscle mass, aerobic capacity, insulin sensitivity and of neuromuscular integrity during long periods of home-confinement, and also to increase muscle mass restoration following prolonged periods of inactivity or immobilisation.

Impact of inactivity on the neuromuscular system and the protective action of exercise: don’t stop the music, your muscles are still listening!

The negative consequences of inactivity on the muscular system have long been recognised since the early 20’s by Cuthbertson (1929) who suggested that prolonged rest in healthy subjects leads to a loss of nitrogen, phosphorous and calcium due to non-use of muscles and bones. Forty years later, Saltin et al. (1968), a pioneer in human applied physiology, showed that in response to 20-day bed confinement, young healthy individuals lose on average 28% of maximum oxygen uptake (VO2max) and 11% of heart volume.

It is now firmly established that inactivity, induced by bed rest, limb casting, limb suspension or by simple sedentarism, causes a rapid loss of muscle mass, particularly of the antigravity muscles that are constantly used for sustaining an upright posture, to perform movement and for maintaining balance. The resulting loss of muscle function affects both muscle strength and power and it is noteworthy that the loss of muscle function typically exceeds that of muscle size, indicating that muscle with disuse becomes intrinsically weaker. Atrophy and loss of contractile force and force per unit cross-sectional area are also found at single fibre level, together with a gradual shift in myosin isoforms towards the fast type. Recent evidence shows that inactivity also causes damage to the neuromuscular junction and muscle denervation (Narici et al., 2020), which suggest that muscle atrophy not only arises from the reduction in mechanical loading but also from neurodegenerative processes. The significant deterioration of the muscular system caused by inactivity emphasises the fundamental importance of exercise for preserving muscle mass and neuromuscular function when unexpected conditions, such as the latest COVID-19 outbreak, cause a drastic restriction of daily movement compared to habitual life.

The impact of sedentarism on muscle mass

A recent survey performed on the impact of sedentarism on 6733 people aged 18–98 years showed a clear association between low physical activity or age, and fat-free mass and body fat, normalised to body height (Kyle, Morabia, Schutz, & Pichard, 2004). Essentially, the study demonstrated that physical activity was successful for maintaining fat-free mass, prevented excess body fat and resulted in lower rates of obesity. Also, when comparing muscle mass and muscle power of sedentary people aged 20–80 years to those of a population of age-matched master power athletes, it is clear that maintaining a high physical activity level preserves muscle mass and power throughout the lifespan (Grassi, Cerretelli, Narici, & Marconi, 1991). This benefit translates into a gain of 20–25 years in terms of biological age when muscle mass and performance of master athletes and sedentary peers and of master weightlifters and active older peers are compared (Grassi et al., 1991; Pearson et al., 2002). Similarly, lifelong trained individuals show 30% greater muscle strength compared to age-matched sedentary people (Aagaard, Magnusson, Larsson, Kjaer, & Krustrup, 2007). Remarkably, the benefits conferred by an active lifestyle protect not only against the loss of muscle mass and strength but also seem to protect against the progressive muscle denervation that accompanies the ageing process and is exacerbated by inactivity. In fact, when comparing muscle biopsies of older sedentary people with those of seniors with a long history of high-level recreational sport activities, significantly fewer denervated fibres are found in the life-long athletes (Mosole et al., 2014).

Lessons from prolonged bed-rest and unloading studies in man

Preservation of muscle mass requires a constant supply of mechanical stimuli that stimulate directly, or indirectly protein synthesis. When we stop loading our muscles, these essential stimuli required for muscle anabolism are removed (see Sect. Physical inactivity and the regulation of muscle mass) and the balance between protein synthesis and protein degradation tips towards degradation. Within a few days, objective signs of muscle atrophy can be found. Indeed, significant quadriceps atrophy is found after just 2 days of leg immobilisation (1.7%) (Kilroe, Fulford, Jackman, Van Loon, & Wall, 2020), 3 days of dry-immersion (2%) (Demangel et al., 2017) or 5 days bed rest (2%) (Mulder et al., 2015), associated with an even greater loss of muscle strength (8–9%) (de Boer, Maganaris, Seynnes, Rennie, & Narici, 2007; Demangel et al., 2017; Mulder et al., 2015). Over the following days and weeks, quadriceps atrophy progresses at an inexorable pace, 6% ca. after 10 days (Narici et al., 2020), 10% after 29 days (Alkner & Tesch, 2004a), 13% after 60 days (Mulder et al., 2015), reaching 18% after 90 days (Alkner & Tesch, 2004b). This rate of muscle atrophy follows an exponential time course, predicting a ∼10% loss of muscle mass in 30 days and ∼15% in 60 days. Similar results are found in other disuse paradigms, such as in unilateral lower limb suspension (ULLS). The lack of use of one lower limb for 3 weeks results in 5% muscle loss after 10 days and 10% after 21 days of ULLS (de Boer, Maganaris, et al., 2007).

Hence it is clear that complete inactivity of the entire body, or segments of it, will lead to an unavoidable and predictable muscle loss.

Inactivity also compromises muscle innervation and nerve-muscle cross-talk

Up to recent times, it was assumed that muscle loss caused by inactivity was simply due to the lack of mechanical loading of muscles. However, there is now increasing evidence that chronic inactivity, caused by bed rest for example, triggers muscle fibre denervation and damage to the neuromuscular junction (NMJ). In humans, the presence of muscle denervation may be demonstrated by measuring neural cell adhesion molecule (NCAM)-positive muscle fibres. NCAM is a glycoprotein normally expressed during embryonic development but absent in adult muscle; hence, its presence in adult muscle is indicative of an ongoing denervation/reinnervation process, as seen in paralysis or in other neurodegenerative disease conditions (Dickson et al., 1987). Indeed, an increase in NCAM positive muscle fibres has been found in three separate bed rest studies lasting 3, 10 and 15 days, respectively (Arentson-Lantz, English, Paddon-Jones, & Fry, 2016; Demangel et al., 2017; Narici et al., 2020). Also, inactivity leads to damage to the NMJ. A decreased expression of Homer protein, a component of the NMJ involved in translating of neuromuscular synaptic input to the calcineurin-NFAT signalling cascade in skeletal muscle fibres, has been found after 60-day bed rest (Salanova et al., 2011). Similarly, increased levels of c-terminal Agrin fragment, a serum marker of NMJ damage (Hettwer et al., 2013), have been recently found after 10 days of bed rest (Narici et al., 2020). Collectively, these findings provide evidence that chronic inactivity triggers neurodegenerative processes inducing muscle denervation and NMJ damage. The speed with which these changes occur emphasise even more the essentiality of exercise as not only muscle, but also innervation and muscle-nerve cross-talk, are compromised by periods of chronic inactivity.

Exercise for neuromuscular health

The evidence that exercise is of vital importance for preserving the integrity and function of the neuromuscular system is incontrovertible. Numerous studies have shown that when resistive exercise, in various forms, is applied during bed rest periods, the loss of muscle mass is significantly mitigated or fully prevented (Alkner & Tesch, 2014a, 2014b; Belavý, Miokovic, Armbrecht, Rittweger, & Felsenberg, 2009; Kawakami et al., 2001). Likewise, the comparison of neuromuscular decline in sedentary versus active seniors, confirms the essential role of exercise for the prevention of neuromuscular system impairment with inactivity. When dealing with inactivity, or reduced activity, the essential goal of any exercise countermeasure programme should be to preserve normal physiological function. In this respect, we should provide our muscular system with loading activities (intensity and duration) similar to those encountered during habitual, unrestricted, ambulatory activities. In so doing we would also “keep in tune” motoneurons and motor end-plates, ensuring uncompromised nerve-muscle cross-talk. As motoneurons are particularly rich in mitochondria, regular physical activity, particularly if aerobic in nature, seems essential for preventing mitochondrial dysfunction and oxidative damage to the motoneuron and the NMJ. Also, exercise is known to maintain neurotrophin release, whose action plays an essential role in maintaining neuromuscular system integrity (Nishimune, Stanford, & Mori, 2014).

Thus to achieve protection of the neuromuscular system, exercise should involve both high intensity resistive exercises for preserving muscle mass as well as aerobic exercise for preserving neuromuscular system integrity and mitochondrial function (see Sect. Physical inactivity and the cardiorespiratory system). Performing high-intensity resistive exercises typically requires the use of weights and specialised machines, such as those found in gyms. However, experimental evidence shows that exercising with slow contractions at a relatively low intensity, about ∼50% of 1 RM (3 s concentric and 3 s eccentric contraction with no rest in between), produces the same gains in muscle size as training at ∼80% of the 1RM (1 s concentric, 1 s eccentric, 1 s rest) (Tanimoto & Ishii, 2006). Performing such lower intensity contractions is possible in home-settings without any specialised equipment or machines, e.g., by bodyweight exercises and resistance elastic bands. It thus seems likely that preserving muscle mass can be achieved at home, without access to classical weight training or sophisticated equipment. It is also noteworthy that training with low loads high volume contractions (30% 1RM, 24 repetitions), has been found to lead to a greater increase in protein synthesis than training with high-load, low volume (90% 1RM, 5 repetitions) contractions (Burd et al., 2010). Hence low to medium-intensity high volume resistive exercise seem particularly effective for preserving, or most likely developing, muscle mass. This seems particularly relevant for the present home-confinement period, in which training with high loads is not feasible and does not seem anyway to produce a greater anabolic response.

As for the aerobic exercise, any workouts involving repeated exercises with large muscle groups such as rope-skipping, jogging in place, burpees, mountain climbers, seem suitable. These exercises could take the form of a circuit training where aerobic exercises are alternated with resistive ones trying to complete a fixed set of repetitions in rapid succession. The intensity and the volume could be manipulated by increasing either the number of repetitions/circuits completed or the speed of execution. This form of training can have many advantages such as reduced monotony, improvements in both aerobic capacity and muscle strength, and ultimately overall health (Muñoz-Martínez, Rubio-Arias, Ramos-Campo, & Alcaraz, 2017).

An extremely effective workout, particularly suited for a young and fit population, is full body high intensity interval training (HIIT). Home-based HIIT workouts do not require any equipment and provide rapid improvements in terms of muscle power, cardiorespiratory fitness and glucose metabolism (Blackwell et al., 2017; Karlsen, Aamot, Haykowsky, & Rognmo, 2017).

Hence, when facing period of restricted activity due to home confinement as in the present COVID-19 pandemic, the main recommendation for preserving neuromuscular health is to exercise daily with slow, low/medium-intensity high volume contractions and to perform aerobic exercise workouts involving large muscle groups. Remember that exercise is music for your muscles, don’t stop playing as they are still listening!

Physical inactivity and the regulation of muscle mass: you keep on moving

A number of factors are reported to increase risk for poor metabolic health and functional decline, including mental disorders, physical disabilities, physical inactivity and sedentary time (time spent sitting). Of these, physical inactivity and time spent sitting appear to be the most prevalent risk factors (de Rezende, Rey-López, Matsudo, & do Carmo Luiz, 2014; Matthews et al., 2012; Wilmot et al., 2012), but unfortunately most individuals are currently unaware of the potential insidious health risks associated with not moving. Time spent sitting has been linked with increased risk of all-cause mortality (Katzmarzyk, Church, Craig, & Bouchard, 2009), cause specific mortality (Katzmarzyk et al., 2009; Wilmot et al., 2012), cardiovascular disease (Stamatakis, Hamer, & Dunstan, 2011) and poor metabolic health (Ford et al., 2010; Hu, Li, Colditz, Willett, & Manson, 2003). A large scale (3720 men and 1412 women) 16-year follow-up study, in which a total of 450 deaths was recorded, however reported no clear associations between any of 5 different indicators of sitting time with mortality risk, and pointed to physical inactivity per se as the central driver of mortality risk (Pulsford, Stamatakis, Britton, Brunner, & Hillsdon, 2015). It is therefore of genuine concern that physical inactivity and sedentary behaviours are likely to be common place during the current coronavirus (COVID-19) pandemic. Moreover, it is vital to raise awareness of the associated health risks. This section will focus on the impact of inactivity on the regulation of muscle mass and what we understand about maintaining muscle mass during and after such physiological insult. Please be aware that inactivity is indeed a physiological insult, and its effects manifest very quickly.

Immobilisation studies

The maintenance of muscle mass is dependent on the balance between rates of muscle protein synthesis and muscle protein breakdown, where a chronic imbalance results in either the loss or gain of muscle mass. Much insight regarding the regulation of muscle mass in humans during inactivity has been gleaned from bed-rest or single limb immobilisation (casting) studies. From such studies it is generally agreed that immobilisation induced suppression of muscle protein synthesis is the primary driver of muscle mass loss in humans. For example, de Boer, Selby, et al., (2007) detected a 50% decline in the rate of post-absorptive myofibrillar protein synthesis measured over several hours following 10 days of limb suspension in healthy, young volunteers when compared to baseline. The authors concluded that the immobilisation induced suppression of muscle protein synthesis was of sufficient magnitude to fully account for the loss of muscle cross sectional area recorded, i.e. the contribution from muscle protein breakdown to total muscle mass loss during immobilisation was small (de Boer, Selby, et al., 2007). It is important to recognise, however, this does not preclude a role for muscle protein breakdown during immobilisation in humans. Indeed, increased amounts of markers of muscle protein breakdown, such as ubiquitin protein conjugates (Abadi et al., 2009) and increased 3-methylhistidine release (Tesch, von Walden, Gustafsson, Linnehan, & Trappe, 2008), have been observed in the first few days of muscle disuse in volunteers pointing to an early and possibly transient contribution of muscle protein breakdown to muscle mass loss. Of further health importance, despite a clear appreciation of the importance of muscle mass to longevity with ageing (Srikanthan & Karlamangla, 2014), some authors have reported three-fold greater muscle mass loss during immobilisation in older compared to young people (Paddon-Jones et al., 2006), whilst others report the diametric opposite (Suetta et al., 2009). In short, we do not yet fully understand the interaction between muscle ageing processes and immobilisation induced muscle mass loss.

Reduced step count studies

In the limited number of studies where semi-quantitative approaches have been used to control physical activity levels, reduced levels of physical activity (from 10,500–1300 steps/day for 2 weeks) induced muscle insulin resistance and the loss of lean leg mass in young males (Krogh-Madsen et al., 2010). Further evidence reports that 2 weeks of reduced physical activity (from >3500 to <1500 steps/day) in healthy older people (>65 years and normally the most inactive proportion of the population) induced a small but measurable increase in whole-body insulin resistance and blunted post-prandial rates of muscle protein synthesis (Breen et al., 2013). Rather alarmingly, severe reductions in daily step counts to far below the recommendation of remaining >5000 steps per day to avoid sedentarism, such as that seen in hospitalised older women (>65 years, n = 239) with an acute medical illness where ambulatory activity was found to be on average 740 steps/day (interquartile range 89–1014 steps/day) (Fisher et al., 2011), can initiate a downward spiral resulting in severe deconditioning and long-lasting functional deficits (Hirsch, Sommers, Olsen, Mullen, & Winograd, 1990). Importantly, what is astonishing is that the time-course of inactivity induced metabolic dysfunction appears to be far quicker than the positive impact of increasing physical activity levels. For example, a 2 week transition period from an ambulatory lifestyle (without structured exercise training) to inactivity, induces insulin resistance, increases central adiposity and reduces muscle mass in healthy, young volunteers (Thyfault & Krogh-Madsen, 2011), whilst restoration of metabolic function and muscle volume, particularly following marked inactivity such as immobilisation, can take longer than might be expected, especially in older people. For example, 4 weeks of supervised strength training involving three sessions each week did not restore muscle volume following only 2 weeks of immobilisation in older males (Suetta et al., 2009). This is clearly of significant concern in the current circumstances of social distancing and isolation that is likely to continue for several months, and moreover where metabolic and physiological fitness appear to be associated with disease susceptibility.

Cellular and molecular mechanisms controlling inactivity induced muscle mass loss

Research has highlighted protein translation initiation, where the ribosomal structure is formed and the associated mRNA transcript becomes bound in response to increased dietary protein intake and/or muscle contraction, as a key point of regulation of muscle protein synthesis. The Akt/mTOR/p70S6K signalling cascade has been assigned a central role in this nutrient and/or contraction mediated activation of protein translation initiation, and is founded on elegant experiments demonstrating high frequency electrical stimulation of rodent muscle occurs in parallel with increased phosphorylation of these signalling proteins (Atherton et al., 2005) and muscle specific over-expression of Akt in transgenic mice results in muscle hypertrophy (Bodine et al., 2001). However, accumulating evidence suggests that the Akt/mTOR/p70S6K signalling cascade has no obvious role in the regulation of the decline in muscle protein synthesis seen during immobilisation, given neither the phosphorylation state nor content of Akt, p70S6K, 4E-BP1 or eIF4E were altered in the post-absorptive state following 10 or 21 days of limb suspension (de Boer, Selby, et al., 2007). Furthermore, although immobilisation blunted the increase in muscle protein synthesis in response to increased amino acid availability (so called anabolic blunting) in healthy volunteers when compared to a non-immobilised contralateral limb (even under conditions of high amino acid provision), this anabolic blunting occurred in the face of similar changes in the phosphorylation state of the Akt/mTOR/p70S6K signalling pathway in both limbs (Glover et al., 2008). Collectively these findings from volunteer studies highlight that Akt/mTOR/p70S6K signalling pathway is unlikely to be regulating the deficits in post-absorptive or post-prandial muscle protein synthesis observed during immobilisation in humans. On balance, it would seem the precise mechanisms responsible for the decline in muscle mass observed during immobilisation in humans remain to be elucidated.

You can’t always get what you want: but if you try sometimes you might just find you get what you need

On a positive note, interventional research trials have indicated that intermittent walking breaks during prolonged periods of sitting can improve indices of metabolic health (Dunstan et al., 2012; Healy et al., 2008), and that reducing sedentary behaviour has measurable positive effect on cardio-metabolic health that can be differentiated from exercise training (Macfarlane, Taylor, & Cuddihy, 2006). From the perspective of the maintenance of muscle mass, we do not yet know the precise relationship between exercise dose (daily frequency and intensity) and muscle mass retention during prolonged periods of immobilisation or inactivity. However, it is known that resistance exercise will be an effective intervention. For example, it has been shown that undertaking resistance exercise during 60 days bed rest maintained, and increased, the cross-sectional area of the soleus and vastus lateralis leg muscles, respectively (Trappe, Creer, Slivka, Minchev, & Trappe, 2007). It also prevented decrements in type I and IIa fibre diameters, maintained the proportion of hybrid fibres (Trappe et al., 2007), and prevented increases in markers of muscle protein breakdown (Salanova, Schiffl, Püttmann, Schoser, & Blottner, 2008). Such findings highlight the effectiveness of resistance exercise countermeasures to prevent muscle atrophy. Furthermore, observations of greater calf muscle cross sectional area compared to baseline in subjects 3, 6 and 12 months after 90 days bedrest (Rittweger & Felsenberg, 2009) highlights the enormous plasticity of the muscle to exercise intervention following prolonged immobilisation, at least in young people. Indeed, most of the exercise induced restoration of calf muscle volume occurred in the first phase of recovery in this study (Rittweger & Felsenberg, 2009), pointing to growth rates not being directly proportional to the magnitude of the exercise stimulus, i.e. muscle is more sensitised to grow in the early period following immobilisation induced atrophy (although it is not clear why). These studies highlight the effectiveness of muscle contraction as a countermeasure to prevent muscle loss during immobilisation and inactivity in young volunteers, and also to increase muscle mass restoration following prolonged periods of inactivity or immobilisation (but maybe less so in older people; Suetta et al., 2009). Importantly, the molecular mechanisms by which exercise exerts such positive effect(s) remain unknown, but such insight would greatly help our understanding of how to maintain muscle mass and metabolic health in any future public health crisis requiring social distancing and isolation.

Physical inactivity and glucose homeostasis

In the present coronavirus disease (COVID-19) pandemic, millions of people world-wide are being confined to little social activity and stay-at-home restrictions. This means that for almost every individual the level of daily physical activity will be reduced considerably and very quickly. We have well-documented information on the importance of being physically active to maintain health, and therefore the present situation of markedly reduced physical activity to levels well below the daily recommendation of 7500–10,000 steps per day will exacerbate health problems arising from physical inactivity (Blair, 2009; Booth, Roberts, Thyfault, Rugsegger, & Toedebusch, 2017). Indeed, unfavorable indicators of body composition and cardiometabolic risk have been consistently associated with taking <5000 steps/day. Importantly, negative health effects can be seen relatively quickly (3–14 days) when the transition is marked, e.g. from >10,000 to less than 5000 or as low as 1500 daily step counts (Tudor-Locke, Craig, Thyfault, & Spence, 2013), as will be happening around the world in the current pandemic.

This section will cover the consequences of inactivity on glucose homeostasis and provide advice on simple measures to offset the negative effects of physical inactivity. The first study demonstrating the deleterious effect of physical inactivity on glucose tolerance was published 75 years ago in patients confined to bed for various length of time, such as patients with hip or femoral fractures, multiple sclerosis, hemiplegia, coxa vara etc. (Blotner, 1945). It is now well established that sedentary activities such as desk work, TV viewing, sitting (Dunstan et al., 2005; Katzmarzyk et al., 2009; Van der Ploeg, Chey, Korda, Banks, & Bauman, 2012) are associated with increased all-cause mortality and increased morbidity (metabolic syndrome, cardiovascular disease). The association is summarised in a recent review that concluded: “Higher levels of total physical activity, at any intensity, and less time spent sedentary are associated with a substantially reduced risk for premature mortality, with evidence of a non-linear dose–response pattern in middle aged and older adults” (Ekelund et al., 2019).

Bed-rest studies

Structured intervention studies with advanced end-point measurements have been carried out in healthy volunteers confined to strict bed-rest. Such studies with 7–10 days bed-rest in healthy individuals (Mikines, Richter, Dela, & Galbo, 1991; Sonne et al., 2010; Stuart, Shangraw, Prince, Peters, & Wolfe, 1988) have shown that immobilisation leads to a 10–34% decrease whole body insulin sensitivity (measured by the hyperinsulinemic, glucose clamp technique). However, the decrease of insulin sensitivity measured by the arterio-venous balance technique in the forearm (Sonne et al., 2010; Stuart et al., 1988) or the leg (Mikines et al., 1991), was much greater, 47–75%. Metabolically speaking, the forearm and the leg consist of predominantly skeletal muscle, emphasising the pivotal role of skeletal muscle in inactivity induced insulin resistance, which appears to be attributable to the reduction in muscle contraction per se (Crossland, Skirrow, Puthucheary, Constantin-Teodosiu, & Greenhaff, 2019). The central role of skeletal muscle in inactivity induced insulin resistance is also highlighted by the fact that hepatic insulin sensitivity is not affected by short-term bed rest (Mikines et al., 1991; Stuart et al., 1988).

Therefore, the mechanisms behind the inactivity induced decrease in whole-body insulin sensitivity and impaired glucose tolerance (Alibegovic et al., 1988; Arciero, Smith, & Calles-Escandon, 1998; Dolkas & Greenleaf, 1977; Hamburg et al., 2007; Knudsen et al., 2012; Krogh-Madsen et al., 2010; Lipman, Schnure, Bradley, & Lecocq, 1970; Mikines et al., 1991; Myllynen, Koivisto, & Nikkila, 1987; Richter, Kiens, Mizuno, & Strange, 1989; Rogers, King, Hagberg, Ehsani, & Holloszy, 1990; Sonne et al., 2010; Sonne et al., 2011; Stuart et al., 1988; Vukovich et al., 1996) are coupled to changes within the skeletal muscle. The decrease in skeletal muscle insulin sensitivity with physical inactivity is not linked to changes in body composition (loss of muscle mass, increase in body fat percentage) (Knudsen et al., 2012) as the insulin resistance develops rapidly (within a few days) and long before muscle atrophy and increases in body fat (or ectopic fat deposition) sets in.

In contrast, there is a reduction in skeletal muscle metabolic capacity with inactivity. GLUT4 transporter protein content and glycogen synthase activation decreases (Bienso et al., 2012; Op’t, Urso, Richter, Greenhaff, & Hespel, 2001; Tabata et al., 1999; Vukovich et al., 1996) as well as mitochondrial DNA content, hexokinase II and sirtuin 1 protein content (Ringholm et al., 2011). Also insulin-induced Akt phosphorylation and 3-hydroxyacyl-CoA dehydrogenase (HAD) activity have been found to decrease in some (Bienso et al., 2012; Krogh-Madsen et al., 2010; Ringholm et al., 2011), but not all (Mikines et al., 1991; Mortensen et al., 2014) bed-rest studies. Muscle capillary density does not change with short-term bed-rest (∼7 days) (Mikines et al., 1991; Ringholm et al., 2011), but microvascular dysfunction will develop (Hamburg et al., 2007; Sonne et al., 2010; Sonne et al., 2011). Of note, after 7-day bed-rest the normal exercise induced response of AMP-activated protein kinase phosphorylation, peroxisome proliferator activated receptor- coactivator-1, and VEGF mRNA content in skeletal muscle is abolished (Ringholm et al., 2011), underlining the profound effect of physical inactivity on muscle metabolism.

On the gene expression level, it has been found that 9 days of bed-rest altered the expression of ∼4500 genes, with downregulation of 34 pathways, mostly associated with mitochondrial function (PPARγ coactivator-1α, NADH dehydrogenase 1 β-subcomplex 6) and insulin resistance (e.g. hexokinase II, ras-related associated with diabetes (RRAD)) (Alibegovic et al., 2010). Notably, these genes reversed to pre- bed-rest levels after 4 wks of re-training (Alibegovic et al., 2010).

Parallel to, and possibly linked with inactivity induced insulin resistance, is the elevated inflammatory burden which may occur with prolonged bed rest (Crossland et al., 2019; Kwon et al., 2015). However, not all studies have found that skeletal muscle inflammation plays a role in short-term bed rest induced insulin resistance (Friedrichsen et al., 2012).

Studies with reduced ambulatory activity

Strict bed-rest is a drastic model, which may not comply with the situation for most people affected by the COVID-19 restrictions, but just reducing daily physical activity has a negative impact on glucose homeostasis. There are many observational studies demonstrating this, but only a few interventional studies. By employing accelerometer controlled reductions in daily step counts from ∼10,000–12,000/day to ∼1000 steps/day, two studies showed that glycemic control and indices of insulin sensitivity markedly deteriorated already after 3 days of daily step reductions (Knudsen et al., 2012; Mikus et al., 2012) in young healthy men. After a total of 14 days of step count reduction, insulin sensitivity was decreased by 17–44% (Knudsen et al., 2012; Krogh-Madsen et al., 2010). Notably, hepatic insulin sensitivity did not change (Krogh-Madsen et al., 2010), again underscoring the important role of skeletal muscle. In older (∼69 years) pre-diabetic people, the same negative effect of reducing daily steps for 2 weeks is seen, but even worse, glycaemic control did not recover after additional 2 weeks with return to normal physical activity (McGlory et al., 2018).

Measures to offset the negative effects of physical inactivity

How low can you go? At the present time we do not know the exercise dose or frequency required to offer protection from inactivity. Exact thresholds for specific minimal physical activity is not possible to define accurately, but measurements of daily steps (measured by pedometers or accelerometers) have provided useful insight. Less than 5000 steps per day seems to be associated with unfavourable indicators of body composition, cardiometabolic risk, insulin sensitivity and glycemic control (Tudor-Locke et al., 2013). For this reason <5000 steps/day has been proposed as the threshold defining a sedentary lifestyle for adults (Tudor-Locke et al., 2013). Fundamentally, the aim must be to increase energy expenditure through muscular work, as light as it may be. Simple measures, such as alternating between sitting and standing for 30 min periods during desk-top work, will result in a small, but meaningfully and significant increase in energy expenditure (Gibbs, Kowalsky, Perdomo, Grier, & Jakicic, 2017).

Intervention studies involving interruption of sitting time with standing (Benatti et al., 2017) or light-intensity walking (Pulsford, Blackwell, Hillsdon, & Kos, 2017) have been carried out in healthy males, aged ∼30 and ∼40 years of age, respectively. One study found that breaking up prolonged sitting with non-ambulatory standing during 9 h, acutely reduced post-prandial glycemic response (Benatti et al., 2017), while another study found the opposite, namely that during 8.5 h interrupting sustained sitting with brief repeated bouts of light-intensity walking but not standing improved glycemic control (Pulsford et al., 2017). Similar experiments have been done over four days in patients with type 2 diabetes, in whom the importance for daily physical activity is even greater. The authors compared breaking up sitting ∼14 h/day with either structured ergometer exercise for ∼1 h or breaking up sitting every half hour with standing (in total 3 h) and light intensity walking (in total 2 h) (Duvivier et al., 2017). The “Sit Less” (interrupting sitting with standing/walking) was superior to structured exercise in terms of glycemic control (Duvivier et al., 2017); a conclusion that was also reached in healthy young individuals with a comparable intervention (Duvivier et al., 2013). Furthermore, the findings in patients with type 2 diabetes (Duvivier et al., 2017) is supported by an earlier study in patients with type 2 diabetes showing that 3 × 10 min exercise per day is preferable to 1 × 30 min per day (Eriksen, Dahl-Petersen, Haugaard, & Dela, 2007).

The cellular mechanisms linking physical inactivity and/or sedentary time to impaired metabolic health are not known in details. Only pieces of information are available, as described above. Unfortunately, most individuals are currently unaware/and or unconvinced of the potential insidious health risks associated with prolonged periods of inactivity and/or sitting. What is also remarkable is that the time-course of inactivity induced metabolic dysfunction appears to be far quicker than the positive impact of increasing physical activity levels. In the times of restrictions due to the COVID16 pandemic it is important to realise that a modest amount of moderate-intensity daily exercise (equivalent to 30 min per day) is necessary (Slentz, Houmard, & Kraus, 2007). Any addition to this minimal regimen will lead to improvements in many health measures. In the words of the Rolling Stones “You Gotta Move”!

Physical inactivity and the cardiorespiratory system: a matter of survival

A study carried out a few years ago by Prof. Bente Pedersen’s group (Krogh-Madsen et al., 2010) anticipated the condition to which hundreds of millions of people, around the world, are now exposed as a consequence of the home confinement in response to the COVID-19 pandemic: a drastic reduction in the level of physical activity. In that study (Krogh-Madsen et al., 2010) a group of healthy young males acutely reduced the number of steps per day, from a baseline of ∼10,000 to ∼1350, and maintained this lower level of activity for 2 weeks. To put this value into the right context: (i) a number of steps/day lower than ∼5000 identifies a “sedentary life-style” (Slentz et al., 2007); (ii) a threshold of ∼4500–6000 steps/day is considered the minimum necessary to avoid an increased cardio-metabolic risk (1); and (iii) ∼10,000 steps/day represents a reasonable target for healthy adults (Slentz et al., 2007). After the 2 weeks of reduced activity the subjects presented a ∼7% decrease in maximal O2uptake (, taken as an index of “cardiorespiratory fitness”), a ∼3% decrease in lean leg mass and a decreased insulin sensitivity (Krogh-Madsen et al., 2010). The parallel decreases of , leg lean mass and insulin sensitivity were considered clinically relevant, since all three factors independently increase mortality.

Decrease in  and impairment of O2 transport and utilisation mechanisms

Interestingly, the rate of decrease in described in the study by Krogh-Madsen et al. (2010), that is ∼7% over 2 weeks, corresponding to a rate of decrease of ∼0.5%/day, was remarkably similar to the average rate of decrease observed in bed rest studies (Ried-Larsen, Aarts, & Joyner, 2017). This rate of decrease is linear over bed rest durations from ∼4 h to 90 days (Ried-Larsen et al., 2017). If we assume, as a first approximation, that the rate of decrease of is linear also following a forced inactivity not associated with bed rest (such as the COVID-19 confinement), over a 2-month period the decrease would be a terrifying −30%! Realistically, during an inactivity such as that elicited by the COVID-19 pandemic, the decrease could be slightly less pronounced, considering that in the studies evaluated by Ried-Larsen et al. (2017) the bed rest was strict, and no countermeasures were provided. But, still, the decrease associated with a prolonged period of forced inactivity would likely be substantial.

The studies mentioned above, were exclusively (Krogh-Madsen et al., 2010), or almost exclusively (Ried-Larsen et al., 2017), conducted on young subjects. What could be the situation in the elderly? Inactivity studies in the elderly are very scarce, mainly for ethical reasons. Some insights could be derived from the limited number of bed rest studies carried out in elderly or middle-aged subjects. In the study by Pišot et al. (2016), for example, the percentage decrease in during a 2-wk bed rest was twice greater in 60-yr old subjects (−15%) vs. that observed in young controls. During a 2 wk-rehabilitation period following the bed rest, moreover, young subjects recovered the pre-bed rest baseline, whereas in the elderly the recovery was minor and incomplete (Pišot et al., 2016). Thus, it is reasonable to assume that also during a period of forced inactivity, not associated with bed rest, the decrease would be more pronounced in the elderly with respect to younger counterparts.

A direct dose–response relationship is observed between exercise “volume” (duration x intensity) and cardiorespiratory fitness. According to Joyner and Green (2009) ∼50% of the protective effects of physical activity are accounted for by a reduction of traditional cardiovascular risk factors, such as high blood pressure and blood lipids. Other protective effects presumably relate to decreased low-grade inflammation of visceral fat tissue and to decreased insulin resistance.

During exercise, sheer stress and other hemodynamic stimuli induce positive effects on the peripheral circulation, favouring vasodilation, proliferation of blood vessels and an anti-atherogenic phenotype. Inactivity inevitably goes in the opposite direction. According to Boyle et al. (2013) a reduction of physical activity to <5000 steps/day for only a few days impairs flow-mediated vasodilation. Preliminary data from our group suggest that 10 days of bed rest induces, in healthy young subjects, an impaired microvascular function, as shown by a blunted blood flow increase during passive leg movement of one leg (an index of nitric oxide [NO]-mediated vasodilation [Gifford & Richardson, 2017]) (Zuccarelli et al., 2020), and by a less pronounced reactive microvascular hyperaemia following a transient ischaemia, in association with signs of impaired NO metabolism (Porcelli et al., 2020).

In terms of mitochondrial respiration in skeletal muscle fibres, the studies dealing with the effects of short-term exposures to bed rest are somewhat controversial. Whereas Miotto et al. (2019) and Dirks et al. (2020) described an impaired mitochondrial function following bed rest periods of 3 and 7 days, respectively, other authors (Larsen et al., 2019; Salvadego et al., 2016; Zuccarelli et al., 2020) did not see impairments following 4 and 10 days of bed rest exposure. An impaired mitochondrial respiration was seen after 21 days of bed rest (Salvadego et al., 2018), confirming the impairment of skeletal muscle oxidative function described in that study by other methods (Salvadego et al., 2018). In a broader perspective, it could be concluded that a few days/weeks of inactivity impair the O2 pathway at all levels, from the cardiovascular system to the oxidative function of skeletal muscles.

“Cardiorespiratory fitness”: effects on health and mortality

is classically considered a variable evaluating the maximal performance of the cardiorespiratory system and skeletal muscles in the transport and in the utilisation of O2 for the purpose of oxidative phosphorylation. Besides being one of the main determinants of exercise tolerance, is considered an index of “cardiorespiratory fitness”. As such, (or a “proxy” of , such as or the number of METs, multiples of resting metabolic rate, that can be reached during exercise) is inversely related to mortality. According to Myers et al. (2002), both in normal subjects and in patients with cardiovascular diseases “exercise capacity (number of METs reached during exercise) is a more powerful predictor of mortality than other established risk factors for cardiovascular diseases”. According to the same authors, for every 1 MET drop in cardiorespiratory fitness mortality increases by 12% (Myers et al., 2002). In an hypothetical sedentary 70-yr subject with a of ∼25 ml kg−1 min−1, a forced inactivity of 4 weeks would likely translate into a ∼15% decrease in (see above), corresponding to a decrease of ∼3.75 ml kg−1 min−1, corresponding to ∼1 MET: this, in turn, would translate into a ∼12% increase in mortality! According to Blair, Kohl, Paffenbarger, Clark, and Gibbons (1989), when cardiorespiratory fitness decreases from 10 to 4 METs the death rate increases ∼4.5 times.

A reduced cardiorespiratory fitness negatively affects mortality also independently from its effects on cardiovascular diseases. According to Booth et al. (2017) for at least 35 chronic diseases/conditions, very relevant in terms of their impact on public health, physical activity has a role in the prevention or as a therapy (see also the review by Pedersen & Saltin, 2015) including: ischaemic heart disease, stroke, hypertension, deep vein thrombosis, chronic heart failure, endothelial dysfunction, peripheral artery disease, type 2 diabetes, metabolic syndrome, osteoporosis, osteoarthritis, falls, balance problems, rheumatoid arthritis, chronic pain, non-alcoholic fatty liver disease, colon cancer, diverticulitis, constipation, breast cancer, ovarian cancer, polycistic ovaric syndrome, gestational diabetes, preeclampsia, cognitive dysfunction, anxiety, depression, sarcopenia, and several others.

Is there a “minimum amount” of exercise to recommend?

What is the minimum amount of exercise needed to prevent the impairment of cardiovascular fitness and prevent, or at least attenuate, the negative health consequences of enforced “lockdown”? Whereas the Physical Activity Guidelines for Americans normally recommend 150–300 min per week of moderate-intensity aerobic physical activity, and 2 sessions per week of muscle strength training, the minimum amount of exercise to recommend in an emergency situation, such as home confinement during the present COVID-19 pandemic, is not clear. Very little is known about this topic, and good quality research is badly needed. According to the 2008 version of the U.S. Physical Activity Guidelines “some physical activity is better than none”. According to Slentz et al. (2007) “a prudent approach would be to recommend that all adults aim for 30 min of moderate-intensity activity each day, and then let body mass changes be the surrogate measure for determining if this amount of activity is adequate”. As mentioned above, a threshold of ∼4500–6000 steps/day has been identified as the minimum required to avoid an increased cardio-metabolic risk (Adams et al., 2019). The vagueness of these recommendations, together with the extraordinary burden of physical inactivity put on hundreds of millions of people by the COVID-19 pandemic, stress the need for more research on the topic.

Awareness of energy intake in physical inactivity to maintain energy balance and prevent metabolic alterations: everything will be all right (Italian motto during the COVID-19 epidemics)

The European population is aging with an increasingly higher percentage of people above 60 years. The absence of vaccines to deal with the sudden COVID-19 pandemic leaves home restriction as the only “therapeutic option”. This countermeasure mainly is going to benefit older people as they seem to be the most affected by the virus. However, domestic restriction has a physio-pathological, psychological and metabolic impact on people.

Physical exercise is a critical element to maintain humans in good health. Humans developed and evolved during ages through continuous physical activity and a human body reaches an optimal physical and mental state when physical activity is balanced with energy intake. While Paleolithic hunter-gatherers (as well as humans living nowadays in a Paleolithic state) are reported to walk up to 16 km per day, civilisation limited walking as a necessity (O'Keefe, Vogel, Lavie, & Cordain, 2010). The effects of reduced mobility have been balanced through history by leisure activities (e.g. sports) but are going to be detrimental in these days, when limitations in walking and outdoor activities are mandatory. This might lead to negative changes in mental and physical status associated with physical inactivity. It is required to define and quantify these alterations in order to counteract their negative effects. In order to maintain body composition and efficiency, a precise matching between exercise-associated energy expenditure and energy intake with nutrition is required.

Negative energy balance

Physical inactivity, bed rest and sedentary lifestyle are associated with decreased activity-associated energy expenditure. Nonetheless, energy intake may not be reduced in parallel with expenditure due to inefficient appetite regulation or to maladaptive behaviour (Panahi & Tremblay, 2018). Indeed, experimental works demonstrate a complex scenario. Experimental bed rest in healthy volunteers as well as long term space-flight are suitable models to investigate physiologic and psychological adaptation to confinement and inactivity. Sixty days of strict bed rest (an experimental approach to study the effects of physical inactivity) in lean healthy women did not change gut hormones or fat mass but reduced muscle mass and, surprisingly, the desire to consume food. In another arm of the study, exercise-induced energy expenditure in bed rest did not induce hunger and directly promoted a negative energy balance (Bergouignan et al., 2010).

The combination of low energy intake and physical inactivity, typically observed in bedridden sick patients, may lead to protein-energy malnutrition, skeletal muscle and fat mass loss, increased complications and, possibly, poor clinical outcome (Ritz & Elia, 1999). Poor energy intake is often observed in astronauts during space missions in microgravity. Astronauts may exhibit alterations in body composition and efficiency commonly observed in bedridden patients (Ritz & Elia, 1999; Wade et al., 2002; Wilson & Morley, 2003). In addition to decreased energy intake, physical inactivity is characterised by anabolic resistance, i.e. a decreased ability to utilise dietary amino acids for synthesis of body proteins. Anabolic resistance to dietary amino acids in association with muscle unloading leads to protein catabolism (Biolo et al., 2004; Ferrando, Lane, Stuart, Davis-Street, & Wolfe, 1996; Stein, Leskiw, Schluter, Donaldson, & Larina, 1999; Stevenson, Giresi, Koncarevic, & Kandarian, 2003) and, ultimately, to muscle dysfunction and atrophy (di Prampero & Narici, 2003; Jackman & Kandarian, 2004). Major triggers of anorexia and decreased food intake in bedridden patients, sedentary healthy humans and astronauts are cytokines and systemic inflammation, disruption of circadian rhythms, alteration in gastrointestinal functions and alterations in neuroendocrine mediators (Da Silva et al., 2002; Stein et al., 1999). Evidence indicates that anorexia in astronauts during long-term space flight can lead to 20–30% decrease in food intake as compared to pre- and/or post-flight conditions (Da Silva et al., 2002; Stein et al., 1999; Wade et al., 2002). By this mechanism, the body weight of an astronaut can decrease by about 0.5 kg for each week spent in space (Wade et al., 2002).

Positive energy balance

In contrast to bedridden sick patients and astronauts, sedentary behaviour in healthy humans may not be associated with decreased appetite. In sedentary healthy humans, humoral and psychological mechanisms of appetite regulation may be altered. Appetite and food intake may not be matched by the decrease in energy requirement associated with inactivity. In this condition, mental work or leisure activities carried out while sedentary may increase the appetite and desire to eat, possibly linked to changes in hormones, neuromediators and gluco-metabolic pattern. Thus, the problem of appetite in sedentariness may not only be attributed to a lack of movement, but also to the stimulation provided by replacing activities (Panahi & Tremblay, 2018). When physical exercise is restricted on condition of sedentary behaviour, energy intake largely depends on psychological mechanisms. Regardless of physiological or psychological mechanisms, positive energy balance in physical inactivity greatly influences metabolic regulation, body composition, muscle efficiency and cardiometabolic risk profile. The combination of positive energy balance with inactivity leads to insulin resistance (Blanc et al., 1998; Stuart et al., 1988), fat accumulation preferentially in the visceral compartments (Olsen, Krogh-Madsen, Thomsen, Booth, & Pedersen, 2008), and lean body mass catabolism (Barbe et al., 1999; Blanc, Normand, Pachiaudi, Duvareille, & Gharib, 2000; Ferrando et al., 1996; Gretebeck, Schoeller, Gibson, & Lane, 1995; Krebs, Schneider, Evans, Kuo, & LeBlanc, 1990; Lovejoy et al., 1999; Scheld et al., 2001; Shackelford et al., 2004; Stein et al., 1999). Excess of food intake, inactivity and fat accumulation trigger a low-grade inflammatory response and enhance oxidative stress (Schaffler, Muller-Ladner, Scholmerich, & Buchler, 2006; Van Guilder, Hoetzer, Greiner, Stauffer, & Desouza, 2006). Inflammation and redox stress lower muscle protein synthesis and accelerate proteolysis (Powers, Kavazis, & McClung, 2007; Schaap, Pluijm, Deeg, & Visser, 2006). It was demonstrated that, in animal muscle, overfeeding lowered protein fractional synthesis rate (Glick, McNurlan, & Garlick, 1982). While, in conditions of activated systemic inflammation and redox imbalance, the rate of utilisation of the tripeptide glutathione, the major cellular defender against oxidative stress, is accelerated (Lu, 1999; Richards, Roberts, Dunstan, McGregor, & Butt, 1998).

Another important component to take in account is ghrelin. This is a circulating hormone produced by enteroendocrine cells especially in the stomach. It is often called a “hunger hormone” because it increases food intake. Blood levels of ghrelin are highest before meals and return to lower levels after feeding. Ghrelin response is altered during overfeeding and may contribute to muscle catabolism (Nagaya et al., 2005; Robertson, Henderson, Vist, & Rumsey, 1998).

We tested the hypothesis that during inactivity (bed rest), positive energy balance leading to fat deposition would accelerate inactivity-induced loss of lean mass and activation of systemic inflammation, free radical production and antioxidant defenses (Biolo et al., 2007). We demonstrated that, during 35 days of bed rest in healthy young volunteers at different levels of energy intake, fat gain was associated with the greatest loss of skeletal muscle mass. Moreover, we also found that a positive energy balance during experimental inactivity, greatly activated the glutathione system (Lu, 1999), providing both local and systemic antioxidant protection (Richards et al., 1998). In contrast, maintenance of near-neutral balance (no significant change in body fat) during bed rest was associated with lower muscle loss and no alteration in systemic inflammation, redox balance and glutathione synthesis. Evidence indicates that proinflammatory mediators up-regulates glutathione synthesis and oxidative stress (Lu, 1999). Plasma C-reactive protein and myeloperoxidase are suitable markers for detecting activation of systemic inflammation (Podrez, Abu-Soud, & Hazen, 2000). After 5 weeks of bed rest at positive energy balance, C-reactive protein levels were higher (p = .04) than in subjects with neutral balance (Biolo et al., 2007). The effects of inactivity and overfeeding on systemic inflammation and redox balance can contribute to muscle mass catabolism during bed rest at positive energy balance (Glick et al., 1982; Powers et al., 2007; Schaap et al., 2006).

We also investigated changes of TNF related apoptosis induction ligand (TRAIL) following bed rest at different levels of energy intake. We showed a strict relationship between TRAIL and levels of energy intake during sedentariness. TRAIL was significantly higher in overfed subjects as compared to those following an eucaloric diet. Energy restriction significantly decreased circulating TRAIL. (Biolo, Secchiero, De Giorgi, Tisato, & Zauli, 2012).

Long-term physical inactivity affected also lipid metabolism (Mazzucco, Agostini, Mangogna, Cattin, & Biolo, 2010). Inactivity, in fact, led to insulin resistance and dyslipidemia, namely an increased levels of triglycerides associated with decreased HDL concentration. CETP is a plasma protein transferring cholesteryl esters and triglycerides from HDL to VLDL and LDL. We have demonstrated that its availability significantly increased after bed rest (Mazzucco et al., 201) explaining how inactivity decreased the ratio between HDL and non-HDL cholesterol. We suggest, therefore, that changes in CETP availability contributes to inactivity-mediated alterations of plasma lipid pattern.

In media stat virtus

Physical inactivity is frequently associated with spontaneous reduction in caloric intake especially in stress conditions such as acute or chronic diseases or long-term space flight. Loss of muscle mass in persons with very low physical activity is faster when energy intake is not adequate and this alteration may rapidly lead to severe malnutrition. This catabolic response may be further amplified by stress mediators, such as cortisol and cytokines. Other potential causes for this weight loss may involve variations in circadian rhythms and busy work schedules.

In contrast to sick or stressed people, reduction of physical activity in healthy humans may lead to excess nutrient intake. It has been shown that, excess fat deposition during physical inactivity is associated with greater muscle loss and greater activation of systemic inflammation and antioxidant defenses. These mechanisms potentially contribute to long-term changes in body composition and to development of cardiometabolic risk in healthy sedentary persons.

Media and science communicators often represent energy balance as the mathematical difference between energy expenditure and energy intake. Nonetheless, food intake and energy expenditure are not independent variables and may influence each other to complicate the physiological scenario and therapeutic strategies. Psychology and personal behaviour further complicate such relationship between food intake and energy expenditure. Increasing the awareness of physiological and psychological mechanisms of overfeeding will contribute to the maintenance of energy balance and metabolic health in conditions of reduced physical activity.

Physical inactivity during COVID-19: nutritional strategies to counteract its effects on metabolism and body composition

The perfect storm

Humans’ evolutionary history suggests that our ancestors were forced to be physically active in order to survive (hunters-gatherers). Only in the last few centuries physical activity has became a leisure/hobby and, until recently, only for the rich and noble. In fact, the treadmill was invented in England 200 years ago as a prison rehabilitation device (Shayt, 1989) but was banned as a cruel and inhumane practice at the beginning of the 1900s (BMJ, 1885). Hunters-gatherers were forced to walk and run during daily activity and also, during non-ambulatory rest, they performed many movements that increase muscle activity unlike the typical sedentary posture of industrialised populations (Raichlen et al., 2020). This fact may explain, in part, the paradoxical negative effect of physical inactivity (PI) on health, considering the evolutionary pressure to save energy. The other side of the coin is, obviously, diet. Even though the diet-centric paradigm has been demonstrated to be partially, flawed (Archer, Lavie, & Hill, 2018), energy intake, dietary nutrients composition, and distribution influence health outcomes and body fat. In this regard it has been demonstrated that physical activity (PA) is important not only for its effects on energy expenditure but also for its influence on energy intake (Shook et al., 2015; Stubbs et al., 2004). That being said, it follows that the relationship between PA and metabolic control is more complex that a simple increase or decrease of energy expenditure; PA and its influence on metabolic flux (liver and muscle glycogen, adipose tissue liposynthesis and lipolysis) may be considered, quite rightly, the major determinant of energy control (energy intake and energy expenditure) and of metabolic control. It follows that PI and sedentary behaviour have a clear negative effect on health. The two terms “physical inactivity” and “sedentary behaviour” have been recently defined (Tremblay et al., 2017) as “an insufficient physical activity level to meet present physical activity recommendations (i.e. for adults (≥ 18 years): not achieving 150 min of moderate-to-vigorous-intensity physical activity per week or 75 min of vigorous-intensity physical activity per week or an equivalent combination of moderate- and vigorous-intensity activity)” and “any waking behaviour characterized by an energy expenditure ≤1.5 metabolic equivalents (METs), while in a sitting, reclining or lying posture”, respectively. It is clear that the recent, COVID-19-related strict limitation to mobility in many countries and the prohibition of moving from home unless for reasons related to work, real necessity or health care, have drastically reduced the citizens’ possibility to walk, run and to exercise in gyms, swimming pools, etc. We define this situation as being more related to PI than to sedentary behaviour, even though the forced lockdown may exacerbate previous bad sedentary habits (i.e. increasing the time spent lying, sitting, etc). Another dangerous factor is the increase of the number of hours devoted to television watching: high levels of moderate intensity PA (60–75 min per day) eliminates the increased risk of death associated with great sitting time but only blunts the increased risk associated with high TV-viewing time (Ekelund et al., 2016). During this period of home isolation, a good indicator of PI is the step-reduction. Many studies have investigated the effects of step-reduction on health parameters, demonstrating that even a short-term reduction in PA has a negative effect on skeletal muscle protein and carbohydrate metabolism. These changes may lead to muscle anabolic resistance, muscle and adipose tissue insulin resistance, and liver triglyceride accumulation with consequent hepatic insulin resistance. The final result is dyslipidaemia, a decrease of muscle mass and strength and, in general, an overall decline in function. Thus, the obligation to stay at home, the high number of tv “on-demand” channels, the increase in spare time, boredom and hunger represent the “perfect storm” for a dramatic future increase of metabolic diseases.

Exercise and nutritional countermeasures to physical inactivity and its consequences

Obviously, the best countermeasure to PI is PA, i.e. trying to exercise even when confined at home; but it is also of paramount importance to modulate the diet to fit the new physical activity context.

In general, many studies provide strong bases for amino acids/protein supplementation in older adults (Volpi et al., 2013) whilst the existence of anabolic resistance related to age is not well defined (Moro et al., 2018). Anyhow, in older healthy adults and healthy adults the ability of amino acids/protein supplementation to improve muscle mass/function is related to the amount and the kind of exercise performed (Churchward-Venne, Holwerda, Phillips, & van Loon, 2016; Morton et al., 2018; Morton, McGlory, & Phillips, 2015). Resistance training, that can be done without the so-called free weights (barbells, dumbbells, kettlebells) but also with bodyweight exercises (Suchomel, Nimphius, Bellon, & Stone, 2018), is the best choice to maintain or increase muscle mass and function. Subjects requested to stay at home during this time of social distancing and isolation should modify their diet according to the reduced activity-induced energy expenditure (up to 35–40%) (EVIDATION, 2020), reducing the total energy intake by about 15–20% (the average activity-induced energy expenditure in general population is about one-third of total energy expenditure) (Westerterp, 2003). It is important to refrain from multiple snacks during the day (nibbling) because, if not well controlled, this behaviour risks an increase in daily energy intake. In addition, in this period, social distancing, isolation and concerns about COVID-19 may increase depression, anxiety and boredom (Wang et al., 2020), factors which are related to an increase of energy intake (Braden, Musher-Eizenman, Watford, & Emley, 2018); thus, it would be helpful to maintain 2–3 meals per day, with a long overnight fast. Kahleova and colleagues (Kahleova, Lloren J, Mashchak, Hill, & Fraser G, 2017) investigated more than 50 thousand adult members of Seventh-day Adventist churches in the United States and Canada. The results showed that eating 1 or 2 meals daily was associated with better health outcomes compared with 3 meals daily. The Seventh-day Adventist is a unique population in which the consumption of alcohol, tobacco, and pork is prohibited and the majority of members adhere to a lacto-ovovegetarian diet (Beeson, Mills, Phillips, Andress, & Fraser, 1989; Phillips, Lemon, Beeson, & Kuzma, 1978). This religious group has a low meal frequency and also a regular meal timing that, together, may positively influence their health (Paoli, Tinsley, Bianco, & Moro, 2019). Seventh-day Adventists have an early dinner and a prolonged fast until breakfast. The long period of fasting may have beneficial effects on inflammation (Paoli et al., 2019; Vasconcelos et al., 2014) and immune system response (Faris et al., 2012; Han et al., 2018; Mindikoglu et al., 2020). We demonstrated that in healthy subjects (Moro et al., 2016) a normal energy time-restricted eating protocol (i.e. a window of 16 h of fasting and a window of 8 h of eating) may reduce many markers of inflammation such as tumour necrosis factor alpha, interleukin 6, and interleukin 1 beta and, at the same time, may increase the anti-inflammatory cytokine adiponectin. Also the energy distribution during the day is important: Jakubowicz, Barnea, Wainstein, and Froy (2013) demonstrated that diets with the same energy but differing in the distribution of calories during the day (high calorie in the morning vs. high calorie in the evening) may have influences on body weight, insulin resistance indices, and subjective appetite feeling in overweight/obese women. These suggest that is preferable for health to consume more calories earlier in the day (breakfast).

We therefore posit that during “stay at home” period, the following dietary practices may be beneficial:•a reduced meal frequency, regular meals and a long fasting period between dinner and breakfast (i.e. more than 12 h);•a reduced energy intake (from 15 up to 20–25%) compared to usual;•consumption of fresh vegetables (if possible), good quality protein sources (fish, poultry, lean meat);•at least 1.3 grams of good quality protein per kilogram of body weight (for an average subjects of 70 Kg it means 91 grams of protein, divided equally between meals);•moderate consumptions of seed and nuts and monounsaturated fat e.g. olive oil, due to the high energy content of fats;•avoid refined foods;•reduce the intake of high glycaemic index, glycaemic load and/or high insulinemic foods;•consume more energy during breakfast (about 40%), less during lunch (30%) and dinner (30%).

In these strange times that reflect some life habits of the mediaeval period, it may be useful to follow this twelfth-century recommendation: “Eat like a king in the morning, a prince at noon, and a peasant at dinner”

Take-home messages

Neuromuscular system

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Sedentarism causes a very rapid loss of muscle mass, detectable after just two days from the onset of inactivity; after 10 days the loss of muscle mass is ∼ 6% and after 30 days ∼10%

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Inactivity also leads to degenerative changes of the neuromuscular system: signs of damage to the neuromuscular junction are found after just 10 days and signs of denervation can be observed after just 3-days of inactivity

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Daily exercise is essential for counteracting the effects of inactivity: low to medium-intensity, high volume resistive exercise seems ideal for preventing neuromuscular degeneration, maximising protein synthesis and combating muscle atrophy

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Neuromuscular integrity is closely linked to mitochondrial function, hence a combination of aerobic as well as low-intensity, high-volume strength training are likely to afford protection against neurodegenerative changes and muscle atrophy

Muscle protein metabolism

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Physical inactivity and time spent sitting increase risk of poor metabolic health, functional decline and all-cause mortality

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Suppression of muscle protein synthesis is the primary driver of muscle mass loss during immobilisation or step count reduction in young, healthy people, and is evident within days

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The precise cellular and molecular mechanisms responsible for the decline in muscle mass observed during immobilisation in humans remain to be elucidated

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We do not yet fully understand the interaction between ageing processes and inactivity induced muscle mass loss

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The precise relationship between exercise dose (daily frequency and intensity) and muscle mass retention during prolonged periods of immobilisation or inactivity is not yet clear, but muscle contraction is a very effective countermeasure to dampen muscle mass loss during inactivity in young volunteers, although maybe less so in older people

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It will take several months to restore muscle mass loss completely following prolonged periods of inactivity or immobilisation in the absence of structured rehabilitation exercise

Glucose homeostasis

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Skeletal muscle has a pivotal role in inactivity-induced insulin resistance

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Inactivity leads to a specific reduction in muscle insulin sensitivity without affecting that of the liver

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Just few days of step-reduction can induce insulin resistance

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Changes in insulin sensitivity precede muscle atrophy and changes in body composition

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Start monitoring your physical activity (smart-phone, wearables)

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Strive to achieve >5000 steps per day

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Any form of energy expenditure is of help to avoid the deleterious effects of sedentarism;

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If possible, go outside in the nature (walking, jogging, running)

•

The advices are important for all, but particularly important for people at risk of diabetes (family history of diabetes) and cardio-vascular disease (elevated blood pressure, overweight/obese, elevated cholesterol, smokers)

Cardiorespiratory system

•

A reduced level of physical activity is inevitably associated with a reduced “cardiorespiratory fitness”, as estimated by the maximal O2 uptake (VO2max) or by other variables

•

Various steps along the O2 pathway are impaired by inactivity, from central and peripheral cardiovascular function to skeletal muscle oxidative metabolism

•

During profound inactivity the rate of loss of VO2max (about −0.5%/day) is similar to that described in bed rest studies. An accelerated decrease may occur in middle-aged and elderly subjects

•

A lower or decreased VO2max is associated with an increased mortality

•

The minimum amount of aerobic exercise needed to counteract the VO2max decrease due to inactivity is not clear. More research is needed. A reasonable estimate could be 4500–6000 steps/day

Energy balance, inflammation, lean and fat body mass

•

Overfeeding and excess fat deposition in healthy sedentary persons is associated with greater muscle loss and activation of systemic inflammation, leading to development of cardio-metabolic risk

•

Increasing the awareness of physiological and psychological mechanisms of overfeeding will contribute to the maintenance of energy balance and metabolic health of sedentary persons

•

Bed rest or inactivity in patients with diseases or in subjects in stressed conditions (e.g. strict home confinements or extreme environments) may be associated with decreased energy intake, rapidly leading to muscle wasting. Nutritional support and/or anabolic countermeasures may be required

Nutritional intake, metabolism and body composition

•

Subjects requested to stay at home during this time of social distancing and isolation reduce their daily activity-induced energy expenditure up to 35–40%;

•

The obligation to stay at home, the high number of tv “on-demand” channels, the increase of spare time, boredom and hunger represent the “perfect storm” for a dramatic future increase of metabolic diseases;

Practical suggestions

•

Reduce the daily energy intake (from 15 up to 20–25%) compared to usual;

•

Consume more fresh vegetables (if possible), good quality protein sources (fish, poultry, lean meat);

•

Consume at least 1.3 grams of good quality protein per kilogram of body weight.

•

Consume (moderately due to the high energy content) seeds. nuts and monounsaturated fats e.g. olive oil;

•

Avoid refined foods

•

Reduce the intake of high glycaemic index, glycaemic load and/or high insulinemic foods;

•

A reduced meal frequency, regular meals and a long fasting period between dinner and breakfast (i.e. more than 12 hours) may have some beneficial effects on metabolism and some health outcomes

•

Consume more energy during breakfast (about 40% of daily total), less during lunch (30% of daily total) and dinner (30% of daily total)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Funding

This work was funded by ASI, MARS-PRE Project, n. DC-VUM-2017-006.

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Osteoporosis→

What is Osteoporosis?

Osteoporosis is a bone disease characterized by low bone density (thickness of the bone), decreased bone strength, and a change in the bone structure, which can lead to an increased risk of fracture. The normal bone structure becomes thinned out and porous with poor nutrition, aging, or when osteoporosis develops, lessening the ability of the bone to withstand the typical forces that are applied in everyday living. Fractures from low bone density and osteoporosis can be serious, causing pain and affecting quality of life.

Bone is living tissue. Normally, one type of cell removes bone and another type of cell adds bone in a balanced, ongoing process. In osteoporosis, bones weaken when not enough new bone is formed and/or too much bone is lost. This imbalance commonly begins in women during the first 5 years of menopause. However, it can also occur in men and in children, often due to diseases that affect bone development, such as celiac disease, inflammatory bowel disease, rheumatoid arthritis, spina bifida, cystic fibrosis, or kidney disease. Some medicines, such as steroids, may increase the risk of developing osteoporosis. Athletes who are underweight during the time of peak bone development are also susceptible.

There are many factors that can cause a person to be at risk for developing osteoporosis. It is important to know your risks so that you can be diagnosed and proactive in your treatment.

Risk Factors for Osteoporosis

Noncontrollable risks

• Female gender

• Small frame

• Advanced age

• Hormone levels

• Genetics

• Predisposing medical conditions

Controllable risks

• Cigarette smoking

• Excessive alcohol intake

• Inactive lifestyle

• Excessive caffeine intake

• Lack of weight-bearing exercise

• Drugs (eg, steroids, heparin)

• Poor health

• Low weight

• Calcium-poor diet

• Low vitamin D levels

How Does it Feel?

Osteoporosis is a disease that can be "silent." There may be no outward symptoms until a fracture occurs. If you are middle-aged or older, you may notice a loss of height or the appearance of a humpback. You may also begin to experience pain between your shoulder blades or above the crest of the pelvis.

People with low bone density may experience fractures in everyday situations that would not occur in persons with healthy bones, such as breaking a hip or a wrist with a fall from a standing height, breaking a rib when opening a window or when receiving a hug, or breaking an ankle after stepping off a curb. These are called fragility fractures and are a red flag for bone disease. Spinal compression fractures, particularly those in the upper back or thoracic spine (area between the neck and the lower back), are the most common fractures, followed by hip and wrist fractures.

How Is It Diagnosed?

If you are seeing a physical therapist for back pain or other rehabilitation issues, the therapist will review your medical, family, medication, exercise, dietary, and hormonal history, conduct a complete physical examination, and determine your risk factors for osteoporosis. The assessment may lead the physical therapist to recommend further testing.

Osteoporosis is best diagnosed through a quick and painless specialized X-ray called the DXA, which measures bone density. The results are reported using T-scores and Z-scores.

• The T-score compares your score to that of healthy 30-year-old adults. If you have a T-score of -1 or less, you have a greater risk of having a fracture.

• If the T-score is -2.5 or less you will receive the diagnosis of osteoporosis.

• The Z-score compares your bone mineral density to those of the same sex, weight, and age. It is used for those whose bone mass has not yet peaked, premenopausal women, and men older than 50.

Other methods of measuring bone density include X-ray, ultrasound, and CT scan. 

How Can a Physical Therapist Help?

Your physical therapist can develop a specific program based on your individual needs to help improve your overall bone health, keep your bones healthy, and help you avoid fracture. Your physical therapist may teach you:

• Specific exercises to build bone or decrease the amount of bone loss

• Proper posture to protect your spine from fracture

• Proper alignment during activities of daily living

• How to improve your balance so as to reduce your risk of falling

• How to adjust your environment to protect your bone health

Healthy bone is built and maintained through a healthy lifestyle. Your physical therapist will teach you specific exercises to meet your particular needs.

The exercise component for bone building or slowing bone loss is very specific and similar for all ages. Bone grows when it is sufficiently and properly stressed, just as muscle grows when challenged by more than usual weight. Two types of exercise are optimal for bone health: weight-bearing and resistance.

It is best for a physical therapist to provide your individual bone-building prescription to ensure that you are neither overexercising nor underexercising. Typically, exercises are performed 2 to 3 times a week as part of an overall fitness program.

Weight-bearing exercises

• Dancing

• Jogging (if your bone density is higher than -3.0)

• Racquet sports

• Heel drops

• Stomping

Resistance exercises

• Weight lifting in proper spine and lower-extremity alignment

• Use of exercise bands

• Gravity resistance (eg, push-ups, prone trunk extension with cushion to protect lowest ribs, single-leg heel raises, squats, lunges, sustained standing yoga poses in neutral spine position)

• Exercises that reduce or stabilize kyphosis (hunchback)

• Balance exercises

If you are diagnosed with osteoporosis or low bone density, your physical therapist will work with you to:

• Build bone or lessen the amount of bone loss at areas most vulnerable to fracture through exercise—hip, spine, shoulder, arms.

• Improve your dynamic balance to avoid falls.

• Improve your posture.

• Adjust your work and living environments to limit risk.

• Help you avoid exercises and movements that may contribute to spinal fracture, including any type of sit-up or crunch, and excessive spinal or hip twisting.

Conservative treatment of a fracture includes bed rest and appropriate pain treatment. Your physical therapist will work with you to:

• Decrease your pain through positioning and other pain-relieving modalities. Individualized physical therapist regimens can help reduce pain without the need for medications, such as opioids.

• Provide appropriate external devices, such as bracing, to promote healing and improve posture.

• Decrease your risk of a fall, strengthen your muscles, and improve your postural alignment.

• Avoid exercises that involve too much forward or side bending or twisting.

• Avoid water or endurance exercises, as they have been shown to negatively affect bone density.

If your pain lasts longer than 6 weeks following a spinal fracture, you can discuss surgical options, such as vertebroplasty or kyphoplasty, with your physical therapist, primary care physician, and surgeon.

Children and adolescents. Physical therapists can educate families and youth groups on proper exercise and posture, and about the need to move daily to build bone strength and prevent bone loss. Children with health issues such as spina bifida, diabetes, Crohn's disease, and cerebral palsy are at a greater risk for bone disease and can particularly benefit from the guidance of a physical therapist. Proper physical conditioning is crucial for children and adolescents: the majority of bone is built during adolescence and peaks by the third decade of life.

Middle-aged and older adults. As people age, they may begin to notice postural, balance, and strength changes. Physical therapists work with middle-aged and older adults to:

• Develop individualized exercise programs to promote bone growth or lessen bone loss

• Improve dynamic balance to avoid falls

• Improve posture

• Improve the strength of back muscles

• Improve hip strength and mobility

Can this Injury or Condition be Prevented?

Osteoporosis can be prevented by building adequate bone density through childhood, adolescence, and early adulthood. Building strong bones requires an adequate intake of calcium and vitamin D, and regular exercise.

There are steps to take to improve bone health at any age. An active lifestyle that includes resistance and weight-bearing exercise is important to maintain healthy bone. It is also important to avoid habits that promote bone loss, such as smoking, excessive alcohol consumption, and an inadequate intake of calcium in your diet. Maintaining good body mechanics and posture also contribute to good bone health. We have no control over the genetic tendencies we have inherited, but we can choose to manage osteoporosis through proper medication, diet, and appropriate exercise.

As with any health issue, an overall healthy lifestyle is important for staying well.

Real Life Experiences

Anna is a 69-year-old retired legal secretary. She has enjoyed her early years of retirement, taking long walks in beautiful settings across the United States. Two years into her retirement, however, she began having knee pain during some of her walks, which gradually grew worse. Last year, she had a total knee replacement due to arthritis. She now walks with a cane because of chronic knee and ankle pain, and has experienced a loss of balance. She also has developed a rounded upper back, and low back pain. She seeks the help of a physical therapist.

Anna's physical therapist performs an assessment that includes a medical review for osteoporosis risk factors and for other health issues. He evaluates her range of motion and strength, testing her arms, legs, and trunk—especially her upper back. He tests the flexibility of her spine and her balance, her walking ability, and her risk of falling. Anna's walking style is uneven and she leans heavily on her cane. A DXA scan reveals that Anna has lost bone density in her spine and both hips. A vertebral fracture assessment X-ray shows that she has painless compression fractures of her spine. Her physical therapist diagnoses osteoporosis of the spine.

Anna first works with her physical therapist to improve her posture and knee function through flexibility and strengthening exercises, so she can walk more normally while working on her balance to lower her fall risk. She tells him her main goal is to be able to take walks in the park again.

Anna’s physical therapist teaches her safe trunk movement to avoid spinal fracture. Anna agrees to wear a dynamic trunk brace 2 hours a day to help make her posture more upright. She practices weight-bearing exercises with considerations for her arthritis, and learns resistive strengthening exercises for her spine and hip. Anna's physical therapist designs a gentle home-exercise program for her as well.

By her last visit, the flexibility and strength of Anna’s trunk and legs and her tolerance of physical activity have improved. The quality of her walking and dynamic balance are measurably improved, and her risk of falling has decreased. Anna feels much more confident about managing her condition.

Just this past week, Anna joined a therapeutic senior walking group that meets at the local botanic garden twice a week. She is thrilled to be enjoying gentle walks in nature again, and looks forward to coordinating other activities with her new group of friends!

This story was based on a real-life case. Your case may be different. Your physical therapist will tailor a treatment program to your specific case.

What Kind of Physical Therapist Do I Need?

All physical therapists are prepared through education and experience to treat those with osteoporosis. However, if you have a diagnosis of osteoporosis or low bone density, you may want to consider:

• A physical therapist who is a board-certified clinical specialist or who completed a residency or fellowship in orthopedic physical therapy or geriatric physical therapy. This physical therapist has advanced knowledge, experience, and skills that may apply to your condition.

• A physical therapist who specializes in the treatment of osteoporosis.

You can find physical therapists with these and other credentials by using Find a PT, the online tool by the American Physical Therapy Association that can help you search for physical therapists with specific clinical expertise in your geographic area.

General tips when you're looking for a physical therapist (or any other health care provider):

• Get recommendations from family and friends or from other health care providers.

• When you contact a physical therapy clinic for an appointment, ask about the physical therapists' experience in helping people who have osteoporosis.

Further Reading

The American Physical Therapy Association (APTA) believes that consumers should have access to information that can help them make health care decisions and also prepare them for a visit with their health care provider.

The following websites are important and reputable resources to obtain more information about improving your bone health:

National Osteoporosis Foundation. Accessed March 28, 2018.   

American Bone Health. Accessed March 28, 2018.

American Bone Health. FORE fracture risk calculator. Accessed March 28, 2018.

Osteoporosis Canada. Accessed March 28, 2018.

Osteoporosis Canada. Too fit to fracture series. Accessed March 28, 2018.

National Bone Health Alliance. Accessed March 28, 2018.

Own the Bone. Accessed March 28, 2018.

National Osteoporosis Foundation and Pilates Anytime. Safe movement video series. Accessed March 28, 2018.

MedBridge. Osteoporosis education courses for physical therapists. Accessed March 28, 2018.

Office of the US Surgeon General. The 2004 Surgeon General’s report on bone health and osteoporosis. Accessed March 28, 2018. 

Physical Activity Guidelines Advisory Committee, US Dept of Health and Human Services. Physical Activity Guidelines Advisory Committee Report, 2008. Washington, DC: US Department of Health and Human Services. Published June 2008. Accessed March 28, 2018. 

The following articles provide some of the best scientific evidence related to physical therapy treatment of osteoporosis and fracture prevention. The articles report recent research and give an overview of the standards of practice both in the United States and internationally. The article titles are linked either to a Pub Med* abstract of the article or to free full text, so that you can read it or print out a copy to bring with you to your health care provider.

Watson SL, Weks BK, Weis LJ, Harding AT, Horan SA, Beck BR. High-intensity resistance and impact training improves bone mineral density and physical function in postmenopausal women with osteopenia and osteoporosis: the LIFTMOR randomized controlled trial. J Bone Miner Res. 2018;33(2):211–220. Article Summary in PubMed.

Beck BR, Daly RM, Singh MA, Taaffe DR. Exercise and Sports Science Australia (ESSA) position statement on exercise prescription for the prevention and management of osteoporosis. J Sci Med Sport. 2017;20(5):438–445. Article Summary in PubMed.

Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol. 2017;4(1):46–56. Free Article.

Giangregorio LM, McGill S, Wark JD, et al. Too fit to fracture: outcomes of a Delphi consensus process on physical activity and exercise recommendations for adults with osteoporosis with or without vertebral fractures. Osteoporos Int. 2015;26(3):891–910. Free Article.

Bansal S, Katzman WB, Giangregorio LM. Exercise for improving age-related hyperkyphotic posture: a systematic review. Arch Phys Med Rehabil. 2014;95(1):129–140. Free Article.

Clark EM, Carter L, Gould VC, Morrison L, Tobias JH. Vertebral fracture assessment (VFA) by lateral DXA scanning may be cost-effective when used as part of fracture liaison services or primary care screening. Osteoporos Int. 2014;25(3):953–964. Article Summary in PubMed.

Siris ES, Adler R, Bilezikian J, et al. The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group. Osteoporos Int. 2014;25(5):1439–1443. Free Article.

Silva BC, Boutroy S, Zhang C, et al. Trabecular bone score (TBS): a novel method to evaluate bone microarchitectural texture in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2013;98(5):1963–1970. Free Article.

Cheung AM, Giangregorio L. Mechanical stimuli and bone health: what is the evidence? Curr Opin Rheumatol. 2012;24:561–566. Article Summary in PubMed.

Pfeifer M, Kohlwey L, Begerow B, Minne HW. Effects of two newly developed spinal orthoses on trunk muscle strength, posture, and quality-of-life in women with postmenopausal osteoporosis: a randomized trial. Am J Phys Med Rehabil. 2011;90:805–815. Article Summary on PubMed.

Kasukawa Y, Miyakoshi N, Hongo M, et al. Relationships between falls, spinal curvature, spinal mobility and back extensor strength in elderly people. J Bone Miner Metab. 2010;28:82–87. Article Summary in PubMed.

Nikander R, Kannus P, Dastidar M, et al. Targeted exercises against hip fragility. Osteoporos Int. 2009;20:1321–1328. Article Summary in PubMed.

Hongo M, Itoi E, Sinaki M, et al. Effect of low-intensity back exercise on quality of life and back extensor strength in patients with osteoporosis: a randomized controlled trial. Osteoporos Int. 2007;18:1389–1395. Article Summary in PubMed.

Vainionpaa A, Korpelainen R, Leppaluoto J, Jamsa T. Effects of high-impact exercise on bone mineral density: a randomized controlled trial in premenopausal women. Osteoporos Int. 2005;16:191–197. Article Summary in PubMed.

*PubMed is a free online resource developed by the National Center for Biotechnology Information (NCBI). PubMed contains millions of citations to biomedical literature, including citations in the National Library of Medicine's MEDLINE database.

Authored by Mary Saloka Morrison, PT, DScPT, MHS. Reviewed by the editorial board.

Thoracic Outlet Syndrome→

Thoracic Outlet Syndrome (TOS) is a potentially painful and disabling condition of the upper extremity. It results from the compression of structures in the thoracic outlet, a space just above the first rib, and behind the clavicle (collar bone). Due to the range of signs and symptoms that can lead to a diagnosis of TOS, the incidence rates of the condition currently are unknown. Physical therapists work with individuals who have TOS to ease their symptoms and restore their upper-body function.

How Does it Feel?

Because TOS generally is classified based upon the type of structures compressed, the symptoms experienced may vary. However, more than 90% of TOS cases are thought to be neurogenic (nerve compression) in nature (categories 3 and 4 below).

Arterial TOS

• Pain in the hand; rarely in shoulder or neck
• Coldness or cold intolerance
• Numbness and tingling

Venous TOS

• Pain in the arm
• Swelling in the arm
• Change in arm coloration (appears bluish)
• Feeling of heaviness in the arm
• Numbness and tingling in fingers and hands

True Neurogenic TOS

• Pain, numbness, and tingling in the hand, arm, shoulder, and often the neck
• Headaches
• Numbness and tingling of the arm, often waking the individual up at night
• Hand clumsiness
• Intolerance to cold
• Hand coldness and color changes

Disputed Neurogenic TOS

• Pain, numbness and tingling in the hand, arm, shoulder and often the neck
• Headaches
• Numbness and tingling of the arm, often waking the individual up at night
• Hand clumsiness
• Intolerance to cold
• Hand coldness and color changes
• Symptoms greater at night vs day
• Tests may come back normal (hence, the term "disputed").

How Is It Diagnosed?

Diagnosis of TOS begins with a thorough health history and clinical examination.

Your physical therapist will likely check for color changes in the affected area, and gently attempt to provoke symptoms by moving the affected limb in different directions.

You also may be referred for diagnostic testing, such as a Doppler ultrasound, which can confirm arterial and venous TOS, or nerve conduction velocity testing to help confirm a true neurogenic TOS.

Your physical therapist may be the first to recognize an onset of TOS, because of its effects on your physical function. Your physical therapist may ask you:

• When did you begin experiencing these symptoms, and when are they the worst?
• Have you noticed any change in your symptoms when the temperature changes?
• Have you noticed any significant changes in your ability to perform physical tasks that require hand movements?
• Have you noticed any changes in the appearance of your arm or hand?

In addition, your physical therapist will rule out other conditions, which may mimic this disorder. Your therapist may ask you to fill out a questionnaire in order to better understand your physical state, and to screen for the presence of other conditions.

How Can a Physical Therapist Help?

Once you have received a diagnosis of TOS, your physical therapist will work with you to develop a treatment plan to help ease the discomfort, and improve your ability to perform daily activities. Most research on this condition recommends a treatment plan that involves physical therapy to help ease your symptoms and improve function.

Physical therapy treatments may include:

Manual Therapy. Manual (hands-on) therapy may be applied to manipulate or mobilize the nerves of the arm to help reduce symptoms, such as pain and numbness/tingling. Your physical therapist also may attempt to gently mobilize your first rib and/or collar bone.

Movement and Strengthening Exercises. Your physical therapist will teach you muscle-strengthening exercises to improve movement and strength in the affected area.

Education. Your physical therapist will teach you strategies that can help minimize your symptoms while performing your daily functional activities.

Activity modification and postural strategies: Your physical therapist will teach you positions and strategies to place less stress on the structures involved with TOS.

Can this Injury or Condition be Prevented?

While some cases of TOS cannot be prevented, such as those due to anatomical variations, congenital conditions, trauma, or space-occupying lesions, others may be avoidable. Understanding risk factors that could make you more likely to develop this condition is the first step in prevention.

Your physical therapist will work with you to develop strategies to help you better understand and manage your risk factors and symptoms. As with many conditions, education is key. Understanding strategies, such as methods of reducing symptoms while performing activities, can help you live a full and functional life after the onset of TOS.

Real Life Experiences

George is a 45-year-old used-car salesman who takes potential customers on test drives in a crowded city area. Recently on a test drive, his customer ran a red light and the vehicle was struck by another motorist on the passenger side, where George was sitting. George was shaken up, although the police assured him the actual collision was minor.

George was taken to the emergency room following the accident, and received an X-ray, which was negative for a fracture of his clavicle. Fearing that he may be having a heart attack, he also followed up with his primary care physician, who was able to rule that out as well.

Over the next few days, George felt pain on his right side, and numbness and tingling down his right arm. His symptoms seemed to be worse at night. He called in sick to work, fearing he could be injured further on the job. He called his physical therapist.

George's physical therapist conducted a full physical examination. During the exam, George reported that he felt very anxious about the recent event, and wasn’t sure he'd be able to trust taking customers on test drives anymore.    

George's physical therapist noticed the presence of a rounded shoulder and forward-head posture, as she examined him. She was able to provoke George’s symptoms by gently placing his arm in particular positions, and gently pressing in the region of George’s first rib. She carefully checked for any other conditions that could be causing his symptoms. She told George that she suspected neurogenic TOS.

She developed a strategy for physical therapy that was best for him, consisting of activities and exercises to increase his strength, confidence, and function, while also easing his pain. She showed him postural activities to reduce compressive forces on his nerves. She also helped him with "nerve gliding" activities (encouraging his nerves to glide normally as his joints moved) to improve the function of the affected nerves.

Despite the complexity of the condition, George did well with his personalized course of physical therapy. Following several weeks of treatment and exercise, he was able to return to work without symptoms, and with a new-found confidence that he could ride in a car with customers again. With his physical therapist's ongoing help, George has returned to his normal activities of daily living.

This story highlights an individualized experience of TOS. Your case may be different. Your physical therapist will tailor a treatment program to your specific needs.

What Kind of Physical Therapist Do I Need?

All physical therapists are prepared through education and clinical experience to treat a variety of conditions or injuries.  You may want to consider:

• A physical therapist who is experienced in treating people with TOS.

• A physical therapist who is a board-certified clinical specialist or who completed a residency or fellowship in physical therapy. This therapist has advanced knowledge, experience, and skills that may apply to your condition.

You can find physical therapists who have these and other credentials by using Find a PT, the online tool built by the American Physical Therapy Association to help you search for physical therapists with specific clinical expertise in your geographic area.

General tips when you're looking for a physical therapist (or any other health care provider):

• Get recommendations from family and friends or from other health care providers.

• When you contact a physical therapy clinic for an appointment, ask about the physical therapists' experience in helping people with TOS.

• During your first visit with the physical therapist, be prepared to describe your symptoms in as much detail as possible. Keeping a journal highlighting when you experience pain will help the physical therapist identify the best treatment approach.

Further Reading

The American Physical Therapy Association (APTA) believes that consumers should have access to information that could help them make health care decisions, and also prepare them for their visit with their health care provider.

The following articles provide some of the best scientific evidence related to physical therapy treatment of TOS. The articles report recent research and give an overview of the standards of practice both in the United States and internationally. The article titles are linked either to a PubMed* abstract of the article or to free full text, so that you can read it or print out a copy to bring with you to your health care provider.

Hooper TL, Denton J, McGalliard MK, Brismée JM, Sizer PS Jr. Thoracic outlet syndrome: a controversial clinical condition; part 1: anatomy and clinical examination/diagnosis. J Man Manip Ther. 2010:18(2):74–83. Free Article. Article Summary in PubMed.

Hooper TL, Denton J, McGalliard MK, Brismée JM, Sizer PS Jr. Thoracic outlet syndrome: a controversial clinical condition; part 2: non-surgical and surgical management. J Man Manip Ther. 2010;18z(3):132–138. Free Article. Article Summary in PubMed.

Watson LA, Pizzari T, Balster S. Thoracic outlet syndrome part 2: conservative management of thoracic outlet. Man Ther. 2010;15(4):305–314. Article Summary in PubMed.

Vanti C, Natalini L, Romeo A, Tosarelli D, Pillastrini P. Conservative treatment of thoracic outlet syndrome: a review of the literature. Eura Medicophys. 2007;43(1):55–70. Article Summary in PubMed.

*PubMed is a free online resource developed by the National Center for Biotechnology Information (NCBI). PubMed contains millions of citations to biomedical literature, including citations in the National Library of Medicine's MEDLINE database.

Authored by Joseph Brence, PT, DPT, FAAOMPT, COMT, DAC. Reviewed by the MoveForwardPT.com editorial board.

Achilles Tendinopathy→

Achilles tendinopathy is an irritation of the Achilles tendon. Achilles tendon pain is one of the most common types of pain felt behind the heel and up the back of the ankle when walking or running. Although Achilles tendinopathy affects both active and inactive individuals, 24% of athletes develop the condition, and an estimated 50% of runners will experience Achilles tendon pain in their running careers. In all individuals, Achilles tendinopathy can result in a limited ability to walk, climb stairs, or participate in recreational activities. Physical therapists help people with Achilles tendinopathy reduce pain in the affected area, and restore strength, flexibility, and mobility to the injured tendon and eliminate swelling when present.

Achilles Tendinopathy

Achilles tendinopathy is an irritation of the Achilles tendon, a thick band of tissue along the back of the lower leg that connects the calf muscles to the heel. The term “tendinopathy” refers to any problem with a tendon, either short- or long-term. The Achilles tendon transmits force from the calf muscles down to the foot when a person pushes the foot off the ground (eg, runs or jumps), and helps control the position of the ankle when the foot touches back down on the ground (eg, lands). Achilles tendinopathy results when the demand placed on the Achilles tendon is greater than its ability to function. The condition can occur after a single incident (acute injury) or after repetitive irritation or "microtrauma" (chronic injury). Most often, Achilles tendon pain is the result of repetitive trauma to the tendon that can result in chronic Achilles tendinopathy—a gradual breakdown of the tissue—and is most often treated with physical therapy.

Achilles tendinopathy is linked to several different factors, including:

• Calf muscle tightness
• Calf muscle weakness
• Abnormal foot structure
• Abnormal foot mechanics
• Improper footwear
• A change in an exercise routine or sport activity
• Obesity

Pain can be present at any point along the tendon; the most common area to feel tenderness is just above the heel (known as midportion Achilles tendinopathy), although it may also be present where the tendon meets the heel (known as insertional Achilles tendinopathy).

How Does it Feel?

With Achilles tendinopathy, you may experience:

• Tenderness in the heel or higher up in the Achilles tendon with manually applied pressure
• Pain and stiffness with walking, at its worst with the first several steps
• Tightness in the calf
• Swelling in the back of the ankle

How Is It Diagnosed?

Your physical therapist will review your medical history and complete a thorough examination of your heel, ankle, and calf. Your physical therapist will assess your foot posture, strength, flexibility, and movement. This process may include watching you stand in a relaxed stance, walk, squat, step onto a stair, or do a heel raise. The motion and strength in other parts of your leg also will be assessed.

Your physical therapist may also ask questions regarding your daily activities, exercise regimens, and footwear, to identify other contributing factors to your condition.

Imaging techniques, such as X-ray or MRI, are often not needed to diagnose Achilles tendinopathy. Although it is unlikely that your condition will ultimately require surgery, your physical therapist will consult with other medical professionals, such as an orthopedist, to determine the best plan of treatment for your specific condition if it does not respond to conservative care.

How Can a Physical Therapist Help?

Physical therapy promotes recovery from Achilles tendinopathy by addressing issues such as pain or swelling of the affected area, and any lack of strength, flexibility, or body control. You and your physical therapist will work together to develop an individualized treatment program to help you achieve your specific goals in the safest and most effective way possible. Your treatment may include:

Education. Your physical therapist will work with you to identify any possible external factors causing your pain, such as faulty footwear or inappropriate movements or exercises. Your physical therapist will assess your footwear and recommend improvements, and develop a personalized exercise program to help ensure a pain-free return to your desired activities.

Pain management. Many pain-relief strategies may be implemented, such as applying ice to the area, putting the affected leg in a brace, using heel lifts, or using therapies such as iontophoresis (a medicated patch placed on the skin that is electrically charged and used to decrease pain and inflammation), or therapeutic ultrasound. These strategies can reduce the need for pain medication, including opioids.

Manual therapy. Your physical therapist may apply hands-on treatments to gently move your muscles and joints in order to improve their motion and function. These techniques often address areas that are difficult to treat on your own.

Range-of-motion treatments. Your ankle, foot, or knee joint may be moving improperly, causing increased strain on the Achilles tendon. Self-stretching and manual therapy techniques (massage and movement) applied to the lower body to help restore and normalize motion in the foot, ankle, knee, and hip can decrease this tension and restore full range of motion.

Gentle exercise. Loading of the tendon (applying weight or resistance to it) through exercise is beneficial for recovery from Achilles tendinopathy. You may begin by performing gentle strengthening exercises in a seated position (eg, pushing and pulling on a resistive band with your foot). You then may advance to exercises in a standing position (eg, standing heel raises).

Muscle-strengthening exercises. Muscle weakness or imbalance can result in excessive strain on the Achilles tendon. Based on your specific condition, your physical therapist will design an individualized, progressive, lower-extremity resistance program for you to help correct any weakness-associated movement errors that may be contributing to your pain.

Functional training. Once your pain eases and your strength and motion improve, you will need to safely transition back into more demanding activities. To minimize the tension placed on the Achilles tendon and your risk of repeated injury, it is important to teach your body safe, controlled movements. Based on your goals and movement assessment, your physical therapist will create a series of activities that will help you learn how to use and move your body correctly to safely perform the tasks required to achieve your goals.

If additional interventions are needed, such as injections, minimally invasive tendon procedures, or surgery, your physical therapist will work with you after your procedure to help you regain motion, strength, and function.

Can this Injury or Condition be Prevented?

Maintaining appropriate lower-extremity mobility and muscular strength, and paying particular attention to your exercise routine—especially changes in an exercise surface, the volume of exercises performed, and your footwear—are the best methods for preventing Achilles tendinopathy.

When you have experienced an injury, your physical therapist will help guide you through a process that will progressively reintegrate more demanding activities into your routine without aggravating your Achilles tendon. Keep in mind that returning to high-level activities too soon after injury can lead to another episode of pain.

What Kind of Physical Therapist Do I Need?

All physical therapists are prepared through education and experience to treat Achilles tendinopathy. However, you may want to consider:

• A physical therapist who is experienced in treating people with Achilles tendinopathy. Some physical therapists have a practice with an orthopedic or musculoskeletal focus.
• A physical therapist who is a board-certified orthopaedic clinical specialist or who completed a residency or fellowship in orthopedic or sports physical therapy. This physical therapist has advanced knowledge, experience, and skills that may apply to your condition.

You can find physical therapists who have these and other credentials by using Find a PT, the online tool built by the American Physical Therapy Association to help you search for physical therapists with specific clinical expertise in your geographic area.

General tips when you're looking for a physical therapist (or any other health care provider):

• Get recommendations from family and friends or from other health care providers.
• When you contact a physical therapy clinic for an appointment, ask about the physical therapists' experience in helping people who have Achilles tendinopathy.
• During your first visit with the physical therapist, be prepared to describe your symptoms in as much detail as possible, and say what makes your symptoms worse.

Further Reading

The American Physical Therapy Association (APTA) believes that consumers should have access to information that could help them make health care decisions and also prepare them for their visit with their health care provider.

The following articles provide some of the best scientific evidence related to physical therapy treatment of Achilles tendinopathy. The articles report recent research and give an overview of the standards of practice both in the United States and internationally. The article titles are linked either to a PubMed* abstract of the article or to free full text, so that you can read it or print out a copy to bring with you to your health care provider.

Martin RL, Chimenti R, Cuddeford T, et al. Achilles pain, stiffness, and muscle power deficits: midportion Achilles tendinopathy revision 2018. J Orthop Sports Phys Ther. 2018;48:A1–A38. Free Article.

Maffulli N, Longo UG, Loppini M, Denaro V. Current treatment options for tendinopathy. Expert Opin Pharmacother. 2010;11:2177–2186. Article Summary on PubMed.

Jonsson P, Alfredson H, Sunding K, Fahistrom M, Cook J. New regimen for eccentric calf-muscle training in patients with chronic insertional Achilles tendinopathy: results of a pilot study. Br J Sports Med. 2008;42:746–749. Article Summary on PubMed.

Alfredson H, Cook J. A treatment algorithm for managing Achilles tendinopathy: new treatment options. Br J Sports Med. 2007;41:211–216. Free Article.

Maffulli N, Wong J, Almekinders LC. Types and epidemiology of tendinopathy. Clin Sports Med. 2003;22:675–692. Article Summary on PubMed.

*PubMed is a free online resource developed by the National Center for Biotechnology Information (NCBI). PubMed contains millions of citations to biomedical literature, including citations in the National Library of Medicine’s MEDLINE database.

Reviewed by Ruth Chimenti, PT, DPT, PhD. Authored by Allison Mumbleau, PT, DPT. Dr Mumbleau is a board-certified sports clinical specialist. Reviewed by the MoveForwardPT.com editorial board.

Guide to Calf Strain→

What is a Calf Strain?

The “calf muscle” consists of 9 different muscles. The gastrocnemius, soleus, and plantaris muscles attach onto the heel bone, and work together to produce the downward motion of the foot. The other 6 muscles cause knee, toe, and foot movements in different directions; these muscles are the popliteus, flexor digitorum longus, flexor hallucis longus, tibialis posterior, and the fibularis (or peroneal) longus and brevis. They extend from the lower leg bones around the sides of the ankle and attach to various parts of the foot and toes. Injuries to these 6 muscles are sometimes wrongly attributed to the first 3 muscles mentioned here, as the pain is felt in similar areas of the calf.

A calf strain is caused by overstretching or tearing any of the 9 muscles of the calf. Calf strains can occur suddenly or slowly over time, and activities, such as walking, climbing stairs, or running can be painful, difficult, or impossible.

A muscle strain is graded according to the amount of muscle damage that has occurred:

• Grade 1. A mild or partial stretch or tearing of a few muscle fibers. The muscle is tender and painful, but maintains its normal strength. Use of the leg is not impaired, and walking is normal.
• Grade 2. A moderate stretch or tearing of a greater percentage of the muscle fibers. A snapping or pulling sensation may occur at the time of the injury and after the injury. There is more tenderness and pain, noticeable loss of strength, and sometimes bruising. Use of the leg is visibly impaired, and limping when walking is common.
• Grade 3. A severe tear of the muscle fibers, sometimes a complete muscle tear. A “popping” sound may be heard or felt when the injury occurs. Bruising is apparent, and sometimes a “dent” in the muscle where it is torn is visible beneath the skin. Use of the leg is extremely difficult, and putting weight on the leg is very painful.

When muscles are strained or torn, muscle fibers and other cells are disrupted and bleeding occurs, which causes bruising. Within a few hours of the injury, swelling can occur, causing the injured area to expand and feel tight and stiff.

After a severe calf strain, bruising may also be seen around the ankle or foot, as gravity pulls the escaped blood toward the lower part of the leg.

How Does it Feel?

If you strain your calf muscles, you may feel:

• Sharp pain or weakness in the back of the lower leg. The pain can quickly resolve, or can persist.
• A throbbing pain at rest with sharp stabs of pain occurring when you try to stand or walk.
• A feeling of tightness or weakness in the calf area.
• Spasms (a gripping or severe tightening feeling in the calf muscle).
• Sharp pain in the back of the lower leg, when trying to stretch or move the ankle or knee.
• A “pop” or hear a “pop” sound at the time of injury (with a Grade 3 calf strain).

Signs and Symptoms

With a calf strain, you may experience:

• A snap or pull felt or heard at the time of injury (with a Grade 1 and 2 calf strain). A "pop" may be felt or heard at the time of injury of a Grade 3 calf strain.
• Pain and weakness in the calf area.
• Swelling in the area.
• Tightness in the area.
• Bruising.
• Weakness in the calf when trying to walk, climb stairs, or stand.
• Limping when walking.
• Difficulty performing daily activities that require standing and walking.
• An inability to run or jump on the affected leg.

How Is It Diagnosed?

If you see your physical therapist first, your physical therapist will conduct a thorough evaluation that includes taking your health history. Your physical therapist will ask you:

• What were you doing when you first felt pain?
• Where did you feel the pain?
• Did you hear or feel a "pop" when it occurred?
• Did you receive a direct hit to your calf area?
• Did you see severe swelling in the first 2 to 3 hours following the injury? 
• Do you feel pain when moving your ankle or knee, standing, or walking?

Your physical therapist will perform special tests to help determine whether you have a calf strain, such as:

• Watch how you walk, and see if you can bear weight on the injured leg.
• Test the different calf muscles for weakness.
• Look for swelling or bruising.
• Gently feel parts of the muscle to determine the specific location of the injury (palpation).

Your physical therapist may use additional tests to assess possible damage to specific muscles of the lower leg.

In certain cases, your physical therapist may collaborate with an orthopedist or other health care provider. The orthopedist may order further tests, such as an x-ray or magnetic resonance imaging (MRI), to confirm the diagnosis and to rule out other potential damage. These tests, however, are not commonly required for a calf strain.

How Can a Physical Therapist Help?

Your physical therapist will design a specific treatment program to speed your recovery, including exercises and treatments that you can do at home to help you return to your normal lifestyle and activities.

The First 24 to 48 Hours

Your physical therapist may advise you to:

• Rest the area by avoiding walking or any activity that causes pain. Crutches or a brace may be recommended to reduce further strain on the muscles when walking.
• Apply ice packs to the area for 15 to 20 minutes every 2 hours.
• Compress the area with an elastic bandage wrap.
• Insert heel lift pads into both of your shoes.
• Consult with another health care provider for further services, such as medication or diagnostic tests.

Treatment Plan

Your physical therapist will provide treatments to:

Reduce Pain. Your physical therapist can use different types of treatments and technologies to control and reduce your pain, including ice, heat, ultrasound, electricity, taping, exercises, heel lifts, and hands-on therapy, such as massage.

Improve Motion. Your physical therapist will choose specific activities and treatments to help restore normal movement in the knee and ankle. These might begin with "passive" motions that the physical therapist performs for you to gently move your knee and ankle, and progress to active exercises and stretches that you perform yourself to increase muscle flexibility.

Improve Strength. Certain exercises will benefit healing at each stage of recovery; your physical therapist will choose the appropriate exercises, and teach you how to safely and steadily restore your strength and agility. These may include using cuff weights, stretchy bands, weight-lifting equipment, and cardio exercise equipment, such as treadmills or stationary bicycles.

Speed Recovery Time. Your physical therapist is trained and experienced in choosing the right treatments and exercises to help you safely heal, return to your normal lifestyle, and reach your goals faster than you are likely to do on your own.

Return to Activities. Your physical therapist will collaborate with you to decide on your recovery goals, including your return to work or sport, and will design your treatment program to help you reach those goals in the safest, fastest, and most effective way possible. Your physical therapist will apply hands-on therapy, such as massage, and teach you exercises, work retraining activities, and sport-specific techniques and drills to help you achieve your goals.

Prevent Future Reinjury. Your physical therapist can recommend a home-exercise program to strengthen and stretch the muscles around your ankle and knee to help prevent future reinjury of your calf. These may include strength and flexibility exercises for the calf, toe, knee, and ankle muscles.

If Surgery Is Necessary

Surgery is rarely necessary in the case of calf strain, but if a calf muscle fully tears and requires surgical repair, your physical therapist will help you minimize pain, restore motion and strength, and return to normal activities in the safest and speediest manner possible after surgery.

Can this Injury or Condition be Prevented?

Calf strains can be prevented by:

• Increasing the intensity of any activity or sport gradually, not suddenly. Avoid pushing yourself too hard, too fast, too soon.
• Always warming up before starting a sport or heavy physical activity.
• Following a consistent strength and flexibility/stretching exercise program to maintain good physical conditioning, even in a sport's off-season.
• Wearing shoes that are in good condition and fit well.

What Kind of Physical Therapist Do I Need?

All physical therapists are prepared through education and experience to treat calf strains. However, you may want to consider:

• A physical therapist who is experienced in treating people with calf strains.
• A physical therapist whose practice focus is in orthopedics or sports rehabilitation.
• A physical therapist who is a board-certified clinical specialist, or who completed a residency or fellowship in sports physical therapy. This therapist has advanced knowledge, experience, and skills that may apply to your condition.

You can find physical therapists who have these and other credentials by using Find a PT, the online tool built by the American Physical Therapy Association to help you search for physical therapists with specific clinical expertise in your geographic area.

General tips when you're looking for a physical therapist (or any other health care provider):

• Get recommendations from family and friends or from other health care providers.
• When you contact a physical therapy clinic for an appointment, ask about the physical therapists' experience in helping people who have calf strains.
• During your first visit with the physical therapist, be prepared to describe your symptoms in as much detail as possible, and describe what makes your symptoms worse.

Authored by Andrea Avruskin, PT, DPT. Reviewed by the MoveForwardPT.com editorial board.