IJGG Journal

Data Extraction and Review Method

Data extraction was conducted using a standardized form, and the analysis was performed independently by two reviewers. Any discrepancies were resolved through consensus or, when necessary, by a third reviewer.

Review Prolonged Immobility Syndrome

Prolonged maintenance of the supine position has been correlated with multisystem alterations that led to the conceptualization of Prolonged Immobility Syndrome (PIS) [55]. This refers to a set of organic dysfunctions arising from the sustained absence of weight-bearing through the lower limbs [21]. The condition is characterized by functional disturbances across several systems, namely the musculoskeletal, cardiovascular, nervous, and metabolic systems, and tends to worsen with advancing age and the presence of comorbidities [52].

Several studies highlight the significant consequences of immobilization, reporting that 25% to 35% of hospitalized older adults lost independence in at least three activities of daily living within just three days. More recent data reinforce the importance of preventive strategies in clinical settings to avoid this accelerated functional decline [53,54].

Somatosensory Deprivation

The lack of mechanical loading selectively affects antigravity muscles—particularly the extensors of the legs and trunk—due to reduced stimulation of plantar mechanoreceptors, especially the Pacinian and Ruffini corpuscles [42]. These receptors are activated by sustained pressure exerted on the plantar surface during upright stance and gait. In their absence, a deficit in afferent signalling to the central nervous system occurs, resulting in reduced muscle tone and subsequent atrophy.

Moreover, these mechanoreceptors directly influence the activation threshold of spinal motor neurons, interacting with vestibular and visual cues. Their continuous stimulation is crucial for postural control and the maintenance of segmental reflex activity [36]. The loss of plantar loading therefore initiates a cascade of neurophysiological changes that go beyond mere disuse, affecting motor coordination, postural stability, and even spatial perception [39-41].

Muscle Atrophy and Metabolic Alterations

Loss of muscle mass is among the most visible consequences of immobility. The literature demonstrates that even a mere reduction in muscular activity can trigger protein catabolism, and the absence of mechanical stimulation significantly exacerbates this process [16]. Experimental models involving lower limb suspension or immobilization have shown that muscle mass may decrease by up to 5% within just one week, with a proportional loss of function [23].

Furthermore, mechanical under-stimulation alters muscle metabolism by reducing protein synthesis and increasing local inflammatory processes. These changes are mediated by molecular pathways such as mTORC1 inhibition and ubiquitin– proteasome pathway activation, leading to accelerated proteolysis [22].

In fact, muscular integrity depends on the interaction between mechanical stimuli, proprioceptive input, motor innervation, and regular contractile activity. In bedridden patients, these stimuli are drastically reduced, resulting in rapid muscle atrophy, particularly in antigravity muscles such as the soleus [24].

During immobilization, muscle strength declines swiftly—by as much as 40% in the first week—due to increased levels of proinflammatory cytokines such as TNF-α and IL-6, which promote protein catabolism and heighten the risk of cardiovascular events [15].

Additionally, the absence of mechanical loading impairs osteomuscular stimulation, compromising bone mineral density and promoting neuromuscular dysregulation. The predominance of type I muscle fibres in postural muscles makes them particularly susceptible to disuse atrophy [19].

Effects on Bone and Cartilage

As with muscular tissue, bone is highly sensitive to mechanical stimuli. The skeletal system responds to external loading not only by altering its mass but also through modifications to its microstructural architecture.

Under conditions of mechanical unloading—such as prolonged bed rest or microgravity—a disequilibrium arises between osteoclastic resorption and osteoblastic formation, favouring bone loss, particularly in trabecular bone, which is metabolically more active. This process, commonly referred to as disuse osteopenia, compromises the structural integrity of the skeleton and increases the risk of fractures and overall morbidity and mortality [26].

Although bone degradation progresses more slowly than muscle loss, its clinical implications are substantial. Bone metabolism is tightly regulated by mechanotransduction—the process by which bone cells convert mechanical stimuli such as compression, tension, and shear into biochemical signals that activate or inhibit specific molecular pathways [33].

One of the core mechanisms of mechanotransduction is the piezoelectric effect of bone. As an anisotropic and semi-crystalline material, bone generates electrical charges when subjected to deformation forces such as bending. During this process, opposing electrical poles are generated: negative charges on the compressed side stimulate osteoblastic activity and bone formation, while positive charges on the tension side promote osteoclastic activity and bone resorption. This phenomenon enables adaptive bone remodelling in response to habitual mechanical loads [29, 34].

The compressive forces generated by upright posture and lowto-moderate impact physical activities are the primary anabolic stimulus for bone. Dynamic forces—which vary in both magnitude and direction—are more effective for osteogenesis than prolonged static loading, as they prevent cellular mechanoreceptor desensitisation. Moreover, even low-magnitude cyclic stimuli have been shown to offer osteoprotective effects, provided they are applied with appropriate frequency and duration [32].

Muscle–bone integrity is interdependent. Muscle contraction exerts tension upon bone, thereby activating osteogenic pathways via local mechanical deformation. Conversely, the quality of bone tissue influences the efficiency of muscular function [25]. Thus, sarcopenia and osteopenia frequently coexist and are mutually reinforcing, particularly in immobilized or elderly individuals [30].

Finally, it should be noted that bone structures with an antigravity function, such as the spine, pelvis and lower limbs, are also the most affected in non-load-bearing contexts [28]. In these regions, the loss of bone mass is more accelerated, which reinforces the need for therapeutic strategies that include regular mechanical stimuli - including in rehabilitation and long-term care contexts.

Hematopoietic effects

Sarcopenia doesn’t just affect the locomotor system. Muscle mass is closely linked to glycaemia homeostasis, lipid metabolism, inflammatory response, and overall functional capacity. Muscle loss compromises lipid oxidation favors insulin resistance and predisposes to sarcopenic obesity - a condition with increased cardiovascular risk [12, 14]. This condition also represents a severe deterioration in body composition, where fat mass accumulates and the adipokines secreted aggravate systemic inflammation and insulin resistance, accentuating the loss of muscle function [14]. Sarcopenic obesity requires dual management strategies: reduction of adiposity and recovery of muscle mass.

In addition, the increase in connective tissue in atrophic muscle, coupled with the reduction in satellite cells and capillarization, establishes an ineffective regenerative environment, exacerbating atrophy.

In the feet in particular, sarcopenia associated with neuropathies and DM can generate structural deformities such as clubfoot and digital claw, making them more susceptible to trophic lesions due to the exposure of bony prominences as a result of plantar pad atrophy [13] Muscle atrophy due to immobilization follows a temporal pattern: in the first 7 to 10 days there is rapid protein degradation; between 2 and 3 months, recovery is still possible with reinnervation; after 7 months, there is stabilization of degeneration with scarce reversibility [18] Early intervention is therefore crucial.

This whole cascade of events associated with sarcopenia can be seen in the following organization chart (Figure 1):

Figure 1: progression of sarcopenia and mechanism of aggravation:

Adapted from Grima-Terrén et al., (2024) [17].

Implications for the Central Nervous System

In humans, as in other arthropods, the support of the lower limbs depends on load detection through exteroceptors and proprioceptors. Exteroceptors respond to muscle contractions and give rise to reflexes that can stiffen the limb or cause flexion or extension movements. Proprioceptors, on the other hand, are divided into two groups: one more related to position and movement detection (such as the chordotonal organs and muscle receptors), and the other more specialized in direct load detection. Both types of proprioceptors contribute to the regulation of limb support, adjusting force and position according to the load detected [37] Control of lower limb support also results from the integration of sensory signals, including those from the skin. These signals can trigger flexion or extension responses of the entire limb, helping to maintain balance and stability. Among the proprioceptors, the fusiforms are important for detecting movement and position, while the Golgi tendon organs, although they can inhibit muscle contraction, have a reduced role during walking, as their effect is often suppressed.

During the support (or stance) phase of gait, afferent signals from multiple load receptors activate the central circuits responsible for limb extension. This mechanism provides a ‘reinforcing force feedback’, which promotes the contraction of the extensor muscles and simultaneously suppresses the activity of the flexor muscles. This organization ensures that the limb remains firm while bearing weight, guaranteeing stability and preventing a premature transition to the swing phase. This type of feedback is only functionally relevant during locomotion. In the immobile animal, this mechanism does not manifest itself, which reinforces the idea that active support of the lower limbs during gait depends on the interaction between sensory feedback and the motor circuits involved in generating the locomotor pattern [37]. Additionally, the lack of load on the limbs leads to a decrease in the activity of the motor cortex and connectivity between areas related to postural and locomotor control. This can result in difficulties in returning to walking after long periods of immobility, even if muscle mass and joints are apparently preserved [18].

Vascular and cardiovascular effects

Reduced movement, especially walking, significantly compromises venous return from the lower limbs. Although decubitus eliminates the effect of gravity, the absence of skeletal muscle contraction represents an independent risk factor for venous stasis, hypercoagulability, and endothelial damage - the three components of Virchow’s triad, which predispose to the development of deep vein thrombosis (DVT) and thromboembolism [43, 45]. The absence of continuous orthostatism reduces the efficiency of venous return, predisposing to stasis and the risk of venous thromboembolism. There is also deconditioning of the cardiovascular system, with a decrease in stroke volume and tolerance to exertion. Studies indicate that aerobic capacity can decline by up to 25 per cent after three weeks of bed rest [49] In bedridden patients, the absence of movement compromises the action of the leg muscle pump (LMP), which is fundamental for venous return. This pump, also known as the ‘peripheral heart’, is based on the compression of the triceps sural over the deep veins during muscle contraction, propelling blood towards the heart. Its inactivity contributes to stasis and increased blood viscosity (Peter & Mladen, n.d.) In addition, the postural diuresis induced by the lying position leads to a gradual loss of plasma volume, reaching up to 15 per cent after four weeks of rest. This increases haematocrit and blood viscosity, favoring the formation of [44] Over time, there is also a reduction in red blood cell mass and hemoglobin levels, worsening tissue oxygenation [46] Immobilization also affects lung function and gas exchange, resulting in tissue hypoxia. The skin, due to its terminal vascularization, is particularly vulnerable to ischemia - which increases the risk of pressure injuries and ulcers [48].

Simple movements such as active or passive plantar flexion have a beneficial effect on venous blood flow, as demonstrated by Doppler ultrasound studies. Regular exercise, even in decubitus, helps to activate the deep venous system and reduce the risk of VT.

On the other hand, suddenly resuming activity after long periods of rest can mobilize previously formed clots near the venous valves, increasing the risk of pulmonary embolism, ischemic stroke or myocardial infarction. For this reason, rehabilitation should be gradual and monitored, especially in individuals with additional risk factors [46].

Intervention Strategies

Understanding the systemic effects of the absence of mechanical load leads to an appreciation of therapeutic strategies that simulate or promote stimulation of the plantar receptors. Plantar tactile stimulation devices, partial unloading supports and closed kinetic chain exercises have been shown to be effective in maintaining muscle tone and proprioceptive function even in contexts of partial immobility.

In addition, the early use of assisted verticalization and dynamic orthoses that promote controlled weight unloading can help maintain the functional integrity of the foot as the first link in the kinetic chain, preparing the system for post-immobilization readaptation [50,51].

The therapeutic approach to sarcopenia must therefore be multifactorial: physical, nutritional, pharmacological, environmental and social, but this article aims to raise awareness among all health professionals that sarcopenia, rather than being treated, must be minimized, given the huge negative impact on the individual’s overall health.

Conclusions

This systematic review, based on the analysis of 54 rigorously selected studies from an initial screening of 332 titles and abstracts, offers compelling evidence regarding the profound systemic consequences of mechanical unloading of the lower limbs. The literature consistently highlights that prolonged immobility— particularly in bedridden or hospitalised individuals—triggers a cascade of multisystem dysfunctions, with pronounced effects on the musculoskeletal, neurological, and vascular systems.

Across the majority of studies reviewed, a recurrent finding was the central role of mechanical loading through the lower limbs, particularly via plantar support, in maintaining postural tone, muscular strength, proprioceptive feedback, and bone density. The absence of such load results in accelerated muscle atrophy, predominantly affecting antigravity muscles, alongside osteopenia, due to the suppression of mechanotransductive stimuli essential for bone remodeling. Furthermore, deficits in plantar sensory input lead to neuromuscular dysfunction, postural instability, and impaired functional recovery.

Another key theme emerging from the evidence is the detrimental impact of somatosensory deprivation and its contribution to systemic inflammation, metabolic derangement, and heightened thrombotic risk. These pathophysiological consequences are often exacerbated by the under-recognition of immobility as a clinical condition, despite its highly preventable nature.

Given the weight of evidence, it is imperative that health professionals remain vigilant to the early signs of functional decline due to immobility. The clinical management of immobilized patients must move beyond passive care and incorporate active strategies that simulate or restore mechanical loading—even in contexts where full mobilization is not yet feasible. Interventions such as plantar stimulation devices, assisted verticalization, closed kinetic chain exercises, and sensory-motor rehabilitation protocols have demonstrated promise in preserving neuromuscular integrity and preventing long-term disability.

This review therefore underscores the urgent need for innovation in rehabilitation paradigms, emphasizing the restoration of mechanical loading as a therapeutic priority. Interdisciplinary approaches and targeted training for healthcare teams are essential to ensure that immobility does not remain a silent and underestimated contributor to functional decline in vulnerable populations.

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