Skeletal muscle immobilisation-induced atrophy: mechanistic insights from human studies.

Periods of skeletal muscle disuse lead to rapid declines in muscle mass (atrophy), which is fundamentally underpinned by an imbalance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB). The complex interplay of molecular mechanisms contributing to the altered regulation of muscle protein balance during disuse have been investigated but rarely synthesised in the context of humans. This narrative review discusses human models of muscle disuse and the ensuing inversely exponential rate of muscle atrophy. The molecular processes contributing to altered protein balance are explored, with a particular focus on growth and breakdown signalling pathways, mitochondrial adaptations and neuromuscular dysfunction. Finally, key research gaps within the disuse atrophy literature are highlighted providing future avenues to enhance our mechanistic understanding of human disuse atrophy.

Changes in brain functional connectivity and muscle strength independent of elbow flexor atrophy following upper limb immobilization in young females.

Muscle disuse induces a decline in muscle strength that exceeds the rate and magnitude of muscle atrophy, suggesting that factors beyond the muscle contribute to strength loss. The purpose of this study was to characterize changes in the brain and neuromuscular system in addition to muscle size following upper limb immobilization in young females. Using a within-participant, unilateral design, 12 females (age: 20.6 ± 2.1 years) underwent 14 days of upper arm immobilization using an elbow brace and sling. Bilateral measures of muscle strength (isometric and isokinetic dynamometry), muscle size (magnetic resonance imaging), voluntary muscle activation capacity, corticospinal excitability, cortical thickness and resting-state functional connectivity were collected before and after immobilization. Immobilization induced a significant decline in isometric elbow flexion (-21.3 ± 19.2%, interaction: P = 0.0440) and extension (-19.9 ± 15.7%, interaction: P = 0.0317) strength in the immobilized arm only. There was no significant effect of immobilization on elbow flexor cross-sectional area (CSA) (-1.2 ± 2.4%, interaction: P = 0.466), whereas elbow extensor CSA decreased (-2.9 ± 2.9%, interaction: P = 0.0177) in the immobilized arm. Immobilization did not differentially alter voluntary activation capacity, corticospinal excitability, or cortical thickness (P > 0.05); however, there were significant changes in the functional connectivity of brain regions related to movement planning and error detection (P < 0.05). This study reveals that elbow flexor strength loss can occur in the absence of significant elbow flexor muscle atrophy, and that the brain represents a site of functional adaptation in response to upper limb immobilization in young females.

Long-term effects of non-weight bearing and immobilization after anterior cruciate ligament reconstruction on joint contracture formation in rats.

PURPOSE: Non-weight bearing improves and immobilization worsens contracture induced by anterior cruciate ligament reconstruction (ACLR), but effect persistence after reloading and remobilization remains unclear, and the combined effects of these factors on ACLR-induced contracture are unknown. We aimed to determine 1) whether the effects of short-term (2-week) non-weight bearing or immobilization after ACLR on contracture would be sustained by reloading or remobilization during a 10-week observation period, and 2) how the combination of both interventions compared to the outcome of either alone. METHODS: We divided 88 ACL-reconstructed male rats into four groups: non-intervention, non-weight bearing, joint immobilization, and both interventions. Interventions were performed for 2 weeks, followed by rearing without intervention. Twelve untreated rats were used as controls. At 2, 4, and 12 weeks post-surgery, we assessed range of motion (ROM) and histological changes. RESULTS: ACLR resulted in persistent loss of ROM, accompanied by synovial shortening, capsule thickening, and osteophyte formation. Two weeks of non-weight bearing increased ROM and reduced osteophyte size, but the beneficial effects disappeared within 10 weeks after reloading. Two-week immobilization decreased ROM and facilitated synovial shortening. After remobilization, ROM partially recovered but remained below non-intervention levels at 12 weeks. When both interventions were combined, ROM was similar to immobilization alone. CONCLUSIONS: The beneficial effects of 2-week non-weight bearing on contracture diminished within 10 weeks after reloading. The adverse effects of 2-week immobilization on contracture persisted after 10 weeks of remobilization. The effects of the combined use of both interventions on contracture were primarily determined by immobilization.

The effect of protein or amino acid provision on immobilization-induced muscle atrophy in healthy adults: A systematic review and meta-analysis.

Bed rest and limb immobilization are models of muscle disuse associated with skeletal muscle atrophy and reduced strength. The purpose of this systematic review was to examine the impact of protein or amino acid provision before and/or during a period of muscle disuse on muscle atrophy (primary outcome), strength and muscle protein synthesis (secondary outcomes) following a disuse period. We performed a systematic review of Embase, MEDLINE, Web of Science, PubMed and Clinical Trials in December 2022. Eligible studies were randomized controlled trials that combined a dietary protein or amino acid intervention versus control during an experimental model of disuse (bed rest or unilateral limb immobilization) in healthy individuals aged ≥18 years. Nine articles from eight independent trials were identified and rated for risk of bias by two authors. A meta-analysis of muscle mass data revealed no effect (standardized mean difference: 0.2; 95% confidence interval: -0.18 to 0.57, P = 0.31) of protein/amino acid intervention in preventing disuse-induced muscle atrophy. Although the meta-analysis was not conducted on strength or muscle protein synthesis data, there was insufficient evidence in the reviewed articles to support the use of protein/amino acid provision in mitigating the disuse-induced decline in either outcome measurement. Additional high-quality studies, including the reporting of randomization procedures and blinding procedures and the provision of statistical analysis plans, might be required to determine whether protein or amino acid provision serves as an effective strategy to attenuate muscle atrophy during periods of disuse.

A bioengineering investigation of cervical collar design and fit: Implications on skin health.

BACKGROUND: Cervical collars restrict cervical spine movement to minimise the risk of spinal cord injury. Collars apply mechanical loading to the skin putting it at risk of skin damage. Indeed, cervical collar-related pressure ulcers are unacceptably prevalent, especially at the occiput, mandibles, and chin. Collar design and fit are often key considerations for prevention. METHODS: This comprehensive study evaluated four commercial prehospital and acute care cervical collars. Pressure, microclimate, transepidermal water loss and skin hydration were measured at the interface between the device and the skin. Range of motion restriction was measured to evaluate effective immobilisation. Head, neck, and shoulder morphology was evaluated using three-dimensional scans. FINDINGS: The occiput experienced significantly higher interface pressures than the chin and mandibles for most collar designs. Interface pressure at the occiput was significantly higher for the Stiffneck extrication collar compared to the other collar designs. The Stiffneck collar also provided the most movement restriction, though not significantly more than other designs. Relative humidity at the device skin interface was significantly higher for the Stiffneck and Philadelphia collars corresponding to closed cell foam padding, in contrast to the open cell foams lined with permeable fabric used in the other collars. Collar discomfort correlated with both occipital pressure and skin humidity. INTERPRETATION: The occiput is at increased risk of cervical collar-related pressure ulcers during supine immobilisation, especially for Stiffneck extrication collars. Lined open-cell foams could be used to minimise skin humidity and increase comfort.

Immobilization in External Rotation Versus Arthroscopic Stabilization After Primary Anterior Shoulder Dislocation: A Systematic Review of Level 1 and 2 Studies.

BACKGROUND: Arthroscopic stabilization has been established as a superior treatment option for primary glenohumeral instability when compared with immobilization in internal rotation. However, immobilization in external rotation (ER) has recently gained interest as a viable nonoperative treatment option for patients with shoulder instability. PURPOSE: To compare the rates of recurrent instability and subsequent surgery in patients undergoing treatment for primary anterior shoulder dislocation with arthroscopic stabilization versus immobilization in ER. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify studies that'evaluated patients being treated for primary anterior glenohumeral dislocation with either arthroscopic stabilization or immobilization in ER. The search phrase used various combinations of the keywords/phrases "primary closed reduction,""anterior shoulder dislocation,""traumatic,""primary,""treatment,""management,""immobilization,""external rotation,""surgical,""operative,""nonoperative," and "conservative." Inclusion criteria included patients undergoing treatment for primary anterior glenohumeral joint dislocation with either immobilization in ER or arthroscopic stabilization. Rates of recurrent instability, subsequent stabilization surgery, return to sports, positive postintervention apprehension tests, and patient-reported outcomes were evaluated. RESULTS: The 30 studies that met inclusion criteria included 760 patients undergoing arthroscopic stabilization (mean age, 23.1 years; mean follow-up time, 55.1 months) and 409 patients undergoing immobilization in ER (mean age, 29.8 years; mean follow-up time, 28.8 months). Overall, 8.8% of operative patients experienced recurrent instability at latest follow-up compared with 21.3% of patients who had undergone ER immobilization (P < .0001). Similarly, 5.7% of operative patients had undergone a subsequent stabilization procedure at latest follow-up compared with 11.3% of patients who had undergone ER immobilization (P = .0015). A higher rate of return to sports was found in the operative group (P < .05), but no other differences were found between groups. CONCLUSION: Patients undergoing arthroscopic treatment for primary anterior glenohumeral dislocation with arthroscopic stabilization can be expected to experience significantly lower rates of recurrent instability and subsequent stabilization procedures compared with patients undergoing ER immobilization.

Tuina in a Frozen Shoulder Rat Model: An Efficient and Reproducible Protocol.

Frozen shoulder (FS) is a common condition with no defined optimal therapy. Tuina therapy, a traditional Chinese medicine (TCM) technique used to treat FS patients in Chinese hospitals, has demonstrated excellent results, but its mechanisms are not fully understood. Building on a previous study, this work aimed to develop a Tuina protocol for an FS rat model. We randomly divided 20 SD rats into control (C; n = 5), FS model (M; n = 5), FS model Tuina treatment (MT; n = 5), and FS model oral treatment (MO; n = 5) groups. This study used the cast immobilization method to establish the FS rat model. The effect of Tuina and oral dexamethasone on the glenohumeral range of motion (ROM) was evaluated, and the histological findings were assessed. Our study showed that Tuina and oral dexamethasone were able to improve shoulder active ROM and preserve the structure of the capsule, with Tuina therapy proving to be more effective than oral dexamethasone. In conclusion, the Tuina protocol established in this study was highly effective for FS.

Changes in passive stiffness and length of the semitendinosus muscles in rats with arthritis-induced knee flexion contracture.

BACKGROUND: Arthritis-induced joint contracture is caused by arthrogenic and myogenic factors. The arthrogenic factor, localized within the joint, is naturally accepted as the cause of contracture. However, the detailed mechanisms underlying arthritis-induced myogenic contracture are largely unknown. We aimed to elucidate the mechanisms of arthritis-induced myogenic contracture by examining the muscle mechanical properties. METHODS: Knee arthritis was induced in rats by injecting complete Freund's adjuvant into the right knees, while the untreated contralateral knees were used as controls. After one or four weeks of injection, passive stiffness, length, and collagen content of the semitendinosus muscles were assessed, along with passive knee extension range of motion. FINDINGS: After one week of injection, flexion contracture formation was confirmed by a decreased range of motion. Range of motion restriction was partially relieved by myotomy, but still remained even after myotomy, indicating the contribution of both myogenic and arthrogenic factors to contracture formation. After one week of injection, the stiffness of the semitendinosus muscle was significantly higher in the injected side than in the contralateral side. After four weeks of injection, the stiffness of the semitendinosus muscle in the injected side returned to levels comparable to the contralateral side, parallel to partial improvement of flexion contracture. Muscle length and collagen content did not change due to arthritis at both time points. INTERPRETATION: Our results suggest that increased muscle stiffness, rather than muscle shortening, contributes to myogenic contracture detected during the early stage of arthritis. The increased muscle stiffness cannot be explained by excess collagen.

Does initial skeletal muscle size or sex affect the magnitude of muscle loss in response to 14 days immobilization?

We aimed to determine whether there was a relationship between pre-immobilization skeletal muscle size and the magnitude of muscle atrophy following 14 days of unilateral lower limb immobilization. Our findings (n = 30) show that pre-immobilization leg fat-free mass and quadriceps cross-sectional area (CSA) were unrelated to the magnitude of muscle atrophy. However, sex-based differences may be present, but confirmatory work is required. In women, pre-immobilization leg fat-free mass and CSA were associated with changes in quadriceps CSA after immobilization (n = 9, r2 = 0.54-0.68; P < 0.05). The extent of muscle atrophy is not affected by initial muscle mass, but there is potential for sex-based differences.

Progression of microstructural deterioration in load-bearing immobilization osteopenia.

PURPOSE: Immobilization osteopenia is a major healthcare problem in clinical and social medicine. However, the mechanisms underlying this bone pathology caused by immobilization under load-bearing conditions are not yet fully understood. This study aimed to evaluate sequential changes to the three-dimensional microstructure of bone in load-bearing immobilization osteopenia using a fixed-limb rat model. MATERIALS AND METHOD: Eight-week-old specific-pathogen-free male Wistar rats were divided into an immobilized group and a control group (n = 60 each). Hind limbs in the immobilized group were fixed using orthopedic casts with fixation periods of 1, 2, 4, 8, and 12 weeks. Feeding and weight-bearing were freely permitted. Length of the right femur was measured after each fixation period and bone microstructure was analyzed by micro-computed tomography. The architectural parameters of cortical and cancellous bone were analyzed statistically. RESULTS: Femoral length was significantly shorter in the immobilized group than in the control group after 2 weeks. Total area and marrow area were significantly lower in the immobilized group than in the control group from 1 to 12 weeks. Cortical bone area, cortical thickness, and polar moment of inertia decreased significantly after 2 weeks. Some cancellous bone parameters showed osteoporotic changes at 2 weeks after immobilization and the gap with the control group widened as the fixation period extended (P < 0.05). CONCLUSION: The present results indicate that load-bearing immobilization triggers early deterioration of microstructure in both cortical and cancellous bone after 2 weeks.

Muscle contractile exercise through a belt electrode device prevents myofiber atrophy, muscle contracture, and muscular pain in immobilized rat gastrocnemius muscle.

PURPOSE: Immobilization of skeletal muscles causes muscle atrophy, muscle contracture, and muscle pain, the mechanisms of which are related to macrophage accumulation. However, muscle contractile exercise through a belt electrode device may mitigate macrophage accumulation. We hypothesized that such exercise would be effective in preventing myofiber atrophy, muscle contracture, and muscular pain. This study tested this hypothesis in immobilized rat gastrocnemius muscle. MATERIALS AND METHODS: A total of 32 rats were divided into the following control and experimental groups: immobilization (immobilized treatment only), low-frequency (LF; immobilized treatment and muscle contractile exercise with a 2 s (do) /6 s (rest) duty cycle), and high-frequency (HF; immobilized treatment and muscle contractile exercise with a 2 s (do)/2 s (rest) duty cycle). Electrical stimulation was performed at 50 Hz and 4.7 mA, and muscle contractile exercise was applied to the lower limb muscles for 15 or 20 min/session (once daily) for 2 weeks (6 times/week). After the behavioral tests, the bilateral gastrocnemius muscles were collected for analysis. RESULTS: The number of macrophages, the Atrogin-1 and MuRF-1 mRNA expression, and the hydroxyproline content in the HF group were lower than those in the immobilization and LF groups. The cross-sectional area (CSA) of type IIb myofibers in the superficial region, the PGC-1α mRNA expression, and the range of motion of dorsiflexion in the HF group were significantly higher than those in the immobilization and LF groups. The pressure pain thresholds in the LF and HF groups were significantly higher than that in the immobilization group, and the nerve growth factor (NGF) content in the LF and HF groups was significantly lower than that in the immobilization group. CONCLUSION: Muscle contractile exercise through the belt electrode device may be effective in preventing immobilization-induced myofiber atrophy, muscle contracture, and muscular pain in the immobilized rat gastrocnemius muscle.

[Optimization of rehabilitation of elderly and senile patients with primary traumatic dislocation of the shoulder.]

Тhe aim of the study is to improve the treatment outcomes of elderly patients with primary traumatic shoulder dislocation by developing an atraumatic rehabilitation method. The study included 56 patients aged over 60 years with primary traumatic dislocation of the shoulder. The patients of the first group (29 patients) after the dislocation of the shoulder was corrected, functional treatment was performed using orthoses and a developed course of physical therapy. Patients of the second group (27 patients) were treated according to the traditional method with the use of plaster immobilization after the dislocation of the shoulder was corrected. Shoulder joint radiography, MRI, determination of potentials in biologically active points (BAT) during the first 2-3 days after dislocation were used to diagnose shoulder dislocation and assess outcomes. To assess the immediate results, the electrical potential in BAHT was studied after 1,3 and 6 months. In 70,3% of group 1 patients, positive outcomes were obtained after 3-6 months on the ASES scale, while in the second group such results were achieved only in 57,3% of patients, and on the UCLA scale 22,8 and 19,2%, respectively. Thus, the use of the proposed tactics of functional treatment makes it possible to significantly (p<0,05) improve outcomes in patients of the older age group.

Soft collar for acute cervical spine injury immobilisation -patient experiences and outcomes: A single centre mixed methods study.

BACKGROUND: Cervical collars are used as standard care for neck immobilisation after cervical spine injury. Although evidence for the most effective type of collar is lacking, there is evidence regarding adverse patient outcomes when managed in a semi or rigid collar. In response to the evidence of complications and adverse effects when using a hard collar, a large Australian adult trauma hospital that specializes in spinal care, changed its policy from hard to soft collars when managing acute cervical spine injury. OBJECTIVE: The aim of this study was to investigate patients' experiences and outcomes when wearing a soft collar for acute cervical spine injury management in hospital. METHOD: A single centre mixed method sequential study design was used. RESULTS: Medical records from 136 patients were examined and no adverse events resulting from collar use were recorded. Interviews with 20 patients revealed that they understood the value of wearing a soft collar. The soft collars were considered supportive and well tolerated, with good adherence to recommendations for use. CONCLUSIONS: Understanding the patients' experiences informs better care management. This study suggests that soft collars are well tolerated, do not result in pressure injuries or other adverse events and are suitable for managing acute cervical spine injury.

Immobilization-Related Hypercalcemia in a COVID-19 Patient With Prolonged Intensive Care Unit Stay.

ABSTRACT: Immobilization-related hypercalcemia is an uncommon finding in patients admitted to intensive care unit. We report a case of severe hypercalcemia in a COVID-19 patient admitted to intensive care unit for hypoxemic respiratory failure. He developed an acute kidney injury requiring continuous renal replacement therapy with regional citrate anticoagulation. Citrate chelates ionized calcium and stop the coagulation cascade locally, preventing filter clotting. Calcium is then given intravenously to a specific target (normocalcemia). It is only when calcium infusion has been stopped that bone resorption and hypercalcemia were unmasked.

Development of a novel knee contracture mouse model by immobilization using external fixation.

AIMS: Several studies have used animal models to examine knee joint contracture; however, few reports detail the construction process of a knee joint contracture model in a mouse. The use of mouse models is beneficial, as genetically modified mice can be used to investigate the pathogenesis of joint contracture. Compared to others, mouse models are associated with a lower cost to evaluate therapeutic effects. Here, we describe a novel knee contracture mouse model by immobilization using external fixation. METHODS: The knee joints of mice were immobilized by external fixation using a splint and tape. The passive extension range of motion (ROM), histological and immunohistochemical changes, and expression levels of fibrosis-related genes at 2 and 4 weeks were compared between the immobilized (Im group) and non-immobilized (Non-Im group) groups. RESULTS: The extension ROM at 4 weeks was significantly lower in the Im group than in the Non-Im group (p < 0.01). At 2 and 4 weeks, the thickness and area of the joint capsule were significantly greater in the Im group than in the Non-Im group (p < 0.01 in all cases). At 2 weeks, the mRNA expression levels of the fibrosis-related genes, except for the transforming growth factor-ß1, and the protein levels of cellular communication network factor 2 and vimentin in the joint capsule were significantly higher in the Im group (p < 0.01 in all cases). CONCLUSION: This mouse model may serve as a useful tool to investigate the etiology of joint contracture and establish new treatment methods.