Skeletal muscle disuse atrophy – pathophysiology, prognosis and treatment
Dr KS Dhillon MBBS, FRCS, LLM
Introduction
Skeletal muscular atrophy can result from disuse or neurological injury/disease. Atrophy can also occur due to ageing (sarcopenia) and it is believed to be due to neural degeneration. Disuse atrophy results from limb immobilisation, bed rest, physical inactivity, joint dysfunction and elimination of gravity (space flights). In the past disuse atrophy of muscles was not given much attention because it was believed to resolve spontaneous with return to normal activities. However with the advent of space flights there has been renewed interest in disuse skeletal muscle atrophy. In recent years there have been more animal and human studies to understand the pathophysiology and prognosis of disuse skeletal muscle atrophy.
Disuse skeletal muscle atrophy
Disuse skeletal muscle atrophy as the name suggests is due to inactivity of the muscle brought about by limb immobilisation, bed rest, physical inactivity, joint dysfunction or elimination of gravity (space flights). It results in loss of muscle bulk and strength. The atrophy starts within a few days and the severity of the atrophy is proportionally more with increase in the duration of disuse of the muscle. Loss of muscle bulk and strength can also result from neurological injury, neurological disease and ageing. Loss of muscle bulk and strength that results from ageing is known as sarcopenia which starts after the age of 40 years and progresses as we age. It is believed to result from neurodegeneration and age related hormonal changes (1).
Pathophysiology
The cellular mechanisms responsible for muscle atrophy have been studied in animals by hind limb suspension or limb immobilisation by cast or external fixation (2). Zarzheveky et al showed that immobilisation of the hind limb of rats with an external fixator for 4 weeks produced about 50% weight loss of the gastrocnemius, quadriceps, plantaris and the soleus. Histological and ultrastructure examination showed marked myopathy changes in the muscles with distortion of the sarcomeres and loss of myofibrils. The acid phosphate activity increased by about 85% and the creatine phosphokinase activity was reduced by about 40% reflecting a significant decrease in protein synthesis in the muscles. The biochemical values and muscle morphology returned to near normal after 4 weeks of mobilisation of the limb in the rats. (2).
Although protein synthesis reduces there is no change in protein degradation in humans which results in the loss of the muscle bulk. However there is no decrease in the number of muscle fibres (3).
Prognosis
Snijders et al studied muscle disuse atrophy in 12 young (24 +/- 1 year old) adults who were subjected to a 2 weeks immobilisation of one lower limb in full length cast. They tested muscle strength; muscle cross sectional area (CT scan) and muscle fibre type characteristic (muscle biopsies), before and after immobilisation as well at 6 weeks after natural rehabilitation. They found that there was considerable loss in skeletal muscle mass and strength after 2 weeks of immobilisation and that the muscle mass and strength returned to the baseline values within 6 weeks of recovery without any specific rehabilitative programme. The loss of muscle mass was attributed to both type I and type II muscle fibre atrophy but there was no decline in satellite cell content (4).
Rittweger and Felsenberg studied the recovery of muscle atrophy and bone loss from 90 days of strict bed rest with -6 degrees head down tilt in 25 young healthy participants. The participants were followed up at 90,180 and 360 days and they were advised to return to their normal activities as soon as possible. No specific post immobilisation rehabilitation was instituted. The study found that the calf cross section as measure with a CT scan recovered rapidly after re-ambulation with the largest part of losses restored within 14 days and full recovery was seen within 90 days. The functional recovery however lagged behind morphological recovery. The vertical jump performance was completely recovered in 180 days. Even the diaphyseal bone losses fully recovered within a year of follow up in all subjects (5).
The loss of muscle mass and strength due to disuse appears to be different in different muscle groups and loss of muscle strength is not proportional to the loss of muscle mass. LeBlanc et al studied the loss of muscle area and strength changes associated with 5 weeks of horizontal bed rest in 9 male volunteers. The subjects underwent a 10 weeks of metabolic study in which they underwent 5 weeks of ambulatory control and 5 weeks of complete horizontal bed rest. They measured the leg muscle area with an MRI before and after bed rest and the strength was measured with a dynamometer. They found that the muscle area of the ankle plantarflexors (gastrocnemius and soleus) decreased by 12% whereas the muscle area of the ankle dorsiflexors did not reduce significantly after 5 weeks of disuse. Similarly the muscle strength of the plantarflexors reduced 26% but there was no significant reduction in the strength of the dorsiflexors. The study showed that there was a differential loss in muscle mass and strength in different muscle groups and the loss of strength was more than the loss of muscle bulk in the same group of muscles (6).
LeBlanc et al in an another study involving 8 male volunteers who underwent 17 weeks of continuous bed rest and another 8 weeks of reambulation found significant loss of muscle volume as measured with MRI scans of the back and the lower limbs. There was a decreased muscle volume of 30% in ankle planterflexors, 21% in ankle dorsiflexors, 16 to 18 % in the quadriceps and hamstrings and 9% in the low back intrinsic muscles (7).
Restoration of Skeletal Muscle after Disuse Atrophy
When the cause of the muscle atrophy is disuse, it is logical that the best way to restore the muscle’s previous function would be a return to normal physical activities. Applying mechanical load would be the most effective method to restore the muscle mass. An isolated bout of concentric or eccentric resistance exercise in young adults can produce a 112% increase in protein fractional synthesis rate at 3 hrs, 65% at 24 hrs and a 35% rate at 48 hrs post exercise. Exercise leads to an increase in muscle net protein balance that persists up to 2 days after an exercise bout and this increase is unrelated to the type of muscle contraction performed (8). Low volume (140 contractions in 14 days) resistance exercise has been found to prevent immobilisation induced atrophy in the quadriceps muscle (9). During bed rest exercise alone can reduce a loss in muscle mass (10).
Most often the muscle atrophy from disuse, recovers completely within 6 weeks, with return to normal activities and without specific rehabilitative exercises (4). In some cases it may take up 90 days for complete recovery from disuse atrophy without specific rehabilitation (5).
Muscle atrophy due to joint dysfunction
There is paucity of literature on muscle atrophy after uncomplicated skeletal injuries, probably due to the fact that the muscle atrophy that occurs due to disuse after fractures recovers spontaneously with fracture healing and after the patient returns to normal activities and whatever residual atrophy that remains does not produce functional disability. On the other hand when musculoskeletal injures produce joint dysfunction some amount of muscle atrophy and loss of muscle strength always does persists. This has been extensively studied in patients with anterior cruciate ligament laxity (ACL).
In assessing muscle bulk of the thigh it has to be remembered that there is a side to side difference in the muscle bulk due limb dominance with the bulk on the right being more than the left. Strandberg et al studied 60 patients who were scheduled for anterior cruciate ligament reconstruction. They performed CT scan of the thigh to measure the cross sectional area (CSA) of the thigh muscles. They found that the quadriceps CSA was 5 % smaller on the injured side and that the difference between the injured and non-injured side was larger for the right side as compared to the left which is suggestive of a larger muscle bulk on the right side (11).
Lorentzon et al also found an average of 5.1% decrease in quadriceps CSA in patients with chronic ACL laxity. The isokinetic mechanical output was on the average 21% less on the injured side. However the isokinetic performance did not correlate with the amount of muscle atrophy and the authors believe that non-optimal activation of the muscles is probably involved in the poorer isokinetic performance (12).
Even after ACL reconstruction some amount of lingering Quadriceps atrophy and weakness persists even after adequate rehabilitation (13) (14). A 20% Quadriceps strength deficit has been found in patients at 1year follow up after reconstruction of the ACL (15).
Conclusion
Skeletal muscle atrophy sets in rapidly within days after immobilisation or disuse. Two weeks of immobilisation can cause considerable loss of muscle mass and strength. Immobilisation produces morphological changes in the muscle as well as alteration of biochemical markers that are indicative of significant decrease in protein synthesis. However no loss of muscle fibres occurs with disuse of muscles.
With mobilisation a rapid change in the level of biochemical markers occurs within hours which is suggestive of a significant increase of protein synthesis. Most of the atrophy from immobilisation returns to normal after mobilisation within 6 weeks and in others it may take up to 180 days depending on the severity of the atrophy. Mechanical loading appears to be the best way to restore the muscle mass and strength. In most instances when no joint dysfunction exists no specific rehabilitative exercises are needed. However when joint dysfunction is present, even intensive rehabilitation may fail to fully restore the muscle strength despite a complete recovery of muscle mass.
References
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