What is the pathophysiology of corticosteroid-induced myopathy?

Updated: Sep 10, 2019
  • Author: Patrick M Foye, MD; Chief Editor: Stephen Kishner, MD, MHA  more...
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Answer

Steroid myopathy may be more frequent with the use of fluorinated steroids, such as dexamethasone [9] or triamcinolone, than with nonfluorinated ones, such as prednisone or hydrocortisone. [10, 11] Although the exact mechanism of the muscle pathology is unclear, it may be related to decreased protein synthesis, increased protein degradation, alterations in carbohydrate metabolism, mitochondrial alterations, electrolyte disturbances, and/or decreased sarcolemmal excitability. Sedentary lifestyle may increase the risk of muscle weakness in a patient taking corticosteroids, since corticosteroids seem to affect less active muscles preferentially. Two distinct types of steroid myopathy exist, acute and chronic. The chronic (or classic) form occurs after prolonged use of corticosteroids and has a more insidious course. The acute form is less common, is associated with rhabdomyolysis, and occurs abruptly while the patient is receiving high-dose corticosteroids.

One study used skeletal muscle biopsy of the vastus lateralis and realtime polymerase chain reaction (PCR) to investigate the effects of dexamethasone on skeletal muscle. Twenty-four subjects were studied before and after the administration of dexamethasone 4 mg by mouth daily for 4 days. Following dexamethasone, all subjects (12 female and 12 male) demonstrated similar decreases in serum testosterone and transcription factor 4 (TCF4), an androgen-responsive transcription factor. Additionally, a significant decrease in skeletal muscle androgen receptor mRNA levels occurred following dexamethasone administration. Furthermore, plasma insulinlike growth factor-1 (IGF-1), produced by the liver, increased significantly following dexamethasone administration, whereas skeletal muscle IGF-1 mRNA levels decreased. Further studies are needed to investigate the significance of these findings. [12]

In a study performed by Levin et al, 60% of participants who used inhaled corticosteroids daily for a year or greater reported muscle weakness and 20% of that group showed objective signs of weakness. These researchers measured inhaled steroid–induced myopathy using a peripheral motor deficits scale, stepper test, ankle/wrist index, neuropathy disability score, and statistical analysis. Peripheral motor deficits scale was formulated to determine early stages of myopathy with physician's rating of the participant's weakness while (1) walking up and down stairs and (2) with difficulty in buttoning/unbuttoning, sewing, or picking up coins. Muscle atrophy measurements were made using an ankle/wrist index, in which the smallest circumference of the dominant leg above the ankle and that of the forearm above the wrist were compared. Neuropathy disability score was determined by evaluation of sensory functions and reflexes. [13]

A study by Minetto et al found that short-term glucocorticoid administration in healthy subjects produced the sorts of changes in muscle fibers that arise prior to the clinical appearance of myopathy in patients treated with glucocorticoids. In the study, in which dexamethasone was administered to five healthy males for 7 days, type 1 and type 2A muscle fibers demonstrated a reduction in cross-sectional area, myosin, and specific force. [14]

Similarly, a study by Nawata et al suggested that steroid therapy is associated with a reduction in muscle volume. The study, which included seven patients with myositis and eight controls, used computed tomography (CT) scanning to observe steroidal effects on a cross section of skeletal muscle at the caudal end of the third lumbar vertebra. The investigators found that in both groups, following treatment with high doses of steroids, the cross-sectional area of skeletal muscle was reduced, while the low muscle-attenuation rate was increased. Nonetheless, the patients with myositis experienced an increase in muscle strength, apparently due to factors other than muscle volume change. [15]


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