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This technique uses a laser to poke a hole in muscle cells. Then the muscle cell is observed in real time as it reseals the hole, a natural repair process. For the second part of the study, scientists tested steroids in mice.
They damaged the leg muscles in mice and noticed the mice receiving the steroids recovered more rapidly from injury. Her work also implies normal muscle injury would improve more quickly by taking a weekly dose of steroids such as prednisone. In the future, McNally would like to test steroids in humans and is considering studying it in forms of muscular dystrophy in which steroids would not normally be given, like Becker Muscular Dystrophy or Limb Girdle Muscular Dystrophy.
Steroid treatment is not usually offered for these diseases since the side effects are thought to outweigh any potential benefit. Type above and press Enter to search. Press Esc to cancel. News Center. J Steroid Biochem Mol Biol. Steroid myopathy: some unresolved issues. J Endocrinol Invest. Acute steroid myopathy: a highly overlooked entity. Drug-induced myopathies. An overview of the possible mechanisms. Pharmacol Rep. Perrot S, Le Jeunne C. Presse Med.
Prevention and management of glucocorticoid-induced side effects: A comprehensive review: Ocular, cardiovascular, muscular, and psychiatric side effects and issues unique to pediatric patients. J Am Acad Dermatol. Glucocorticoids and Skeletal Muscle. Adv Exp Med Biol. Steroid myopathy in patients with chronic respiratory diseases. J Neurol Sci. Steroid-induced weakness in patients with primary brain tumors. Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. Silver EM, Ochoa W.
Am J Case Rep. A rare case of severe myositis as paraneoplastic syndrome on breast cancer. World J Surg Oncol. LaPier TK. Glucocorticoid-induced muscle atrophy. The role of exercise in treatment and prevention. J Cardiopulm Rehabil.
Corticosteroid-induced myopathy mimicking therapy-resistant asthma. Ann Allergy Asthma Immunol. Corticosteroid Induced Myopathy. In: StatPearls [Internet]. In this Page. Bulk Download. Related information. Similar articles in PubMed. Review Corticosteroid-induced myopathy of the respiratory muscles. Circulating glucose and insulin levels are elevated in response to prednisone, indicating that glucose metabolism is more affected than protein metabolism by glucocorticoids.
We also thank the Department of Radiology and members of the GCRC dietary, nursing, and support staff for their help in carrying out these studies. Diabetes 38 : — Google Scholar. Rizza FA , Mandarino LJ , Gerich JE Cortisone-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization to a post-receptor defect of insulin action. J Clin Endocrinol Metab 54 : — J Clin Endocrinol Metab 79 : — J Clin Endocrinol Metab 86 : — Clin Endocrinol Oxf 18 : — J Clin Endocrinol Metab 61 : 83 — Eur J Clin Invest 15 : — Chrysis D , Underwood LE Regulation of components of the ubiquitin system by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone.
Endocrinology : — Clin Chim Acta : 47 — J Endocrinol : 83 — J Parenteral Enteral Nutr 24 : 30 — Biochem J : — J Appl Physiol 66 : — Br J Nutr 79 : — Muscle Nerve 9 : 1 — Diabetes 48 : — J Clin Invest 86 : — J Clin Invest 82 : — Eur J Clin Invest 21 : — Diabetes 47 : — J Clin Invest 95 : — Muscle Nerve Suppl 5 : S93 — S Am Biotechnol Lab 12 : 45 — Metabolism 31 : — Anal Biochem : 77 — Anal Biochem : — Lowry O , Passoneu J A flexible system of enzymatic analysis.
New York : Academic. J Orthopaed Res 22 : — Circ Res 92 : 81 — J Clin Endocrinol Metab 68 : — Mauras N , Beaufrere B Recombinant human insulin-like growth factor-1 enhances whole body protein anabolism and significantly diminishes the protein catabolic effects of prednisone in humans without diabetogenic effect. J Clin Endocrinol Metab 80 : — Biochem Biophys Res Commun : — Lawler, MA , Rotwein P Coordinate control of muscle cell survival by distinct insulin-like growth factor activated signalling pathways.
J Cell Biol : — Proc Soc Exp Biol Med : — Hilding A , Brismar K , Thoren M , Hall K Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.
J Clin Endocrinol Metab 77 : — J Endocrinol : — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation.
Close mobile search navigation Article Navigation. Volume Article Contents Abstract. Subjects and Methods. Journal Article.
Short , Kevin R. Oxford Academic. Jonas Nygren. Maureen L. Sreekumaran Nair. Nair, M. Cite Cite Kevin R. Select Format Select format. Permissions Icon Permissions. Abstract Glucocorticoids can cause muscle atrophy, but the effect on muscle protein metabolism in humans has not been adequately studied to know whether protein synthesis, breakdown, or both are altered.
TABLE 1. Plasma metabolites and hormones. P value. Open in new tab. TABLE 2. Amino acid. Alanine 1. TABLE 3. Open in new tab Download slide. TABLE 4. Citrate synthase activity Contribution of insulin resistance to catabolic effect of prednisone on leucine metabolism in humans. Google Scholar Crossref. Search ADS. Currently, a non-immune cell mediated mechanism in myositis has been proposed [ 21 ].
It was reported that the endoplasmic reticulum ER stress pathways are chronically activated in patients with myositis [ 21 ]. Additionally, the biopsy specimens from patients with myositis and mice models of myositis demonstrated an increase in levels of Grp78 also known as HSPA5 , which is an ER stress-related protein [ 22 ].
The biopsy specimens from patients with myositis also showed co-localization of MHC class I and the ER marker, calnexin [ 22 ]. These results suggest the possibility of the involvement of ER stress in the pathogenesis of myositis.
Xiao et al. In contrast, serum HSPA5 levels did not change in non-responders [ 23 ]. The results of the previous study suggest that steroid therapy reduces ER stress in steroid-responsive patients with myositis. ER stress is known to increase reactive oxygen species, which are closely associated with mitochondrial dysfunction, depressed force generation, and activation of muscle catabolic and autophagy pathways [ 21 ]. We speculate that steroid therapy improves muscle strength via the reduction of ER stress and reactive oxygen species followed by an improvement in mitochondrial function.
Our study suggests that the improvement in muscle strength after steroid therapy is not influenced by an improvement in muscle volume, but rather by an improvement in other factors, such as amelioration of mitochondrial dysfunction. Our study has a few limitations. First, this was a retrospective study and the number of patients was small. The non-significant change in the low muscle attenuation rate after steroid therapy and the non-significant change between the rate of change of muscle volume in patients with myositis associated with COPD and cancer may be partly due to the small sample size.
Second, the regimens for steroid reduction and the timing of implementation of the second CT were different for each of the patients, which makes it difficult to accurately assess the correlations between muscular changes and clinical factors.
Third, though patients who experienced disuse syndrome were excluded from the control group, exact scores from the MMT muscular strength of the control group were unknown, which makes it difficult to assess the change of muscle strength in the control group. However, our study suggests the importance of therapies that not only improve muscle mass but also improve the quality of muscle strength for the treatment of myositis.
Hence, this study may provide novel insights into therapies for myositis. Nonetheless, further studies are needed to reveal the mechanism and treatment of muscle weakness in patients with myositis. In patients with myositis treated with steroid therapy, muscle mass decreased after steroid therapy, suggesting that the improvement in muscle strength was due to factors other than changes in muscle volume.
Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. Article PubMed Google Scholar. Mechanisms of glucocorticoid-induced myopathy. J Endocrinol. Steroid myopathy in connective tissue disease. Am J Med. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunol. Diagnosis and classification of idiopathic inflammatory myopathies.
J Intern Med. Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy. Bioelectrical impedance analysis in clinical practice: a new perspective on its use beyond body composition equations. Regional skeletal muscle measurement: evaluation of new dual-energy X-ray absorptiometry model.
J Appl Physiol Biomarkers of sarcopenia in clinical trials-recommendations from the international working group on sarcopenia. J Cachexia Sarcopenia Muscle. Skeletal muscle area correlates with body surface area in healthy adults. Hepatol Res. MR imaging of skeletal muscle signal alterations: systematic approach to evaluation. Eur J Radiol. Measurement of skeletal muscle radiation attenuation and basis of its biological variation.
Acta Physiol Oxf. Quantitative analysis of skeletal muscle mass in patients with rheumatic diseases under glucocorticoid therapy--comparison among bioelectrical impedance analysis, computed tomography, and magnetic resonance imaging. Mod Rheumatol. Bohan A, Peter JB.
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First, this was a retrospective study and the number of patients was small. The non-significant change in the low muscle attenuation rate after steroid therapy and the non-significant change between the rate of change of muscle volume in patients with myositis associated with COPD and cancer may be partly due to the small sample size.
Second, the regimens for steroid reduction and the timing of implementation of the second CT were different for each of the patients, which makes it difficult to accurately assess the correlations between muscular changes and clinical factors. Third, though patients who experienced disuse syndrome were excluded from the control group, exact scores from the MMT muscular strength of the control group were unknown, which makes it difficult to assess the change of muscle strength in the control group.
However, our study suggests the importance of therapies that not only improve muscle mass but also improve the quality of muscle strength for the treatment of myositis. Hence, this study may provide novel insights into therapies for myositis. Nonetheless, further studies are needed to reveal the mechanism and treatment of muscle weakness in patients with myositis.
In patients with myositis treated with steroid therapy, muscle mass decreased after steroid therapy, suggesting that the improvement in muscle strength was due to factors other than changes in muscle volume. Mechanisms involved in the side effects of glucocorticoids.
Pharmacol Ther. Article PubMed Google Scholar. Mechanisms of glucocorticoid-induced myopathy. J Endocrinol. Steroid myopathy in connective tissue disease. Am J Med. Steroid myopathy: incidence and detection in a population with asthma. J Allergy Clin Immunol. Diagnosis and classification of idiopathic inflammatory myopathies. J Intern Med. Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy.
Bioelectrical impedance analysis in clinical practice: a new perspective on its use beyond body composition equations.
Regional skeletal muscle measurement: evaluation of new dual-energy X-ray absorptiometry model. J Appl Physiol Biomarkers of sarcopenia in clinical trials-recommendations from the international working group on sarcopenia.
J Cachexia Sarcopenia Muscle. Skeletal muscle area correlates with body surface area in healthy adults. Hepatol Res. MR imaging of skeletal muscle signal alterations: systematic approach to evaluation. Eur J Radiol. Measurement of skeletal muscle radiation attenuation and basis of its biological variation. Acta Physiol Oxf. Quantitative analysis of skeletal muscle mass in patients with rheumatic diseases under glucocorticoid therapy--comparison among bioelectrical impedance analysis, computed tomography, and magnetic resonance imaging.
Mod Rheumatol. Bohan A, Peter JB. Polymyositis and Dermatomyositis first of two parts. N Engl J Med. Statistical methodology for the concurrent assessment of interrater and intrarater reliability: using goniometric measurements as an example. Phys Ther. Morel-Lavallee lesions-review of pathophysiology, clinical findings, imaging findings and management.
J Clin Diagn Res. Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. Fahal IH. Uraemic sarcopenia: aetiology and implications.
Nephrol Dial Transplant. Role of glucocorticoids in the molecular regulation of muscle wasting. Crit Care Med. Ann Rheum Dis. Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction.
Arthritis Rheum. Increased levels of HSPA5 in the serum of patients with inflammatory myopathies--preliminary findings. Clin Rheumatol. Download references. All data generated during this study are included in this article. You can also search for this author in PubMed Google Scholar. TNawata wrote the manuscript. All authors read and approved the final manuscript. Correspondence to Makoto Kubo. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Reprints and Permissions. This is even more important in patients with underlying neuromuscular diseases, in which the symptoms of steroid myopathy can be easily attributed to their pre-existing disease.
In such cases, timely dose reduction, or preferably, drug discontinuation if possible, are likely to be followed by a significant improvement in muscle strength. Currently, the great diversity in the presentation of early steroid myopathy; the frequent ascribing of symptoms to the primary disease; and poor awareness of this entity, all contribute to delayed recognition and belated treatment. Steroid myopathy. Clinical, histologic and cytologic observation.
Johns Hopkins Med J ; : — Google Scholar. Acute hydrocortisone myopathy. Acute hydrocortisone myopathy in acute severe asthma. Thorax ; 41 : — 2. Acute myopathy in severe acute asthma treated with intravenously administered corticosteroids. Am Rev Respir Dis ; : — 3. Acute myopathy and neuropathy in status asthmaticus: case report and literature review.
Muscle Nerve ; 16 : 84 — Steroid myopathy in connective tissue disease. Kumar S. Steroid-induced myopathy following a single oral dose of prednisone. Neurol India ; 51 : — 6. Khan MA , Larson E. Acute myopathy secondary to oral steroid therapy in a year-old man: a case report. J Med Case Rep ; 5 : Acute myopathy following short-term low-dose oral steroid therapy. J Ind Acad Clin Med ; 10 : 65 — 8. Acute myopathy following intra-muscular injection of compound betamethasone.
Medicine Baltimore ; 96 : e Steroid myopathy induced by epidural triamcinolone injection. Brit J Rheumatol ; 34 : — 6. Herzog AG. Proximal myopathy associated with inhaled steroids.
JAMA ; : Dekhuizen PN , Decramer M. Steroid-induced myopathy and its significance to respiratory disease: a known disease rediscovered. Eur Respir J ; 5 : — Respiratory muscle fibres: specialisation and plasticity. Thorax ; 59 : — Gupta A , Gupta Y. Glucocorticoid-induced myopathy: pathophysiology, diagnosis, and treatment. Indian J Endocrinol Metab ; 17 : — 6. The effects of non-genomic glucocorticoid mechanisms on bodily functions and the central neural system.
A critical evaluation of findings. Front Neuroendocrinol ; 29 : — Minireview: rapid glucocorticoid signaling via membrane-associated receptors. Endocrinology ; : — Buttgereit F , Scheffold A. Rapid glucocorticoid effects on immune cells.
Steroids ; 67 : — Oxidative stress-associated mitochondrial dysfunction in corticosteroid-treated muscle cells. Muscle Nerve ; 30 : 49 — Chronic corticosteroid administration causes mitochondrial dysfunction in skeletal muscle. J Neurol ; : — 9.
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Volume The present study results indicate that there are no apparent disturbances in muscle protein metabolism, at least in young healthy people. The threshold for glucocorticoid effects may differ with age or health status. For example, it was reported that dexamethasone has more deleterious effects on older rats 18 months , compared with younger rats 6—8 months The effect of glucocorticoids on protein metabolism may also be less evident in the postabsorptive state, compared with after a meal.
The elevation of glucose, insulin, C-peptide, and glucagon in the present study suggests that carbohydrate metabolism may be more likely to be impaired by glucocorticoids in the postabsorptive state than protein metabolism 1 — 4. Prednisone use resulted in elevated insulin and IGF-I levels.
The rise in these two hormones may provide an anabolic stimulus to counteract the glucocorticoid effect on protein metabolism.
A major action of insulin on protein metabolism is suppression of muscle protein breakdown 24 , Thus, elevated insulin levels during prednisone administration may have prevented an increase in protein breakdown in the current study. Arguing against this possibility, however, is the fact that short-term glucocorticoid use can increase the rate of whole-body protein catabolism, whereas circulating insulin is also elevated 3 , 4 , 19 , There is also evidence that glucocorticoids may actually blunt the ability of insulin to suppress protein breakdown 1 , 3.
Thus, the interplay between insulin and glucocorticoids is not yet sufficiently resolved to reliably determine whether the rise in circulating insulin could have prevented some or all of the predicted effects of glucocorticoids in the current study. This suggests that there may be a minimal level of IGF-I required to counter the glucocorticoid effects on protein. Thus, the elevated IGF-I may play a counterregulatory role to maintain protein turnover at normal levels.
Thus, insulin action specifically on glucose metabolism appears to be diminished by prednisone treatment, but the compensatory increase in insulin seems to reduce IGFBP-1 levels. Consistent with our findings, Miell et al. Collectively the data suggest that changes in the IGF system during glucocorticoid treatment are mostly responses to the changing metabolic condition rather than direct effects of glucocorticoids Finally, there were almost no changes in muscle function in response to the short-term use of prednisone because muscle strength and nearly all of the measures of muscle mitochondrial function were unchanged.
To our knowledge such a finding has not been previously reported. The other mitochondrial enzymes and ATP production measurements tested, which are part of or share the common pathways of the Krebs cycle and respiratory chain, were also unchanged.
Thus, at least one other unique step in fatty acid transport or oxidation was affected by prednisone to cause the increase in ATP production with palmitoyl- l -carnitine. Carnitine palmitoyl transferase is a likely candidate because it has been shown to be a rate-limiting step in fat oxidation It should be noted, however, that despite the apparent increase in muscle energy production from fat in response to prednisone administration, there was no change in the whole-body substrate use during the study as measured by indirect calorimetry.
It is possible that shifts in fuel metabolism were localized only to muscle or that the muscle adaptations preceded other steps in fat mobilization and transport required to actually alter substrate use. These possibilities require further study. In conclusion, the current study demonstrates that short-term use of a moderate dose of prednisone has no effect on whole-body or leg muscle protein metabolism.
There is also no effect on muscle strength or muscle mitochondrial function. Circulating glucose and insulin levels are elevated in response to prednisone, indicating that glucose metabolism is more affected than protein metabolism by glucocorticoids. We also thank the Department of Radiology and members of the GCRC dietary, nursing, and support staff for their help in carrying out these studies.
Diabetes 38 : — Google Scholar. Rizza FA , Mandarino LJ , Gerich JE Cortisone-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization to a post-receptor defect of insulin action. J Clin Endocrinol Metab 54 : — J Clin Endocrinol Metab 79 : — J Clin Endocrinol Metab 86 : — Clin Endocrinol Oxf 18 : — J Clin Endocrinol Metab 61 : 83 — Eur J Clin Invest 15 : — Chrysis D , Underwood LE Regulation of components of the ubiquitin system by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone.
Endocrinology : — Clin Chim Acta : 47 — J Endocrinol : 83 — J Parenteral Enteral Nutr 24 : 30 — Biochem J : — J Appl Physiol 66 : — Br J Nutr 79 : — Muscle Nerve 9 : 1 — Diabetes 48 : — J Clin Invest 86 : — J Clin Invest 82 : — Eur J Clin Invest 21 : — Diabetes 47 : — J Clin Invest 95 : — Muscle Nerve Suppl 5 : S93 — S Am Biotechnol Lab 12 : 45 — Metabolism 31 : — Anal Biochem : 77 — Anal Biochem : — Lowry O , Passoneu J A flexible system of enzymatic analysis.
New York : Academic. J Orthopaed Res 22 : — Circ Res 92 : 81 — J Clin Endocrinol Metab 68 : — Mauras N , Beaufrere B Recombinant human insulin-like growth factor-1 enhances whole body protein anabolism and significantly diminishes the protein catabolic effects of prednisone in humans without diabetogenic effect. J Clin Endocrinol Metab 80 : — Biochem Biophys Res Commun : — Lawler, MA , Rotwein P Coordinate control of muscle cell survival by distinct insulin-like growth factor activated signalling pathways.
J Cell Biol : — Proc Soc Exp Biol Med : — Hilding A , Brismar K , Thoren M , Hall K Glucagon stimulates insulin-like growth factor binding protein-1 secretion in healthy subjects, patients with pituitary insufficiency, and patients with insulin-dependent diabetes mellitus.
J Clin Endocrinol Metab 77 : — J Endocrinol : — Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Sign In. Endocrine Society Journals. Advanced Search. Search Menu. Article Navigation. Close mobile search navigation Article Navigation.
Volume Article Contents Abstract. Subjects and Methods. Journal Article. Short , Kevin R. Oxford Academic. Jonas Nygren. Maureen L. Sreekumaran Nair. Nair, M. Cite Cite Kevin R. Select Format Select format. Permissions Icon Permissions.
Abstract Glucocorticoids can cause muscle atrophy, but the effect on muscle protein metabolism in humans has not been adequately studied to know whether protein synthesis, breakdown, or both are altered. TABLE 1. Plasma metabolites and hormones.
P value. Open in new tab. TABLE 2. Amino acid. Alanine 1. TABLE 3. Open in new tab Download slide. TABLE 4.
Citrate synthase activity Contribution of insulin resistance to catabolic effect of prednisone on leucine metabolism in humans. Google Scholar Crossref. Search ADS.
Metrics details. Steroid therapy, a key therapy for inflammatory, allergic, and immunological disorders, is often associated with steroid myopathy as one of the side effects. Steroid therapy is considered the first-line therapy for myositis; however, there have been no reports strictly comparing the muscle mass in patients with myositis before and after steroid therapy.
Thus, it is currently unclear whether steroid therapy for such patients affects muscle volume in addition to muscle strength. We aimed to determine the change in muscle mass after steroid therapy via cross-sectional computed tomography CT in patients with myositis. Data from seven patients with myositis and eight controls, who were all treated with high doses of steroids, were assessed before and after steroid therapy.
Clinical factors in patients with myositis included serum muscle enzyme levels and muscular strength. The cross-sectional area of skeletal muscle and the low muscle attenuation rate at the level of the caudal end of the third lumbar vertebra were obtained using CT and measured using an image analysis program for all patients.
Data were subjected to statistical analysis using several well-established statistical tests. The Wilcoxon signed-rank test was used for comparing paired data for each patient. The Mann-Whitney U test was used to compare sets of data sampled from two groups.
Muscular strength and serum muscle enzyme levels improved following steroid therapy in patients with myositis. In patients with myositis treated with steroid therapy, muscle mass decreased after steroid therapy suggesting that the improvement in muscle strength was due to factors other than a change in muscle volume.
Our study suggests the importance of therapies that not only improve muscle mass but also improve the quality of muscle strength. Peer Review reports. Although steroid therapy is useful, there are various side effects, such as an associated increased susceptibility to infection or glucose intolerance [ 1 ].
Steroid myopathy is another side effect of steroid therapy, which is induced by the catabolic action of steroids on skeletal muscles [ 12 ]. Muscle weakness in steroid myopathy usually begins in the proximal portion of the lower extremities, progresses to the upper proximal extremities, and finally affects the distal extremities [ 3 ]. It is known that steroid myopathy occurs in a dose-related manner.
Idiopathic inflammatory myopathies, collectively termed myositis, are autoimmune diseases characterized by skeletal muscle inflammation. Patients with myositis present with muscle weakness and atrophy in the proximal muscles and increases in serum levels of muscular enzymes [ 5 ]. Steroid therapy is considered the first-line therapy for myositis. With steroid therapy, patients with myositis show an improvement in muscle strength [ 6 ]; however, to our knowledge, there have been no reports strictly comparing the muscle mass of patients with myositis before and after steroid therapy.
Therefore, it is unclear whether steroid therapy for patients with myositis improves not only muscle strength but also muscle volume. Recently, several methods for quantifying muscle mass have been proposed. Bioelectrical impedance analysis and dual X-ray absorptiometry estimate the fat-free mass of the whole body or body segments [ 78 ]. Computed tomography CT and magnetic resonance imaging MRI are also used to measure cross-sectional images that enable the estimation of muscle mass [ 910 ].
Yoshizumi et al. It has been reported that MRI is a useful tool to diagnose muscle disorders. MRI makes it easy to assess not only muscle mass but also muscle quality, especially chemical shift imaging and Dixon based T2W imaging, which are new useful tools to assess fatty infiltration [ 11 ]. It has also been proposed that CT allows for the assessment of low attenuation of skeletal muscle i. With regard to the muscle volume of patients with rheumatic diseases, Hosono et al.
In this study, we retrospectively compared the changes in muscle volume before and after steroid therapy in patients with myositis and in steroid-treated patients without myositis by measuring the skeletal muscle area with CT.
Seven patients with recent-onset myositis diagnosed from to were included in this study five patients had dermatomyositis and two had mixed connective tissue disease. All patients fulfilled the diagnostic criteria proposed by Bohan and Peter [ 14 ]. The mean age was 55 years range, 15—95 years and four patients were female. Eight patients without myositis were also included as a control group. The mean age of the patients in the control group was 70 years range, 46—94 years and six patients were female.
The control group also underwent high-dose steroid therapy at the same maximum corticosteroid dose as the myositis group. Patients who experienced disuse syndrome were excluded prior to the inclusion of the final eight patients in the control group Table 2.
The muscular strength of patients with myositis were measured using a manual muscle test MMT before and after steroid therapy. All patients underwent CT to assess the general involvement before and after steroid therapy, and we retrospectively analyzed the change in muscle mass by comparing the CT findings.
The first CT was performed within 6 weeks before the initiation of high-dose steroid therapy. The second CT was performed during the tapering of steroid therapy. CT data, including images of the caudal end of the third lumbar vertebra, were obtained using standard procedures.
Two radiologists measured the cross-sectional area of the skeletal muscles and the low muscle attenuation rate at the level of caudal end of the third lumbar vertebra. Measurement of the cross-sectional area of skeletal muscle at the level of the caudal end of the third lumbar vertebra.
Muscle volume was measured in the psoas muscle and other muscles. The Wilcoxon signed-rank test was used to compare paired data for each patient. The Mann-Whitney U test was used to compare two sets of data sampled from the two groups. The inter-reader agreement showed excellent correlation between the two readers, ranging from 0.
Seven patients with myositis and eight controls were analyzed in this study. The muscle strength, measured using MMT, improved after steroid therapy in all patients with myositis Table 1. Table 1. The most frequent underlying diseases in patients with myositis were chronic obstructive pulmonary disease COPD and interstitial lung disease followed by cancer e.
No patients with cancer underwent chemotherapy. All underlying diseases were detected within 2 months of the diagnosis of myositis. Conversely, chronic kidney disease was the most frequent underlying disease in the control group Table 3. With regard to the rate of muscle volume change between the groups, although the myositis group showed greater muscle volume loss in comparison to the control group, the difference was not statistically significant Fig. CT computed tomography. Although all patients with myositis showed improvements in muscle strength and serum muscle enzyme levels after steroid therapy, there was a significant loss of muscle volume.
The loss of muscle mass is induced by both extrinsic causes and intrinsic causes. Extrinsic causes of focal muscle atrophy often developed after traumatic injury such as Morel-Lavallee syndrome which is a post-traumatic closed degloving injury [ 16 ]. Our patients did not have a history of trauma. Therefore, we think that extrinsic causes had little involvement in the change of muscle mass in our patients. With regard to intrinsic causes, previous studies have reported that patients with cancer, COPD, and chronic kidney disease exhibited a loss of muscle volume [ 171819 ].
In the present study, some of the patients had these conditions as underlying diseases. Therefore, the involvement of these underlying diseases may be associated with the observed muscle volume loss in our patients especially in patients with cancer and COPD in the myositis group.
However, the patients with myositis who did not develop these underlying diseases also showed a loss of muscle volume.
This suggests that steroid therapy itself decreases muscle volume in patients with myositis. Thus, an improvement in muscle strength in patients with myositis may be attributed to other factors and not to muscle volume change.
Some mechanisms have been proposed to explain the etiology of the loss of muscle volume. One of these mechanisms is an imbalance of protein synthesis and catabolism [ 20 ]. Steroid myopathy is induced by the hypercatabolism of skeletal muscle, which might have resulted in the loss of muscle volume in our patients. However, despite the loss of muscle mass, improvement in muscle strength was also observed in patients with myositis who were treated with steroids.
As such, we hypothesize that the improvement in muscle strength is influenced by an improvement in mitochondrial function. Currently, a non-immune cell mediated mechanism in myositis has been proposed [ 21 ]. It was reported that the endoplasmic reticulum ER stress pathways are chronically activated in patients with myositis [ 21 ]. Additionally, the biopsy specimens from patients with myositis and mice models of myositis demonstrated an increase in levels of Grp78 also known as HSPA5which is an ER stress-related protein [ 22 ].
The biopsy specimens from patients with myositis also showed co-localization of MHC class I and the ER marker, calnexin [ 22 ]. These results suggest the possibility of the involvement of ER stress in the pathogenesis of myositis.
Xiao et al. In contrast, serum HSPA5 levels did not change in non-responders [ 23 ]. The results of the previous study suggest that steroid therapy reduces ER stress in steroid-responsive patients with myositis. ER stress is known to increase reactive oxygen species, which are closely associated with mitochondrial dysfunction, depressed force generation, and activation of muscle catabolic and autophagy pathways [ 21 ].
We speculate that steroid therapy improves muscle strength via the reduction of ER stress and reactive oxygen species followed by an improvement in mitochondrial function.
Our study suggests that the improvement in muscle strength after steroid therapy is not influenced by an improvement in muscle volume, but rather by an improvement in other factors, such as amelioration of mitochondrial dysfunction. Our study has a few limitations. First, this was a retrospective study and the number of patients was small. The non-significant change in the low muscle attenuation rate after steroid therapy and the non-significant change between the rate of change of muscle volume in patients with myositis associated with COPD and cancer may be partly due to the small sample size.
Second, the regimens for steroid reduction and the timing of implementation of the second CT were different for each of the patients, which makes it difficult to accurately assess the correlations between muscular changes and clinical factors. Third, though patients who experienced disuse syndrome were excluded from the control group, exact scores from the MMT muscular strength of the control group were unknown, which makes it difficult to assess the change of muscle strength in the control group.
However, our study suggests the importance of therapies that not only improve muscle mass but also improve the quality of muscle strength for the treatment of myositis. Hence, this study may provide novel insights into therapies for myositis. Nonetheless, further studies are needed to reveal the mechanism and treatment of muscle weakness in patients with myositis.
In patients with myositis treated with steroid therapy, muscle mass decreased after steroid therapy, suggesting that the improvement in muscle strength was due to factors other than changes in muscle volume. Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther. Article PubMed Google Scholar.
Weekly doses of glucocorticoid steroids, such as prednisone, help speed recovery in muscle injuries, reports a new Northwestern Medicine. There is evidence that physical training improves muscle mass and strength in Evidence that prednisone-induced myopathy is reversed by physical training. It is known that steroid myopathy occurs in a dose-related manner. It has been reported that muscle strength in patients treated with > 40 mg/. This condition can develop after prolonged administration of prednisone at a dose of. Prednisone directly causes. All gave their signed informed consent for publication, specifying their wish to facilitate recognition in time to allow reversibility of muscle weakness. In patients with myositis treated with steroid therapy, muscle mass decreased after steroid therapy suggesting that the improvement in muscle strength was due to factors other than a change in muscle volume. Related Posts. The true extent of the problem is hard to estimate. Mammen AL.Federal government websites often end in. Before sharing sensitive information, make sure you're on a federal government site. The site is secure. NCBI Bookshelf. Natalya Surmachevska ; Vivekanand Tiwari. Authors Natalya Surmachevska 1 ; Vivekanand Tiwari 2. Corticosteroid-induced myopathy is an iatrogenic myopathy caused by chronic high to moderate systemic corticosteroid use. This is a common condition that must be differentiated from other iatrogenic and organic causes of myopathy.
Diagnosis is based on a high degree of clinical suspicion in patients on chronic steroids; prompt initiation of treatment in the form of corticosteroid withdrawal, if possible, should be initiated to avoid the morbidity associated with the condition. This activity reviews the characteristics, evaluation, and management of corticosteroid-induced myopathy and highlights the role of the interprofessional team in the care of patients with this condition. Objectives: Outline the epidemiology of corticosteroid-induced myopathy.
Explain the pathophysiology of corticosteroid-induced myopathy. Describe the evaluation of corticosteroid-induced myopathy. Identify opportunities for improving care coordination within the interprofessional team to improve outcomes for patients affected by corticosteroid-induced myopathy. Access free multiple choice questions on this topic. Corticosteroid-induced myopathy is a highly prevalent toxic noninflammatory myopathy, which occurs as an adverse effect of prolonged oral or intravenous glucocorticoid use.
It was first described in by Harvey Cushing, as part of a constellation of symptoms seen in Cushing syndrome. With the broader use of corticosteroids as therapeutic tools in the s, corticosteroid-induced myopathy became a more well-known entity.
Acute steroid-induced myopathy in the critical care setting is another presentation. Workup typically reveals normal creatine kinase and no other signs of inflammatory disease, with EMG studies unremarkable and biopsy showing atrophy of type 2b fast-twitch muscle fibers. The diagnosis requires a high index of suspicion and is confirmed when muscle weakness improves after 3 to 4 weeks of tapering steroids, although improvement may take months to a year.
Other than steroid withdrawal, other options include switching from fluorinated to nonfluorinated glucocorticoids, or alternate day dosing. Additionally, physical therapy in the form of resistance and aerobic exercise has shown in some studies to prevent and treat steroid-induced myopathy.
Corticosteroid-induced myopathy is a toxic noninflammatory myopathy caused by exogenous corticosteroid administration. Oral and intravenous formulations are most associated with corticosteroid myopathy, although case reports exist regarding steroid myopathy following inhaled corticosteroids and epidural, intramuscular, or intra-articular injection. Additional risk factors for corticosteroid-induced myopathy include patients with prior muscle disease or spinal cord injury, chronic respiratory illness, poor nutritional status, and sedentary lifestyle.
Corticosteroid-induced myopathy is believed to occur through both catabolic and anti-anabolic mechanisms. In terms of catabolic mechanisms, corticosteroids upregulate proteolytic systems such as the ubiquitin-proteasome system, cathepsins lysosomes , and calpains calcium-dependent systems.
This increases the proteolysis of myofibrillar proteins by dissociating actin from myosin. Additionally, corticosteroids with high mineralocorticoid activity lower serum potassium and phosphate, which may contribute to muscle weakness.
Muscle biopsy, if performed, reveals atrophy of type 2b or fast-twitch muscle fibers, with less impact on type 1 or slow-twitch muscle fibers, with variability in fiber size and centralization of nuclei, without evidence of inflammation or necrosis. Symptoms of corticosteroid-induced myopathy consist of muscle weakness, typically in a symmetric distribution involving the proximal extremity muscles, with the hip girdle affected more and earlier than the shoulders. It is associated with long-term muscle atrophy, notably with very minimal or no associated pain.
Patients often complain of difficulty rising from a seated position, climbing stairs, and trouble with overhead activities. It is important to observe that the higher doses are more likely to induce clinical myopathy. They may have metabolic complications, including obesity, diabetes, adrenal insufficiency, hyperlipidemia, hypertension, skin, and bone disorders, including osteoporosis and avascular necrosis.
Corticosteroid-induced myopathy is a clinical diagnosis that requires a high index of suspicion. Labwork including creatine kinase CK , aspartate aminotransferase AST , lactate dehydrogenase LDH , and aldolase are typically normal, although these may be elevated very early in the disease process or acute steroid myopathy of critically ill patients. EMG findings are typically normal, with an occasional slight reduction in the amplitude of the motor unit potentials.
This occurs as EMG measures both type 1 and type 2 fiber activity, and does not differentiate in the preferential atrophy of type 2b muscle fibers. Determination of corticosteroid-induced myopathy is ultimately tested and confirmed when symptoms improve with tapering or discontinuing corticosteroids.
Corticosteroid-induced myopathy is an often overlooked diagnosis, as symptoms are occasionally attributed to the primary illness that the corticosteroid is treating. This prolongs time to diagnosis and increases morbidity. Thus, a high index of suspicion must be maintained when patients present with muscle weakness in any muscle group with particular emphasis on pelvic girdle with any dose, route, or duration of steroids.
For patients unable to taper off steroids, replacement of fluorinated glucocorticoids with non-fluorinated glucocorticoids, such as dexamethasone with prednisone or hydrocortisone should be considered. Although the mechanism is not clear, fluorinated glucocorticoids are known to be much more potent than non-fluorinated glucocorticoids, and this may contribute to their higher toxicity.
Diagnosis is confirmed when muscle strength improves within 3 to 4 weeks of tapering steroids, although recovery may take months to a year. Physical therapy with aerobic and resistance exercises is effective at modulating muscle atrophy in patients who have corticosteroid-induced myopathy. However, they have not been conclusively evaluated in humans and are not currently recommended. Other medications known to cause drug-induced myopathy include colchicine, antimalarials, and antiretrovirals.
Drug-induced myopathy should be considered mainly for patients taking two myopathic agents such as hydroxychloroquine and glucocorticoids for inflammatory disorders. In contrast to corticosteroid-induced myopathy, these present with elevated muscle enzymes, worsening muscle weakness with discontinuation of steroids, systemic signs of muscle breakdown and inflammation, and characteristic "early recruitment" findings on EMG.
Metabolic myopathies related to carbohydrate, lipid, and purine metabolism, and congenital myopathies are more rare causes of muscle weakness and have distinct patterns of presentation. Corticosteroid-induced myopathy is reversible, with improvement in myopathy within 3 to 4 weeks of tapering corticosteroids, although recovery can take months to a year. Switching from fluorinated glucocorticoids like dexamethasone to nonfluorinated glucocorticoids such as prednisone can sometimes help.
It should be recognized that many of the patients on the chronic steroid therapy would need to be weaned off slowly from their steroid regimen to avoid adrenal insufficiency or exacerbation of the disease process for which they have been on long-term steroids.
Physical therapy, with both resistance and endurance exercise, taking into account baseline functional status, is recommended to help prevent and treat glucocorticoid-induced myopathy. Complications of corticosteroid-induced myopathy include the morbidity and subsequent mortality associated with chronic muscle weakness. Patients experience decreased quality of life through the inability to perform activities of daily living and are at increased risk for falls and injury.
Patients should routinely be educated on the risk versus benefit profile of corticosteroids, including the risk of corticosteroid-induced myopathy. Patients should be advised to contact their provider if they notice weakness developing.
Patients should be informed that physical activity can help prevent and mitigate the effects of corticosteroid-induced myopathy, and should be prescribed physical therapy as part of a preventive and treatment regimen.
Given the high incidence of corticosteroid-induced myopathy in patients receiving glucocorticoid therapy for a wide range of clinical indications, an interprofessional team should implement systematic clinical screening for corticosteroid-induced myopathy in the appropriate patient populations.
Since primary care clinicians are the most frequently and consistently involved specialty in taking care of such patients, they should maintain a high degree of suspicion for this diagnosis. Additionally, providers and team members should systematically recommend and prescribe physical therapy to prevent and treat corticosteroid-induced myopathy.
This book is distributed under the terms of the Creative Commons Attribution 4. Turn recording back on. Help Accessibility Careers. StatPearls [Internet]. Search term. Continuing Education Activity Corticosteroid-induced myopathy is an iatrogenic myopathy caused by chronic high to moderate systemic corticosteroid use.
Introduction Corticosteroid-induced myopathy is a highly prevalent toxic noninflammatory myopathy, which occurs as an adverse effect of prolonged oral or intravenous glucocorticoid use.
Etiology Corticosteroid-induced myopathy is a toxic noninflammatory myopathy caused by exogenous corticosteroid administration. Pathophysiology Corticosteroid-induced myopathy is believed to occur through both catabolic and anti-anabolic mechanisms.
Histopathology Muscle biopsy, if performed, reveals atrophy of type 2b or fast-twitch muscle fibers, with less impact on type 1 or slow-twitch muscle fibers, with variability in fiber size and centralization of nuclei, without evidence of inflammation or necrosis.
History and Physical Symptoms of corticosteroid-induced myopathy consist of muscle weakness, typically in a symmetric distribution involving the proximal extremity muscles, with the hip girdle affected more and earlier than the shoulders. Evaluation Corticosteroid-induced myopathy is a clinical diagnosis that requires a high index of suspicion. Differential Diagnosis Other medications known to cause drug-induced myopathy include colchicine, antimalarials, and antiretrovirals.
Prognosis Corticosteroid-induced myopathy is reversible, with improvement in myopathy within 3 to 4 weeks of tapering corticosteroids, although recovery can take months to a year. Complications Complications of corticosteroid-induced myopathy include the morbidity and subsequent mortality associated with chronic muscle weakness. Deterrence and Patient Education Patients should routinely be educated on the risk versus benefit profile of corticosteroids, including the risk of corticosteroid-induced myopathy.
Enhancing Healthcare Team Outcomes Given the high incidence of corticosteroid-induced myopathy in patients receiving glucocorticoid therapy for a wide range of clinical indications, an interprofessional team should implement systematic clinical screening for corticosteroid-induced myopathy in the appropriate patient populations.
Review Questions Access free multiple choice questions on this topic. Comment on this article. References 1. Glucocorticoid-induced myopathy. Joint Bone Spine. Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients. Med Sci Sports Exerc. Evidence that prednisone-induced myopathy is reversed by physical training. J Clin Endocrinol Metab. Corticosteroid-induced adverse events in adults: frequency, screening and prevention.
Drug Saf. Gupta A, Gupta Y. Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment. Indian J Endocrinol Metab. Glucocorticoid-induced apoptosis and cellular mechanisms of myopathy.
J Steroid Biochem Mol Biol. Steroid myopathy: some unresolved issues.
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