Hanks GW, Trueman T, Twycross RG.
Corticosteroids in terminal cancer--a prospective analysis of current practice.
Postgrad Med J. 1983 Nov;59(697):702-6. doi: 10.1136/pgmj.59.697.702.
Abstract/Text
Over half of a group of 373 inpatients with advanced malignant disease were treated with corticosteroids for a variety of reasons. They received either prednisolone or dexamethasone, or replacement therapy with cortisone acetate. Forty percent of those receiving corticosteroids benefited from them. A higher response rate was seen when corticosteroids were prescribed for nerve compression pain, for raised intracranial pressure, and when used in conjunction with chemotherapy. No significant difference in efficacy was noted between the 2 drugs. The results, however, suggest that with a larger sample, dexamethasone would have been shown to be significantly better than prednisolone in the management of nerve compression pain. The incidence of side effects was broadly similar with dexamethasone and prednisolone. The most common side effect was oral candidosis and there was a highly significant relationship between the use of corticosteroids and the prescription of nystatin suspension. Dexamethasone was more likely than prednisolone to cause oro-pharyngeal candidosis. Dexamethasone was also associated with significantly more cases of psychological disturbance and hyperactivity. On the other hand, dexamethasone seems less likely to cause oedema, weight gain and dyspepsia. Corticosteroids were withdrawn because of side effects in only 11 patients (5%)--6 were receiving dexamethasone and 5 prednisolone. Dexamethasone has been adopted as the standard corticosteroid for terminal cancer patients at Sir Michael Sobell House.
Leatherman JW, Fluegel WL, David WS, Davies SF, Iber C.
Muscle weakness in mechanically ventilated patients with severe asthma.
Am J Respir Crit Care Med. 1996 May;153(5):1686-90. doi: 10.1164/ajrccm.153.5.8630621.
Abstract/Text
Patients who undergo mechanical ventilation for severe asthma are at risk of developing diffuse muscle weakness because of acute myopathy. The relative importance of corticosteroids and neuromuscular paralysis in causing the myopathy is controversial, and it is uncertain whether the chemical structure of the drug used to induce paralysis influences the risk of myopathy. Using a retrospective cohort study design, we evaluated 107 consecutive episodes of mechanical ventilation for severe asthma to assess (1) the incidence of clinically significant weakness in patients treated with corticosteroids alone versus corticosteroids with neuromuscular paralysis, (2) the influence of the duration of paralysis on the incidence of muscle weakness, and (3) the relative risk of weakness in patients paralyzed with the nonsteroidal drug atracurium versus an aminosteroid paralytic agent (pancuronium, vecuronium). The use of corticosteroids and a neuromuscular blocking agent was associated with a much higher incidence of muscle weakness as compared with the use of corticosteroids alone (20 of 69 versus O of 38, p < 0.001). The 20 weak patients were paralyzed significantly longer than the 49 patients who received a neuromuscular blocking agent without subsequent weakness (3.4 +/- 2.4 versus 0.6 +/- 0.7 d, p < 0.001). Eighteen of the 20 weak patients had been paralyzed for more than 24 h. The incidence of weakness was not reduced when paralysis was achieved with atracurium as opposed to an aminosteroid neuromuscular blocking agent. In conclusion, corticosteroid-treated patients with severe asthma who undergo prolonged neuromuscular paralysis are at significant risk for the development of muscle weakness, and the risk of weakness is not reduced by use of atracurium.
Behbehani NA, Al-Mane F, D'yachkova Y, Paré P, FitzGerald JM.
Myopathy following mechanical ventilation for acute severe asthma: the role of muscle relaxants and corticosteroids.
Chest. 1999 Jun;115(6):1627-31. doi: 10.1378/chest.115.6.1627.
Abstract/Text
BACKGROUND: Acute myopathy following mechanical ventilation for near-fatal asthma (NFA) has been described recently, and some researchers have suggested that this complication is related to the use of neuromuscular blocking agents (NMBAs) and corticosteroids (CSs).
OBJECTIVES: To determine the incidence of acute myopathy in a group of patients and to examine the most important predictors of its development.
DESIGN AND METHODS: A retrospective cohort study over a 10-year period (1985 to 1995) of all asthma patients who received mechanical ventilation at two centers in Vancouver (designated center 1 and center 2).
RESULTS: In center 1, there were 58 patients who had 64 episodes of NFA, and in center 2, there were 28 patients who had 30 episodes. NMBAs were used in 30 of 86 admissions for acute severe asthma (35%). The mean (+/- SD) duration of muscle paralysis was 3.1+/-2.3 days. A total of 9 patients (10.4%) developed significant myopathy. The incidence of myopathy was 9 of 30 (30%) among patients who received NMBAs. In a multiple logistic regression model, the development of myopathy was only significantly associated with the duration of muscle relaxation. The odds ratio for the development of myopathy increased by 2.1 (95% confidence interval, 1.4 to 3.2) with each additional day of muscle relaxation. The dose and the type of the CS were not significantly associated with the myopathy in the multiple logistic regression analysis.
CONCLUSION: Our study showed that there is a high incidence of acute myopathy when NMBAs are used for NFA. The incidence of myopathy increases with each additional day of muscle relaxation.
Askari A, Vignos PJ Jr, Moskowitz RW.
Steroid myopathy in connective tissue disease.
Am J Med. 1976 Oct;61(4):485-92. doi: 10.1016/0002-9343(76)90327-2.
Abstract/Text
In eight women with polymyositis (three patients), systemic lupus erythematosus (SLE) (three patients), rheumatoid arthritis (one patient) and shoulder-hand syndrome (one patient), weakness developed during high dose prednisone therapy. These women were studied using serial functional and manual muscle tests, determination of serum glutamic oxaloacetic transminase (SGOT), creatine phosphokinase (CPK) and serum aldolase levels, and urinary excretion of creatine. Insidious onset of weakness was characteristic. Myalgias were seen in five patients and unusual sudden weakness in two. Weakness was always most severe in the pelvic girdle muscles; there was a lesser involvement of shoulder girdle and distal muscles. Serum muscle enzyme levels were normal in all cases, but urinary creatine excretion was invariably increased and proved to be the most sensitive laboratory indicator for clinical diagnosis and for monitoring patient improvement. Serial urinary creatine excretion and serum enzyme studies were of value in differenting steroid myopathy from a flare of myositis in patients with connective tissue disease. Diagnosis and effective management were achieved by the use of readily available laboratory and clinical procedures without resorting to muscle biopsy.
Bowyer SL, LaMothe MP, Hollister JR.
Steroid myopathy: incidence and detection in a population with asthma.
J Allergy Clin Immunol. 1985 Aug;76(2 Pt 1):234-42. doi: 10.1016/0091-6749(85)90708-0.
Abstract/Text
Sixty steroid-treated patients with asthma were evaluated for the presence of muscle weakness by use of both manual muscle testing and the Cybex II isokinetic dynamometer. The patients were compared to age and sex-matched sedentary control subjects. Forty-eight percent of the patients (12/25) taking greater than or equal to 40 mg per day of prednisone had hip flexor strength greater than or equal to 2 SD below the mean of age and sex-matched control subjects by Cybex testing (CT). Sixty-four percent of the patients (16/25) taking greater than or equal to 40 mg per day of prednisone were found on manual muscle testing to have hip flexor weakness. Only one patient taking less than 30 mg per day of prednisone was found to have muscle weakness. Biochemical parameters, including CPK, aldolase, SGOT, LDH, and LDH isoenzymes were measured to assess the degree of steroid-induced muscle damage. They neither correlated with the degree of hip flexor weakness as measured by CT, nor did they discriminate between patients receiving small doses and large doses of steroids. Changes in urinary excretion of creatine did not help to confirm the diagnosis of steroid myopathy. Although CT provides an objective means of assessing muscle strength in these patients, at this time no definitive chemical test is available for the diagnosis of steroid myopathy.
Shimohata T, Umeda M, Tanaka K, Nishizawa M.
[Reevaluation of validity of percent creatinuria for diagnosing steroid myopathy].
No To Shinkei. 2006 Jan;58(1):39-42.
Abstract/Text
Steroid myopathy is usually a slowly progressive disease, which causes weakness primarily to the proximal muscles of the upper and lower extremities. The monitoring of this problem is difficult in situations in which the primary disease itself produces muscle weakness. The distinguishing feature in steroid myopathy is the occurrence of creatinuria in the presence of normal muscle enzymes including creatine kinase and aldolase. To evaluate the usefulness of percent creatinuria {urinary excretion of creatine/(urinary excretion of creatine + urinary excretion of creatinine)} in the diagnosis of steroid myopathy, we measured percent creatinuria in 26 patients (14 male and 12 female) without muscle diseases before the initiation of steroid treatment We found that the median values of percent creatinuria of the male and female patients were 2.5% and 17.1%, and that the ratios of the male and female patients presenting with an elevated percent creatinuria (more than 10%) were 3 out of 14 patients (21.4%) and 8 out of 12 patients (66.7%), respectively. We also found one patient with mild renal dysfunction presenting with an elevated percent creatinuria but without muscle weakness or myalgia. These findings suggest that the measurement of percent creatinuria is of little value in the diagnosis of steroid myopathy with a cutoff value of 10%. Furthermore, it is important to measure percent creatinuria before the steroid treatment, while paying close attention to the measurement method, sex, renal function and protein level of the diet.
Wilson AM, Blumsohn A, Jung RT, Lipworth BJ.
Asthma and Cushing's syndrome.
Chest. 2000 Feb;117(2):593-4. doi: 10.1378/chest.117.2.593.
Abstract/Text
A female patient was treated with high-dose inhaled fluticasone propionate for her asthma. Over 2 years, she developed features of Cushing's syndrome with proximal myopathy, osteopenia, hypertension, depressive psychosis, and cushingoid appearance. She had biochemical evidence of marked adrenal suppression with a 9:00 AM serum cortisol of 20 nmol/L that returned to normal (315 mol/L) after her therapy was changed to budenoside, 0.8 mg/d. Her appearance, mental state, and myopathy also improved with no loss of asthma control. This case illustrates the potential for developing clinically relevant adverse effects of inhaled corticosteroids when given at licensed doses.
Levin OS, Polunina AG, Demyanova MA, Isaev FV.
Steroid myopathy in patients with chronic respiratory diseases.
J Neurol Sci. 2014 Mar 15;338(1-2):96-101. doi: 10.1016/j.jns.2013.12.023. Epub 2013 Dec 17.
Abstract/Text
BACKGROUND: Corticosteroid-induced myopathy is a well known clinical entity, and experimental studies showed decreased rate of protein synthesis and increased rate of protein breakdown in muscles of chronically treated animals.
OBJECTIVE: The present observational study was aimed to evaluate skeletal muscle functions in asthmatics and patients with other chronic respiratory diseases treated by inhaled or oral corticosteroids.
METHODS: Thirty six patients with respiratory diseases were included into the study. The physician-rated peripheral motor deficits scale, stepper test and ankle/wrist index were used for assessment of muscle functions. The effects of length of glucocorticoids intake on muscle functions were evaluated.
RESULTS: Sixty five per cent of patients using corticosteroids daily during 1 year and longer reported weakness in legs, and 20% of these patients demonstrated objective signs of the muscle weakness. The performance on the stepper test was significantly worse in patients chronically using corticosteroids in comparison with the control group (10.9 ± 3.4 steps vs 16.1 ± 2.4 steps per 10s, respectively; F=21.6, p<0.001). In addition, a proportion of patients using corticosteroids for at least 18 months were characterized by muscle hypotrophy at a dominant leg.
CONCLUSION: Chronic intake of inhaled corticosteroids induces clinically significant decrease of muscle functions at least after 1-year of daily treatment.
Copyright © 2013 Elsevier B.V. All rights reserved.
Janssens S, Decramer M.
Corticosteroid-induced myopathy and the respiratory muscles. Report of two cases.
Chest. 1989 May;95(5):1160-2. doi: 10.1378/chest.95.5.1160.
Abstract/Text
Two women with connective tissue disease developed a characteristic steroid-induced myopathy. Reduced maximal transrespiratory pressures indicated reduced respiratory muscle strength. Gradual steroid dosage tapering resulted in prompt clinical improvement and marked increases in respiratory muscle strength, maximal inspiratory pressure increasing by 33 percent in one patient and by 70 percent in the other. This reversible steroid-induced respiratory muscle weakness may be of great significance in reconsidering long-term steroid therapy in patients with underlying lung disease.
Decramer M, Stas KJ.
Corticosteroid-induced myopathy involving respiratory muscles in patients with chronic obstructive pulmonary disease or asthma.
Am Rev Respir Dis. 1992 Sep;146(3):800-2. doi: 10.1164/ajrccm/146.3.800.
Abstract/Text
We made observations on two patients with asthma and one with COPD who developed steroid-induced myopathy during prolonged treatment with high doses of corticosteroids. On admission, quadriceps force was on the average reduced to 31% of predicted (range 16 to 46% of predicted, nondominant leg), and urinary excretion of creatine in 24 h averaged 687 mg (range 275 to 1,045 mg/24 hr). Respiratory muscle involvement was evidenced by reductions in PImax and PEmax, being 38% (range 36 to 39) and 48% of predicted (range 36 to 68), respectively. Tapering of treatment with corticosteroids resulted in important recovery of quadriceps force and respiratory muscle force. In all three patients, a correlation between muscle forces and steroid dose was present during reduction of the dose. After 6 months quadriceps force averaged 62% of predicted (range 31 to 85), and PImax and PEmax reached 74% (range 52 to 92) and 92% of predicted (range 80 to 106), respectively, after 3 months. Consequently, respiratory muscle force appeared to recover faster than quadriceps force. The implications of these observations for patients treated with the usual doses of corticosteroids for shorter periods require further investigation.
Hopkinson NS, Man WD, Dayer MJ, Ross ET, Nickol AH, Hart N, Moxham J, Polkey MI.
Acute effect of oral steroids on muscle function in chronic obstructive pulmonary disease.
Eur Respir J. 2004 Jul;24(1):137-42. doi: 10.1183/09031936.04.00139003.
Abstract/Text
Prospective data to support the hypothesis that corticosteroids are a significant cause of muscle weakness in patients with chronic obstructive pulmonary disease (COPD) are lacking. The authors studied respiratory and quadriceps muscle function, using both volitional techniques and magnetic nerve stimulation, as well as measuring metabolic parameters during incremental cycle ergometry, in 25 stable COPD patients. The forced expiratory volume in one second was 37.6 +/- 21.4% predicted, before and after a 2-week course of o.d. prednisolone 30 mg. Quadriceps strength was also assessed in 15 control patients on two occasions. Only two patients met the British Thoracic Society definition of steroid responsiveness. There was no change either in sniff transdiaphragmatic pressure (pre: 96.8 +/- 19.7 cmH2O; post: 98.6 +/- 22.4 cmH2O) or in twitch transdiaphragmatic pressure elicited by bilateral anterolateral magnetic phrenic-nerve stimulation (pre: 16.8 +/- 9.1 cmH2O; post: 17.9 +/- 10 cmH2O). Quadriceps twitch force did not change significantly either in the steroid group (pre: 9.5 +/- 3.1 kg; post: 8.9 +/- 3.7 kg) or in the control patients (pre: 8.1 +/- 2.7 kg; post: 7.9 +/- 2.2 kg). There were no changes in either peak or isotime ventilatory and metabolic parameters during exercise. In conclusion, in stable patients with chronic obstructive pulmonary disease, a 2-week course of 30 mg prednisolone daily does not cause significant skeletal muscle dysfunction or alter metabolic parameters during exercise.
Hatakenaka M, Soeda H, Okafuji T, Yabuuchi H, Shiokawa S, Nishimura J, Honda H.
Steroid myopathy: evaluation of fiber atrophy with T2 relaxation time--rabbit and human study.
Radiology. 2006 Feb;238(2):650-7. doi: 10.1148/radiol.2381041720. Epub 2005 Dec 21.
Abstract/Text
PURPOSE: To determine whether muscle fiber atrophy associated with steroid myopathy can be detected with T2 relaxation time.
MATERIALS AND METHODS: Animal and human studies were approved by the ethics committee. Informed consent was obtained. Twelve rabbits were divided into a group that received 3 mg/kg of triamcinolone subcutaneously each day for 10 consecutive days (n = 6) and a control group that received saline (n = 6). Magnetic resonance (MR) imaging was performed before and after treatment. T2 and fat deposition ratio (FDR) of soleus and gastrocnemius muscles before and after treatment and between control rabbits and rabbits treated with steroids were compared by using two-way repeated analysis of variance and Bonferroni post hoc test to evaluate effects of steroid treatment. After imaging, rabbits were sacrificed. Extracellular space ratio (ECSR) and fiber diameter were examined. Correlation among T2, ECSR, and diameter of type 2 muscle fibers was analyzed with a Pearson correlation test with Bonferroni correction in gastrocnemius to determine factors affecting T2. In humans, T2 relaxation time and FDR of both muscles were compared between volunteers not treated with steroids and patients treated with steroids by using an unpaired t test to evaluate the effects of steroids.
RESULTS: In rabbits, T2 of gastrocnemius muscle was significantly (P < .01) longer after steroid treatment than before steroid treatment and was also significantly (P < .01) longer than after saline administration. T2 of the gastrocnemius showed no significant difference in control rabbits before or after saline administration or in control rabbits and rabbits before steroid administration. T2 of the soleus muscle or FDR of either muscle showed no significant difference. There was a significant correlation (P < .01) among T2, ECSR, and diameter of type 2 muscle fibers in the gastrocnemius. In humans, T2 of the gastrocnemius was significantly (P < .01) longer in patients than in volunteers. T2 of the soleus or FDR of either muscle showed no significant difference.
CONCLUSION: Muscle fiber atrophy associated with steroid myopathy is detectable as prolongation of T2 relaxation time in the gastrocnemius muscle; the authors believe prolongation of T2 relaxation time is mainly due to increased ECSR reflecting type 2 muscle fiber atrophy.
(c) RSNA, 2005
Martucci MG, McIlduff CE, Shin C, Gutierrez HV, Nam JY, Greenstein P, Phillips K, Uhlmann EJ, Wong ET, Rutkove SB.
Quantitative ultrasound of muscle can detect corticosteroid effects.
Clin Neurophysiol. 2019 Aug;130(8):1460-1464. doi: 10.1016/j.clinph.2019.04.709. Epub 2019 May 10.
Abstract/Text
OBJECTIVES: In this study, we sought to determine whether quantitative ultrasound (QUS) could detect the impact of corticosteroids on muscle in the absence of frank weakness.
METHODS: QUS was performed on selected limb muscles of 20 brain tumor patients treated with dexamethasone and 30 healthy controls. Echointensity was quantified using gray scale level (GSL) analysis and compared between groups; correlation to corticosteroid exposure was also performed.
RESULTS: Average 4-muscle GSL (±standard deviation) was greater in patients compared to controls (35.5 ± 5.61 arbitrary units (AU) versus 30.4 ± 4.17 AU, p = 0.001), with the greatest differences in tibialis anterior. Average muscle GSL also correlated to length of corticosteroid therapy (rho = 0.52, p = 0.01).
CONCLUSIONS: These findings suggest that QUS may be able to quantify skeletal muscle alterations associated with chronic corticosteroid use. Further study of this approach is warranted.
SIGNIFICANCE: The findings of this study may provide a tool to evaluate corticosteroid myopathy.
Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.
Minetto MA, Caresio C, Salvi M, D'Angelo V, Gorji NE, Molinari F, Arnaldi G, Kesari S, Arvat E.
Ultrasound-based detection of glucocorticoid-induced impairments of muscle mass and structure in Cushing's disease.
J Endocrinol Invest. 2019 Jul;42(7):757-768. doi: 10.1007/s40618-018-0979-9. Epub 2018 Nov 15.
Abstract/Text
PURPOSE: To investigate the glucocorticoid-induced impairments of muscle mass and structure in patients presenting different stages of steroid myopathy progression.
METHODS: Thirty-three patients (28 women) affected by active (N = 20) and remitted (N = 13) Cushing's disease were recruited and the following variables were assessed: walking speed, handgrip strength, total body and appendicular muscle mass by bioelectrical impedance analysis (BIA), thickness and echo intensity of lower limb muscles by ultrasonography.
RESULTS: The two groups of patients showed comparable values of both handgrip strength [median (interquartile range) values: active disease: 27.4 (7.5) kg vs. remitted disease: 26.4 (9.4) kg; P = 0.58] and walking speed [active disease: 1.0 (0.2) m/s vs. remitted disease: 1.1 (0.3) m/s; P = 0.43]. Also, the thickness of the four muscles and all BIA-derived sarcopenic indices were comparable (P > 0.05 for all comparisons) between the two groups. On the contrary, the echo intensity of vastus lateralis, tibialis anterior (lower portion), and medial gastrocnemius was significantly (P < 0.05 for all comparisons) higher in patients with active disease compared to patients with remitted disease. Finally, significant negative correlations were found in the whole group of patients between muscle echo intensity and muscle function assessments.
CONCLUSIONS: We provided preliminary evidence that the ultrasound-derived measurements of muscle thickness and echo intensity can be useful to detect and track the changes of muscle mass and structure in patients with steroid myopathy and we suggest that the combined assessment of muscle mass, strength, and performance should be systematically applied in the routine examination of steroid myopathy patients.
Menezes LG, Sobreira C, Neder L, Rodrigues-Júnior AL, Martinez JA.
Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats.
J Appl Physiol (1985). 2007 Feb;102(2):698-703. doi: 10.1152/japplphysiol.01188.2005. Epub 2006 Oct 19.
Abstract/Text
The objective of the present study was to investigate whether creatine (Cr) could attenuate the deleterious effects of high doses of dexamethasone (Dexa) on body mass, exercise performance, and respiratory variables of rodents. Forty-four Wistar rats performed incremental maximal exercise tests. They were then assigned to four groups: G1: subcutaneous (s.c.) and intraperitoneal (i.p.) saline; G2: s.c. saline and i.p. Cr (250 mg x kg(-1) x day(-1)); G3: s.c. Dexa (7.5 mg x kg(-1) x day(-1)) and i.p. saline; G4: s.c. Dexa and i.p. Cr. New exercise tests and analysis of the respiratory pattern under resting conditions and after stimulation with doxapram (2 mg/kg i.p.) were performed after 18 days. Post- minus pretreatment differences were compared between groups. G3 and G4 showed a significant impairment in body mass gain compared with G1 and G2 (P < 0.05) (G1: 65.3 +/- 26.1, G2: 93.1 +/- 27.4, G3: -18.4 +/- 20.1, G4: 9.8 +/- 23.1 kg x 10(-3)). Similar results were observed for maximal oxygen consumption (G1: 9.5 +/- 8.5, G2: 25.8 +/- 14.5, G3: -25.5 +/- 6.0, G4: -4.8 +/- 9.5 ml x kg(-1) x min(-1)) and test duration (G1: 43.0 +/- 45.0, G2: 72.0 +/- 59.5, G3: -165.0 +/- 60.6, G4: -48.0 +/- 48.5 s). Simultaneous use of Cr significantly attenuated the Dexa-induced impairment of the last two variables. Cr attenuated Dexa-induced gastrocnemius and diaphragm muscle weight losses and the atrophy of gastrocnemius type IIb fibers. Cr supplementation had only small effects on Dexa-induced respiratory changes. These results suggest that Cr may play a role in the prophylaxis or treatment of steroid-induced myopathy.
Kanda F, Takatani K, Okuda S, Matsushita T, Chihara K.
Preventive effects of insulinlike growth factor-I on steroid-induced muscle atrophy.
Muscle Nerve. 1999 Feb;22(2):213-7. doi: 10.1002/(sici)1097-4598(199902)22:2<213::aid-mus9>3.0.co;2-m.
Abstract/Text
We examined the effects of simultaneous administration of recombinant insulinlike growth factor-I (IGF-I) and glucocorticoid on the diameter of muscle fibers in rats. The steroid group received subcutaneous injection of triamcinolone, the IGF-treated group received IGF-I alone, and the steroid plus IGF group received both triamcinolone and IGF-I. After 14 days, each rat was subjected to muscle biopsy of the extensor digitorum longus and soleus. Glucocorticoid treatment caused significant reduction in diameter of muscle fibers, compared to controls. Simultaneous administration of IGF-I significantly attenuated glucocorticoid-induced muscle atrophy. Glucocorticoid increased both urinary concentration of 3-methylhistidine and urinary creatine/creatinine ratio. IGF-I reduced those changes in the urine. We conclude that IGF-I administration prevents, at least partially, the development of steroid myopathy.
Petrof BJ, Gottfried SB, Eby J, Lamanca J, Levine S.
Growth hormone does not prevent corticosteroid-induced changes in rat diaphragm structure and function.
J Appl Physiol (1985). 1995 Nov;79(5):1571-7. doi: 10.1152/jappl.1995.79.5.1571.
Abstract/Text
The present study tested the hypothesis that growth hormone (GH), an anabolic agent, could prevent the abnormalities of diaphragm structure and function associated with short-term administration of the corticosteroid triamcinolone (TR). During a 10-day period, male rats (n = 33) were assigned to control (CTL), TR (1 mg.kg-1.day-1 im), and TR-GH (2 mg.kg-1.day-1 im) groups. Diaphragm weight was significantly reduced in the TR and TR-GH animals compared with the CTL animals, but there was no difference in the diaphragm-to-body weight ratio. Fiber type (I, IIa, and IIx/b) proportions did not differ among the three groups. However, in TR rats there was a significant reduction in the contribution of type IIx/b fibers to total diaphragm cross-sectional area due to marked atrophy (approximately 42% decrease in mean fiber cross-sectional area). There was no significant reversal of TR-induced type IIx/b fiber atrophy by concomitant GH administration. TR and TR-GH groups both exhibited a left-ward shift of the force-frequency relationship and enhanced in vitro fatigue resistance, whereas maximal specific force was unaltered. We conclude that GH does not prevent corticosteroid-induced effects on the diaphragm under these conditions, possibly as a result of reduced nutritional intake associated with TR administration.
Matsushita T, Kanda F, Sugio T, Okuda S, Chihara K.
[Growth hormone prevents the steroid myopathy in rats].
Rinsho Shinkeigaku. 1996 Jun;36(6):752-6.
Abstract/Text
To clarify whether growth hormone possesses the counteracting effect on steroid myopathy, we examined the influence of simultaneous administration of recombinant human growth hormone (rhGH) with glucocorticoid on the diameter of muscle fibers in rats. Female Sprague-Dawley rats weighing 120-140 g were divided into four groups. A group treated with glucocorticoid alone was subcutaneously injected with 5 mg/kg/day triamcinolone, a GH-treated group with 10 IU/kg/day rhGH alone, a steroid-GH-group with the same doses of glucocorticoid and rhGH. The control rats were injected with the vehicle alone. After 14 days of treatment, each rat was anesthetized with ether and subjected to muscle biopsy of extensor digitorum longus (EDL) and soleus. Administration of rhGH alone failed to affect the diameter of muscle fibers in either EDL or soleus. Glucocorticoid treatment caused a significant reduction in the diameter of muscle fibers in the EDL, compared with the control. In the type II muscle fibers of the EDL, simultaneous administration of rhGH attenuated glucocorticoid-induced muscle atrophy significantly. We concluded that GH administration would at least partially prevents steroid myopathy.
Yamamoto D, Maki T, Herningtyas EH, Ikeshita N, Shibahara H, Sugiyama Y, Nakanishi S, Iida K, Iguchi G, Takahashi Y, Kaji H, Chihara K, Okimura Y.
Branched-chain amino acids protect against dexamethasone-induced soleus muscle atrophy in rats.
Muscle Nerve. 2010 Jun;41(6):819-27. doi: 10.1002/mus.21621.
Abstract/Text
We investigated the utility of branched-chain amino acids (BCAA) in dexamethasone-induced muscle atrophy. Dexamethasone (600 microg/kg, intraperitoneally) and/or BCAA (600 mg/kg, orally) were administered for 5 days in rats, and the effect of BCAA on dexamethasone-induced muscle atrophy was evaluated. Dexamethasone decreased total protein concentration of rat soleus muscles. Concomitant administration of BCAA reversed the decrease. Dexamethasone decreased mean cross-sectional area of soleus muscle fibers, which was reversed by BCAA. Dexamethasone increased atrogin-1 expression, which has been reported to play a pivotal role in muscle atrophy. The increased expression of atrogin-1 mRNA was significantly attenuated by BCAA. Furthermore, dexamethasone-induced conversion from microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II, which is an indicator of autophagy, was blocked by BCAA. These findings suggest that BCAA decreased protein breakdown to prevent muscle atrophy. BCAA administration appears to be useful for prevention of steroid myopathy.
Izumi Y, Miyashita T, Kitajima T, Yoshimura S, Takeoka A, Eguchi K, Motomura M, Kawakami A, Migita K.
Two cases of refractory polymyositis accompanied with steroid myopathy.
Mod Rheumatol. 2015 Jan;25(1):143-9. doi: 10.3109/14397595.2013.874750. Epub 2014 Feb 18.
Abstract/Text
Polymyositis (PM) is an inflammatory muscle disease characterized by chronic inflammation in skeletal muscle. Although most patients with PM respond to corticosteroids, some cases show an unsatisfactory response and other therapeutic options must be considered. Furthermore, glucocorticosteroid (GC) toxicity leads to a significant disability known as steroid myopathy, particularly in elderly patients. Here we report two patients with refractory PM. Combined treatment with high-dose GCs, tacrolimus, and intravenous immunoglobulin resulted in beneficial effects against myositis. However, muscle weakness and the disability progressed due to steroid myopathy, and subsequent oral intake became impossible because of swallowing disturbance in these two patients. Nutritional intervention, including branched-chain amino acids (BCAAs) and rehabilitation, was undertaken in addition to treatment against myositis. These treatments finally improved the muscle weakness and activities of daily living, and the two patients were discharged after recovery. The high-dose GC treatment caused elevation of serum levels of amino acids, including BCAAs, but these amino acids subsequently declined during BCAA replacement therapy. These findings suggest that the catabolic effects of the glucocorticoid treatment impair the balance of amino acids, including BCAAs, within the muscle, leading to steroid myopathy.
Yoshikawa N, Shimizu N, Uehara M, Oda A, Matsumiya R, Matsubara E, Kobayashi H, Hosono O, Kuribara-Souta A, Baba H, Nagamura F, Kiryu S, Tanaka H.
The effects of bolus supplementation of branched-chain amino acids on skeletal muscle mass, strength, and function in patients with rheumatic disorders during glucocorticoid treatment.
Mod Rheumatol. 2017 May;27(3):508-517. doi: 10.1080/14397595.2016.1213480. Epub 2016 Sep 28.
Abstract/Text
OBJECTIVES: To test the effects of bolus supplementation of branched-chain amino acids (BCAA) on skeletal muscle mass, strength, and function in patients with rheumatic disorders taking glucocorticoid (GC).
METHODS: Patients with rheumatic disorders treated with prednisolone (≥10 mg/day) were randomized to ingest additional daily 12 g of BCAA (n = 9) or not (n = 9) for 12 weeks. At baseline, and 4, 8, and 12 weeks, they underwent bioelectrical impedance analysis, muscle strength and functional tests, and computed tomography analysis for cross-sectional area of mid-thigh muscle.
RESULTS: Disease activities of the patients were well controlled and daily GC dose was similarly reduced in both groups. Limb muscle mass was recovered in both groups. Whole-body muscle mass and muscle strength and functional mobility were increased only in BCAA (+) group. The effects of BCAA supplementation on recovering skeletal muscle mass were prominent in particular muscles including biceps femoris muscle.
CONCLUSIONS: This trial is the first-in-man clinical trial to demonstrate that BCAA supplementation might be safe and, at least in part, improve skeletal muscle mass, strength, and function in patients with rheumatic disorders treated with GC.
Mughal S, Sabater-Arcis M, Artero R, Ramón-Azcón J, Fernández-Costa JM.
Taurine activates the AKT-mTOR axis to restore muscle mass and contractile strength in human 3D in vitro models of steroid myopathy.
Dis Model Mech. 2024 Apr 1;17(4). doi: 10.1242/dmm.050540. Epub 2024 Apr 24.
Abstract/Text
Steroid myopathy is a clinically challenging condition exacerbated by prolonged corticosteroid use or adrenal tumors. In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin-proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin-proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT-mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.
© 2024. Published by The Company of Biologists Ltd.
Braith RW, Welsch MA, Mills RM Jr, Keller JW, Pollock ML.
Resistance exercise prevents glucocorticoid-induced myopathy in heart transplant recipients.
Med Sci Sports Exerc. 1998 Apr;30(4):483-9. doi: 10.1097/00005768-199804000-00003.
Abstract/Text
PURPOSE: To determine the effect of resistance exercise training (ET) on glucocorticoid-induced myopathy in heart transplant recipients (HTR), 14 male HTR were randomly assigned to a ET group that trained for 6 months (54 +/- 3 yr old; mean +/- SD) or a control group (51 +/- 8 yr old; mean +/- SD).
METHODS: Fat mass, fat-free mass, and total body mass were measured by dual-energy x-ray absorptiometry before and 2 months after transplantation (Tx), and after 3 and 6 months of ET or control period. The exercise regimen consisted of lumbar extension (MedX) performed 1 d.wk-1 and variable resistance exercises (Nautilus) performed 2 d.wk-1. PreTx body composition did not differ between groups.
RESULTS: At 2 months after Tx, fat-free mass was significantly decreased below baseline in both control (-3.4 +/- 2.1%) and ET groups (-4.3 +/- 2.4%). Fat mass was significantly increased at 2 months after Tx in both the control (+8.3 +/- 2.8%) and ET groups (+7.3 +/- 4.0%). Six months of ET restored fat-free mass to levels 3.9 +/- 2.1% greater (P < or = 0.05) than before Tx. Fat-free mass of the control group decreased progressively to levels that were 7 +/- 4.4% lower than preTx values (P < or = 0.05). Both groups increased knee extension, chest press, and lumbar extensor strength, but improvements in the ET group were four- to six-fold greater (P < or = 0.05).
CONCLUSION: Our results demonstrate that glucocorticoid-induced changes in body composition in HTR occur early after Tx. However, 6 months of specific ET restores fat-free mass to levels greater than before Tx and dramatically increases skeletal muscle strength. Resistance exercise, as part of a strategy to prevent steroid-induced myopathy, appears to be safe and should be initiated early after heart Tx.
Nagashima M, Takahashi D, Mizushima T, Yamauchi K.
Effects of exercise in patients with connective tissue disease receiving high-dose glucocorticoids: A pilot prospective cohort study.
Eur J Appl Physiol. 2021 Aug;121(8):2253-2263. doi: 10.1007/s00421-021-04697-2. Epub 2021 Apr 29.
Abstract/Text
PURPOSE: High doses of glucocorticoids induce skeletal muscle weakness. The aim of this study was to evaluate the effects of exercise therapy on skeletal muscle strength, mass, and exercise capacity in patients with connective tissue disease treated with high doses of glucocorticoids.
METHODS: This prospective, observational, single-center, cohort study included 35 patients aged ≥ 15 years diagnosed with connective tissue disease who received high-dose glucocorticoids and physical training. Exercise therapy, including moderate aerobic and strength training, was performed five times a week. Knee extension strength, skeletal muscle mass, anaerobic threshold, and peak oxygen consumption were measured at the beginning of exercise therapy and at discharge.
RESULTS: After 6 weeks of aerobic and strength exercises, skeletal muscle mass significantly decreased by 5.5%, right knee extension decreased by 11.6%, and left knee extension decreased by 9.7%. The anaerobic threshold and peak oxygen consumption significantly increased by 13.0% and 9.0%, respectively. The increase in glucocorticoid dose was inversely correlated with changes in knee extension strength.
CONCLUSION: In patients with connective tissue disease being treated with high-dose glucocorticoids, exercise therapy might attenuate the decrease in skeletal muscle mass and strength and increase the anaerobic threshold and peak oxygen consumption, thus moderating the side effects of high-dose glucocorticoid treatment. Trial registration The trial is registered with UMIN (University Hospital Medical Information Network), ID number UMIN000038836.
