Anabolic Effects of Oxandrolone After Severe Burn

Hart, David K.; Wolf, Steven E.; Ramzy, Peter I.; Chinkes, David L.; Beauford, Robert B.; Ferrando, Arny A.; Wolfe, Robert R.; Herndon, David N.

doi:10.1097/00000658-200104000-00012

Cited by 244 publications

(134 citation statements)

References 42 publications

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“…These results suggest that oxandrolone may slow down or stabilize the progression of weakness. Oxandrolone has also been used successfully to enhance lean body mass in other debilitating clinical situations such as human immunodeficiency syndrome infection and chronic alcoholic cirrhosis, lean body mass and upper-and lower-body maximal voluntary strength in the elderly, and linear growth in Turner syndrome and improves albumin levels, net protein balance, and lean body mass in severely burned children (20,45,48,54). An acute anabolic effect of oxandrolone on the fractional synthesis rate (FSR) of mixed muscle protein has also been reported in healthy young men (46).…”

mentioning

confidence: 99%

Oxandrolone enhances skeletal muscle myosin synthesis and alters global gene expression profile in Duchenne muscular dystrophy

Balagopal

Olney

Mougey³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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(DMD) involves an imbalance between the rates of synthesis and degradation of muscle proteins. Although previous studies have suggested that oxandrolone may be beneficial in DMD, the mechanism of action of oxandrolone on muscle in DMD remains unclear. To address these issues, we combined stable isotope studies and gene expression analysis to measure the fractional synthesis rate of myosin heavy chain (MHC), the key muscle contractile protein, the transcript levels of the isoforms of MHC, and global gene expression profiles in four children with DMD before and after 3 mo of treatment with oxandrolone. Gastrocnemius muscle biopsies and blood samples were collected during the course of a primed 6-h continuous infusion of L-[U-13 C]leucine on two separate occasions, before and after the 3-mo treatment with oxandrolone (0.1 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 ). Gene expression analysis was done with microarrays and RT-qPCR. In response to the treatment, MHC synthesis rate increased 42%, and this rise was accounted for, at least in part, by an upregulation of the transcript for MHC8 (perinatal MHC). Gene expression data suggested a decrease in muscle regeneration as a consequence of oxandrolone therapy, presumably because of a decrease in muscle degeneration. These findings suggest that 1) oxandrolone has a powerful protein anabolic effect on a key contractile protein and 2) larger and longer-term studies are warranted to determine whether these changes translate into meaningful therapy for these patients. microarray; stable isotope; mass spectrometry DUCHENNE MUSCULAR DYSTROPHY (DMD) is a severe and progressive form of human muscular dystrophy with a lethal outcome. Although the absence of the protein dystrophin, which is part of a glycoprotein complex located on the intracellular surface of the cellular membrane, was identified as the molecular basis of the disease (25, 28), and despite advances in our understanding of dystrophin function, the precise pathogenesis of the severe muscle damage remains unclear. The most striking manifestations of this disorder are loss of skeletal muscle mass and strength, resulting in severe disability. Previous studies in DMD have suggested that the loss of muscle is likely the result of an imbalance between muscle protein synthesis and degradation (18,42). In DMD, dystrophin deficiency is present in muscle from fetal life onward. However, the loss of muscle is progressive. The progressive nature of the muscle loss implies that there are crucial secondary factors that compound the problems caused by dystrophin deficiency. The gradual loss of regenerating capacity of muscle, which depends on protein synthesis, may be an important factor in this pathogenetic process (18,41,42).The absence of a cure for DMD underscores the importance of adjunctive therapeutic strategies. A recent study by Fenichel et al. (13) suggested an ameliorative effect of oxandrolone, an oral synthetic analog of testosterone, on muscle strength in DMD. Although a subsequent study by the same group did not find a significant ch...

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mentioning

confidence: 99%

Oxandrolone enhances skeletal muscle myosin synthesis and alters global gene expression profile in Duchenne muscular dystrophy

Balagopal

Olney

Mougey³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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show abstract

“…89,90 Therefore, we and others determined the effects of oxandrolone, a synthetic testosterone analogue on the postburn response, and found that oxandrolone increased LBM and shortened acute hospitalization. 18,91,92 We suggest that changes in protein expression are driven by the inflammatory response. 3,20 Cytokines and pro-inflammatory mediators are known via cellular mediators to block and therefore decrease endogenous anabolic agents.…”

Section: Discussionmentioning

confidence: 91%

The Pathophysiologic Response to Severe Burn Injury.

Jeschke

Finnerty

Norbury

et al. 2006

Critical Care Medicine

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Objective-To improve clinical outcome and to determine new treatment options, we studied the pathophysiologic response postburn in a large prospective, single center, clinical trial.Summary Background Data-A severe burn injury leads to marked hypermetabolism and catabolism, which are associated with morbidity and mortality. The underlying pathophysiology and the correlations between humoral changes and organ function have not been well delineated.Methods-Two hundred forty-two severely burned pediatric patients [>30% total body surface area (TBSA)], who received no anabolic drugs, were enrolled in this study. Demographics, clinical data, serum hormones, serum cytokine expression profile, organ function, hypermetabolism, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout acute hospital course.Results-Average age was 8 ± 0.2 years, and average burn size was 56 ± 1% TBSA with 43 ± 1% third-degree TBSA. All patients were markedly hypermetabolic throughout acute hospital stay and had significant muscle protein loss as demonstrated by a negative muscle protein net balance (−0.05% ± 0.007 nmol/100 mL leg/min) and loss of lean body mass (LBM) (−4.1% ± 1.9%); P < 0.05. Patients lost 3% ± 1% of their bone mineral content (BMC) and 2 ± 1% of their bone mineral density (BMD). Serum proteome analysis demonstrated profound alterations immediately postburn, which remained abnormal throughout acute hospital stay; P < 0.05. Cardiac function was compromised immediately after burn and remained abnormal up to discharge; P < 0.05. Insulin resistance appeared during the first week postburn and persisted until discharge. Patients were hyperinflammatory with marked changes in IL-8, MCP-1, and IL-6, which were associated with 2.5 ± 0.2 infections and 17% sepsis.Conclusions-In this large prospective clinical trial, we delineated the complexity of the postburn pathophysiologic response and conclude that the postburn response is profound, occurring in a timely manner, with derangements that are greater and more protracted than previously thought.

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“…Inclusion criteria included an age of 12-18 years, thermal / flame burns covering ≥20% of total body surface area and participation in the exercise program within 6 months post-burn. Children were excluded from the study if they had one or more of the following: leg (whole or segmental) amputation, limitation of range of motion (ROM) of lower limb joints, anoxic brain injury, and psychological or severe behaviour disorders 14 .…”

Section: Subjectsmentioning

confidence: 99%

“…Administration of oxandrolone (anabolic synthetic androgenic drug) 0.1 mg/kg/day for one year post burn may cause significant increase in lean body mass , improve long term recovery , attenuate muscle catabolism , decrease resting energy expenditure. The maximal effect of onxadrolone is observed in children aged 7-18 years while its therapeutic benefits may last up to 5 years post burn 14 .…”

Section: Introductionmentioning

confidence: 99%

Effect of Aerobic Exercise on Common Peroneal Nerve Conduction in Post Burn Children

Zoheiry¹

2016

jmscr

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Anabolic Effects of Oxandrolone After Severe Burn

Cited by 244 publications

References 42 publications

Oxandrolone enhances skeletal muscle myosin synthesis and alters global gene expression profile in Duchenne muscular dystrophy

Oxandrolone enhances skeletal muscle myosin synthesis and alters global gene expression profile in Duchenne muscular dystrophy

The Pathophysiologic Response to Severe Burn Injury.

Effect of Aerobic Exercise on Common Peroneal Nerve Conduction in Post Burn Children

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