The effect of oxandrolone on the endocrinologic, inflammatory, and hypermetabolic responses during the acute phase postburn

Abstract

Objective and summary background data: Postburn long-term oxandrolone treatment improves hypermetabolism and body composition. The effects of oxandrolone on clinical outcome, body composition, endocrine system, and inflammation during the acute phase postburn in a large prospective randomized single-center trial have not been studied.

Methods: Burned children (n = 235) with >40% total body surface area burn were randomized (block randomization 4:1) to receive standard burn care (control, n = 190) or standard burn care plus oxandrolone for at least 7 days (oxandrolone 0.1 mg/kg body weight q.12 hours p.o, n = 45). Clinical parameters, body composition, serum hormones, and cytokine expression profiles were measured throughout acute hospitalization. Statistical analysis was performed by Student t test, or ANOVA followed by Bonferroni correction with significance accepted at P < 0.05.

Results: Demographics and clinical data were similar in both groups. Length of intensive care unit stay was significantly decreased in oxandrolone-treated patients (0.48 +/- 0.02 days/% burn) compared with controls (0.56 +/- 0.02 days/% burn), (P < 0.05). Control patients lost 8 +/- 1% of their lean body mass (LBM), whereas oxandrolone-treated patients had preserved LBM (+9 +/- 4%), P < 0.05. Oxandrolone significantly increased serum prealbumin, total protein, testosterone, and AST/ALT, whereas it significantly decreased alpha2-macroglobulin and complement C3, P < 0.05. Oxandrolone did not adversely affect the endocrine and inflammatory response as we found no significant differences in the hormone panels and cytokine expression profiles.

Conclusions: In this large prospective, double-blinded, randomized single-center study, oxandrolone shortened length of acute hospital stay, maintained LBM, improved body composition and hepatic protein synthesis while having no adverse effects on the endocrine axis postburn, but was associated with an increase in AST and ALT.

FIGURE 1. Percent change in body composition from admit to discharge. Both groups had an increase in total whole body fat from admit to discharge with no difference between controls and oxandrolone. Oxandrolone treatment reversed catabolism and preserved body and muscle mass by increasing total whole body mass and lean body mass when compared with controls. *Significant difference between controls versus oxandrolone, P < 0.05.

FIGURE 2. Serum IGF-I and IGFBP-3 decreased immediately after burn in both groups with significant difference between controls and oxandrolone. Serum GH was in the normal range immediately postburn, but started to decrease 2 to 7 days postburn. There was no difference between controls and oxandrolone. Serum estrogen (β-estradiol) and testosterone decreased in both groups postburn. Oxandrolone had no effect on serum β-estradiol, but significantly increased serum testosterone at various time points compared with controls. *Significant difference between controls versus oxandrolone, P < 0.05. Dashed lines represent upper and lower limit of the normal range.

FIGURE 3. Serum liver enzymes AST and ALT increased postburn but decreased to the normal range. Oxandrolone caused a significant increase in serum AST and ALT beginning at 17 days postburn. *Significant difference between controls versus oxandrolone, P < 0.05. Dashed lines represent upper and lower limit of the normal range.

FIGURE 4. Serum constitutive hepatic and acute phase proteins. Oxandrolone increased total serum proteins and prealbumin, whereas it decreased acute phase proteins α2-macroglobulin and complement C3. Oxandrolone significantly decreased serum free fatty acids. *Significant difference between controls versus oxandrolone, P < 0.05. Dashed lines represent upper and lower limit of the normal range.

FIGURE 5. A, The effect of oxandrolone on pro- and anti-inflammatory cytokines. Oxandrolone did not have any significant effect on the inflammatory response. Dashed lines represent upper and lower limit of the normal range. Normal ranges: IL-6: <8 pg/mL, IL-8: <7 pg/mL, GM-CSF: 0 pg/mL, TNF: <0.7 pg/mL, IL-1β: <0.8 pg/mL, IL-17: 0 pg/mL, IL-2: 0 pg/mL, IL-4: 0 pg/mL, IL-10: <1.4 mg/dL, IFN-γ: <1.3 pg/mL, IL-7: <4 pg/mL, IL-12 p70: 0 pg/mL. B, Heat map comparing normal (noninjured, nonburned children), controls at each time point [C (0–1 day postburn), C (2–7 days postburn), C (8–10 days postburn), C (11–16 days postburn), C (17–22 days postburn), C (23–28 days postburn), and C (29–40 days postburn)], and normal and oxandrolone at each time point [O (0–1 day postburn), O (2–7 days postburn), O (8–10 days postburn), O (11–16 days postburn), O (17–22 days postburn), O (23–28 days postburn), and O (29–40 days postburn)] serum cytokine protein expression profiles. Values are log₁₀ (average cytokine concentration, pg/mL); the color range for each cytokine is based on the detected values with blue indicating lower levels, yellow indicating highest levels, and black in the middle. Gray squares indicate that no expression was detected.

FIGURE 6. Muscle strength was tested before the beginning of the rehabilitation-exercise program. Burn injury caused significant decrease in muscle strength (peak torque from normal, nonburned children: 95 ± 5 N m). oxandrolone almost doubled muscle strength and significantly increased peak torque compared with controls. *Significant difference between controls versus oxandrolone, P < 0.05.