Oxandrolone in burn patients

Overview

Oxandrolone is a synthetic 17-alpha-alkylated testosterone analog that was widely used as an anabolic agent in burn care for over two decades. It demonstrated efficacy in counteracting postburn muscle catabolism, preserving lean body mass, improving protein synthesis efficiency, and shortening hospitalization ^[1][2][3]. The standard dose of 0.1 mg/kg orally twice daily was established primarily through pediatric burn research at Shriners Hospitals for Children ^[4]. Oxandrolone has been removed from the US market by the FDA and is no longer available for clinical use domestically. This page documents the historical evidence base for reference and for centers outside the United States where the drug may remain available.

Mechanism of action

Oxandrolone binds to androgen receptors and stimulates protein synthesis with relatively weak androgenic effects compared with testosterone ^[3][4]. Hart et al. demonstrated in a prospective cohort study of severely burned children that oxandrolone improved muscle protein metabolism primarily through enhanced protein synthesis efficiency rather than decreased protein breakdown ^[2]. Net muscle protein balance improved in the oxandrolone group while it decreased in controls ^[2]. This mechanism distinguished oxandrolone from propranolol, which modulates catabolism through different pathways ^[5].

Efficacy evidence

Lean body mass and protein metabolism

A randomized, double-blind, placebo-controlled trial by Gusti et al. found that oxandrolone prevented the reduction in lean body mass seen in placebo-treated severe burn patients over a 14-day treatment period (delta eLBM: 0.38 +/- 1.64 vs. -1.32 +/- 1.23 in the placebo group; P = 0.049) ^[6]. Miller and Btaiche reviewed eight clinical studies in pediatric patients and confirmed that oxandrolone at 0.1 mg/kg twice daily increased protein synthesis, lean body mass accretion, muscle strength, serum visceral protein concentrations, weight gain, and bone mineral content ^[4].

Length of stay and surgical burden

The most recent and comprehensive meta-analysis by Lou et al. (2025) evaluated 14 randomized controlled trials encompassing 2,822 patients ^[1]. Oxandrolone significantly reduced surgical procedures (SMD = -1.25; 95% CI -2.45 to -0.04; P = 0.04) and length of stay normalized to TBSA (LOS/TBSA) (SMD = -1.07; P = 0.007) ^[1]. Enhanced anabolic recovery was evidenced by increased weight gain (SMD = 0.58; P < 0.001) and lean mass (SMD = 1.30; P < 0.001) ^[1].

Mortality and infection

Oxandrolone did not demonstrate a mortality benefit (RR = 1.04; 95% CI 0.47-2.32; P = 0.913) and did not reduce infection rates (RR = 0.83; 95% CI 0.67-1.02; P = 0.639) ^[1]. Kopel et al. confirmed in their review that three separate meta-analyses showed oxandrolone did not affect mortality, infection, or liver function at a clinically significant level ^[3].

Metabolic bundle approach

Taha et al. described outcomes from 50 patients receiving a standardized "metabolic bundle" that included oxandrolone (20 mg/day), propranolol, early surgical excision, enteral feeding with glutamine and trace elements, and thermoregulation ^[7]. Definitive surgical excision was completed within 7 days in 88% of patients ^[7]. Despite transitory hepatic enzyme elevations, none were sufficiently concerning to merit cessation of treatment ^[7].

Safety and adverse effects

Hepatotoxicity

Transaminitis is the most frequent adverse effect of oxandrolone. Kiracofe et al. found in a single-center retrospective analysis that 42% (28/66) of patients developed transaminitis (AST or ALT > 100 mg/dL), substantially higher than previously reported rates ^[8]. A subsequent multicenter analysis of 309 patients confirmed a 41.4% incidence of transaminitis, occurring after a median of 13 days on oxandrolone ^[9]. Independent predictors included younger age, intravenous vasopressor use, and concurrent amiodarone use ^[9]. Importantly, transaminitis was not significantly associated with length of stay or mortality ^[9].

Other adverse effects

The 2025 meta-analysis noted a nonsignificant increase in treatment-related side effects (hepatic dysfunction/edema; RR = 1.82; 95% CI 0.52-6.42; P = 0.34), with notably higher transaminase elevations in adults (19% vs. 5% placebo; P = 0.002) ^[1]. In pediatric populations, mild and reversible sexual changes were observed during therapy ^[4]. Close monitoring of liver function, sexual development (in children), and growth patterns was recommended during treatment ^[4].

FDA removal from market

Oxandrolone has been removed from the US market by the FDA. The drug is no longer manufactured or distributed for clinical use in the United States. This represents a significant loss to the burn care pharmacologic armamentarium, as oxandrolone was one of the three most cost-effective and least toxic therapies identified for postburn hypermetabolism modulation [VERIFY -- confirm specific FDA action date and rationale]. Centers outside the United States should consult their local regulatory authorities regarding availability.

Controversies and Evidence Gaps

The extreme heterogeneity (I-squared greater than or equal to 95%) across randomized trials limits the strength of meta-analytic conclusions ^[1]. The majority of foundational efficacy data originated from a single study center (Shriners/UTMB Galveston) ^[4]. The true incidence of clinically significant hepatotoxicity (as opposed to isolated transaminase elevation) remains poorly characterized. Long-term effects on bone mineral density and lean body mass beyond the acute hospitalization require further study. The removal from the US market leaves a gap in available anabolic therapies for burn patients, and no direct replacement has been established. Whether alternative anabolic agents (testosterone, nandrolone) can replicate oxandrolone's benefit profile is unknown.

References

[1] Lou J et al. "Oxandrolone for burn patients: a systematic review and updated meta-analysis of randomized controlled trials from 2005 to 2025." World J Emerg Surg 2025;20:75. PMID: 41023744 [2] Hart DW et al. "Anabolic effects of oxandrolone after severe burn." Ann Surg 2001;233:556-564. PMID: 11303139 [3] Kopel J et al. "A Reappraisal of Oxandrolone in Burn Management." J Pharm Technol 2022;38:232-238. PMID: 35832568 [4] Miller JT et al. "Oxandrolone in pediatric patients with severe thermal burn injury." Ann Pharmacother 2008;42:1310-1315. PMID: 18682543 [5] Knuth CM et al. "Burn-induced hypermetabolism and skeletal muscle dysfunction." Am J Physiol Cell Physiol 2021;321:C58-C71. PMID: 33909503 [6] Gusti NRL et al. "Effects Of Oxandrolone On Lean Body Mass (LBM) In Severe Burn Patients: A Randomized, Double Blind, Placebo-Controlled Trial." Ann Burns Fire Disasters 2022;35:55-61. PMID: 35582088 [7] Taha H et al. "A 'metabolic bundle' including Oxandrolone in optimising the metabolic status of severely burn injured patients: a retrospective analysis of the first 50 patients." GMS Interdiscip Plast Reconstr Surg DGPW 2019;8:Doc17. PMID: 31815086 [8] Kiracofe B et al. "Incidence of oxandrolone induced hepatic transaminitis in patients with burn injury." Burns 2018;45:891-897. PMID: 30545697 [9] Kiracofe B et al. "Risk Factors Associated with the Development of Transaminitis in Oxandrolone-Treated Adult Burn Patients." J Burn Care Res 2019;40:406-411. PMID: 31220261 [10] Dobbe L et al. "Assessment of the impact of oxandrolone on outcomes in burn injured patients." Burns 2018;45:841-848. PMID: 30527646