FIVE-YEAR OUTCOMES AFTER LONG-TERM OXANDROLONE ADMINISTRATION IN SEVERELY BURNED CHILDREN: A RANDOMIZED CLINICAL TRIAL.
Administration of oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ≥30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term oxandrolone administration (p < 0.0009). Fewer patients receiving oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with oxandrolone administration. Long-term oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of oxandrolone. A comparison of the current patients receiving long-term oxandrolone to previously described patients receiving 12 months of oxandrolone revealed that long-term oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p < 0.05). In conclusion, the administration of oxandrolone for up to 24 months to severely burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term oxandrolone was more efficacious than administration for 12 months. Additionally, fewer patients in the oxandrolone cohort met the diagnostic criteria for pediatric osteoporosis, pointing to a reduced risk for future bone fracture. This study demonstrates that administering oxandrolone for up to 2 years following severe burn injury results in greater improvements in BMC, BMD, and height velocity.
*School of Medicine, University of Texas Medical Branch at Galveston †Shriners Hospitals for Children®-Galveston ‡Department of Surgery §Department of Preventative Medicine and Community Health ||The Institute for Translational Sciences ¶School of Health Professions **Departments of Psychiatry and Pediatrics, University of Texas Medical Branch, Galveston, Texas.
Patrick T
PT
Reeves
David N
DN
Herndon
Jessica D
JD
Tanksley
Kristofer
K
Jennings
Gordon L
GL
Klein
Ronald P
RP
Mlcak
Robert P
RP
Clayton
Nancy N
NN
Crites
Joshua P
JP
Hays
Clark
C
Andersen
Jong O
JO
Lee
Walter
W
Meyer
Oscar E
OE
Suman
Celeste C
CC
Finnerty
D000284:Administration, Oral; D015519:Bone Density / Q000187:drug effects*; D002056:Burns / Q000188:drug therapy / Q000503:physiopathology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053580:Muscle Strength / Q000187:drug effects*; D010074:Oxandrolone / Q000008:administration & dosage*; D013997:Time Factors; D015599:Trauma Severity Indices
D010074:Oxandrolone