TY - JOUR
T1 - Five-year outcomes after long-term oxandrolone administration in severely burned children
T2 - A randomized clinical trial
AU - Reeves, Patrick T.
AU - Herndon, David N.
AU - Tanksley, Jessica D.
AU - Jennings, Kristofer
AU - Klein, Gordon L.
AU - Mlcak, Ronald P.
AU - Clayton, Robert P.
AU - Crites, Nancy N.
AU - Hays, Joshua P.
AU - Andersen, Clark
AU - Lee, Jong O.
AU - Meyer, Walter
AU - Suman, Oscar E.
AU - Finnerty, Celeste C.
N1 - Publisher Copyright:
Copyright © 2015 by the Shock Society.
PY - 2016/3/23
Y1 - 2016/3/23
N2 - 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 μg/kg oxandrolone orally twice daily for 24 months (n=35). Patientswere 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-termoxandrolone 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-termoxandrolone 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.
AB - 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 μg/kg oxandrolone orally twice daily for 24 months (n=35). Patientswere 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-termoxandrolone 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-termoxandrolone 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.
KW - Bone mineral content
KW - Bone mineral density
KW - Burns
KW - Hypermetabolism
KW - Outcomes
KW - Oxandrolone
KW - Pediatric
UR - http://www.scopus.com/inward/record.url?scp=84945261294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84945261294&partnerID=8YFLogxK
U2 - 10.1097/SHK.0000000000000517
DO - 10.1097/SHK.0000000000000517
M3 - Article
C2 - 26506070
AN - SCOPUS:84945261294
SN - 1073-2322
VL - 45
SP - 367
EP - 374
JO - Shock
JF - Shock
IS - 4
ER -