Investigation into Possible Association of Oxandrolone and Heterotopic Ossification Following Burn Injury

Abstract

Oxandrolone, a testosterone analog, is used to counteract the catabolic effects of burn injury. Recent animal studies suggest a possible hormonal association with heterotopic ossification (HO) development postburn. This work examines oxandrolone administration and HO development by exploring historical clinical data bridging the introduction of oxandrolone into clinical practice. Additionally, we examine associations between oxandrolone administration and HO in a standardized mouse model of burn/trauma-related HO. Acutely burned adults admitted between 2000 and 2014, survived through discharge, and had a HO risk factor of 7 or higher were selected for analysis from a single burn center. Oxandrolone administration, clinical and demographic data, and elbow HO were recorded and were analyzed with logistic regression. Associations of oxandrolone with HO were examined in a mouse model. Mice were administered oxandrolone or vehicle control following burn/tenotomy to examine any potential effect of oxandrolone on HO and were analyzed by Student's t test. Subjects who received oxandrolone had a higher incidence of elbow HO than those that did not receive oxandrolone. However, when controlling for oxandrolone administration, oxandrolone duration, postburn day oxandrolone initiation, HO risk score category, age, sex, race, burn size, and year of injury, there was no significant difference between rates of elbow HO between the two populations. In agreement with the review, in the mouse model, while there was a trend toward the oxandrolone group developing a greater volume of HO, this did not reach statistical significance.

Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation

“…Testosterone might play a role in the gender difference of burn-induced HO. Thorpe et al [62] found that acutely burned patients who received a testosterone analog treatment presented a higher incidence of elbow HO than patients without testosterone analog treatment. In a mouse model following burn/tenotomy, testosterone analog treatment conferred a trend of developing a larger volume of HO lesions [62].…”

Histology Scoring System for Murine Cutaneous Wounds

“…Burn wounds. A dorsal burn injury with concurrent Achilles tenotomy was induced on 6-week-old male C57BL/6 mice as previously described [13]. The mice were housed individually under standard conditions with free access to drinking water and food.…”