Treatment Effects of Bisphosphonates Compared to Oxandrolone on Burn-Induced Bone Loss and Recovery in Mice.

OBJECTIVE: Severe burn injuries can lead to systemic bone loss, increasing the risk of secondary fragility fractures. Evaluating treatments aimed at mitigating post-traumatic systemic bone loss is critically important for preventing secondary fractures in burn patients. This study evaluated the efficacy of bisphosphonate (alendronate), oxandrolone, and vitamin D/calcium supplementation in mitigating post-traumatic bone loss and promoting recovery of bone in a murine model of burn-induced systemic bone loss, in which a full-thickness thermal skin burn involving approximately 15% total body surface area was used to model severe burn injury. METHODS: Male C57BL/6J mice were divided into five groups: control, burn with no treatment, burn + alendronate, burn + vitamin D/calcium, and burn + oxandrolone. Full thickness burn injuries were induced on the back of mice by submerging in 65° C water for 20 s; debridement and matrix application were performed 48 hours after injury, and treatments were administered starting on the day of injury. Whole-body and site-specific bone mineral density (BMD) and bone mineral composition (BMC) were assessed weekly using dual energy x-ray absorptiometry. Micro-computed tomography and 3-point bending were performed at weeks 2 and 6 post-injury to assess bone microstructure and mechanical properties. RESULTS: Untreated burned mice exhibited significant losses in BMD (-12.0 ± 7.6% from baseline, p=0.025) and BMC (-14.7 ± 13.4% from baseline, p=0.021), peaking at 3 weeks post-injury. Alendronate treatment ameliorated loss of BMD (-5.7 ± 10.6% from baseline, p=0.006 compared to untreated Burn mice) and BMC (-4.2 ± 11.6% from baseline, p=0.006 compared to untreated Burn mice) and accelerated the recovery process, reaching BMD and BMC values greater than baseline by week 6. Vitamin D/calcium supplementation (peak BMD loss -8.6 ± 8.1%, p=0.974; BMC -17.6 ± 14.2%, p=0.973) and oxandrolone treatments (peak BMD loss -17.1 ± 12.5%, p=0.408; BMC -19.5 ± 16.4%, p=0.404) demonstrated no protective or improved recovery effects for bone loss following burns. CONCLUSION: Alendronate was the superior protective treatment for preventing burn-induced bone loss and enhancing recovery in a murine model of post-burn systemic bone loss compared with oxandrolone, Vitamin D/ Calcium supplementation, and no treatment. These findings suggest that early administration of bisphosphonates in burn patients may be a promising method for mitigating post-traumatic bone loss.