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

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 patients with burn. 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 .

Male C57BL/6J mice were divided into 5 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 seconds; 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 content (BMC) were assessed weekly using dual-energy X-ray absorptiometry. Micro-computed tomography and 3-point bending were performed at weeks 2 and 6 postinjury to assess bone microstructure and mechanical properties.

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 postinjury. Alendronate treatment ameliorated loss of BMD (-5.7 ± 10.6% from baseline, P = 0.006 compared with untreated Burn mice) and BMC (-4.2 ± 11.6% from baseline, P = 0.006 compared with 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 after burns.

Alendronate was the superior protective treatment for preventing burn-induced bone loss and enhancing recovery in a murine model of postburn systemic bone loss compared with oxandrolone, Vitamin D/Calcium supplementation, and no treatment. These findings suggest that early administration of bisphosphonates in patients with burn may be a promising method for mitigating post-traumatic bone loss.