Abstract
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 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
.
METHODS:
Design:
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.
Outcome Measures:
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.
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 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.
CONCLUSIONS:
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.