Topical Application of Estrogen Nanocapsules on Skin Incision Improves Fracture Healing in Osteoporotic Rats

Objective  The challenge of consolidating osteoporotic fractures, particularly exacerbated by postmenopausal estrogen deficiency, underscores the urgent need for effective interventions. This study aims to evaluate the impact of locally administered estrogen via nanocapsules on the consolidation of osteoporotic fractures in ovariectomized rats, while also assessing the systemic effects of this hormone, using the uterus as a sentinel organ. Methods  Forty-five animals underwent standardized femoral fractures and were divided into three groups: G1 (control), G2 (conventional estrogen), and G3 (estrogen nanocapsules). The estrogen was applied topically to the skin incision region (trichotomized area). Fracture healing was assessed at 15- and 30-days postfracture through radiographic and histological analyses, with uterine histology conducted to evaluate systemic effects. Results  In terms of radiographic analysis of callus formation, G3 (8.75 ± 0.77 mm) exhibited significantly higher callus formation than the control group (7.18 ± 0.4 mm) at day 15, with histological analysis revealing increased callus formation in G3 at day 30, indicating an accelerated healing process. Furthermore, uterine histological analysis at day 30 showed a reduction in endometrial thickness in G3 (510,073 ± 54,705.11 μm) compared with G2 (623,729 ± 101,592 μm). Conclusion  These findings suggest that topical estrogen nanocapsules may enhance callus formation in the treatment of osteoporotic femoral fractures in rats, potentially with fewer systemic effects.