Anatomical adaptation of a custom 3D prosthesis for canine laryngeal stenosis: a preliminary cadaveric study.

With the ongoing global demographic aging, the prevalence of PMOP has been escalating, posing a growing, and severe public health challenge []. Osteoporosis not only significantly reduces the quality of life for patients but is also often accompanied by fractures, widespread pain, and psychological disorders [, ]. In patients with osteoporotic fractures, the integration of metal implants (such as titanium alloys) with bone tissue is often poor, increasing the risk of aseptic loosening of the implants []. Currently, osteoporosis treatments primarily aim to inhibit bone loss or promote increased bone density []. However, these treatments have several limitations, including limited efficacy, high costs, and potential significant side effects []. Therefore, gaining deeper insights into the molecular pathways underlying osteoporosis and designing more effective therapeutic solutions is essential. Unlike apoptosis and necrosis, ferroptosis is a distinct form of cell death caused by iron metabolism disorders []. During ferroptosis, there is an accumulation of iron ions, along with lipid peroxidation and an increase in reactive oxygen species (ROS) levels []. The cystine/glutamate transporter (SLC7A11) and glutathione peroxidase 4 (GPX4) play crucial roles in inhibiting lipid peroxidation in cells []. The ferroptosis inhibitor Ferrostatin‐1 (Fer‐1) effectively prevents the progression of ferroptosis by regulating intracellular iron metabolism and oxidative stress []. Research has shown that ferroptosis is closely linked to the progression of various diseases, including tumors, neurological disorders, cardiovascular diseases, autoimmune diseases, and osteoporosis [, , ]. Additionally, ferroptosis may influence the progression of many estrogen‐related diseases []. Therefore, ferroptosis may play a critical role in the pathogenesis of PMOP, and targeting ferroptosis could become an effective therapeutic approach for treating estrogen deficiency‐related diseases, including PMOP. Valproic acid (VPA) is a widely prescribed drug for managing epilepsy, seizures, and mood disorders [, ]. Recent studies have revealed that long‐term use of VPA may exert dual effects on skeletal health. On one hand, VPA is strongly associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fractures []. On the other hand, VPA exhibits potential osteogenic effects under specific conditions. For instance, in a rat model of glucocorticoid‐induced femoral head necrosis, VPA significantly increased bone formation and reduced bone loss by enhancing osteoblast proliferation and differentiation []. Furthermore, VPA promotes osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) and upregulates the expression of osteogenic markers such as osteocalcin []. These properties provide a theoretical foundation for VPA application in osteoporosis management. Emerging evidence highlights novel mechanisms of VPA in regulating cell death. Studies have confirmed VPA's ability to inhibit ferroptosis in renal tubular epithelial cells [], yet its potential to ameliorate PMOP through ferroptosis regulation remains unexplored. To address this knowledge gap, the present study established BMSC ferroptosis models and OVX rat bone integration models, aiming to investigate VPA's regulatory effects on BMSC ferroptosis and bone integration, thereby providing new insights for targeted osteoporosis therapies.