This study explores parallels between systemic hypoxia adaptation in high-altitude populations and tumorigenesis. We identified EPAS1, a gene critical for hypoxia adaptation in populations such as Tibetans and Sherpas, as playing a similar adaptive role in tumors arising under hypoxic conditions. Tumors from patients with chronic hypoxia displayed impaired DNA repair and frequent emergence of EPAS1 variants, with frequencies reaching up to 90%, echoing the positive selection seen in high-altitude dwellers. Mechanistically, EPAS1 gain-of-function mutations promote COX4I2 expression, reducing cellular oxygen consumption and supporting tumor proliferation in hypoxia. Analysis of clinical data from patients with hypoxia revealed tissue-specific and time-sensitive tumorigenic effects, particularly impacting oxygen-sensitive cells in the postnatal period. Our findings suggest that EPAS1-driven adaptation mechanisms in high-altitude populations provide a model for understanding tumor evolution under hypoxic stress, highlighting how genetic adaptations to diverse stressors in natural populations may yield insights into tumorigenesis and cancer progression. Significance: This study reveals a broad convergence in genetic adaptation to hypoxia between natural populations and tumors, suggesting that insights from natural populations could enhance our understanding of cancer biology and identify novel therapeutic targets. See related commentary by Lee, p. 875

Introduction: Osteosarcomas of the jaw (OSJs) are rare tumors with distinct characteristics from osteosarcomas affecting other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of OSJs. Methods: A retrospective, descriptive cross-sectional study including patients diagnosed with OSJ registered at the “La Paz” University Hospital, Madrid, was performed. Results: Data of eight patients with a diagnosis of OSJ were obtained during the study period of 22 years (2002–2024). The mean age of the patients was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most predominant histological type. Survival rate at 5 years was 50%, which decreased to 25% at 10 years. Conclusions: OSJs differ from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment. However, more studies are needed through which more standardized protocols can be proposed for adjuvant therapeutic management.

Aims: Electromagnetic induction heating has demonstrated in vitro antibacterial efficacy over biofilms on metallic biomaterials, although no in vivo studies have been published. Assessment of side effects, including thermal necrosis of adjacent tissue, would determine transferability into clinical practice. Our goal was to assess bone necrosis and antibacterial efficacy of induction heating on biofilm-infected implants in an in vivo setting.Methods: Titanium-aluminium-vanadium (Ti6Al4V) screws were implanted in medial condyle of New Zealand giant rabbit knee. Study intervention consisted of induction heating of the screw head up to 70°C for 3.5 minutes after implantation using a portable device. Both knees were implanted, and induction heating was applied unilaterally keeping contralateral knee as paired control. Sterile screws were implanted in six rabbits, while the other six received screws coated with Staphylococcus aureus biofilm. Sacrifice and sample collection were performed 24, 48, or 96 hours postoperatively. Retrieved screws were sonicated, and adhered bacteria were estimated via drop-plate. Width of bone necrosis in retrieved femora was assessed through microscopic examination. Analysis was performed using non-parametric tests with significance fixed at p ≤ 0.05.Results: The width of necrosis margin in induction heating-treated knees ranged from 0 to 650 μm in the sterile-screw group, and 0 to 517 μm in the biofilm-infected group. No significant differences were found between paired knees. In rabbits implanted with sterile screws, no bacteria were detected. In rabbits implanted with infected screws, a significant bacterial load reduction with median 0.75 Log10 colony-forming units/ml was observed (p = 0.016).Conclusion: Induction heating was not associated with any demonstrable thermal bone necrosis in our rabbit knee model, and might reduce bacterial load in S. aureus biofilms on Ti6Al4V implants.Cite this article: Bone Joint Res 2024;13(12):695–702.