Background: Osteosarcoma is the most frequent form of malignant pediatric bone tumor. Despite the current therapeutic arsenal, patient life-expectancy remains low if metastases are detected at the time of diagnosis, justifying research into better knowledge at all stages of osteosarcoma ontogenesis and identification of new therapeutic targets. Receptor Activator of Nuclear factor κB (RANK)expression has been reported in osteosarcoma cells, raising the question of Receptor Activator of Nuclear factor κB Ligand (RANKL)/RANK signaling implications in these tumor cells (intrinsic), in addition to previously reported implications through osteoclast activation in the tumor microenvironment (extrinsic). Methods: Based on in vitro and in vivo experimentations using human and mouse osteosarcoma cell lines, the consequences on the main cellular processes of RANK expression in osteosarcoma cells were analyzed. Results: The results revealed that RANK expression had no impact on cell proliferation and tumor growth, but stimulated cellular differentiation and, in an immune-compromised environment, increased the number of lung metastases. The analysis of RANKL, RANK and osteoprotegerin (OPG) expressions in biopsies of a cohort of patients revealed that while RANK expression in osteosarcoma cells was not significantly different between patients with or without metastases at the time of diagnosis, the OPG/RANK ratio decreased significantly. Conclusion: Altogether, these results are in favor of RANKL-RANK signaling inhibition as an adjuvant for the treatment of osteosarcoma.

Background: Osteosarcoma is an aggressive bone tumor with a high risk of lung metastasis, which severely affects patient survival. EMT plays a major role in tumor spread, therapy resistance, and cancer stemness. This review explores how EMT contributes to osteosarcoma metastasis and the underlying molecular mechanisms. Methods: We reviewed recent studies on EMT-related signaling pathways, transcription factors, and regulatory RNAs in osteosarcoma. We also examined the role of the tumor microenvironment. Results: EMT promotes cell detachment, migration, and lung colonization. Key pathways such as TGF-β, MAPK, PI3K/Akt, STAT3, Notch, and Wnt/β-catenin are involved. Non-coding RNAs further regulate EMT by interacting with these pathways. The tumor microenvironment, including hypoxia and immune cells, also supports EMT and metastasis. Conclusions: EMT is a key driver of metastasis and poor outcomes in osteosarcoma. Targeting EMT and its regulators may help prevent lung spread and improve treatment. Future strategies combining EMT inhibition with existing therapies could be promising for clinical application.

Background: While changes in clinical practice during the COVID-19 pandemic in Japan have been widely studied, data specific to bone and soft tissue tumor care remain limited. Methods: A nationwide web-based survey was conducted among hospitals specializing in musculoskeletal tumors. It assessed the occurrence of COVID-19-related events (patient infections, outbreak clusters, and staff infections), delays in referral and diagnosis, postponement or cancellation of specific treatments, and changes in institutional management strategies. Results: Seventy-eight hospitals (91.7% of all specialized centers) responded. Patient infections, outbreak clusters, and staff infections were reported by 28.2%, 48.7%, and 53.8% of hospitals, respectively. While radiological exams and biopsies were largely maintained, patient referrals decreased significantly. Surgical treatment was more affected than chemotherapy or radiotherapy. Strategy changes included surgery delays or cancellations (48.7%) and prolonged follow-up intervals (20.5%). Among COVID-19-related factors, only direct patient infections were significantly associated with institutional changes in treatment policy. Conclusions: The pandemic substantially disrupted outpatient services and surgical care in musculoskeletal oncology. Patient infection was the main driver of treatment strategy modifications.