Vitamin D receptor (VDR) expression in osteosarcoma and its association with histological subtypes and metastasis

Osteosarcoma is a primary malignant bone tumor most common in children and also occurs in older adults. Although it has several histopathological subtypes, it is generally aggressive and tends to metastasize. Vitamin D, through its active form 1,25(OH)2D3, binds to the vitamin D receptor (VDR) and influences pathways that inhibit tumor growth and metastasis. High VDR expression has been linked to better outcomes in various cancers, but its specific role in osteosarcoma is still unclear. VDR expression was evaluated immunohistochemically in paraffin-embedded osteosarcoma tissues from patients diagnosed at Dr. Sardjito General Hospital (2019–2025). VDR expression was categorized as significant or non-significant, and its relationship with histological subtype and metastasis was statistically analyzed. Fifty-seven patients were included, with a mean age of 19.91 ± 10.8 years. Conventional osteosarcoma (94.7%) and high-grade tumors (94.7%) were most common. Significant VDR expression was seen in 43.9% of cases, and metastasis occurred in 43.9% of patients. VDR expression was not linked to histological subtype (p = 0.499) or grade (p = 0.120), but it was significantly associated with metastasis (p < 0.001). Additionally, combined VDR expression and serum vitamin D levels were associated with metastasis (p = 0.040). This study shows that VDR expression is strongly associated with metastasis in osteosarcoma, especially in patients with low serum vitamin D. It suggests that VDR is a context-dependent biomarker: receptor expression without sufficient ligand indicates impaired vitamin D/VDR signaling and more aggressive tumors. Combining tumor VDR levels with systemic vitamin D status could improve metastasis risk assessment and support vitamin D-based therapies in osteosarcoma.