Background/Aim: Metastatic osteolytic bone tumors represent a clinical challenge as their pathogenesis and progression involve complex interactions within the bone microenvironment. Sclerostin, a key inhibitor of the Wnt signaling pathway, is critical to bone metabolism; however, its involvement in metastatic bone tumors remains insufficiently characterized. This study investigated sclerostin’s role in metastatic osteolytic tumors, specifically its relationship with other bone remodeling molecules, including DKK1, BMP6, and the proliferation marker Ki67. Patients and Methods: Tumor specimens were collected from nine patients who underwent surgery for metastatic bone tumors in the femur or tibia. Sclerostin, DKK1, BMP6, and Ki67 expression was assessed using immunohistochemical staining. Positivity rates were determined for each protein. Correlations between their expression levels were examined using Pearson’s correlation coefficient. Results: All tumor samples demonstrated a certain degree of positivity for sclerostin, DKK1, BMP6, and Ki67. The mean proportion of sclerostin-positive cells was 7.3%. Sclerostin and DKK1 exhibited a moderately negative correlation (r=−0.45), suggesting their distinct roles in the tumor microenvironment. Sclerostin and BMP6A exhibited a weak positive correlation (r=0.25), while sclerostin and Ki67 showed no significant correlation. The cohort’s one-year survival rate was 72.9%. Conclusion: Sclerostin contributes to the bone formation processes within the osteolytic metastatic tumor microenvironment, possibly through interactions with BMP6 and modulation of Wnt signaling, thus highlighting its potential as a novel therapeutic target for the treatment of metastatic bone tumors. Further studies with larger, more homogeneous patient cohorts are warranted to validate these findings and elucidate the precise molecular mechanisms involved.
HASHIMOTO et al. (2026) studied this question.