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Figure 1. Comparison of osteolytic ER+ BMET progression in young vs. skeletally mature mice supplemented with 0.72 mg E₂. (A) Osteolytic lesion incidence and (B) osteolytic lesion area in young (5-week-old) and skeletally mature (16-week-old) mice supplemented with 0.72 mg E₂ and inoculated with ER+ tumor cells (n = 8-13/group). Inset, representative immunohistochemical (IHC) images demonstrating cytokeratin+ (left panel; brown), ERα+ (right panel; brown) human breast cancer tumors in tibiae. ***P ≤ 0.001, ****P ≤ 0.0001 young vs. skeletally mature mice, by 2-way ANOVA with Sidak’s post-test. There was no significant difference (n.s.) in osteolytic lesion incidence by Log-rank (Mantel-Cox) test. (C) Representative hind limb radiographs in young (top) vs. mature (bottom) age-matched control (left panels), naive E₂ (0.72 mg)-supplemented (middle panels), or tumor cell-inoculated and E₂ (0.72 mg)-supplemented mice (right panels) 6 weeks post-inoculation and E₂ supplementation. Osteolytic lesions are marked by arrows.