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Figure 3. Comparison of dose effects of E₂ on bone mineral density in tumor-naive vs. osteolytic ER+ BMET progression in tumor-inoculated mice. (A) Areal bone mineral density (BMD) of tibiae in tumor-naive 4-week-old mice treated with the indicated doses of E₂ (vs. age-matched controls), as measured by DXA (n = 6-8/group). *P ≤ 0.01 0.72 mg E₂ vs. control; **P ≤ 0.01 for each E₂ dose vs. control, with no statistical differences between E₂ doses, by mixed-effects analysis with Tukey post-test. (B) Osteolytic lesion incidence and (C) osteolytic lesion area in age-matched mice inoculated at 5 weeks of age with ER+ tumor cells (n = 10-13/group) 3 days post-supplementation with the same E₂ doses (vs. no E₂ controls; open circles). P-values for E₂ dosing trends were calculated using Kaplan Meier analysis with log-rank test for incidence, or 1-way ANOVA of AUC data with post-test for linear trend for lesion area. ^P ≤ 0.05 0.72 mg E₂ vs. 0.05 mg E₂ by log-rank (Mantel-Cox) test. *P ≤ 0.05 vs. controls or 0.05 mg E₂; **P ≤ 0.05 vs. control, 0.05, 0.10, or 0.72 mg E₂; ***P ≤ 0.05 vs. every dose, by 2-way ANOVA with Holm-Sidak post-test.