Osteoclasts do not affect leukemia progression. Albino C57BL/6 mice were treated at 2 months of age subcutaneously with 10 mg/kg of murine RANK-muFc or vehicle 3 times per week. In leukemic animals, the treatment started 2 days prior to EL4 cell injection and continued until the time of death. Healthy mice were treated for 4 weeks. Serum levels of osteocalcin (A) and C-telopeptide (CTX) (B), and bone mineral density (BMD) at the spine (C) and femur (D) in WT and leukemic mice treated with either RANK-Fc or vehicle. (E) TRAP⁺ osteoclasts (black arrows) in spine sections of WT and leukemic mice treated with RANK-Fc or vehicle. (F) Whole body luminescence counts. (G) Representative in vivo images showing leukemia progression. (H) Survival probability in mice injected with EL4 cells and treated with either RANK-Fc or vehicle (n = 4-7 mice per group). *^{, #,❖}P < .05 (*, relative to WT vehicle; #, relative to WT LP533401; and ❖, relative to leukemia vehicle). ND, not detected.