Prophylactic dosing with CCX721 reduces both myeloma tumor burden and myeloma-triggered OC formation. (A) Schematic diagram of the 28-day study with naive syngeneic female C57BL/KaLwRijHsd mice that were inoculated intravenously with 5TGM1-GFP MM cells, randomized into groups, and dosed twice daily by oral gavage with either vehicle or CCX721 (100 mg/kg); an additional control group received zoledronic acid (120 μg/kg) by subcutaneous injection twice weekly. (B) Serum monoclonal IgG2_bK paraprotein titers from samples taken on day 28 after tumor cell inoculation. (C) Representative whole-skeleton fluorescence scans detecting fluorescent myeloma foci in bone (image negatives shown; see supplemental Figure 10 for green fluorescence color originals). (D) OC activity assessed by TRAP staining (red) in the long bones of tumor-bearing mice, representative images using an Olympus BX41 microscope (10× magnification). (E) Histomorphometric analysis of the number of OCs per bone surface. **P < .01 (Mann-Whitney test); ***P < .001 (Mann-Whitney test).