Treatment with anti-sclerostin antibody reduces formation of osteolytic bone lesions. (A) Schematic describing the study design for investigations of bone lesions in 5T2MM-bearing mice. (Bi) TRAP/hematoxylin-stained histologic section of a tibia from a 5T2MM-bearing mouse. Slides were scanned on a Scanscope CS2 (Aperio) up to original magnification ×40, and images were captured by using an Aperio Imagescope at digital magnification ×2. Scale bar represents 500 µm; black arrows point to cortical lesions. (Bii) Higher magnification (×12 and ×30) images that demonstrate the temporal development of CB lesions in the 5T2MM model. (1) Initial erosion of the endosteal surface of the CB by red TRAP-positive osteoclasts (black arrows) adjacent to tumor cells in the BM. (2) Formation of a CB lesion (blue dotted line) by osteoclasts (black arrows). (3) A cortical lesion that has penetrated the cortex with the tumor (blue dotted line) extending into the surrounding soft tissue. (Top panel) scale bar represents 100 µm; (bottom panel) scale bar represents 50 µm. (C) Representative 3D reconstruction of tibia from each treatment group showing full cortex penetration lesions (white arrows) in the 5T2MM⁺ control and 5T2MM⁺ anti-sclerostin antibody groups. (D) Dot plots of lesion number per bone for femora and tibiae (n = 7-8 per group; data are mean ± 1 SEM; *P < .05).