EphrinB2-Fc and EphB4-Fc affect MM bone disease and tumor growth in SCID-hu mice. SCID-hu mice (n = 15) engrafted with primary myeloma cells from a single patient were treated with Fc, ephrinB2-Fc, or EphB4-Fc (5 mice/group) for 4 weeks using Alzet pumps that released 0.11 μg/hr of each compound directly into the implanted bones. (A) Changes in BMD of the implanted bone from pretreatment levels, histomorphometric parameters, and numbers of osteocalcin-expressing osteoblasts and TRAP-expressing osteoclasts in myelomatous bones. Note EphrinB2-Fc and EphB4-Fc increased bone formation and osteoblast numbers, but only EphB4-Fc reduced the number of osteoclasts. (B) Representative x-ray radiographs of myelomatous bones treated with indicated agents. Note that, in contrast to Fc, ephrinB2-Fc and EphB4-Fc treatment resulted in increased bone mass. (C) Changes in human Ig levels (left panel) and MM tumor area (right panel) in the implanted human bone after treatment with control Fc, ephrinB2-Fc, or EphB4-Fc for 4 weeks. Note inhibition of MM growth by EphB4-Fc but not ephrinB2-Fc. (D) Representative bone sections with immunohistochemical (IHC) staining for osteocalcin (left panels) or stained for TRAP (right panels). Note that ephrinB2-Fc and EphB4-Fc increased numbers of osteoblasts, but only EphB4-Fc reduced numbers of osteoclasts in myelomatous bones.