SHIP1 inhibitor (SHIPi) reduces bone mass. Male 6–12-month-old C57BL6/J mice were injected intraperitoneally with vehicle or SHIPi, a SHIP1 inhibitor, at 25 mg/kg three times per week for 4, 8, and 12 weeks. Significant decrease was observed in (A) whole-body BMD by DEXA analysis in SHIPi-treated group (open square) versus vehicle group (open circle) (±SEM ***P≤0.0001 Student's unpaired, two-tailed t-test). (B) Metaphyseal histomorphometric parameter, Bv/Tv was significantly decreased after SHIPi treatment in the SHIPi group (open squares) in comparison to vehicle group (open circles) (±SEM *P≤0.05 Student's unpaired, two-tailed t-test, each symbol represents an individual mouse).