A SHIP-deficient MS/PC compartment limits bone apposition and causes osteoporosis. Mineral apposition rate (MAR) was calculated by measuring the distance from the oxytetracycline band to the endosteal surface. (A) Reduced bone MAR was observed in 3-week-old OSXCreSHIPflox/flox in comparison to SHIPflox/flox controls. (n≥4, ±SEM **P ≤ 0.001 Student's unpaired, two-tailed t-test) (B) Representative images of oxytetracycline band seen in SHIPflox/flox (+/+) and OSXCreSHIPflox/flox (−/−) C, cortical bone. (C) Whole-body bone mineral density (BMD) and (D) bone mineral content (BMC) by DEXA analysis of 6–20-week-old SHIPflox/flox (+/+) and OSXCreSHIPflox/flox (−/−) mice; (n≥7,±SEM. *P≤0.05, **P≤0.001 and ***P≤0.0001 Student's unpaired, two-tailed t-test, each symbol represents an individual mouse). (E) Metaphyseal histomorphometric parameters, bone volume over tissue volume (Bv/Tv), measured at 2, 4, 8 and, 16 weeks in SHIPflox/flox (+/+) and OSXCreSHIPflox/flox (−/−) mice (±SEM ***P≤0.0001 Student's unpaired two-tailed t-test). Representative micro computed tomography (microCT) scans of sagittal sections through the proximal metaphysis taken from 4- and 16-week-old SHIPflox/flox (+/+) and OSXCreSHIPflox/flox (−/−) mice (inset). (F) Metaphyseal thickness (μm) of 4, 8, and 16 week-old-male SHIPflox/flox (+/+) (black circles) and OSXCreSHIPflox/flox (−/−) (gray squares) mice (±SD *P≤0.05 and ***P≤0.0001 Student's unpaired, two-tailed t-test). Significant difference in metaphyseal thickness was also observed in female SHIPflox/flox and OSXCreSHIPflox/flox littermates. Note: results presented for MAR, BMC, and Bv/Tv represent pooled male and female SHIPflox/flox and OSXCreSHIPflox/flox mice. Color images available online at www.liebertpub.com/scd