In the present study, we revealed that inactivation of STAT3 in osteoblast lineage cells, but not osteoclasts, induced a series of remarkable bone developmental dysplasia, including dwarfism with short limbs, craniofacial malformations, osteoporosis, and bone fragility, which were similar to the bone defects in AD-HIES. The gene discussed is STAT3; the disease is osteoporosis.