Bone mineral density (BMD), the major factor determining bone strength, is closely related to osteoporotic fracture risk and is determined largely by multiple genetic factors. Semaphorin 7a (SEMA7A), a recently described member of the semaphorin family, has been shown to play a critical role in the activation of monocyte/macrophages that share progenitors with bone-resorbing osteoclasts and thus might contribute to osteoclast development. In the present study, we directly sequenced the SEMA7A gene in 24 Korean individuals, and identified 15 sequence variants. Five polymorphisms (+ 15667G> A,+ 15775C> G,+ 16285C> T,+ 19317C> T,+ 22331A> G) were selected and genotyped in postmenopausal Korean women (n= 560) together with measurement of the areal BMD (g/cm 2) of the anterior-posterior lumbar spine and the non-dominant proximal femur using dual-energy X-ray absorptiometry. We found that polymorphisms of the SEMA7A gene were associated with the BMD of the lumbar spine and femoral neck. SEMA7A+ 15775C> G and SEMA7A+ 22331A> G were associated with low BMD of the femoral neck (P= 0.02) and lumbar spine (P= 0.04) in a recessive model. SEMA7A-ht4 also showed an association with risk of vertebral fracture (OR= 1.87–1.93, P= 0.02–0.03). Our results suggest that variations in SEMA7A may play a role in decreased BMD and risk of vertebral fracture.