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/cm2) 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.