Neutrophils, as the most abundant innate immune cells, are being increasingly acknowledged as multifaceted regulators in the pathogenesis of osteoporosis, beyond their traditional role as “inflammatory effector cells.” They not only promote osteoclast differentiation by releasing RANKL and ROS and by forming NETs but also inhibit osteoblast function and the regulation of MSC fate. This evidence concerns the gene TNFSF11 and osteoporosis.