Mice with hyperactive bone cells including osteoclasts (hypS3 mice) show strong bone loss and have increased osteoclast numbers. When hypS3 mice also suffer genetic neutrophil loss, their bone loss becomes excessive, and their osteoclast numbers are very high. This can be recapitulated in wild-type mice by antibody-mediated neutrophil depletion. But a short-term (2-week) depletion has the unexpected effect of saving bone. This is because of increases in immature bone marrow neutrophils by the treatment. Only long-term (6-week) antibody-mediated neutrophil loss reduces preneutrophils and leads to bone loss in wild-type and exaggerated bone loss in hypS3 mice. Hence, preneutrophils and immature neutrophils control bone loss by inhibiting osteoclastogenesis.