Osteoporosis is a serious clinical problem that often follows the accelerated bone loss that occurs after the estrogen withdrawal of menopause. In order to better understand the mechanism that produces estrogen withdrawal–induced bone loss, Yu and Pal et al., as reported in this issue of the JCI, examined mice that underwent ovariectomy (OVX). In C57BL/6 mice with enhanced Th17 cells in gut tissue, the authors demonstrated that OVX increased migration of TNF-expressing Th17 cells from the gut to the bone marrow. Furthermore, they found that manipulation of the pathways by which lymphocytes migrate and home to bone marrow prevented the increase of TNF+, Th17 cells in bone marrow after OVX in mice and the trabecular, but not cortical, bone loss in this model. These results argue that interactions of the gut microbiota with the immune system are involved in the effects of estrogen withdrawal on trabecular bone.