In that declining estrogen levels have long been associated with osteoporosis, while bone density starts to decline years before these levels drop, Joseph Cannon, from Medical College of Georgia (Georgia, USA), and colleagues investigated the hormonal mechanisms behind this relationship.  Noting that during the time that estrogen declines, a corresponding increase in follicle-stimulating hormone (FSH) occurs, the team speculates that higher levels of FSH decrease bone mineral density by increasing cytokines, regulatory proteins produced by white blood cells. One cytokine in particular, interleukin-1, signals certain cells to transform into osteoclasts, which break down and resorb bone.  In a group of 36 women, ages 20 to 50 years, the team found that higher FSH levels correlated to lower bone mineral density. When they incubated FSH with white blood cells isolated from the women, it stimulated production of interleukin-1. Moreover, higher circulating levels of IL-1 correlated with lower bone mineral density, if the levels of interleukin-1 inhibitory factors were taken into account. Additionally, they found that study participants who exercised more than 180 minutes a week retained greater bone density.  As such, the team’s study suggests that exercise may promote inhibitory factors that help keep interleukin-1 and bone breakdown under control.