We know that not exercising takes a toll on our bones; it’s part of the reason astronauts suffer dramatic bone loss (shown in artist’s illustration above.) But how does exercise prevent this, specifically? To find out, researchers investigated a hormone known as irisin. Previous research found that exercise prompts muscles to secrete this protein fragment into the bloodstream, and that it may help burn fat by causing energy-storing white fat cells to act like energy-burning brown fat cells, although its activity in humans is still controversial. The team gave mice weekly injections of irisin for a month, then conducted a series of tests to gauge the size and strength of their shin and thigh bones. Cortical bone—one of the two types of bone tissue—was stronger in the treated mice than the controls, the researchers report online today in the Proceedings of the National Academy of Sciences. (For example, the bones of treated mice scored an average of 19% higher on a measure of the ability to resist twisting stress, known as the polar moment of inertia.) They don’t yet know which receptors irisin interacts with, but they suggest it prompts the production of proteins that in turn increase the expression of key genes—those that drive immature cells to differentiate into osteoblasts, which synthesize new bone. If more research can demonstrate a similar effect in humans, the authors say, irisin could offer a new therapy for osteoporosis.