X-linked Hyper IgM Syndrome strikes about one in a million American--all males--and is caused by a deficiency in an important immune system protein known as CD40 ligand. This protein is crucial for the development and maturation of immune cells, and without it people with X-linked Hyper IgM Syndrome are susceptible to a range of opportunistic infections. Last year, an NIAID doctor treating children with this disease observed that several of them sustained unexplained rib fractures that he hypothesized could be, like osteoporosis, caused by a loss of bone mineral density. A new study, published online this week, confirms this unexpected connection. CD40 ligand appears to regulate cells that secrete chemicals that block bone metabolism, and the loss of this protein in people with X-linked Hyper IgM Syndrome appears to accelerate bone loss. The next step, say the researchers, is to determine whether experimental treatments designed to correct the immune deficiency of X-linked Hyper IgM Syndrome can also reverse the bone loss. If so, the knowledge gained from these studies may benefit people at risk of developing osteoporosis.