Subjects with sclerosteosis, van Buchem disease, or HBM associated with LRP5 mutations often suffer from neuropathies and other sequelae due to nerve impingements caused by increased bone mass.11–15 We show here that when treated with Wnt secretion inhibitors, genetic mouse models that replicate human HBM exhibit reduced levels of bone mass, and these levels are similar to normal levels. The gene discussed is LRP5; the disease is sclerosteosis.