The alteration of Wnts causes human skeletal diseases, with mutations in Wnts such as Wnt1 causing osteoporosis and osteogenesis imperfecta.333–336 Studies demonstrate that Wnt1 mutation results in decreased β-catenin and thus the decreased Wnt/β-catenin signaling, which causes osteoporosis.333,335 Wnt3 expression is essential at the early stages of human limb formation. This evidence concerns the gene WNT1 and osteoporosis.