SPP1 and Cowden syndrome 1: As OPN may well be an important factor that contributes to osteopenia and osteoporosis in CS and other RASopathies, future studies may address yet unknown OPN-related properties that would contribute to bone health such as its phosphorylation status, amount of soluble OPN that may positively stimulate osteoclastogenesis, osteoblast responsiveness to growth factors61, and activation of CD44 and/or integrins62.