Deficiency of protein C or protein S as a possible cause of osteoporosis

Proteins C and S are vitamin K-dependent anticoagulative factors that also exert a significant influence on bone quality. Clinical studies have linked the deficiency of proteins C and S to lower bone mineral density and the onset of femoral head osteonecrosis in children. Rare foundational studies analyzing this topic have demonstrated that activated protein C, upon binding to the endothelial protein C receptor expressed on the surface of osteoblasts, promotes osteoblast proliferation. It is also established that proteins C and S play crucial roles in proper collagen synthesis and in maintaining the number of osteoclasts and blood vessels. However, the association between protein C and/or S deficiency and the gradual onset of osteoporosis remains largely uninvestigated. Calculations based on data from peer-reviewed journals suggest that approximately one in every 10 individuals may develop osteoporosis due to congenital protein C or S deficiency. Moreover, when secondary causes of protein C and S deficiency are also considered, the proportion likely further increases. In this paper, we discuss the pathophysiological background of the potential relationship between protein C and S deficiency and the genesis of osteoporosis.