SFRP4 and Pyle disease: A whole-genome sequencing (WES) study showed that Pyle's disease was caused by sFRP4 deficiency, that cortical bone and trabecular bone homeostasis were regulated by different mechanisms, and that sFRP4-mediated cross-regulation of Wnt and BMP signaling was essential to obtain proper cortical bone thickness and stability (Kiper et al., 2016; Chen et al., 2019).