FIGURE 5.

A potential explanation of the CKD-MBD bone-vascular paradox. CKD induces osteoblastic/osteocytic transdifferentiation of vascular smooth muscle cells. The osteoblastic/osteocytic cells stimulate vascular calcification and express high levels of sclerostin as shown by Mace et al. (2021); Mace et al. (2022) and others. Sclerostin secretion to the circulation decreases skeletal remodeling and inhibits skeletal calcification (an explanation of the paradox). Skeletal osteocytes also contribute to the elevated circulating sclerostin levels in CKD. How CKD stimulates VSMC transdifferentiation is unknown, although hyperphosphatemia is a contributor in the late stages of the syndrome.