Role of Klotho in bone and implication for CKD

Klotho is a transmembrane protein that acts as a co-receptor for fibroblast growth factor 23 (FGF23). Recent investigations have discovered the presence of Klotho in bone-forming osteoblasts and osteocytes. This review summarizes emerging literature on the roles of bone Klotho in mineral and bone metabolism and discusses their possible involvement in renal osteodystrophy.

Mouse genetic studies have demonstrated that loss of Klotho in osteocytes leads to increased bone formation and bone volume. The identification of Klotho expression in bone cells pointed to the possibility that the bone is another target organ for FGF23, providing a new basis for extending the interpretation of previous research findings. Along with this paradigm shift, recent investigations uncovered the autocrine/paracrine functions of FGF23 as a critical regulator of its own production and the Wnt-mediated bone formation. These effects may, however, be offset by down-regulation of bone Klotho in renal failure.

Klotho expressed in bone cells has functional roles in controlling bone formation and regulating FGF23 production. Additional studies are needed to translate these findings into the development of new therapeutic approaches for the treatment of bone fragility in patients with renal osteodystrophy and other bone diseases.