Osteoprotegerin affects the responsiveness of fibroblast growth factor-23 to high oral phosphate intake

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

“…This result possibly indicates another compensatory reaction of OPG synthesis in response to increased Pi levels. An experimental study has shown that OPG may play a key role in mediating the response of FGF-23 to an oral phosphate load in bone cells [19]. Consistent with our results, others have also found FGF-23 levels to be increased and significantly associated with PTH in children with different stages of CKD [33,34].…”

“…In fact, studies regarding OPG [13][14][15][16][17] and RANKL [17,18] in the pediatric population with CKD are few, and no studies have assessed the relationship of the OPG/RANKL system with FGF-23. Findings from one animal study have shown that OPG may play a key role in mediating the response of FGF-23 to an oral phosphate load in bone cells [19].…”

Serum osteoprotegerin measurement for early diagnosis of chronic kidney disease‐mineral and bone disorder

“…The increase of OPG might be induced by the loss of compensation of FGF‐23. Interestingly, a previous research indicated that OPG could affect the responsiveness of FGF‐23 to high oral phosphate intake 24 . The interaction between FGF‐23 and OPG needs further investigation.…”

FGF23/Klotho New Regulators of Vitamin D Metabolism

“…More studies are needed to investigate the relationship between phosphate deposition in bone and FGF23 regulation; however, a phosphate-sensing mechanism linked to bone buffering capacity might reconcile the fact that in vitro phosphate does not regulate FGF23 expression nor FGF23 promoter transcriptional activities whereas in vivo phosphate loading can regulate FGF23 secretion [81] independently of 1,25(OH) 2 D. Consistent with this possibility, the antiresorptive agent osteoprotegerin produced a profound reduction in bone resorption and formation in male and oophorectomized female mice, accompanied by an increase in serum levels of FGF23 [107]. Theoretically, high rates of bone turnover would release calcium and phosphate from bone, leading to calcium-mediated suppression of PTH and elevated FGF23 to prevent hyperphosphatemia, but a role of primary increases in bone resorption leading to increased FGF23 is not supported by existing data, since OPG-null mice with high bone resorption have low FGF23 levels [108]. There is an association of increased FGF23 and plasma cell dyscrasias [109], but a formal assessment of the effect of increased osteoclastic-mediated bone resorption of FGF23 expression in bone has not been performed.…”