Sclerostin, Osteocytes, and Chronic Kidney Disease - Mineral Bone Disorder.
Osteocytes respond to kidney damage by increasing production of secreted factors important to bone and mineral metabolism. These circulating proteins include the antianabolic factor, sclerostin, and the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Elevated sclerostin levels correlate with increased FGF23, localized reduction in Wnt/β-catenin signaling in the skeleton and reduced osteoblast differentiation/activity. Decreased Wnt/β-catenin signaling occurs regardless of the overall changes in bone formation rates, suggesting that a reduction in the anabolic response may be a common feature of renal bone disorders but additional mechanisms may contribute to the diversity of osteodystrophy phenotypes. Recent preclinical studies support this hypothesis, as treatment with antisclerostin antibodies improved bone quality in the context of low but not high turnover renal osteodystrophy. Sclerostin also appears in the circulation suggesting additional roles outside the skeleton in normal and disease states. In patients with chronic kidney disease (CKD), serum levels are elevated several fold relative to healthy individuals. Emerging data suggest that these changes are associated with increased fracture rates but the relationship between sclerostin and cardiovascular disease is unclear. Additional epidemiologic studies that examine stage specific and patient sub-populations are needed to assess whether sclerostin elevations influence comorbidities associated with CKD.
Medicine Master Degree Program, Universidade Nove de Julho, UNINOVE, São Paulo, Brazil.|Nephrology Division, Universidade de São Paulo, São Paulo, Brazil.
Rosa M A
RM
Moysés
Boston, MA.
Susan C
SC
Schiavi
D048868:Adaptor Proteins, Signal Transducing; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D000089703:Fibroblast Growth Factor-23; D005819:Genetic Markers; D006801:Humans; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; C000717427:FGF23 protein, human; D005819:Genetic Markers; C422903:SOST protein, human; D000089703:Fibroblast Growth Factor-23