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Evocalcet Rescues Secondary Hyperparathyroidism-driven Cortical Porosity in CKD Male Rats

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Title: Evocalcet Rescues Secondary Hyperparathyroidism-driven Cortical Porosity in CKD Male Rats
Authors: Hasegawa, Tomoka Browse this author →KAKEN DB
Tokunaga, Shin Browse this author
Yamamoto, Tomomaya Browse this author →KAKEN DB
Sakai, Mariko Browse this author
Hongo, Hiromi Browse this author →KAKEN DB
Kawata, Takehisa Browse this author
Amizuka, Norio Browse this author →KAKEN DB
Keywords: secondary hyperparathyroidism
cortical porosity
Issue Date: 11-Feb-2023
Publisher: Endocrine Society
Journal Title: Endocrinology
Volume: 164
Issue: 4
Start Page: bqad022
Publisher DOI: 10.1210/endocr/bqad022
PMID: 36718587
Abstract: To elucidate the effect of evocalcet, a new oral calcimimetic to bone of secondary hyperparathyroidism (SHPT) with chronic kidney disease (CKD), the rats were 5/6 nephrectomized and fed on a high-phosphate diet. The treated rats were then divided into vehicle groups and evocalcet administered groups. The rats in the vehicle groups exhibited increased levels of serum PTH and inorganic phosphate (Pi) levels, high bone turnover, and severe cortical porosity, mimicking SHPT (CKD-SHPT rats). The cortical bone of the CKD-SHPT rats showed broad demineralization around the osteocytes, suppression of Phex/small integrin-binding ligand N-linked glycoprotein-mediated mineralization in the periphery of the osteocytic lacunae, and increased levels of osteocytic cell death, all of which were considered as the first steps of cortical porosity. In contrast, evocalcet ameliorated the increased serum PTH levels, the enlarged osteocytic lacunae, and the cortical porosity of the CKD-SHPT rats. Osteocytes of CKD-SHPT rats strongly expressed PTH receptor and Pit1/Pit2, which sense extracellular Pi, indicating that PTH and Pi affected these osteocytes. Cell death of cultured osteocytes increased in a Pi concentration-dependent manner, and PTH administration rapidly elevated Pit1 expression and enhanced osteocytic death, indicating the possibility that the highly concentrated serum PTH and Pi cause severe perilacunar osteolysis and osteocytic cell death. It is likely therefore that evocalcet not only decreases serum PTH but also reduces the exacerbation combined with PTH and Pi to the demineralization of osteocytic lacunae and osteocytic cell death, thereby protecting cortical porosity in CKD-SHPT rats.
Type: article
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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