Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease
Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in re...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/15/8/952 |
| _version_ | 1797431864207605760 |
|---|---|
| author | Yi-Chou Hou Cai-Mei Zheng Hui-Wen Chiu Wen-Chih Liu Kuo-Cheng Lu Chien-Lin Lu |
| author_facet | Yi-Chou Hou Cai-Mei Zheng Hui-Wen Chiu Wen-Chih Liu Kuo-Cheng Lu Chien-Lin Lu |
| author_sort | Yi-Chou Hou |
| collection | DOAJ |
| description | Renal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased renal phosphate excretion, resulting in potentiating bone resorption and decreased bone quantity and quality. Calcium-sensing receptors (CaSRs) are group C G-proteins and negatively regulate the parathyroid glands through (1) increasing CaSR insertion within the plasma membrane, (2) increasing 1,25-dihydroxy vitamin D3 within the kidney and parathyroid glands, (3) inhibiting fibroblast growth factor 23 (FGF23) in osteocytes, and (4) attenuating intestinal calcium absorption through Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6). Calcimimetics (CaMs) decrease PTH concentrations without elevating the serum calcium levels or extraosseous calcification through direct interaction with cell membrane CaSRs. CaMs reduce osteoclast activity by reducing stress-induced oxidative autophagy and improving Wnt-10b release, which promotes the growth of osteoblasts and subsequent mineralization. CaMs also directly promote osteoblast proliferation and survival. Consequently, bone quality may improve due to decreased bone resorption and improved bone formation. CaMs modulate cardiovascular fibrosis, calcification, and renal fibrosis through different mechanisms. Therefore, CaMs assist in treating SHPT. This narrative review focuses on the role of CaMs in renal osteodystrophy, including their mechanisms and clinical efficacy. |
| first_indexed | 2024-03-09T09:51:27Z |
| format | Article |
| id | doaj.art-f53f7353c8bd4f6f95dbf167d0696e18 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T09:51:27Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-f53f7353c8bd4f6f95dbf167d0696e182023-12-02T00:08:51ZengMDPI AGPharmaceuticals1424-82472022-07-0115895210.3390/ph15080952Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney DiseaseYi-Chou Hou0Cai-Mei Zheng1Hui-Wen Chiu2Wen-Chih Liu3Kuo-Cheng Lu4Chien-Lin Lu5Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, TaiwanDivision of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, New Taipei City 11031, TaiwanTMU Research Centre of Urology and Kidney, Taipei Medical University, New Taipei City 11031, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 11490, TaiwanDivision of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, School of Medicine, Buddhist Tzu Chi University, Hualien 97004, TaiwanDivision of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, TaiwanRenal osteodystrophy is common in patients with chronic kidney disease and end-stage renal disease and leads to the risks of fracture and extraosseous vascular calcification. Secondary hyperparathyroidism (SHPT) is characterized by a compensatory increase in parathyroid hormone (PTH) secretion in response to decreased renal phosphate excretion, resulting in potentiating bone resorption and decreased bone quantity and quality. Calcium-sensing receptors (CaSRs) are group C G-proteins and negatively regulate the parathyroid glands through (1) increasing CaSR insertion within the plasma membrane, (2) increasing 1,25-dihydroxy vitamin D3 within the kidney and parathyroid glands, (3) inhibiting fibroblast growth factor 23 (FGF23) in osteocytes, and (4) attenuating intestinal calcium absorption through Transient Receptor Potential Vanilloid subfamily member 6 (TRPV6). Calcimimetics (CaMs) decrease PTH concentrations without elevating the serum calcium levels or extraosseous calcification through direct interaction with cell membrane CaSRs. CaMs reduce osteoclast activity by reducing stress-induced oxidative autophagy and improving Wnt-10b release, which promotes the growth of osteoblasts and subsequent mineralization. CaMs also directly promote osteoblast proliferation and survival. Consequently, bone quality may improve due to decreased bone resorption and improved bone formation. CaMs modulate cardiovascular fibrosis, calcification, and renal fibrosis through different mechanisms. Therefore, CaMs assist in treating SHPT. This narrative review focuses on the role of CaMs in renal osteodystrophy, including their mechanisms and clinical efficacy.https://www.mdpi.com/1424-8247/15/8/952calcimimeticscalcium-sensing receptorsCKD–MBDfibroblast growth factor 23secondary hyperparathyroidism |
| spellingShingle | Yi-Chou Hou Cai-Mei Zheng Hui-Wen Chiu Wen-Chih Liu Kuo-Cheng Lu Chien-Lin Lu Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease Pharmaceuticals calcimimetics calcium-sensing receptors CKD–MBD fibroblast growth factor 23 secondary hyperparathyroidism |
| title | Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease |
| title_full | Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease |
| title_fullStr | Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease |
| title_full_unstemmed | Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease |
| title_short | Role of Calcimimetics in Treating Bone and Mineral Disorders Related to Chronic Kidney Disease |
| title_sort | role of calcimimetics in treating bone and mineral disorders related to chronic kidney disease |
| topic | calcimimetics calcium-sensing receptors CKD–MBD fibroblast growth factor 23 secondary hyperparathyroidism |
| url | https://www.mdpi.com/1424-8247/15/8/952 |
| work_keys_str_mv | AT yichouhou roleofcalcimimeticsintreatingboneandmineraldisordersrelatedtochronickidneydisease AT caimeizheng roleofcalcimimeticsintreatingboneandmineraldisordersrelatedtochronickidneydisease AT huiwenchiu roleofcalcimimeticsintreatingboneandmineraldisordersrelatedtochronickidneydisease AT wenchihliu roleofcalcimimeticsintreatingboneandmineraldisordersrelatedtochronickidneydisease AT kuochenglu roleofcalcimimeticsintreatingboneandmineraldisordersrelatedtochronickidneydisease AT chienlinlu roleofcalcimimeticsintreatingboneandmineraldisordersrelatedtochronickidneydisease |