{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:20Z","timestamp":1787028440552,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We have previously demonstrated calcimimetics optimize the balance between osteoclastic bone resorption and osteoblastic mineralization through upregulating Wingless and int-1 (Wnt) signaling pathways in the mouse and cell model. Nonetheless, definitive human data are unavailable concerning therapeutic effects of Cinacalcet on chronic kidney disease and mineral bone disease (CKD-MBD) and osteoclast\u2013osteoblast interaction. We aim to investigate whether Cinacalcet therapy improves bone mineral density (BMD) through optimizing osteocytic homeostasis in a human model. Hemodialysis patients with persistently high intact parathyroid hormone (iPTH) levels &gt; 300 pg\/mL for more than 3 months were included and received fixed dose Cinacalcet (25 mg\/day, orally) for 6 months. Bone markers presenting osteoclast\u2013osteoblast communication were evaluated at baseline, the 3rd and the 6th month. Eighty percent of study patients were responding to Cinacalcet treatment, capable of improving BMD, T score and Z score (16.4%, 20.7% and 11.1%, respectively). A significant correlation between BMD improvement and iPTH changes was noted (r = \u22120.26, p &lt; 0.01). Nonetheless, baseline lower iPTH level was associated with better responsiveness to Cinacalcet therapy. Sclerostin, an inhibitor of canonical Wnt\/\u03b2-catenin signaling, was decreased from 127.3 \u00b1 102.3 pg\/mL to 57.9 \u00b1 33.6 pg\/mL. Furthermore, Wnt-10b\/Wnt 16 expressions were increased from 12.4 \u00b1 24.2\/166.6 \u00b1 73.3 pg\/mL to 33.8 \u00b1 2.1\/217.3 \u00b1 62.6 pg\/mL. Notably, procollagen type I amino-terminal propeptide (PINP), a marker of bone formation and osteoblastic activity, was increased from baseline 0.9 \u00b1 0.4 pg\/mL to 91.4 \u00b1 42.3 pg\/mL. In contrast, tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), a marker of osteoclast activity, was decreased from baseline 16.5 \u00b1 0.4 mIU\/mL to 7.7 \u00b1 2.2 mIU\/mL. Moreover, C-reactive protein levels were suppressed from 2.5 \u00b1 0.6 to 0.8 \u00b1 0.5 mg\/L, suggesting the systemic inflammatory burden may be benefited after optimizing the parathyroid\u2013bone axis. In conclusion, beyond iPTH suppression, our human model suggests Cinacalcet intensifies BMD through inhibiting sclerostin expression and upregulating Wnt-10b\/Wnt 16 signaling that activates osteoblastic bone formation and inhibits osteoclastic bone resorption and inflammation. From the perspective of translation to humans, this research trial brings a meaningful insight into the osteoblast\u2013osteoclast homeostasis in Cinacalcet therapy for CKD-MBD.<\/jats:p>","DOI":"10.3390\/ijms21228712","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T07:41:00Z","timestamp":1605685260000},"page":"8712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Therapeutic Effect of Calcimimetics on Osteoclast\u2013Osteoblast Crosslink in Chronic Kidney Disease and Mineral Bone Disease"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9023-8925","authenticated-orcid":false,"given":"Kuo-Chin","family":"Hung","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Min-Sheng General Hospital, Taoyuan City 330, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-7473","authenticated-orcid":false,"given":"Jia-Feng","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City 320, Taiwan"},{"name":"Department of Nursing, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan"},{"name":"Renal Care Joint Foundation, New Taipei City 220, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Ho","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City 320, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-6779","authenticated-orcid":false,"given":"Chih-Yu","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City 237, Taiwan"},{"name":"Renal Care Joint Foundation, New Taipei City 220, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai-Szu","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Yi","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Jen","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Si","family":"Syu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Min-Sheng General Hospital, Taoyuan City 330, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2263-5993","authenticated-orcid":false,"given":"Ting-Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, School of Medicine, National Taiwan University, Taipei 106, Taiwan"},{"name":"Department of Orthopaedic Surgery, National Taiwan University Hospital, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Chin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, En Chu Kong Hospital, New Taipei City 237, Taiwan"},{"name":"Department of Biomedical Engineering, Yuanpei University of Medical Technology, Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lie-Yee","family":"Hung","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-3951","authenticated-orcid":false,"given":"Cai-Mei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Taipei Medical University-Research Center of Urology and Kidney (TMU-RCUK), School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-8560","authenticated-orcid":false,"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1053\/j.ajkd.2017.07.019","article-title":"KDOQI US Commentary on the 2017 KDIGO Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)","volume":"70","author":"Isakova","year":"2017","journal-title":"Am. 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BMC Nephrol., 17.","DOI":"10.1186\/s12882-016-0392-6"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8712\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:33:51Z","timestamp":1760178831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,18]]},"references-count":37,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21228712"],"URL":"https:\/\/doi.org\/10.3390\/ijms21228712","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,18]]}}}