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Peripheral blood mononuclear cells of 19 pediatric patients with CKD1-5D and 6 healthy donors (HD) were differentiated into mature osteoclasts with receptor activator of NF-\u03baB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The effects of single or combined treatment with active vitamin D (1.25-D) and\/or calcimimetic KP2326 were evaluated on osteoclastic differentiation and osteoclastic-mediated bone resorption. Although 1.25-D inhibited osteoclastic differentiation, a significant resistance to 1.25-D was observed when glomerular filtration rate decreased. A significant albeit less important inhibitory effect of KP2326 on osteoclastic differentiation was also found both in cells derived from HD and CKD patients, through a putative activation of the Erk pathway. This inhibitory effect was not modified by CKD stage. Combinatorial treatment with 1.25-D and KP2326 did not result in synergistic effects. Last, KP2326 significantly inhibited osteoclast-mediated bone resorption. Both 1.25-D and KP2326 inhibit osteoclastic differentiation, however, to a different extent. There is a progressive resistance to 1.25-D in advanced CKD that is not found with KP2326. KP2326 also inhibits bone resorption. Given that 1.25-D has no effect on osteoclastic resorption activity and that calcimimetics also have direct anabolic effects on osteoblasts, there is an experimental rationale that could favor the use of decreased doses of 1.25-D with low doses of calcimimetics in SHPT in dialysis to improve the underlying osteodystrophy. However, this last point deserves confirmatory clinical studies. \u00a9 2020 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.4122","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T14:03:18Z","timestamp":1593439398000},"page":"2265-2274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibition of Osteoclast Differentiation by 1.25-D and the Calcimimetic KP2326 Reveals 1.25-D Resistance in Advanced CKD"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-1507","authenticated-orcid":false,"given":"Julie","family":"Bernardor","sequence":"first","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine Universit\u00e9 de Nice Sophia Antipolis Nice France"},{"name":"Centre de R\u00e9f\u00e9rence des Maladies R\u00e9nales Rares, H\u00f4pital Femme M\u00e8re Enfant Hospices Civils de Lyon Bron 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