{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:04:24Z","timestamp":1710374664119},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2007,5,1]],"date-time":"2007-05-01T00:00:00Z","timestamp":1177977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vitamin D analogs are being developed that retain therapeutic effects but are less calcemic and phosphatemic, a concern in CKD patients who are prone to vascular calcification. We tested a new analog of vitamin D, 2MbisP, and found that it suppresses PTH at doses that do not affect serum Ca or P.<\/jats:p>\n               <jats:p>Introduction: Calcitriol is used for the treatment of secondary hyperparathyroidism. However, its use is often limited by the development of hypercalcemia and hyperphosphatemia, an important consideration in patients with chronic kidney disease (CKD) because they are prone to vascular calcification. To minimize this toxicity, structural modifications in the vitamin D molecule have led to the development of calcitriol analogs with selective actions.<\/jats:p>\n               <jats:p>Materials and Methods: In this study, we compared the effects of 1,25(OH)2D3 and a new analog, 2-methylene-19-nor-(20S)-1\u03b1-hydroxy-bishomopregnacalciferol (2MbisP), on the development of secondary hyperparathyroidism and established secondary hyperparathyroidism in uremic rats and on mobilization of calcium and phosphorus from bone in parathyroidectomized rats. The clearance from circulation, half-life, and binding affinities to the vitamin D\u2013binding protein and vitamin D receptor of this compound were also evaluated.<\/jats:p>\n               <jats:p>Results: Uremia produced a marked rise in plasma PTH, but treatment every other day for 2 wk with either 1,25(OH)2D3 (4 ng) or 2MbisP (250, 750, 1500, or 3000 ng) suppressed this increase by &amp;gt;50%. The suppression by 1,25(OH)2D3, however, was accompanied by increases in ionized calcium, phosphorus, and the calcium \u00d7 phosphorus product, whereas these three parameters were unchanged by 2MbisP. The binding affinity of 2MbisP was 10\u201320 times less for the vitamin D receptor and 1000 times less for the serum vitamin D\u2013binding protein compared with 1,25(OH)2D3. Also, 2MbisP was cleared more rapidly from the circulation (t\u00bd = 10 min) than 1,25-(OH)2D3 (t\u00bd=7\u20139 h). In parathyroidectomized rats fed calcium-or phosphorus-deficient diets, daily injections of 2MbisP (1500 or 3000 ng), unlike 1,25(OH)2D3 (50 ng), had no effect on calcium or phosphorus mobilization from bone.<\/jats:p>\n               <jats:p>Conclusions: In uremic rats, 2MbisP can suppress PTH at doses that do not affect plasma calcium, phosphorus, and calcium \u00d7 phosphorus product. This new vitamin D analog may represent an important tool in the treatment of secondary hyperparathyroidism in patients with CKD.<\/jats:p>","DOI":"10.1359\/jbmr.070202","type":"journal-article","created":{"date-parts":[[2007,2,5]],"date-time":"2007-02-05T20:09:06Z","timestamp":1170706146000},"page":"686-694","source":"Crossref","is-referenced-by-count":13,"title":["Effect of 2-Methylene-19-nor-(20S)-1\u03b1-Hydroxy-Bishomopregnacalciferol (2MbisP), an Analog of Vitamin D, on Secondary Hyperparathyroidism"],"prefix":"10.1093","volume":"22","author":[{"given":"Eduardo","family":"Slatopolsky","sequence":"first","affiliation":[{"name":"Renal Division, Washington University Medical School, St Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane L","family":"Finch","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University Medical School, St Louis, Missouri, 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