{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:29:25Z","timestamp":1778502565121,"version":"3.51.4"},"reference-count":32,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,15]],"date-time":"2019-10-15T00:00:00Z","timestamp":1571097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Osteoporosis, a systemic skeleton disease, can be prevented by increasing calcium levels in serum via administration of calcium salts. However, traditional calcium-based formulations have not appeared to be effective, hence the purpose of the present work has been to prepare and test in vitro\/vivo a formulation able to gradually release calcium during transit over the GI tract, thus increasing bioavailability and reducing daily dose, and hence, side effects. Calcium controlled-release granules based on zeolite and Precirol\u00ae were prepared. In the best case, represented by granules sized 1.2 mm, containing 20% Precirol\u00ae, 19% zeolite, 60% calcium (granule), the release lasted \u22486 h. The release is controlled by diffusion of calcium ions through the aqueous channels forming within granules, once these come into contact with physiological fluids. Such a diffusion is hindered by the interaction of calcium ions with the negatively charged surface of the zeolite. Ovariectomy was used to make rats osteopenic. For in vivo studies, rats were divided into the following groups. Sham: not treated; ova: ovariectomized (ova); CaCl2 1.0 g: ova, treated with 1.0 g\/die Ca2+; CaCl2 0.5 g: ova, treated with 0.5 g\/die Ca2+; granule 1.0 g, or granule 0.5 g: ova, treated with granules equivalent to 1.0 g\/die or 0.5 g\/die Ca2+ in humans. Ca2+ amounts in femur bone and bone marrow, femur mechanical characteristics, and femur medullary canalicule diameter were measured and the same efficacy rank order was obtained: ova &lt; CaCl2 0.5 g &lt; CaCl2 1.0 g &lt; granule 0.5 g \u2248 granule 1.0 g \u2248 sham. The results show promise of an effective prevention of osteoporosis, based on a controlled-rate administration of a calcium dose half that administered by the current therapy, with reduced side effects.<\/jats:p>","DOI":"10.3390\/nu11102467","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T03:32:54Z","timestamp":1571196774000},"page":"2467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A New Calcium Oral Controlled-Release System Based on Zeolite for Prevention of Osteoporosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Angela","family":"Fabiano","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4082-6400","authenticated-orcid":false,"given":"Anna Maria","family":"Piras","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutraceuticals and Food for Health, University of Pisa, via Borghetto 80, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2431-6248","authenticated-orcid":false,"given":"Lara","family":"Testai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutraceuticals and Food for Health, University of Pisa, via Borghetto 80, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Flori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9251-4388","authenticated-orcid":false,"given":"Dario","family":"Puppi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry, University of Pisa, Udr INSTM Pisa, Via Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4680-9975","authenticated-orcid":false,"given":"Federica","family":"Chiellini","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Industrial Chemistry, University of Pisa, Udr INSTM Pisa, Via Moruzzi 13, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0064-233X","authenticated-orcid":false,"given":"Ylenia","family":"Zambito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy"},{"name":"Interdepartmental Research Center Nutraceuticals and Food for Health, University of Pisa, via Borghetto 80, 56124 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Consensus Development Conference (1993). 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