Comparison of 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 and 1α, 25-Dihydroxyvitamin D3 on the Resorption of Bone Explants Ex Vivo
26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 [F6-1, 25-(OH)2D3] is more potent than 1α, 25-dihydroxyvitamin D3 [l, 25(OH)2D3] in stimulating bone resorption in vitro and in vivo. The reason why F6-1, 25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing act...
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| Veröffentlicht in: | Journal of Nutritional Science and Vitaminology 1999, Vol.45(3), pp.239-249 |
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| creator | MIYAHARA, Tatsuro HARADA, Masahiro KOZAKAI, Akinori MATSUMOTO, Masa-aki HASHIMOTO, Kazuhiro INOUE, Hirohumi YODA, Kayo NAKATSU, Takumi KAJITA, Sumiyo YAMAZAKI, Ryuzaburo HIGUCHI, Syouhei KOZUKA, Hiroshi NEMOTO, Nobuo |
| description | 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 [F6-1, 25-(OH)2D3] is more potent than 1α, 25-dihydroxyvitamin D3 [l, 25(OH)2D3] in stimulating bone resorption in vitro and in vivo. The reason why F6-1, 25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F6-1, 25(OH)2D3 or 1, 25(OH)2D3 on 45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog /g body weight, was examined. F6-1, 25(OH)2D3 was more potent than 1, 25(OH)2D3 during each in vivo time period. 1, 25(OH)2D3 at 3h after the injection was more active compared to the control (no injection of 1, 25(OH)2D3), but not at 14 and 24h. The radioactivity of the bones after the injection of [3H]-F6-, 25(OH)2D3 was retained even at 24h. In the case of [3H]-1, 25(OH)2D3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [3H]-F6-1, 25(OH)2D3 alone was detected at 3 h after the injection and both [3H]-F6-1, 25(OH)2D3 and [3H]-26, 27-hexafluoro-1α, 23S, 25-trihydroxy-vitamin D3 [F6-1, 23, 25(OH)3D3] were detected at 14 and 24h after the injection. [3H]-1, 25(OH)2D3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F6-1, 23, 25(OH)3D3 was less than that of F6-1, 25(OH)2D3 but similar to that of 1, 25(OH)2D3. The present study indicates that F6-1, 25(OH)2D3 is more active and more long-lasting than 1, 25(OH)2D3 in the ex vivo method. A higher potency of F6-1, 25(OH)2D3 is explained, at least partly, by the results that the amounts of both F6-1, 25(OH)2D3 and its active metabolite, F6-1, 23, 25(OH)3D3, in the bones are higher than that of 1, 25(OH)2D3, and that F6-1, 25(OH)2D3 and its metabolite are retained in bones longer than 1, 25(OH)2D3. |
| doi_str_mv | 10.3177/jnsv.45.239 |
| format | Article |
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The reason why F6-1, 25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F6-1, 25(OH)2D3 or 1, 25(OH)2D3 on 45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog /g body weight, was examined. F6-1, 25(OH)2D3 was more potent than 1, 25(OH)2D3 during each in vivo time period. 1, 25(OH)2D3 at 3h after the injection was more active compared to the control (no injection of 1, 25(OH)2D3), but not at 14 and 24h. The radioactivity of the bones after the injection of [3H]-F6-, 25(OH)2D3 was retained even at 24h. In the case of [3H]-1, 25(OH)2D3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [3H]-F6-1, 25(OH)2D3 alone was detected at 3 h after the injection and both [3H]-F6-1, 25(OH)2D3 and [3H]-26, 27-hexafluoro-1α, 23S, 25-trihydroxy-vitamin D3 [F6-1, 23, 25(OH)3D3] were detected at 14 and 24h after the injection. [3H]-1, 25(OH)2D3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F6-1, 23, 25(OH)3D3 was less than that of F6-1, 25(OH)2D3 but similar to that of 1, 25(OH)2D3. The present study indicates that F6-1, 25(OH)2D3 is more active and more long-lasting than 1, 25(OH)2D3 in the ex vivo method. A higher potency of F6-1, 25(OH)2D3 is explained, at least partly, by the results that the amounts of both F6-1, 25(OH)2D3 and its active metabolite, F6-1, 23, 25(OH)3D3, in the bones are higher than that of 1, 25(OH)2D3, and that F6-1, 25(OH)2D3 and its metabolite are retained in bones longer than 1, 25(OH)2D3.</description><identifier>ISSN: 0301-4800</identifier><identifier>EISSN: 1881-7742</identifier><identifier>DOI: 10.3177/jnsv.45.239</identifier><identifier>PMID: 10524344</identifier><language>eng</language><publisher>Tokyo: Center for Academic Publications Japan</publisher><subject>1α,25-dihydroxyvitamin D3 ; 26,27-hexafluoro-1α,25-dihy-droxyvitamin D3 ; 26,27-hexafluoro-lα,23,25-trihydroxyvitamin D3 ; Animals ; Animals, Newborn - metabolism ; Biological and medical sciences ; Bone and Bones - drug effects ; Bone and Bones - metabolism ; Bone Resorption ; Calcitriol - administration & dosage ; Calcitriol - analogs & derivatives ; Calcitriol - pharmacokinetics ; Calcitriol - pharmacology ; Calcium Radioisotopes - metabolism ; Chromatography, High Pressure Liquid ; ex vivo bone resorption ; Fundamental and applied biological sciences. Psychology ; Kinetics ; Mice ; neonatal mouse calvaria ; Skeleton and joints ; Tritium ; Vertebrates: osteoarticular system, musculoskeletal system</subject><ispartof>Journal of Nutritional Science and Vitaminology, 1999, Vol.45(3), pp.239-249</ispartof><rights>the Center for Academic Publications Japan</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1935679$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10524344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MIYAHARA, Tatsuro</creatorcontrib><creatorcontrib>HARADA, Masahiro</creatorcontrib><creatorcontrib>KOZAKAI, Akinori</creatorcontrib><creatorcontrib>MATSUMOTO, Masa-aki</creatorcontrib><creatorcontrib>HASHIMOTO, Kazuhiro</creatorcontrib><creatorcontrib>INOUE, Hirohumi</creatorcontrib><creatorcontrib>YODA, Kayo</creatorcontrib><creatorcontrib>NAKATSU, Takumi</creatorcontrib><creatorcontrib>KAJITA, Sumiyo</creatorcontrib><creatorcontrib>YAMAZAKI, Ryuzaburo</creatorcontrib><creatorcontrib>HIGUCHI, Syouhei</creatorcontrib><creatorcontrib>KOZUKA, Hiroshi</creatorcontrib><creatorcontrib>NEMOTO, Nobuo</creatorcontrib><title>Comparison of 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 and 1α, 25-Dihydroxyvitamin D3 on the Resorption of Bone Explants Ex Vivo</title><title>Journal of Nutritional Science and Vitaminology</title><addtitle>J Nutr Sci Vitaminol</addtitle><description>26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 [F6-1, 25-(OH)2D3] is more potent than 1α, 25-dihydroxyvitamin D3 [l, 25(OH)2D3] in stimulating bone resorption in vitro and in vivo. The reason why F6-1, 25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F6-1, 25(OH)2D3 or 1, 25(OH)2D3 on 45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog /g body weight, was examined. F6-1, 25(OH)2D3 was more potent than 1, 25(OH)2D3 during each in vivo time period. 1, 25(OH)2D3 at 3h after the injection was more active compared to the control (no injection of 1, 25(OH)2D3), but not at 14 and 24h. The radioactivity of the bones after the injection of [3H]-F6-, 25(OH)2D3 was retained even at 24h. In the case of [3H]-1, 25(OH)2D3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [3H]-F6-1, 25(OH)2D3 alone was detected at 3 h after the injection and both [3H]-F6-1, 25(OH)2D3 and [3H]-26, 27-hexafluoro-1α, 23S, 25-trihydroxy-vitamin D3 [F6-1, 23, 25(OH)3D3] were detected at 14 and 24h after the injection. [3H]-1, 25(OH)2D3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F6-1, 23, 25(OH)3D3 was less than that of F6-1, 25(OH)2D3 but similar to that of 1, 25(OH)2D3. The present study indicates that F6-1, 25(OH)2D3 is more active and more long-lasting than 1, 25(OH)2D3 in the ex vivo method. A higher potency of F6-1, 25(OH)2D3 is explained, at least partly, by the results that the amounts of both F6-1, 25(OH)2D3 and its active metabolite, F6-1, 23, 25(OH)3D3, in the bones are higher than that of 1, 25(OH)2D3, and that F6-1, 25(OH)2D3 and its metabolite are retained in bones longer than 1, 25(OH)2D3.</description><subject>1α,25-dihydroxyvitamin D3</subject><subject>26,27-hexafluoro-1α,25-dihy-droxyvitamin D3</subject><subject>26,27-hexafluoro-lα,23,25-trihydroxyvitamin D3</subject><subject>Animals</subject><subject>Animals, Newborn - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bone and Bones - drug effects</subject><subject>Bone and Bones - metabolism</subject><subject>Bone Resorption</subject><subject>Calcitriol - administration & dosage</subject><subject>Calcitriol - analogs & derivatives</subject><subject>Calcitriol - pharmacokinetics</subject><subject>Calcitriol - pharmacology</subject><subject>Calcium Radioisotopes - metabolism</subject><subject>Chromatography, High Pressure Liquid</subject><subject>ex vivo bone resorption</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Kinetics</subject><subject>Mice</subject><subject>neonatal mouse calvaria</subject><subject>Skeleton and joints</subject><subject>Tritium</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><issn>0301-4800</issn><issn>1881-7742</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkbtOwzAUhi0EgnKZ2JEHxESKb7GdEVpuEhISAtbIiR3qKomDnVbtC_A-vAjPhKsWWFhs63yffvv4AHCM0ZBiIS6mbZgPWTokNNsCAywlToRgZBsMEEU4YRKhPbAfwhQhlkkmd8EeRilhlLEB-Bi5plPeBtdCV0HCzyERyZ1ZqKqeOe8S_PUZS2mi7WSpvVss57ZXjW3hmELVavjDx__wmNlPDHwywfmut-srrlxr4PWiq1Xbh3iAr3buDsFOpepgjjb7AXi5uX4e3SUPj7f3o8uHZEqE7BNqSiZSUjBRqIxgTRGtqlIbnSEZ-1aGcSIQFZrzShSpJBJFzDniupAalfQAnK1zO-_eZyb0eWNDaer4GONmIRdIMi5lFsWTjTgrGqPzzttG-WX-83NRON0IKpSqrrxqSxv-vIymXKxyxmttGnr1Zn658r0ta5OvhoczQXOW5pslzvEXlxPlc9PSb8DulMI</recordid><startdate>1999</startdate><enddate>1999</enddate><creator>MIYAHARA, Tatsuro</creator><creator>HARADA, Masahiro</creator><creator>KOZAKAI, Akinori</creator><creator>MATSUMOTO, Masa-aki</creator><creator>HASHIMOTO, Kazuhiro</creator><creator>INOUE, Hirohumi</creator><creator>YODA, Kayo</creator><creator>NAKATSU, Takumi</creator><creator>KAJITA, Sumiyo</creator><creator>YAMAZAKI, Ryuzaburo</creator><creator>HIGUCHI, Syouhei</creator><creator>KOZUKA, Hiroshi</creator><creator>NEMOTO, Nobuo</creator><general>Center for Academic Publications Japan</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>1999</creationdate><title>Comparison of 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 and 1α, 25-Dihydroxyvitamin D3 on the Resorption of Bone Explants Ex Vivo</title><author>MIYAHARA, Tatsuro ; HARADA, Masahiro ; KOZAKAI, Akinori ; MATSUMOTO, Masa-aki ; HASHIMOTO, Kazuhiro ; INOUE, Hirohumi ; YODA, Kayo ; NAKATSU, Takumi ; KAJITA, Sumiyo ; YAMAZAKI, Ryuzaburo ; HIGUCHI, Syouhei ; KOZUKA, Hiroshi ; NEMOTO, Nobuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j278t-3ec4752b47ba921d303ffcded908881ae4627037d66f7b58280fcd6606db8d0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>1α,25-dihydroxyvitamin D3</topic><topic>26,27-hexafluoro-1α,25-dihy-droxyvitamin D3</topic><topic>26,27-hexafluoro-lα,23,25-trihydroxyvitamin D3</topic><topic>Animals</topic><topic>Animals, Newborn - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bone and Bones - drug effects</topic><topic>Bone and Bones - metabolism</topic><topic>Bone Resorption</topic><topic>Calcitriol - administration & dosage</topic><topic>Calcitriol - analogs & derivatives</topic><topic>Calcitriol - pharmacokinetics</topic><topic>Calcitriol - pharmacology</topic><topic>Calcium Radioisotopes - metabolism</topic><topic>Chromatography, High Pressure Liquid</topic><topic>ex vivo bone resorption</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Kinetics</topic><topic>Mice</topic><topic>neonatal mouse calvaria</topic><topic>Skeleton and joints</topic><topic>Tritium</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MIYAHARA, Tatsuro</creatorcontrib><creatorcontrib>HARADA, Masahiro</creatorcontrib><creatorcontrib>KOZAKAI, Akinori</creatorcontrib><creatorcontrib>MATSUMOTO, Masa-aki</creatorcontrib><creatorcontrib>HASHIMOTO, Kazuhiro</creatorcontrib><creatorcontrib>INOUE, Hirohumi</creatorcontrib><creatorcontrib>YODA, Kayo</creatorcontrib><creatorcontrib>NAKATSU, Takumi</creatorcontrib><creatorcontrib>KAJITA, Sumiyo</creatorcontrib><creatorcontrib>YAMAZAKI, Ryuzaburo</creatorcontrib><creatorcontrib>HIGUCHI, Syouhei</creatorcontrib><creatorcontrib>KOZUKA, Hiroshi</creatorcontrib><creatorcontrib>NEMOTO, Nobuo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Nutritional Science and Vitaminology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MIYAHARA, Tatsuro</au><au>HARADA, Masahiro</au><au>KOZAKAI, Akinori</au><au>MATSUMOTO, Masa-aki</au><au>HASHIMOTO, Kazuhiro</au><au>INOUE, Hirohumi</au><au>YODA, Kayo</au><au>NAKATSU, Takumi</au><au>KAJITA, Sumiyo</au><au>YAMAZAKI, Ryuzaburo</au><au>HIGUCHI, Syouhei</au><au>KOZUKA, Hiroshi</au><au>NEMOTO, Nobuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 and 1α, 25-Dihydroxyvitamin D3 on the Resorption of Bone Explants Ex Vivo</atitle><jtitle>Journal of Nutritional Science and Vitaminology</jtitle><addtitle>J Nutr Sci Vitaminol</addtitle><date>1999</date><risdate>1999</risdate><volume>45</volume><issue>3</issue><spage>239</spage><epage>249</epage><pages>239-249</pages><issn>0301-4800</issn><eissn>1881-7742</eissn><abstract>26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 [F6-1, 25-(OH)2D3] is more potent than 1α, 25-dihydroxyvitamin D3 [l, 25(OH)2D3] in stimulating bone resorption in vitro and in vivo. The reason why F6-1, 25(OH)2D3 is more active remains unclear. To clarify the relationship between the bone-resorbing activity of each vitamin D3 analogue and the metabolism of each analogue, in the present study, we used an ex vivo method that was established by Reynolds et al (Calcif Tissue Res, 1974, 15, 333-339). The effect of F6-1, 25(OH)2D3 or 1, 25(OH)2D3 on 45Ca release from parietal bones, prepared at 3, 14 and 24 h after injection of 1.9, 3.8, 7.6 or 15.2 pmol vitamin D analog /g body weight, was examined. F6-1, 25(OH)2D3 was more potent than 1, 25(OH)2D3 during each in vivo time period. 1, 25(OH)2D3 at 3h after the injection was more active compared to the control (no injection of 1, 25(OH)2D3), but not at 14 and 24h. The radioactivity of the bones after the injection of [3H]-F6-, 25(OH)2D3 was retained even at 24h. In the case of [3H]-1, 25(OH)2D3, the radioactivity of bones decreased with an increase in the in vivo period. In a HPLC analysis of the lipid extract of bone homogenate, [3H]-F6-1, 25(OH)2D3 alone was detected at 3 h after the injection and both [3H]-F6-1, 25(OH)2D3 and [3H]-26, 27-hexafluoro-1α, 23S, 25-trihydroxy-vitamin D3 [F6-1, 23, 25(OH)3D3] were detected at 14 and 24h after the injection. [3H]-1, 25(OH)2D3 was highly detected at 3 h after the injection, but it decreased with an increase in the in vivo period. In the ex vivo test, the activity of F6-1, 23, 25(OH)3D3 was less than that of F6-1, 25(OH)2D3 but similar to that of 1, 25(OH)2D3. The present study indicates that F6-1, 25(OH)2D3 is more active and more long-lasting than 1, 25(OH)2D3 in the ex vivo method. A higher potency of F6-1, 25(OH)2D3 is explained, at least partly, by the results that the amounts of both F6-1, 25(OH)2D3 and its active metabolite, F6-1, 23, 25(OH)3D3, in the bones are higher than that of 1, 25(OH)2D3, and that F6-1, 25(OH)2D3 and its metabolite are retained in bones longer than 1, 25(OH)2D3.</abstract><cop>Tokyo</cop><pub>Center for Academic Publications Japan</pub><pmid>10524344</pmid><doi>10.3177/jnsv.45.239</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0301-4800 |
| ispartof | Journal of Nutritional Science and Vitaminology, 1999, Vol.45(3), pp.239-249 |
| issn | 0301-4800 1881-7742 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70846889 |
| source | J-STAGE Free; MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | 1α,25-dihydroxyvitamin D3 26,27-hexafluoro-1α,25-dihy-droxyvitamin D3 26,27-hexafluoro-lα,23,25-trihydroxyvitamin D3 Animals Animals, Newborn - metabolism Biological and medical sciences Bone and Bones - drug effects Bone and Bones - metabolism Bone Resorption Calcitriol - administration & dosage Calcitriol - analogs & derivatives Calcitriol - pharmacokinetics Calcitriol - pharmacology Calcium Radioisotopes - metabolism Chromatography, High Pressure Liquid ex vivo bone resorption Fundamental and applied biological sciences. Psychology Kinetics Mice neonatal mouse calvaria Skeleton and joints Tritium Vertebrates: osteoarticular system, musculoskeletal system |
| title | Comparison of 26, 27-Hexafluoro-1α, 25-dihydroxyvitamin D3 and 1α, 25-Dihydroxyvitamin D3 on the Resorption of Bone Explants Ex Vivo |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T19%3A45%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comparison%20of%2026,%2027-Hexafluoro-1%CE%B1,%2025-dihydroxyvitamin%20D3%20and%201%CE%B1,%2025-Dihydroxyvitamin%20D3%20on%20the%20Resorption%20of%20Bone%20Explants%20Ex%20Vivo&rft.jtitle=Journal%20of%20Nutritional%20Science%20and%20Vitaminology&rft.au=MIYAHARA,%20Tatsuro&rft.date=1999&rft.volume=45&rft.issue=3&rft.spage=239&rft.epage=249&rft.pages=239-249&rft.issn=0301-4800&rft.eissn=1881-7742&rft_id=info:doi/10.3177/jnsv.45.239&rft_dat=%3Cproquest_pubme%3E70846889%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70846889&rft_id=info:pmid/10524344&rfr_iscdi=true |