Abstract
Two metabolites of vitamin D3, 25-hydroxycholecalciferol (25-OHD3) and 1,25-dihydroxy-cholecalciferol (1,25-(OH)2D3) are potent stimulators of bone resorption in two test systems whereas vitamin D3 itself is inactive. These substances were tested (a) by directly comparing their action on bone explants of mouse half-calvariain vitro, and (b) by injecting them into young mice and measuring the degree of resorptionin vitro when explants were made 18 hours atter the injection. In both tests the 1,25-metabolite was about 100 times more potent than 25-OHD3. The dose-response curve for 1,25-(OH)2D3 indicates that doses above about 0.2 ng/g body weight are capable of inducing an increase in bone resorption in normal young mice. These data show that 1,25-(OH)2D3 is one of the most potent substances known that affects bone metabolism. The results are discussed in relation to the possible role of 1,25-(OH)2D3 in the normal mobilization of calcium from bone.
Résumé
Deux métabolites de la vitamine D3, le 25-hydroxycholecalciferol (25-OHD3) et 1,25-dihydroxycholecalciferol (1,25-(OH)2D3), stimulent la résorption osseuse dans deux systèmestests alors que la vitamine D3 est inactive. Ces substances sont testées a) en comparant directement leur action dans les explants osseux de calottes craniennes de sourisin vitro et b) en les injectant dans de jeunes souris et en mesurant le degré de résorptionin vitro, lorsque les explants sont réalisés 18 heures après l'injection. Dans les deux tests, le métabolite 1,25 est environ 100 fois plus puissant que 25-OHD3. La courbe dose-résponse de 1,25-(OH)2D3 indique que des doses au-dessus d'environ 0.2 ng/g de poids corporel sont capables d'induire une augmentation de la résorption osseuse chez de jeunes souris normales. Ces résultats montrent que 1,25-(OH)2D3 est une des substances connues les plus actives qui agit sur le métabolisme osseux. Le rôle possible de 1,25-(OH)2D3 sur la mobilisation normale du calcium osseux est envisagé.
Zusammenfassung
Bei Anwendung zweier verschiedener Versuchsanordnungen konnte gezeigt werden, daß die beiden Vitamin D3-Metaboliten 25-Hydroxycholecalciferol (25-OHD3) und 1,25-Dihydroxycholecalciferol (1,25-(OH)2D3) als starke Stimulatoren der Knochenresorption wirken, während sich Vitamin D3 selbst inaktiv verhält. Diese Substanzen wurden folgendermaßen geprüft: a) durch direkten Vergleich ihrer Wirkung auf Knochenexplantate (Hälften von Mäusecalvarien)in vitro und b) indem die Metaboliten jungen Mäusen injiziert wurden und der Resorptionsgrad an Explantaten 18 Std nach Injektionin vitro gemessen wurde. Bei beiden Versuchsanordnungen war der 1,25-Metabolit etwa 100mal wirksamer als der 25-OHD3-Metabolit. Aus der Dosiswirkungskurve für 1,25-(OH)2D3 geht hervor, daß es möglich ist, mit Dosen über ca. 0,2 ng/g Körpergewicht bei normalen jungen Mäusen bereits eine erhöhte Knochenresorption auszulösen. Diese Resultate zeigen, daß 1,25-(OH)2D3 eine der wirksamsten bisher bekannten Substanzen ist, die auf den Knochenmetabolismus einwirken können. Die Ergebnisse werden im Zusammenhang mit der Rolle, die das 1,25-(OH)2D3 bei der normalen Freisetzung von Calcium aus dem Knochen spielt, besprochen.
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Reynolds, J.J., Holick, M.F. & De Luca, H.F. The role of vitamin D metabolites in bone resorption. Calc. Tis Res. 12, 295–301 (1973). https://doi.org/10.1007/BF02013742
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DOI: https://doi.org/10.1007/BF02013742