Chapter category: Endocrine
Surface Signaling Steroids—Real Anabolics or Pseudo-Anabolics?
Growing Bone
Second Edition
Edited by: James F. WhitfieldISBN: 978-1-58706-156-1
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Chapter authors:
James F. Whitfield
In 1998 Sicinski et al reported the synthesis of new 1a, 25-(OH)2-19-nor-vitamin D3 analogs such as 2MD (2-methylene-19-nor-(20S)-1a,25(OH)2D3) which are super-potent derivatives of the natural 1a, 25-(OH)2-vitamin D3. Four years later Shevde et al. (2002) reported that 2MD is a far more potent stimulator of osteoblast activities than 1a, 25-(OH)2-vitamin D3. Indeed, Shevde et al. (2002) have written “...there is little evidence that vitamin D plays a direct role in new bone formation, apart from its action to maintain calcium and phosphorus levels in the blood ”. But this osteoblast stimulation is compromised by 2MD being a 100-fold better stimulator of the RANKL gene (which has a vitamin D-responsive site in its promoter [Kitazawa et al., 2003]) and down-regulator of osteoprotegrin expression by presumably immature osteoblastic cells than the natural hormone. The result of this is the formation of more, bigger and better-bone-digging osteoclasts, which make 2 MD a 30-fold more effective mobilizer of bone Ca2+.
James F. Whitfield
Institute for Biological Sciences
National Research Council of Canada
Ottawa, Ontario, Canada
Additional chapters from this book:
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