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https://hdl.handle.net/2440/53422
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Type: | Journal article |
Title: | Vitamin D Depletion Induces RANKL-Mediated Osteoclastogenesis and Bone Loss in a Rodent Model |
Author: | Anderson, P. Sawyer, R. Moore, A. May, B. O'Loughlin, P. Morris, H. |
Citation: | Journal of Bone and Mineral Research, 2008; 23(11):1789-1797 |
Publisher: | Amer Soc Bone & Mineral Res |
Issue Date: | 2008 |
ISSN: | 0884-0431 1523-4681 |
Statement of Responsibility: | Paul H Anderson, Rebecca K Sawyer, Alison J Moore, Brian K May, Peter D O’Loughlin and Howard A Morris |
Abstract: | The association between increased risk of hip fracture and low vitamin D status has long been recognized. However, the level of vitamin D required to maintain bone strength is controversial. We used a rodent model of vitamin D depletion to quantify the 25-hydroxyvitamin D (25D) levels required for normal mineralization. Six groups of 10-wk-old male Sprague-Dawley rats (n = 42) were fed a diet containing 0.4% calcium and various levels of dietary vitamin D3 for 4 mo to achieve stable mean serum 25D levels ranging between 10 and 115 nM. At 7 mo of age, animals were killed, and the histomorphometry of distal and proximal femora and L2 vertebra was analyzed. Total RNA was extracted from whole femora for real-time RT-PCR analyses. In the distal femoral metaphysis, trabecular bone mineral volume (BV/TV) showed a significant positive association with circulating 25D levels (r2 = 0.42, p < 0.01) in the animals with serum 25D levels between 20 and 115 nM. Osteoclast surface (Oc.S) levels were positively associated with RANKL:OPG mRNA ratio, higher in groups with lower serum 25D levels, and were independent of serum 1,25D levels. Serum 25D levels <80 nM gave rise to osteopenia as a result of increased osteoclastogenesis, suggesting that levels of 25D >80 nM are needed for optimal bone volume. These data indicate that serum 25D levels are a major determinant of osteoclastogenesis and bone mineral volume and are consistent with the levels of 25D recommended to reduce the risk of fracture in humans. |
Keywords: | Femur Animals Rats Rats, Sprague-Dawley Osteomalacia Bone Resorption Vitamin D Deficiency Disease Models, Animal Parathyroid Hormone 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Vitamin D RNA, Messenger Organ Size Regression Analysis Gene Expression Regulation, Enzymologic Calcification, Physiologic Osteogenesis Male RANK Ligand |
Description: | Copyright ©2008 by the American Society for Bone and Mineral Research |
DOI: | 10.1359/JBMR.080616 |
Published version: | http://dx.doi.org/10.1359/jbmr.080616 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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