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Vitamin D [1,25(OH)2D], calcium absorption and bone quality in mice



DOI:10.1038/bonekey.2012.133

Knockout mice unable to express the gene for the vitamin D receptor (VDR) in intestinal tissue or osteoblasts were bred to assess the impact of reduced calcium absorption on serum calcium, skeletal calcium and bone homeostasis.

The results demonstrate that a reduction in Vdr-mediated 1,25(OH)2D activity led to significant robbing of skeletal calcium to maintain calcium levels in serum. Increased calcium mobilization from bone was due to an increase in bone resorption mediated by parathyroid hormone (PTH) and 1,25(OH)2D, compounded with 1,25(OH)2D-mediated suppression of bone mineralization.

The net phenotypic result was osteopenia, hyperosteoidosis and hypomineralization of the bone cortex. Reduced bone mass in Vdr knockout mice caused bone fragility, with spontaneous fractures and healing calluses observed at an incidence of 10%; wild type mice showed no evidence of spontaneous fractures.

The authors conclude that in mice at least, 1,25(OH)2D signaling is essential for absorption of calcium from the intestine, even if the diet does not lack calcium. If the absorption process is impaired, serum levels are maintained at the expense of the skeleton.

Editor's comment: Vdr knockout mice with the very high serum 1,25(OH)2D levels observed represent a different situation compared to patients treated with active vitamin D or its analogs where serum PTH and bone resorption markers are both suppressed. The relevance of these findings to human disease needs further exploration.


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