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Vitamin D therapy limits osteoclast precursor migration



DOI:10.1038/bonekey.2013.125

Sphingosine-1 phosphate (S1P), a lipid mediator present in blood serum, controls the migration and eventual location of monocyte precursors that are destined to differentiate into osteoclasts. Kikuta et al. investigated the impact of vitamin D therapy on this process.

S1PR2, a receptor for circulating S1P, is normally expressed by these osteoclast precursors. Experiments performed in vitro and in vivo showed that expression of S1PR2 was reduced by active vitamin D, provided either by calcitriol, the active hormonal form of vitamin D, or by eldecalcitol, a therapeutic vitamin D analog. In vivo in mice, vitamin D and eldecalcitol also reduced the loss of bone density associated with ovariectomy.

Intravital multiphoton bone microscopy was then used to look at the mobility of osteoclast precursors in living bone. Vitamin D and eldecalcitol both reduced migration of precursors from bone to blood, so helping to limit bone resorption by osteoclasts. This explains why active vitamin D has therapeutic benefits on bone density.

Editor’s comment: Demonstration of the suppressive effect of an active vitamin D compound on S1PR2 explains nicely the discrepancy between the in vivo and in vitro effects of active vitamin D on bone resorption. Moreover, eldecalcitol has a much higher affinity for the serum vitamin D binding protein than alfacalcidol, and this may be why eldecalcitol is a superior suppressor of bone resorption.


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