@article {10131,
	title = {1,25(OH)2D3 Alters Growth Plate Maturation and Bone Architecture in Young Rats with Normal Renal Function},
	journal = {PLOS ONE},
	volume = {6},
	number = {6},
	year = {2011},
	abstract = {Whereas detrimental effects of vitamin D deficiency are known over century, the effects of vitamin D receptor activation by 1,25(OH)2D3, the principal hormonal form of vitamin D, on the growing bone and its growth plate are less clear. Currently, 1,25(OH)2D3\&nbsp;is used in pediatric patients with chronic kidney disease and mineral and bone disorder (CKD-MBD) and is strongly associated with growth retardation. Here, we investigate the effect of 1,25(OH)2D3\&nbsp;treatment on bone development in normal young rats, unrelated to renal insufficiency. Young rats received daily i.p. injections of 1 {\textmu}g/kg 1,25(OH)2D3\&nbsp;for one week, or intermittent 3 {\textmu}g/kg 1,25(OH)2D3\&nbsp;for one month. Histological analysis revealed narrower tibial growth plates, predominantly in the hypertrophic zone of 1,25(OH)2D3-treated animals in both experimental protocols. This phenotype was supported by narrower distribution of aggrecan, collagens II and X mRNA, shown by\&nbsp;in situ\&nbsp;hybridization. Concomitant with altered chondrocyte maturation, 1,25(OH)2D3\&nbsp;increased chondrocyte proliferation and apoptosis in terminal hypertrophic cells.\&nbsp;In vitro\&nbsp;treatment of the chondrocytic cell line ATDC5 with 1,25(OH)2D3\&nbsp;lowered differentiation and increased proliferation dose and time-dependently. Micro-CT analysis of femurs from 1-week 1,25(OH)2D3-treated group revealed reduced cortical thickness, elevated cortical porosity, and higher trabecular number and thickness. 1-month administration resulted in a similar cortical phenotype but without effect on trabecular bone. Evaluation of fluorochrome binding with confocal microscopy revealed inhibiting effects of 1,25(OH)2D3\&nbsp;on intracortical bone formation. This study shows negative effects of 1,25(OH)2D3\&nbsp;on growth plate and bone which may contribute to the exacerbation of MBD in the CKD pediatric patients.},
	url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113808/},
	author = {Idelevich, Anna and Kerschnitzki, Michael and Ron Shahar and Monsonego-Ornan, Efrat}
}
