Effects of deficiency of active vitamin D on bone marrow ablation of femur in mice

Abstract

The aim of this study was to investigate the effect of active vitamin D deficiency on bone marrow ablation (BMX) repair in mice. Six-week-old α(OH)ase knockout [1α(OH)ase-/-] mice and control wild type mice were used to generate the BMX model. Serum Ca, P and PTH (parathyroid hormone) concentration were determined at 0 week (before operation), 1 week (1W), 2 weeks (2W) and 3 weeks (3W) post-operation. Callus formation and absorption 1W, 2W and 3W post-operation were observed by imaging and histochemistry. The morphological changes and osteoblast/osteoclast content in callus were determined by immunohistochemical analysis. The expression of gene and protein associated with bone resorption were determined in callus tissue to evaluate the impact of vitamin D on bone formation. The results showed that 1α(OH)ase-/- mice suffered from low Ca, low P and hyper PTH due to deficiency of active vitamin D, and the symptoms persisted in the process of BMX and subsequent bone repair. In control mice, new calluses were observed in the medullary cavity at the first week, then part of the callus was absorbed in the second week, and most of the callus was absorbed in the third week. In the experimental group, new calluses were observed in the first week and reached its peak in the second week, and most of these calluses were mineralized in the third week. Meanwhile, the cortical bone became thinner and callus mineralization was decreased in 1α(OH)ase-/- mice compared to the control mice. In conclusion, active vitamin D deficiency causes hyper PTH in mice. Hyper PTH promotes trabecular bone formation and decreases bone turnover; increases cortical bone formation and bone resorption while improving bone turnover.