Objective：To explore whether p53 heterozygote attenuates osteoporosis phenotype of 1，25（OH）2D3 deficient mice by enhancing the antioxidant capacity. Methods：The long bones of 10-week-old wild type（WT）mice，p53 heterozygote（p53+/-）mice， 1α-hydroxylase knockout［1α（OH）ase-/-］mice，and 1α（OH）ase-/-p53+/- mice，fed on a high-calcium and high-phosphorus diet，were analyzed and compared using X-ray，micro -CT，histopathological and molecular biology methods to observe and compare changes in serum levels，bone mineralization，bone formation，bone absorption，and oxidative stress expression. Results：Compared with WT mice， p53+/- mice showed no significant differences in serum calcium，phosphorus，parathyroid hormone（PTH），and 1，25（OH）2D3 levels，but had the increased bone density，total collagen（T-col）positive area，osteoblast number，alkaline phosphatase（ALP），and typeⅠcollagen （col-Ⅰ）positive area，along with the decreased levels of reactive oxygen species and the increased expression of the antioxidant enzyme SOD1. Compared with 1α（OH）ase-/- mice，1α（OH）ase-/-p53+/- mice showed no significant differences in serum calcium，phosphorus， and PTH levels，with undetectable levels of 1，25（OH）2D3 in the serum，but showed significantly increased bone density，Tcol positive area，osteoblast number，ALP and Col-Ⅰ positive area，decreased osteoclast number and reactive oxygen species levels，and increased expression of SOD1. Conclusion：Half-dose deletion of p53 can attenuate osteoporosis phenotype of 1，25（OH）2D3 deficient mice by enhancing the antioxidant capacity.
