NR1I3 and osteoporosis: In bone metabolism, CAR was first shown to be associated with BMD in postmenopausal women and rat primary osteoblasts and is believed to be involved in the progression of osteoporosis.223 Further studies revealed that CAR-deficient mice present increased bone mass, possibly due to reduced testosterone metabolism due to Cyp2b downregulation rather than reduced osteogenic differentiation or increased osteoclast numbers.224 In addition, glycolithocholic acid (GLCA), a metabolite of the intestinal microbiota, enhances the differentiation of CD4 T cells into Tregs by activating CAR.