Osteocalcin is one of the most abundant non-collagenous proteins in bone that is commonly used as a preliminary biomarker in bone formation. Osteocalcin also regulates energy metabolism as a hormone. Estrogen-related receptor alpha (ERRα) is primarily thought to regulate energy homeostasis through interacting with peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). Intriguingly, ERRα may play a functional role in bone formation. We have found there are 3 ERRα response elements (ERR response element, ERRE) in the osteocalcin promoter, and ERRα interacted cooperatively with PGC-1α could improve the osteocalcin promoter activity, whereas ERRα specific antagonist, XCT-790, inhibits this enhancement. XCT-790 inhibits osteocalcin and ERRα target gene PDKs expression in osteoblast cells. Thus ERRs might have physiological roles in bone formation and energy metabolism through modulating osteocalcin gene expression.