Similarly, a clinical trial conducted by Kadriu et al. reported that MDD patients had a lower level of OPN and OPN/RANKL ratio than healthy controls, and a significant increase in the level of OPN and OPN/RANKL ratio and occurred at days 1 and 3 following a single ketamine infusion, which suggested ketamine may be able to correct abnormal bone metabolic state in MDD patients [7]. This evidence concerns the gene SPP1 and major depressive disorder.