Lan, Xiaofeng, Liu, Haiyan, Wang, Chengyu, Li, Weicheng, Zhang, Fan, Hu, Zhibo, Chen, Xiaoyu, You, Zerui, Ning, Yuping, and Zhou, Yanling
Background: Patients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression. Methods: A total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26). Results: Linear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009). Conclusions: Our results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn Plain language summary: Depression and low bone mineral density (BMD) are epidemiologically linked and traditional antidepressants may act as a risk factor for BMD. However, it is unclear whether the novel antidepressant, ketamine, has effects on bone markers in patients with depression and whether there are sex differences on these effects. Ketamine infusions may be associated with modulation of bone markers and may exert a positive effect on BMD in patients with depression, which present sex differences. The study results may inform potential strategies for prevention of low BMD during the treatment of depression. Clinicians should be aware of the bone markers because some of them may be associated antidepressant response. Highlights: Depression is usually associated with low bone mineral density (BMD) and traditional antidepressants have negative effects on BMD. Ketamine, as a novel antidepressant, modulated multiple bone markers and might exert a positive effect on BMD in patients with depression, which present sex differences. Increases of leptin were positively associated with depressive symptom improvements in females across six ketamine infusions. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males. [ABSTRACT FROM AUTHOR]