Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression
Abstract 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 differenc...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Biology of Sex Differences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13293-024-00587-2 |
| _version_ | 1797276155994177536 |
|---|---|
| author | Xiaofeng Lan Haiyan Liu Chengyu Wang Weicheng Li Fan Zhang Zhibo Hu Xiaoyu Chen Zerui You Yuping Ning Yanling Zhou |
| author_facet | Xiaofeng Lan Haiyan Liu Chengyu Wang Weicheng Li Fan Zhang Zhibo Hu Xiaoyu Chen Zerui You Yuping Ning Yanling Zhou |
| author_sort | Xiaofeng Lan |
| collection | DOAJ |
| description | Abstract 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 |
| first_indexed | 2024-03-07T15:24:16Z |
| format | Article |
| id | doaj.art-cf7d5a9b6ffc49b79bed37a0c7a329e0 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-03-07T15:24:16Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-cf7d5a9b6ffc49b79bed37a0c7a329e02024-03-05T17:26:23ZengBMCBiology of Sex Differences2042-64102024-01-0115111110.1186/s13293-024-00587-2Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depressionXiaofeng Lan0Haiyan Liu1Chengyu Wang2Weicheng Li3Fan Zhang4Zhibo Hu5Xiaoyu Chen6Zerui You7Yuping Ning8Yanling Zhou9Department of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityDepartment of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical UniversityAbstract 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.cnhttps://doi.org/10.1186/s13293-024-00587-2KetamineDepressionBone mineral densityBone markersLeptinOsteocalcin |
| spellingShingle | Xiaofeng Lan Haiyan Liu Chengyu Wang Weicheng Li Fan Zhang Zhibo Hu Xiaoyu Chen Zerui You Yuping Ning Yanling Zhou Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression Biology of Sex Differences Ketamine Depression Bone mineral density Bone markers Leptin Osteocalcin |
| title | Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression |
| title_full | Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression |
| title_fullStr | Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression |
| title_full_unstemmed | Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression |
| title_short | Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression |
| title_sort | sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression |
| topic | Ketamine Depression Bone mineral density Bone markers Leptin Osteocalcin |
| url | https://doi.org/10.1186/s13293-024-00587-2 |
| work_keys_str_mv | AT xiaofenglan sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT haiyanliu sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT chengyuwang sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT weichengli sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT fanzhang sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT zhibohu sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT xiaoyuchen sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT zeruiyou sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT yupingning sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression AT yanlingzhou sexdifferencesintheeffectsofrepeatedketamineinfusionsonbonemarkersinpatientswithunipolarandbipolardepression |