Dataset Information

Decreased bone mineral density in ovariectomized mice is ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine.

ABSTRACT:

Aim

Depression is a common symptom in people with osteoporosis. (R)-ketamine produced greater potency and longer-lasting antidepressant-like actions than (S)-ketamine in rodents. Here, we examined the effects of two ketamine enantiomers on the reduced bone mineral density (BMD) in the ovariectomized (OVX) mice which is an animal model of postmenopausal osteoporosis.

Methods

Female ddY mice were OVX or sham-operated. Subsequently, saline (10 mL/kg/d, twice weekly), (R)-ketamine (10 mg/kg/d, twice weekly), or (S)-ketamine (10 mg/kg/d, twice weekly) was administered intraperitoneally into OVX or sham mice for the 6 weeks. The femur from all mice was collected 3 days after the final injection, and BMD in the femur was measured.

Results

The reduction of cortical BMD and total BMD in the OVX mice was significantly ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine.

Conclusion

The study shows that (R)-ketamine can ameliorate the reduced cortical BMD and total BMD in OVX mice. Therefore, (R)-ketamine would be a novel therapeutic drug for women with osteoporosis.

SUBMITTER: Fujita Y

PROVIDER: S-EPMC7722686 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Decreased bone mineral density in ovariectomized mice is ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine.

Fujita Yuko Y Hashimoto Kenji K

Neuropsychopharmacology reports 20200819 4

<h4>Aim</h4>Depression is a common symptom in people with osteoporosis. (R)-ketamine produced greater potency and longer-lasting antidepressant-like actions than (S)-ketamine in rodents. Here, we examined the effects of two ketamine enantiomers on the reduced bone mineral density (BMD) in the ovariectomized (OVX) mice which is an animal model of postmenopausal osteoporosis.<h4>Methods</h4>Female ddY mice were OVX or sham-operated. Subsequently, saline (10 mL/kg/d, twice weekly), (R)-ketamine (10 ...[more]

PMID: 32812706

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Project description:IntroductionEmerging off-label medical uses of ketamine for the treatment of persistent conditions such as depression and chronic pain often require repeated administration. Cases reported by other countries suggest that long-term and repeated exposure to ketamine may be associated with several risks, including but not limited to hepatobiliary damage.ObjectiveWe aimed (1) to characterize the association between repeated administration of ketamine for off-label medical use and hepatobiliary events and (2) to describe recent trends in the use of ketamine across different clinical settings.MethodsWe conducted a retrospective case series analysis, utilizing reports identified from the US Food and Drug Administration Adverse Event Reporting System database as well as the medical literature. We included all cases reported through July 2018 describing both repeated exposure to ketamine in a hospital or ambulatory setting and a hepatobiliary adverse event. We excluded cases describing ketamine abuse. We identified adverse hepatobiliary events using the Medical Dictionary for Regulatory Activities (MedDRA®) and summarized various case characteristics including: patient demographics, route of ketamine administration, dose, time to onset of event, type of event, and pre-existing risk factors for hepatobiliary disease. To assess trends in the demand for ketamine, we used IQVIA, National Sales Perspectives™ to provide the nationally estimated number of vials sold for ketamine from the manufacturer to all US channels of distribution from 2013 through 2017.ResultsWe identified 14 unique cases that met selection criteria with 21 hepatobiliary adverse events including liver enzyme elevation in all cases, biliary dilation with liver cirrhosis (n = 1), biliary dilation with cholangitis (n = 1), and pericholeductal fibrosis (n = 1). Most cases received ketamine for the treatment of complex regional pain syndrome or chronic pain. In cases with a reported time to onset, the majority of events occurred within 4 days. The nationally estimated number of ketamine vials sold in the USA from manufacturers to various channels of distribution increased from 1.2 million in 2013 to 2.1 million in 2017.ConclusionsWe report an association between repeated or continuous administration of ketamine and hepatobiliary adverse events. Increased awareness among clinicians may mitigate these adverse outcomes, especially in the context of growing ketamine sales.

Project description:Genetic risk of low bone mineral density in women remains unclear. This study found that a large percentage of Caucasian women have a high genetic risk of osteoporosis, and genetic risk scores are significantly associated with BMD variation in a bone healthy sample of Caucasian women.IntroductionWe aimed to examine the distribution of risk alleles in an independent sample and to determine if such genetic components are associated with bone mineral density (BMD) variation in the sample.MethodsExisting genotype data of 1205 women in the cross-sectional Genomic Wide Scans for Female Osteoporosis Gene Study (GWSFO) were analyzed. Multi-loci genetic risk scores (GRSs) based on 62 BMD-associated single nucleotide polymorphisms (SNPs) were calculated. Regression analysis was employed to assess the association between GRSs and BMD. To examine the effect of SNPs clustered within key pathways associated with the development of osteoporosis, subtype weighted GRS specific to WNT signaling (6 SNPs), RANK-RANKL-OPG (3 SNPs), and mesenchymal stem differentiation (3 SNPs) were generated for analysis.ResultsThe unweighted GRS ranged from 48 to 80. One third of the women carried 66% risk alleles. After adjusting for age, height, and body weight, each unit increase of weighted GRS was associated with a decrease in BMD of 0.097 at femur (p < 0.0001) and 0.110 (p < 0.0001) at lumbar spine. The weighted GRS accounted for only 3.17-4.52% of BMD variance. The WNT signaling pathway GRS (6 SNPs) and the RANK-RANKL-OPG signaling pathway GRS (3 SNPs) both were significantly associated with decreased BMD at femur neck (p = 0.0004 and p = 0.0063, respectively) and lumbar spine (p < 0.0001 and p = 0.0001, respectively), while the mesenchymal stem cell differentiation pathway (3 SNPs) GRSs were associated only with the lumbar spine BMD (p = 0.045).ConclusionsA substantially large percentage of healthy Caucasian women have a high genetic risk of osteoporosis. Weighted GRS was significantly associated with decreased BMD. The contribution of subtype GRS to the BMD variation differs by specific biological pathway and skeletal regions.

Dataset Information

Decreased bone mineral density in ovariectomized mice is ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine.

Aim

Methods

Results

Conclusion

Publications

Decreased bone mineral density in ovariectomized mice is ameliorated after subsequent repeated intermittent administration of (R)-ketamine, but not (S)-ketamine.

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