Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
Neuropsychopharmacol Rep. 2020 Dec;40(4):401-406. doi: 10.1002/npr2.12132. Epub 2020 Aug 19.
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.
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.
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.
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.
抑郁是骨质疏松症患者常见的症状。（R）-氯胺酮在啮齿类动物中比（S）-氯胺酮产生更强的效力和更持久的抗抑郁作用。在这里，我们研究了两种氯胺酮对去卵巢（OVX）小鼠（绝经后骨质疏松症的动物模型）骨密度（BMD）降低的影响。
雌性 ddY 小鼠行 OVX 或假手术。随后，每周两次腹膜内给予生理盐水（10mL/kg/d）、（R）-氯胺酮（10mg/kg/d）或（S）-氯胺酮（10mg/kg/d），持续 6 周。所有小鼠的股骨在最后一次注射后 3 天收集，测量股骨的 BMD。
在随后反复间歇性给予（R）-氯胺酮后，OVX 小鼠皮质 BMD 和总 BMD 的降低得到明显改善，但（S）-氯胺酮则没有。
该研究表明（R）-氯胺酮可以改善 OVX 小鼠皮质 BMD 和总 BMD 的降低。因此，（R）-氯胺酮可能成为治疗骨质疏松症女性的一种新型治疗药物。
