Ketamine, Bones, and Biology

In recent decades it has become increasingly well recognized that depression is as much a disease of the body as it is a disease of the mind. Years of research point to the fact that the mechanism by which depression manifests is largely biochemical in nature, and the effect of this disorder can be felt throughout the entire body, resulting in somatic symptoms including muscle aches, headaches, back pain, constant fatigue and loss of appetite. Recent research suggests that depression may result in yet another, perhaps surprising, physiological change: bone loss.

Repeated studies have found a statistically significant correlation between Major Depression and low bone mineral density. Low bone density, referred to as osteopenia or osteoporosis (in more extreme cases), is a serious condition that results when a patient’s cells do not make new bone as fast as old bone is destroyed. Most notably, patients with osteopenia and osteoporosis are at increased risk for bone fracture.

Depression and Bone Loss

While the correlation between depression and bone loss is still actively under investigation, research in mouse models suggests that this correlation is in fact causal. Researchers now believe that depression-induced bone loss is caused by increases in skeletal norepinephrine and serum corticosteroid levels—both of which are involved in the stimulation of the sympathetic nervous system.

Researchers investigating IV ketamine therapy are now turning their eyes towards this seemingly odd symptom of depression. Amazingly, they are discovering that ketamine may actually reverse depression-induced bone loss! Researchers at the National Institute of Mental Health studying this phenomenon began by looking at something called the OPG/RANKL ratio. OPG and RANKL are two important cellular factors important for maintaining bone density, and they can be used as an indicator of healthy bone growth and bone density.

These researchers found that, at baseline, depressed patients had significantly decreased OPG/RANKL ratios, indicating low bone density. However, they discovered that a treatment regimen of six ketamine infusions restored OPG/RANKL ratios to levels near that of a healthy individual. Additionally, this infusion regimen was found to lower OPG levels in the blood, another indicator of bone loss.

This study and its findings have major implications for the use of therapeutic ketamine. For one, it indicates that in addition to ketamine’s powerful effect on mood, the therapy may also be capable of ameliorating some of the serious physiological complications associated with depression. More generally, this research helps to further cement the biological basis of ketamine therapy for the treatment of depression.

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