Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder

Area of Science:

• Bone biology and metabolism
• Neuropsychiatry
• Pharmacology

Background:

• Major depressive disorder (MDD) is associated with significant decreases in bone mineral density (BMD).
• The osteoprotegerin (OPG)-RANK-RANKL system and osteopontin (OPN) are critical regulators of bone metabolism and strength.
• Understanding the role of these bone markers in MDD and the effects of ketamine is crucial for managing comorbid conditions.

Purpose of the Study:

• To investigate the involvement of the OPG-RANK-RANKL system and OPN in the bone abnormalities seen in MDD.
• To determine if ketamine treatment can ameliorate these bone abnormalities in MDD patients.

Main Methods:

• A study involving 28 medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs).
• Measurement of peripheral bone marker levels (OPG, RANKL, OPN) at baseline and at four time points post-intravenous ketamine infusion.
• Comparison of bone marker levels between MDD patients and HCs, and assessment of ketamine's effects.

Main Results:

• Patients with MDD exhibited significantly lower baseline OPG/RANKL ratios and plasma OPN levels compared to HCs.
• Ketamine administration significantly increased the OPG/RANKL ratio and plasma OPN levels in MDD patients.
• Ketamine treatment also significantly decreased RANKL levels in MDD patients, while bone markers remained stable in HCs.

Conclusions:

• The OPG-RANK-RANKL system and OPN are implicated in the bone abnormalities associated with MDD.
• Ketamine treatment demonstrates a positive effect on these bone markers, suggesting a potential therapeutic benefit for bone health in MDD patients.
• Ketamine may offer a dual therapeutic effect, addressing both depressive symptoms and a significant medical complication of the illness.