Brain-bone axis dysregulation: Biological code underlying the bidirectional association between depression and...

Area of Science:

• Neuroscience
• Immunology
• Endocrinology
• Orthopedics
• Psychiatry

Background:

• Depression prevalence is rising globally, coinciding with a high burden of musculoskeletal disorders.
• Significant bidirectional links exist between depression and conditions like osteoporosis, fractures, osteoarthritis, and rheumatoid arthritis.
• Shared neuroimmune-inflammatory, endocrine, and metabolic pathways underlie these comorbidities.

Purpose of the Study:

• To review the epidemiological and pathophysiological links between depression and musculoskeletal disorders.
• To synthesize shared mechanisms involving the neuroimmune-endocrine axis and metabolic factors.
• To highlight the impact of depression on orthopedic outcomes and treatment.

Main Methods:

• Literature review synthesizing evidence on depression and musculoskeletal disorders.
• Analysis of shared neuroimmune-inflammatory, endocrine, and metabolic pathways.
• Examination of the effects of depression on bone health, cartilage, and disease activity.

Main Results:

• Depression-associated inflammation and autonomic/endocrine dysregulation contribute to bone resorption, cartilage degradation, and increased fracture risk.
• Selective serotonin reuptake inhibitors (SSRIs) may negatively impact bone mineral density, while serotonin-norepinephrine reuptake inhibitors (SNRIs) may benefit osteoarthritis.
• Depression exacerbates orthopedic outcomes, increasing pain, disability, and reducing treatment response.

Conclusions:

• Integrated care models and novel neuroimmune targets are crucial for managing depression and musculoskeletal comorbidities.
• Bidirectional screening, enhanced orthopedics-psychiatry referrals, and combination care bundles are recommended low-cost actions.
• These interventions hold potential to reduce fracture risk, pain, and disability, improving patient recovery trajectories.