Mechano responsiveness of neuroimmune cross-talk in bone and joints: A narrative review with implications for...

Recent advances in osteoimmunology have illuminated the significant role of neuroimmune interactions in bone and joint health. The neuroimmune system critically regulates bone cell function through a complex network of molecular mediators - including signals from the sympathetic and parasympathetic nervous systems, pro- and anti-inflammatory cytokines, cortisol and other hormones, and growth factors. These mediators interact within a nonlinear network where each component can influence others reciprocally, with the brain serving as a central coordinator.

Our goal in this narrative review is to: 1) Provide an overview of roles the neuroimmune system is involved in bone and joint health; 2) Review which therapeutic interventions delivered by musculoskeletal clinicians might influence bone-related neuroimmune responses (or could be biologically plausible); and 3) Discuss clinical implications and gaps in the literature that need to be filled.

Considerable evidence exists for the effects of physical activity on bone and bone-related neuroimmune responses. In contrast, there is a paucity of evidence in the literature for actual changes induced in bone by any force-based manipulation (e.g. acupuncture, massage therapy, manual therapy, spinal manipulation). Yet, a number of early studies examining the responses of bone-related neuroimmune responses to force-based manipulations have found to exert some neuroimmune modulatory effects. Clinicians should tailor physical activity, manual therapy and exercise interventions based on patient-specific factors like age, hormonal status, and comorbidities, which affect neuroimmune responses and bone health.