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

INTRODUCTION: 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. AIM: 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. IMPLICATIONS: 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.