The Calci‐Inflammatory Axis: A Paradigm Shift in Understanding Milk Fever

This review highlights a paradigm shift in our understanding of hypocalcemia during milk fever by introducing the concept of the Calci-Inflammatory Axis. Traditionally viewed as a pathological deficiency necessitating rapid correction (e.g., through calcium borogluconate infusions or dietary adjustments like dietary cation-anion difference), periparturient hypocalcemia is reinterpreted here as an adaptive, protective response. Within this new framework, reduced circulating calcium levels may help temper systemic inflammation by limiting lipopolysaccharide (LPS) aggregation and curbing excessive macrophage activation. The review discusses how calcium signaling, the cal-cium-sensing receptor (CaSR), and immune cell functions adapt under hypocalcemic conditions to modulate inflammatory processes. This integrated perspective not only redefines the role of hy-pocalcemia but also proposes the Calci-Inflammatory Axis as a novel concept through which we can understand how changes in calcium homeostasis mitigate inflammatory cascades—potentially lowering the incidence of periparturient diseases and enhancing overall cow health and farm productivity. Future research should investigate the long-term effects of hypocalcemia, the envi-ronmental influences on this Calci-Inflammatory Axis, and their collective impact on disease sus-ceptibility and inflammation.