Calcium Homeostasis and Parturient Paresis in Ruminants: Mechanistic Insights and Clinical Management

Parturient paresis remains a major economic challenge in global ruminant production, causing acute periparturient hypocalcemia and predisposing high-yielding animals to a cluster of secondary pathologies. Traditional narratives often treat regulatory pathways in isolation, whereas this review synthesizes multi-organ endocrine networks to address the kinetic dyssynchrony between mammary calcium drain and homeostatic recruitment velocity. Beyond the classical parathyroid hormone-vitamin D axis, we integrate the mammary-gut-bone axis into a unified endocrine model, highlighting the critical role of the serotonin-parathyroid hormone-related protein rheostat for skeletal mineral mobilization and the fibroblast growth factor 23-Klotho axis in prepartum phosphorus-induced feedback suppression. We evaluate the molecular mechanisms underlying target-organ receptor resistance, driven by vitamin D receptor downregulation and epigenetic aging, which precipitate homeostatic feedback failure. Regarding clinical management, this synthesis contrasts reactive parenteral interventions with proactive nutritional priming strategies, such as negative dietary cation-anion difference acidification, zeolite-based gastrointestinal binders, and exogenous vitamin D or 5-hydroxytryptophan supplementation. Additionally, the role of microbiota-derived short-chain fatty acids in gut-bone communication and the potential of genomic selection to breed livestock with heritable metabolic resilience are explored. Ultimately, this comprehensive framework emphasizes a paradigm shift from emergency treatment to precision nutritional and genetic prophylaxis to mitigate PP across diverse ruminant species.