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 dysynchrony 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.