The Impact of Targeted Therapies on the Bone-Vascular Axis in Psoriasis: A Narrative Review

Abstract: This narrative review elucidates the impact of biologics and small-molecule inhibitors on bone metabolism and cardiovascular risk in patients with psoriasis. Psoriasis is a systemic immune-mediated disorder characterized by a “Calcification Paradox”—the simultaneous occurrence of skeletal bone loss and vascular calcification. We explore the molecular mechanisms of the “Bone–Vascular Axis”, highlighting how the IL-23/IL-17 axis disrupts the RANKL/OPG balance and drives the osteogenic transdifferentiation of vascular smooth muscle cells. We critically evaluate the therapeutic impact of targeted agents, noting that IL-23 and dual IL-17A/F inhibitors offer significant structural protection in psoriatic arthritis. Regarding oral therapies, while JAK inhibitors necessitate cardiovascular risk stratification, the novel TYK2 inhibitor deucravacitinib demonstrates a favorable cardiovascular safety profile based on long-term extension data, although large-scale, hard endpoint-driven cardiovascular outcome trials (CVOTs) remain necessary to confirm definitive long-term protection. We conclude that effective management must shift from skin-focused control to a comprehensive systemic strategy targeting the bone–vascular axis to mitigate long-term comorbidities. Keywords: psoriasis, bone-vascular axis, biological drugs, JAK inhibitors, TYK2 inhibitor