The Bone–Vascular Axis: Managing the Skeletal and Cardiovascular Burden of Psoriasis

A recent narrative review explored the emerging concept of the bone–vascular axis in psoriasis and evaluated how targeted therapies may influence both skeletal integrity and cardiovascular risk.¹ To do this, researchers searched PubMed, MEDLINE, and Embase for related publications up to January 2026.

Overview of the Bone–Vascular Axis

Psoriasis is increasingly recognized as a systemic, immune-mediated disease associated with significant comorbidities, including psoriatic arthritis (PsA), osteoporosis, and cardiovascular disease. A central feature of this systemic involvement is the so-called “calcification paradox,” in which patients experience reduced bone mineral density (BMD) alongside increased vascular calcification. This paradox reflects a shared inflammatory pathophysiology rather than independent processes.

At the molecular level, the IL-23/IL-17 axis plays a pivotal role in driving this phenomenon. Chronic activation of Th17 pathways leads to elevated levels of proinflammatory cytokines, including IL-17A, IL-17F, TNF-α, and IL-6. In bone, these cytokines disrupt the RANKL/OPG balance, promoting osteoclast differentiation and activity, which accelerates bone resorption.² In parallel, within the vasculature, inflammatory signaling induces osteogenic transdifferentiation of vascular smooth muscle cells, mediated by pathways such as NF-κB and Wnt/β-catenin, ultimately contributing to vascular calcification. These findings underscore the importance of systemic inflammation as a unifying driver of both skeletal and vascular pathology in psoriasis.

Efficacy of Biologic Therapies in Joint and Bone Health

Biologic therapies targeting key inflammatory pathways have transformed psoriasis management and show promise in modifying components of the bone–vascular axis. IL-23 inhibitors, such as guselkumab and risankizumab, provide upstream suppression of the Th17 pathway and have demonstrated significant reductions in radiographic progression in PsA. Similarly, IL-17 inhibitors, particularly dual IL-17A/F blockade with bimekizumab, offer enhanced inflammatory control and robust inhibition of structural joint damage. Clinical trial data consistently show high rates of minimal radiographic progression and joint integrity preservation with these agents.

Despite these advances, the impact of biologics on systemic BMD remains less clear. While some studies report modest improvements in lumbar spine BMD with anti-TNF therapy, others show minimal or no change. This discrepancy likely reflects the complex, time-dependent nature of bone remodeling, in which suppression of inflammation can rapidly reduce bone resorption. Still, restoration of bone formation requires longer periods of time and is influenced by additional factors such as nutrition, physical activity, and metabolic health.

Risk Stratification and Safety

Cardiovascular disease represents another major comorbidity in psoriasis, driven in part by chronic inflammation. Imaging studies using FDG-PET/CT have demonstrated increased vascular inflammation in patients with psoriasis, even in the absence of traditional risk factors. Some targeted therapies appear to reduce vascular inflammation, suggesting potential cardiovascular benefit. However, these findings are based on surrogate markers, and robust evidence demonstrating reductions in major adverse cardiovascular events (MACE) is still lacking. Importantly, clinical improvements in skin disease do not always correlate with improvements in vascular inflammation, highlighting the need for a more comprehensive treatment approach.

Janus kinase inhibitors, such as tofacitinib and upadacitinib, have demonstrated efficacy in PsA but require careful cardiovascular risk assessment due to concerns raised in other inflammatory populations. Current evidence suggests relatively low event rates in psoriatic disease, but patient selection remains critical. In contrast, the TYK2 inhibitor deucravacitinib offers a more selective mechanism of action and has shown a favorable cardiovascular safety profile in long-term extension studies, with stable rates of adverse events and minimal impact on lipid profiles. Nonetheless, large-scale cardiovascular outcomes trials are needed to confirm these observations.

The review also highlights limitations in traditional cardiovascular risk assessment tools, which may underestimate inflammation-driven risk in psoriasis. Incorporating disease-specific factors, biomarkers such as GlycA, and advanced imaging techniques may improve risk stratification. Adjunctive therapies, including statins and glucagon-like peptide-1 receptor agonists, may provide additional cardiometabolic benefits when integrated into patient care.

Future Directions

In conclusion, this review emphasizes that psoriasis management should extend beyond skin clearance to address systemic inflammation and its downstream effects on bone and vascular health. The authors stress that a multidisciplinary, individualized approach that incorporates cardiometabolic risk management and ongoing monitoring is essential to improve long-term outcomes. Future research should focus on longitudinal studies, validated biomarkers, and end point–driven trials to better define the role of targeted therapies in mitigating the broader disease burden of psoriasis.

References

1. Zeng H, Chen Y, Yang L. The impact of targeted therapies on the bone-vascular axis in psoriasis: a narrative review. Clin Cosmet Investig Dermatol. 2026;19. doi:10.2147/CCID.S595065

2. Walsh MC, Choi Y. Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front Immunol. 2014;5:511. doi:10.3389/fimmu.2014.00511