# PDE4 Inhibition Reduced Osteoclast Differentiation in Psoriatic Patients

## TL;DR

This study shows that apremilast, a drug for psoriasis, reduces bone-resorbing cells in psoriatic patients, potentially protecting against bone loss.

## Contribution

The study demonstrates that PDE4 inhibition with apremilast modulates osteoclastogenesis in psoriasis patients.

## Key findings

- Apremilast treatment significantly reduced osteoclast and RANKL levels in psoriatic patients after 52 weeks.
- Bioexperienced patients showed lower osteoclast counts and RANKL levels compared to bionaïve patients.

## Abstract

Background: Psoriatic skin inflammation has been linked to joint inflammation and bone structural alterations, contributing to a “pro-osteoclastogenic march.” Osteoclasts (OCs), responsible for bone resorption, originate from monocytes/macrophages and are regulated by the RANKL-RANK signaling pathway. The cyclic AMP (cAMP) pathway plays a crucial role in OC maturation, and phosphodiesterases (PDEs) control its intracellular levels. Apremilast, a selective PDE4 inhibitor used for psoriasis (Pso) and psoriatic arthritis (PsA) treatment, may modulate osteoclastogenesis. Methods: Seventeen patients with moderate-to-severe psoriasis without arthritis, eligible for systemic apremilast therapy, were enrolled. Blood samples were collected at baseline and after 52 weeks of treatment to evaluate in vitro osteoclastogenesis from peripheral blood monocytes/macrophages and to measure serum RANKL levels. Results: After 52 weeks of apremilast treatment, OC and RANKL levels were significantly reduced in psoriatic patients compared to baseline. A sub-analysis was performed on two age- and sex-matched subgroups: a bionaïve group and a bioexperienced group. Bioexperienced patients exhibited lower OCP counts and reduced plasma RANKL levels compared to bionaïve patients. Conclusions: Our findings highlight the role of PDE4 in the pro-osteoclastogenic process in psoriasis and suggest that apremilast may counteract bone resorption by modulating RANKL levels and osteoclast differentiation, with potential clinical implications.