Altered Bone Remodeling in Psoriatic Disease: New Insights and Future Directions

Abstract

Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder that occurs in patients with psoriasis and predominantly affects musculoskeletal structures, skin, and nails. The etiology of PsA is not well understood but evidence supports an interplay of genetic, immunologic, and environmental factors which promote pathological bone remodeling and joint damage in PsA. Localized and systemic bone loss due to increased activity of osteoclasts is well established in PsA based on animal models and translational studies. In contrast, the mechanisms responsible for pathological bone remodeling in PsA remain enigmatic although new candidate molecules and pathways have been identified. Recent reports have revealed novel findings related to bone erosion and pathologic bone formation in PsA. Many associated risk factors and contributing molecular mechanisms have also been identified. In this review, we discuss new developments in the field, point out unresolved questions regarding the pathogenetic origins of the wide array of bone phenotypes in PsA, and discuss new directions for investigation.

Keywords: Axial spondyloarthritis; Bone remodeling; Osteoblast; Osteoclast; Psoriasis; Psoriatic arthritis.

Figure 1. Schematic representation of bone remodeling in PsA

Genetic predisposition, skin inflammation, mechanical stress, dysbiosis in gut microbiota, gut inflammation can lead to immune dysregulation causing elevation of various inflammatory cytokines and alteration in key signaling molecules that regulate inflammation and the activity OC and OB cells. These resulting systemic and localized alterations manifest as clinical symptoms of psoriatic diseases. Metabolic dysregulation, obesity and environmental triggers can further compound such alterations. Such alterations results into decoupling of OB-OC interactions ultimately lead to increased bone erosion as well as aberrant formation in PsA patients.