Circulating mediators of bone remodeling in psoriatic arthritis: implications for disordered osteoclastogenesis and bone erosion

Abstract

Introduction: Diverse bone pathologies are observed in patients with psoriatic arthritis (PsA). Uncoupling of bone remodeling with disordered osteoclastogenesis has been implicated in the pathogenesis of PsA. The aim of this study was to examine the role of soluble mediators of bone remodeling within the circulation of patients with PsA.

Methods: Patients with PsA (n = 38), with psoriasis (n = 10), and healthy controls (n = 12) were studied. Serum was obtained for testing of Dikkopf-1 (Dkk-1), macrophage-colony stimulating factor (M-CSF), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) with ELISA. Patients with PsA also had bone densitometry, plain radiographs of the hands and feet, and assessment of peripheral blood osteoclast precursors. Radiographs were scored for erosion, joint-space narrowing, osteolysis, and new bone formation.

Results: Compared with those with psoriasis and healthy controls, patients with PsA had higher circulating concentrations of Dkk-1 and M-CSF. In patients with PsA, M-CSF and RANKL, but not Dkk-1, concentrations positively correlated with radiographic erosion, joint-space narrowing, and osteolysis scores. Mediators of bone remodeling did not correlate with the number of joints with new bone formation or with total hip-bone mineral density. Peripheral blood CD14+/CD11b+ cells, and the number of osteoclast-like cells and resorptive pits after culture with RANKL and M-CSF also correlated with radiographic damage scores. Circulating M-CSF concentrations correlated with the percentage of peripheral blood CD14+/CD11b+ cells.

Conclusions: Systemic expression of soluble factors that promote osteoclastogenesis is disordered in patients with PsA and may contribute to periarticular bone loss in this disease.

Figure 1

Soluble mediators of bone remodeling in the circulation of patients with PsA. Box-and-whisker plots showing concentrations of (a) Dkk-1, (b) M-CSF, (c) OPG, and (d) RANKL in healthy controls (HCs), patients with psoriasis (Ps) and patients with PsA. Box-and-whisker plots showing concentrations of (e) Dkk-1, (f) M-CSF, (g) OPG, and (h) RANKL in patients with psoriasis (Ps) and patients with nonerosive PsA, and patients with erosive PsA. Median values for RANKL for the healthy control, all PsA, and erosive PsA groups were 0.031 pmol/L. *P < 0.05; **P < 0.01; ***P < 0.001; one-way ANOVA with Dunn's multiple comparison test.