Background/Purpose: Psoriatic arthritis (PsA) is an inflammatory arthritis that develops in about a third of patients with cutaneous psoriasis (PsC). The identification of biomarkers to aid in the early diagnosis of PsA in patients with PsC may prevent disability and improve the quality of life for those affected.   Inflammation in peripheral and/or axial joints in PsA is associated with abnormal bone metabolism, including erosions and bone formation. The goal of the current study was to determine if markers of bone remodeling are associated with PsA patients with active disease compared to patients with PsC only.

Methods: PsA patients with active disease (≥ 3 tender and swollen joints) and PsC patients were identified from the cohort of patients followed prospectively. Patients were matched for age, sex, PASI score and psoriasis duration and were not receiving treatment with biologic agents. PsA patients satisfied CASPAR criteria and PsC patients were examined by a rheumatologist to exclude arthritis. Patients were not receiving treatment with methotrexate for a minimum of two years before the sampling date. Serum biomarkers measured included DKK1, FGF23, IL-6, IL-1β, leptin, osteocalcin, osteoprotegerin, osteopontin, sclerostin and TNFα. All proteins were measured simultaneously using the Millipore Milliplex MAP human bone magnetic bead panel, according to the manufacturer’s instructions. Data was acquired using the Luminex 200 system and analyzed with the Biorad Bio-Plex Manager software. Significant differences were determined by performing paired t-tests between the PsA and PsC cohorts (p<0.05).

Results: The levels of bone biomarkers were measured in 60 PsA patients (mean age 51 years, 50% males, psoriasis duration 18 years, PASI 4.24, 11.4 tender joints, 6.3 swollen joints) and 60 PsC patients (mean age 52 years, 50% males, psoriasis duration 20 years, PASI 3.7). DKK1, leptin, osteoprotegerin, osteopontin, and sclerostin were significantly elevated in PsA patients compared to PsC patients (Table 1, paired student’s t-test). TNFα levels were significantly reduced in PsA (3.7 pg/ml) patients compared to those with psoriasis only (10.6 pg/ml). Elevation in markers of bone resorption (DKK1, OPN, SOST) and ossification (leptin, OPG) in PsA relative to PsC were found, reflecting the balance in both synthesis and degradation that is disrupted in PsA. Using a reduced conditional logistic regression model that included all markers tested, IL-6, osteopontin, sclerostin and TNFα were independently associated with PsA.

Conclusion: Serum markers of bone remodeling were elevated in PsA patients with active disease compared to patients with PsC only. Future studies will focus on validating these markers in a large, independent cohort, to determine whether these genes can serve as biomarkers of PsA susceptibility.

Table 1: Expression of bone biomarkers (p<0.05) in serum of PsA and PsC patients