Abstract
Background: First-degree relatives (FDRs) of rheumatoid arthritis (RA) patients are known to have increased risk of developing the disease. The detection of altered bone metabolism in FDRs could be a predictor of the disease. Preclinical phase of RA is characterized by a state of autoimmunity and inflammation. Musculoskeletal ultrasound (MSUS) is known for its ability to detect subclinical joint inflammation in RA, but changes in FDRs are not yet described.Objectives: To study serum osteopontin (OPN) and osteoprotegerin (OPG) levels in first degree relatives (FDRs) of rheumatoid arthritis (RA) as markers of altered bone metabolism in relation to clinical, laboratory and musculoskeletal ultrasound (MSUS) findings. Methods: Fifty-five individuals were included, 20 had definite RA, 25 were FDRs of RA patients, and 10 healthy controls. Clinical evaluation for joint swelling/tenderness was performed for all. ESR, CRP, rheumatoid factor (RF), anti-citrullinated antibodies (ACPA), OPN, OPG, and MSUS by the US7 score were evaluated.Results: OPG was significantly higher in RA (143.89 pg/ml±365.47) than in FDRs (22.23 pg/ml±65.73; p=0.009) and controls (6.20 pg/ml±12.43; p=0.003). OPN was also higher in RA (3.66 ng/ml±4.20) than in FDRs (1.97 ng/ml±1.04) and controls (2.81 ng/ml±1.31), though not significant (p=0.102). Eight of 25 FDRs (32%) had arthralgia without clinical arthritis and 17/25 (68%) were asymptomatic. FDRs with arthralgia had significantly higher ESR and CRP levels than asymptomatic FDRs (9.82 mm/h±4.13; p=0.003, and 3.93 mg/l±3.58; p=0.003). OPG was higher in FDRs than in controls, and also in those with arthralgia (51.55 pg/ml±114.68) than in those without (8.44 pg/ml±9.67), though without significant difference. OPN was higher in FDRs with arthralgia (2.09 ng/ml±1.19) than in asymptomatics (1.70 ng/ml±0.55), also without significant difference. Pathologic findings by US7 were detected in 10/25 (40%) FDRs, of which three (12%) had arthralgia and seven (28%) were asymptomatic. Conclusions: The raised OPG and lower OPN in FDRs than in controls reflect an altered bone metabolism which could precede clinical disease phase. OPN and OPG could serve as markers of altered preclinical bone metabolism in FDRs of RA. US7 score might be a useful screening tool to identify ‘at-risk’ individuals.
Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first‐degree relatives
