Effect of Osteoprotegerin and Dickkopf-Related Protein 1 on Radiological Progression in Tightly Controlled Rheumatoid Arthritis

Abstract

ObjectiveTo analyze the association between circulating osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and radiological progression in patients with tightly controlled rheumatoid arthritis (RA).MethodsSerum levels of OPG and DKK-1 were measured in 97 RA patients who were treated according to a treat-to-target strategy (T2T) aimed at remission (DAS28<2.6). Radiologic joint damage progression was assessed by changes in the total Sharp-van der Heijde score (SHS) on serial radiographs of the hands and feet. The independent association between these biomarker levels and the structural damage endpoint was examined using regression analysisResultsThe mean age of the 97 RA patients (68 women) at the time of the study was 54 ± 14 years, and the median disease duration was 1.6 ± 1.5 years. Most patients were seropositive for either RF or ACPA, and the large majority (76%) were in remission or had low disease activity.After a median follow-up time of 3.3 ± 1.5 years (range, 1–7.5 yrs.), the mean total SHS annual progression was 0.88 ± 2.20 units. Fifty-two percent of the patients had no progression (defined as a total SHS of zero). The mean serum OPG level did not change significantly over the study period (from 3.9 ± 1.8 to 4.07 ± 2.23 pmol/L), whereas the mean serum DKK-1 level decreased, although not significantly (from 29.9 ± 10.9 to 23.6 ± 18.8 pmol/L).In the multivariate analysis, the predictive factors increasing the likelihood of total SHS progression were age (OR per year = 1.10; p = 0.003) and a high mean C-reactive protein level over the study period (OR = 1.29; p = 0.005). Circulating OPG showed a protective effect reducing the likelihood of joint space narrowing by 60% (95% CI: 0.38–0.94) and the total SHS progression by 48% (95% CI: 0.28–0.83). The DKK-1 levels were not associated with radiological progression.ConclusionIn patients with tightly controlled RA, serum OPG was inversely associated with progression of joint destruction. This biomarker may be useful in combination with other risk factors to improve prediction in patients in clinical remission or low disease activity state.

Rheumatoid arthritis in tight disease control is no longer risk of bone mineral density loss

“…Strictly controlled disease activity should improve inflammation associated with RA and thus improve the activities of daily living (ADLs) [ 22 ]. Moreover, improved disease control may contribute to the remodeling of bone metabolism to form normal bone structure not only in the joints but also in the entire body [ 23 ], which will subsequently normalize bone mineral density (BMD). In this study, we investigated if RA is associated with a high risk of osteoporosis even when disease activity is well-controlled by determining if patients with RA have a lower BMD than those without RA.…”

The association of serum RANKL levels with disease activity and hematological parameters in Syrian patients with rheumatoid arthritis

“…This could be due to the small number of RA patients (N = 26) and the healthy group (N = 10) [ 39 ]. Carmen study et al in Spain showed that serum RANKL values were below the detection limit in 85% of RA patients because 76% of them were in clinical remission or in low disease activity [ 40 ]. Our study also found an elevation in RANKL levels in post-menopausal patients compared to post-menopausal healthy group, this confirms its importance in bone loss and pathogenic mechanism of rheumatoid arthritis as found a similar in Çakırca et al study in Turkey [ 41 ].…”

The Association of Serum RANKL Levels with disease activity and Hematological Parameters in Syrian Patients with Rheumatoid Arthritis

“…The reason for the discrepancy is that 76% of their patients were in the clinical remission or in the phase of low disease activity, as TNF-α antagonists and some DMARDs used in the RA treatment have inhibited the expression of RANKL by synovial cells 38 . Our study found an elevation in RANKL levels in post-menopausal patients compared to post-menopausal healthy group, this confirms its importance as a biomarker interferes in the bone loss and pathogenic mechanism of rheumatoid arthritis.…”