Background Rheumatoid arthritis (RA) is a paradigm of chronic and inflammatory polyarthritis, particularly of the small joints of the hands and feet. Periarticular osteoporosis adjacent to the affected joints is one of the earliest radiologic manifestations of RA . Bone resorption in RA is dependent on receptor activator of nuclear factor kappa beta ligand (RANKL) which is essential for osteoclast formation, activity and survival in normal and pathologic states of bone remodelling . The understanding of periarticular bone loss in RA and its relationship to serum RANKL hasn't been widely addressed in literature. Therefore, elucidating the role of RANKL in periarticular osteoporosis in patients with RA is crucial as it may lead to novel drug targets and new therapeutic strategies for RA.
Objectives Assessment of serum RANKL level in early RA patients and its correlation with hand bone mineral density (BMD) to investigate the possible role of RANKL in RA- related periarticular bone loss.
Methods This was a cohort study, we recruited 64 RA patients with disease duration less than 2 years attending the early arthritis clinic and 40 age and gender matched control subjects. BMD assessment was done using Dual Energy X-Ray Absorptiometry (DEXA) scans on both hands. Blood samples were assessed for RANKL, C- reactive protein (CRP), rheumatoid factor (RF) and anti-CCP levels. Plain X-ray of both hands for qualitative assessment of bone erosions was done. We used the disease activity score (DAS-28) CRP to assess disease activity. Functional evaluation was done using the modified health assessment questionnaire (M-HAQ).
Results Females constitute 53% of RA patients and 55% of control group. About 32.3% of the female patients and 31.8% of the female controls were post-menopausal. Mean age was 50.06 years in RA patients versus 49.05 in control group. Mean disease duration was 17.05 months. Serum RANKL was significantly higher in RA patients (794.09 pmol/L) versus controls (273.6 pmol/L), P value <0.001. BMD of both hands were significantly lower in RA patients versus controls, 0.401 vs. 0.441 g/cm2 for right hand (RH) and 0.397 vs. 0.437 g/cm2 for left hand (LH) respectively, P value <0.05.Prevalence of hand bone erosions was 17.2% in RA patients. There was a negative correlation between serum RANKL and BMD of both hands (r = -0.389, P value <0.01 for RH, r = -0.325, P value <0.03 for LH). Serum RANKL was positively correlated with CRP (r=0.494, P value <0.001), anti-CCP (r=0.309, P value <0.01).
There was a positive correlation between serum RANKL and DAS 28 (r=0.401, P value <0.005). Anti CCP has a negative correlation with BMD of both hands (r=-0.269 and -0.293 for RH and LH respectively, P value <0.03.
Conclusions In early RA patients, increased serum RANKL level is associated with decreased hand BMD. Therefore, RANKL could be used as a marker of early detection of periarticular osteoporosis before irreversible damage occurs and this could support the future use of anti-RANKL therapy in early RA patients.
Chad Deal. Bone Loss in Rheumatoid Arthritis: Systemic, Periarticular, and Focal. Current Rheumatology Reports, 2012;14(3):231.
Vis M, Güler-Yüksel M, Lems WF. Can bone loss in rheumatoid arthritis be prevented? Osteoporosis Int. 2013 Jun 18;24(10):2541-2553.
Disclosure of Interest None declared