Background/Purpose

Rheumatoid arthritis (RA) is known as a cause of secondary osteoporosis. The previous studies reported that receptor activator for nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) were involved in patients with osteoporosis of various causes. Serum soluble RANKL (sRANKL) is a molecule that may possibly be related to RANKL expression in osteoblasts. The purpose of this study is to investigate serum levels of sRANKL, OPG and several bone metabolism markers in patients with RA.

Methods

RA patients and healthy controls were recruited at Toho University Omori Hospital and the Research Center for Clinical Pharmacology of Kitasato University, respectively. 360 patients with RA [mean age 61.5±13.4 (SD) years, male 66 and female 294 (menopause 229), mean disease duration 119±6.0 (SD) months] were included. We measured serum levels of sRANKL and OPG in RA patients and healthy controls. Serum levels of bone formation markers [intact aminoterminal propeptide of type I procollagen (P1NP) and bone specific alkaline phosphatase (BAP)], and bone resorption markers [type I collagen cross-linked N- telopeptide (NTX) and tartrate-resistant acid phosphatase form 5b (TRACP-5b)] were measured in the same subjects. In addition to these, we observed the background of the RA patients, such as age, sex, disease duration, stage classification, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Disease Activity Score (DAS) 28-ESR, Health Assessment Questionnaire (HAQ), Sharp score, and bone mineral density (BMD).

Results

The serum level of sRANKL [median (25th to 75th percentile range)] in patients with RA [0.09 (0.01-0.21) pmol/L] was significantly increased compared to that of healthy controls [0.03(0-0.19) pmol/L]. As well, the serum level of OPG of RA [5.24 (4.04-5.67) pmol/L] was significantly increased in comparison to healthy subjects [3.61(3.04-4.13) pmol/L]. The serum sRANKL level was negatively correlated with age, CRP and ESR by univariate analysis. In multivariate analysis, sRANKL was negatively correlated with age and disease duration, whereas, it was positively correlated with HAQ. The serum level of OPG was positively correlated with CRP, DAS28-ESR and MMP-3 as well as age by univariate analysis. In multivariate analysis, OPG was positively correlated with age and MMP-3. Both of serum sRANKL and OPG did not correlate with Sharp score and BMD in RA patients. There was no statistical correlation between the serum levels of sRANKL and OPG in RA patients and healthy controls.

Conclusion

In this study, we showed that both of the serum levels of sRANKL and OPG were significantly higher than those in healthy controls. Since sRANKL was correlated with disability index of HAQ, it is suggested that we should pay attention to deterioration of osteoporosis especially in the RA patients with severely impaired activities of daily living. On the other hand, OPG was correlated with disease activity of RA, suggesting that further attention to osteoporosis will be necessary even for the RA patients with the lower disease activities or remission.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/significance-of-serum-srankl-and-osteoprotegerin-concentration-in-patients-with-rheumatoid-arthritis/