Changes in hand bone mineral density and the association with the level of disease activity in patients with rheumatoid arthritis: Bone mineral density measurements in a multicenter randomized clinical trial

Abstract

Objective. To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission. Methods. mBMD was measured by digital x-ray radiogrammetry in consecutive radiographs of 145 patients with RA with either continuous high disease activity (HDA; Disease Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 > DAS < 2.4), or continuous clinical remission (CR; DAS <1.6) during a 1-year observation period. The association of mBMD changes with disease activity was investigated with multinomial regression analysis. Next, clinical variables associated with mBMD gain were identified. Results. Mean change in mBMD in CR patients was ؊0.03%, compared to ؊3.13% and ؊2.03% in HDA and LDA patients, respectively (overall, P < 0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to ؊4.6 mg/cm 2 /year), compared to 62% and 66% of the patients with HDA or LDA, respectively, whereas 26% of the patients in CR had mBMD gain (>4.6 mg/cm 2 /year), compared to 2% of the patients with HDA and 5% of the patients with LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0 -18.7 and RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower age were significant independent predictors of mBMD gain. Conclusion. In RA, mBMD gain occurs primarily in patients in continuous (>1 year) CR and rarely in patients with continuous HDA or LDA. This suggests that mBMD loss is driven by inflammation.

High‐fat diet exacerbates pain‐like behaviors and periarticular bone loss in mice with CFA‐induced knee arthritis

“…RA is associated with periarticular osteopenia, systemic osteoporosis, and bone erosion, which increase in severity as the disease progresses . In our study, microCT analysis revealed that HFD exacerbates the severity of bone loss induced by experimental arthritis.…”

Bone Effects of Biologic Drugs in Rheumatoid Arthritis

“…A large randomized clinical trial [51], in which the differences on bone loss between traditional disease-modifying antirheumatic drugs and various anti-TNF α regimens were evaluated, showed that conventional treatment alone was associated with a greater hand bone loss compared to the association with anti-TNF α therapy; however, these effects disappeared when results were adjusted for disease activity. Further, a post hoc analysis grouping patients by therapeutic response showed that the protective effect on bone was associated with clinical remission, irrespective of treatment with anti-TNF α [52]. Conversely, a second well-powered randomized clinical trial showed that the anti-TNF α Adalimumab in combination with Methotrexate reduced hand bone loss independently of clinically assessed disease activity and inflammatory status [53], suggesting that the beneficial effects of anti-TNF α therapy could not be limited to the control of inflammation, but also to its ability to inhibit the direct effect of TNF α on osteoclast activation by binding to TNF α receptor placed on osteoclast precursors.…”

Effects of anti-tumor necrosis factor α agents on bone

“…Only radiographic disease progression, post-menopausal status, and inflammation were associated with hand bone loss after adjustment for various covariates [81]. A post-hoc analysis of the data grouping patients by therapeutic response instead of treatment regimen, found that gain in metacarpal bone occurred in association with clinical remission, regardless of the previous or current use of anti-TNF therapy [82••], supporting the hypothesis that anti-TNF therapy decreases bone loss through tight control of disease activity.…”