Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: Subanalysis of the PREMIER study

Hoff, Mari; Kvien, Tore K; Kälvesten, Johan; Elden, Aake; Kavanaugh, Arthur; Haugeberg, Glenn

doi:10.1186/1471-2474-12-54

Cited by 42 publications

(31 citation statements)

References 17 publications

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“…Recent results from a study of the RANKL inhibitor denosumab further support the important role of the osteoclast, since this drug inhibited erosions and hand DXA-BMD loss, but not cartilage destruction or inflammation [Cohen et al, 2008;Deodhar et al, 2008]. In addition, anti-TNF therapy has been found to decrease hand bone loss independent of disease activity, supporting the hypothesis that TNF has a direct influence on the osteoclast [Hoff et al, 2009d].…”

Section: Predictors Of Hand Bone Loss and The Association With Inflammentioning

confidence: 92%

Using hand bone mass measurements to assess progression of rheumatoid arthritis

Haugeberg

2010

Therapeutic Advances in Musculoskeletal

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In rheumatoid arthritis (RA) bone involvement presents as joint erosions in addition to generalized and periarticular osteoporosis. Joint erosions on radiographs of the hands and feet are considered to be the gold standard to evaluate progression of bone and joint damage in RA, even though erosions on radiographs are not used as a marker of early bone involvement. Periarticular bone loss seen on radiographs may be the first sign of bone involvement in RA. Over the last decade there has been an increased awareness of the importance of early aggressive treatment in RA, leading to a need for methods which can identify bone involvement in the early stages of RA. As inflammatory bone loss, especially at the hand, has been shown to occur early in RA, quantitative measures of hand bone loss have been proposed as an outcome measure for the detection of bone involvement. In this review article we present data supporting the hypothesis that both erosions and osteoporosis in RA occur as a result of the same pathophysiological mechanisms activating the osteoclast. Furthermore the role of hand bone loss as an early marker of inflammatory bone involvement, a predictor of subsequent radiographic joint damage and a response variable to anti-inflammatory treatment is discussed.

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Section: Predictors Of Hand Bone Loss and The Association With Inflammentioning

confidence: 92%

Using hand bone mass measurements to assess progression of rheumatoid arthritis

Haugeberg

2010

Therapeutic Advances in Musculoskeletal

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“…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.…”

Section: Treatment Of Ra With Biologic Drugs and Bone Lossmentioning

confidence: 99%

Bone Effects of Biologic Drugs in Rheumatoid Arthritis

Corrado

Neve

Maruotti

et al. 2013

Clinical and Developmental Immunology

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Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNFα, IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNFα, IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

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“…In this trial, hand bone loss was associated with no use of adalimumab, increasing age and inflammation [78]. A sub-analysis of the data showed that patients in the MTX monotherapy group with high/moderate disease activity (DAS28>3.2) or high levels of C reactive protein (CRP≥10 ng/ml) had greater bone loss in the hands compared to those in remission/low disease activity (DAS≤3.2) or low levels of CRP (<10 ng/ml) [79]. In the group receiving both drugs, bone loss was similar regardless of the disease activity and inflammatory status, and was comparable to patients who had low disease activity with MTX only.…”

Section: Anti-tnf Agents and Bone Loss In Patients With Rheumatoid Armentioning

confidence: 99%

“…In the group receiving both drugs, bone loss was similar regardless of the disease activity and inflammatory status, and was comparable to patients who had low disease activity with MTX only. These last findings suggest that the benefits of anti-TNF therapy may not be limited to control of inflammation, but also to the ability to block the direct effect of TNFα on osteoclast activation [79••]. …”

Section: Anti-tnf Agents and Bone Loss In Patients With Rheumatoid Armentioning

confidence: 99%

Effects of anti-tumor necrosis factor α agents on bone

Kawai

Stein²,

Perrien³

et al. 2012

Current Opinion in Rheumatology

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Purpose of the review TNF inhibitors are effective for achieving disease control in several inflammatory diseases. Although anti-TNF agents can inhibit bone loss in vitro, their role in the prevention of clinically relevant outcomes such as osteoporosis and fractures has not been clearly established. Recent findings There are many studies of the effects of TNF inhibitors on markers of bone turnover; however few have measured bone mineral density (BMD) or fractures. Most of these studies have small sample sizes and a minority had a placebo control group. Overall these studies suggest that the anti-resorptive effects of anti-TNF therapy are related to control of disease activity. Summary The antiresorptive effects of TNF inhibitors are likely related to their anti-inflammatory properties. Studies to date have not demonstrated any advantages of TNF inhibitors over traditional non biologic therapies in the prevention of bone loss and fractures.

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Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response: Subanalysis of the PREMIER study

Cited by 42 publications

References 17 publications

Using hand bone mass measurements to assess progression of rheumatoid arthritis

Using hand bone mass measurements to assess progression of rheumatoid arthritis

Bone Effects of Biologic Drugs in Rheumatoid Arthritis

Effects of anti-tumor necrosis factor α agents on bone

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