Decline in Hand Bone Mineral Density Indicates Increased Risk of Erosive Change in Early Rheumatoid Arthritis

Black, Robert; Spargo, Llewellyn; Schultz, Christopher G.; Chatterton, Barry E.; Cleland, Leslie G.; Lester, Sue; Hill, Catherine; Proudman, Susanna

doi:10.1002/acr.22199

Cited by 14 publications

(18 citation statements)

References 26 publications

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“…Our data in AIA rats confirmed some clinical results performed only in early RA, where bone loss in metacarpal heads (MCH) was associated with high risk of erosive disease, assessed with 2D imaging (Black et al, ; Wevers‐de Boer et al, ). By using high‐resolution peripheral quantitative CT in humans, reproducible analysis of bone microarchitecture was proposed in RA (Barnabe and Feehan, ).…”

Section: Discussionsupporting

confidence: 86%

Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model

Courbon

Cleret

Linossier

et al. 2017

Journal Cellular Physiology

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Synovitis is usually observed before loss of articular function in rheumatoid arthritis (RA). In addition to the synovium and according to the "Inside-Outside" theory, bone compartment is also involved in RA pathogenesis. Then, we investigated time dependent articular bone loss and prediction of early bone loss to late arthritis severity on the rat adjuvant-induced arthritis (AIA) model. Lewis female rats were longitudinally monitored from arthritis induction (day 0), with early (day 10) and late (day 17) steps. Trabecular and cortical microarchitecture parameters of four ankle bones were assessed by microcomputed tomography. Gene expression was determined at sacrifice. Arthritis occurred at day 10 in AIA rats. At this time, bone erosions were detected on four ankle bones, with cortical porosity increase (+67%) and trabecular alterations including bone volume fraction (BV/TV: -13%), and trabecular thickness decrease. Navicular bone assessment was the most reproducible and sensitive. Furthermore, strong correlations were observed between bone alterations at day 10 and arthritis severity or bone loss at day 17, including predictability of day 10 BV/TV to day 17 articular index (R = 0.76). Finally, gene expression at day 17 confirmed massive osteoclast activation and interestingly provided insights on strong activation of bone formation inhibitor markers at the joint level. In rat AIA, bone loss was already observed at synovitis onset and was predicted late arthritis severity. Our results reinforced the key role of subchondral bone in arthritis pathogenesis, in favour to the "Inside-Outside" theory. Mechanisms of bone loss in rat AIA involved resorption activation and formation inhibition changes. J. Cell. Physiol. 232: 1318-1325, 2017. © 2016 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 86%

Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model

Courbon

Cleret

Linossier

et al. 2017

Journal Cellular Physiology

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“…Similar observations have also been reported in patients with early RA [ 30 ], suggesting an association between disease activity and bone loss. Hand BMD loss has also been shown to indicate an increased risk of erosive disease [ 10 , 11 , 31 , 32 ]. Data from an observational study demonstrated that BMD loss at 6 months was associated with higher erosion scores, and a higher proportion of patients with BMD loss at 6 months had at least one erosion and a higher risk of erosion progression at 12 months [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort

et al. 2018

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IntroductionTo assess the relationship between low bone mineral density (BMD), anti-cyclic citrullinated peptide-2 (anti-CCP2) antibodies, and disease activity in patients with established rheumatoid arthritis (RA).MethodsPatients enrolled in a single-center, observational cohort registry of patients with RA. Eligible patients had known BMD, as measured by digital X-ray radiogrammetry (DXR–BMD), and anti-CCP2 antibody measurements at the same time point or within 6 months. Anti-CCP2–immunoglobulin (Ig)G-positive (+) patients (≥ 20 U/mL) were distributed into three equal groups (Gp1–3), representing increasing anti-CCP2 antibody concentrations. Associations between BMD and anti-CCP2 antibody status and titer were explored in multivariate regression analyses controlling for covariates (including age, duration of RA, use of steroids, use of osteoporosis medication). Association between disease activity (DAS28 [CRP] < 2.6) and bone loss was also explored.ResultsA total of 149 patients (all women) were included (47 anti-CCP2 antibody negative [−], 102 anti-CCP2+ [34\titer group]). Mean disease duration was greater in the three anti-CCP2+ groups vs. the anti-CCP2− group. DXR–BMD was lower in the anti-CCP2+ vs. the anti-CCP2− groups (Gp1–3 vs. anti-CCP2−: P < 0.0001 for left and right hands). DXR–BMD decreased with increasing anti-CCP2 titer (P < 0.001 for left and right hands). Patients with low DXR–BMD were less likely to have a DAS28 (CRP) < 2.6 (P = 0.0181).ConclusionAmong patients with established RA, data suggest that anti-CCP2+ patients, particularly those with high anti-CCP2 antibody titers, have lower hand BMD, and patients with lower hand BMD are less likely to have low disease activity.FundingBristol-Myers Squibb.Trial RegistrationClinicaltrials.gov identifier, NCT01793103.Electronic supplementary materialThe online version of this article (10.1007/s12325-017-0657-x) contains supplementary material, which is available to authorized users.

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“…A longitudinal study of 50 patients with early RA (whose hand BMD was measured at baseline, 6 and 12 mo) indicated that the baseline value of hand BMD was associated with radiographic scores at 12 mo [101]. Another longitudinal study consisting of 64 patients with RA confirmed the predictive value of hand BMD loss in the first year for the subsequent radiographic progression (6.4 year follow up) [103]. A longitudinal study by Black et al [104] showed hand BMD loss in the first 6 mo might be a predictor for erosions at 12 mo.…”

Section: Relationship Of Bone Mineral Density (Bmd) and Different Artmentioning

confidence: 97%

Osteoporosis, Mineral Metabolism and Arthritis

Elmesiry¹

2016

J Osteopor Phys Act

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Bone gives the potency and hardness of the skeleton in addition to play an important role in the storage of calcium and other mineral salts. It has a rich blood supply, contains connective tissue of cells in a fibrous organic matrix soaked in inorganic bone salts [1]. Bone is reported to be negatively feigned by several diseases as well as the therapy itself such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and spondyloarthritides, and osteoarthritis [2]. The clinical importance of the bone is still not fully defined as most patients do not examined for bone densitometry in routine orthopedic work. This review focuses on the problem of osteoporosis and mineral metabolism in relation to different arthritis conditions. We must take in consideration that greater understanding of this problem will increase the health care level and rheumatic patients live. Bone Cells There are three main types of bone cells: osteoblasts, osteoclasts, and osteocytes Osteoblasts (OBs) These cells originate from bone marrow-derived stromal cells [3] and are responsible for the deposition of the extracellular matrix and its mineralization [4]. They are highly differentiated columnar-shaped cells (20-30 µm in diameter), usually found in a layer one cell thick, intimately opposed to areas of bone formation or remodeling. Osteoclasts (OCs) Osteoclasts are responsible for the resorption of calcified bone and cartilage. They are derived from hemopoietic stem cells and are formed by the fusion of mononuclear cell precursors [5]. Their morphological and phagocytic characteristics are similar to other cells of the mononuclear phagocytic cell line. They are typically large (up to 200000 µm 3) and may contain up to 100 nuclei. The cells show cellular polarity, and resorption occurs along the 'ruffled' border of the cell opposed to the bone surface. Osteocytes Osteocytes are osteoblasts that remain behind in lacunae when the bone-forming surface advances. They are the result of osteoblasts 'selfentombed' by their own bone matrixsecreting activity. Osteocytes communicate with one another via cytoplasmic processes that pass through the bone canaliculi. These processes may help to coordinate the response of bone to stress or deformation [6]. Bone Proteins and Minerals Normal adult bone is termed lamellar bone. Each lamella is a thin plate 5-7 µm thick and made up of bone matrix consisting of protein fibers impregnated with bone salts. In each lamella, the protein fibers are largely oriented parallel to one another. The organic matrix constitutes 30-40%, and mineral salts 60-70%, of the dry weight of bone. Water makes up 20% of the weight of the matrix of mature bone. The principal organic component in bone is type I collagen, which constitutes 90-95% of the organic matrix. The important ionic Manuscript Click here to download Manuscript review 4.docx 2 components of the bone matrix are calcium, phosphate, magnesium, carbonate, hydroxyl, fluoride, citrate, and chloride. The most important crystalline component of bone i...

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Decline in Hand Bone Mineral Density Indicates Increased Risk of Erosive Change in Early Rheumatoid Arthritis

Cited by 14 publications

References 26 publications

Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model

Early Subchondral Bone Loss at Arthritis Onset Predicted Late Arthritis Severity in a Rat Arthritis Model

Association of Low Bone Mineral Density with Anti-Citrullinated Protein Antibody Positivity and Disease Activity in Established Rheumatoid Arthritis: Findings from a US Observational Cohort

Osteoporosis, Mineral Metabolism and Arthritis

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