Biomechanical effects of inflammatory diseases on bone-rheumatoid arthritis as a paradigm

Abdulghani, Saba; Caetano-Lopes, Joana; Canhão, Helena; Fonseca, João Eurico

doi:10.1016/j.autrev.2009.02.021

Cited by 15 publications

(6 citation statements)

References 22 publications

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“…Although chronic inflammatory diseases like RA and psoriatic arthritis are classically associated with increased bone resorption ( 50 – 55 ), our data in AS patients (including or excluding HLA-B27-negative patients without syndesmophytes) show decreased indicators of OC formation and bone resorption, suggesting reduced capacity of OCPs to differentiate into OC and resorb bone.…”

Section: Discussionmentioning

confidence: 56%

Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

et al. 2017

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IntroductionAnkylosing spondylitis (AS) is typically characterized by focal bone overgrowth and also by systemic bone loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) to differentiate into osteoclasts (OCs). Therefore, our aim was to characterize bone remodeling and pro-osteoclastogenesis inflammatory environment, monocytes’ phenotype, and in vitro osteoclast differentiation in AS patients.MethodsPatients with active AS without any ongoing therapy and age- and gender-matched healthy donors were recruited. Receptor activator of nuclear factor-κβ (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations were assessed. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and quantitative reverse transcription real-time PCR for OC-specific genes were performed.ResultsPro- and anti-inflammatory cytokine serum levels were higher in AS patients than in controls. RANKL neutrophil expression was higher in AS patients when compared to healthy donors, but CD51/CD61 expression was lower in the classical monocyte subpopulation. Concerning osteoclastogenesis, we found no differences in the in vitro osteoclast differentiating potential of these cells when compared to healthy donors. However, we observed low expression of CSF1R, RANK, and NFATc1 in AS OCPs.ConclusionDespite the high levels of pro-inflammatory cytokines present in AS patients, no differences in the number of OC or resorbed area were found between AS patients and healthy donors. Moreover, we observed that OCPs have low OC-specific gene expression. These findings support our hypothesis of an impaired response of OCPs to pro-osteoclastogenic stimuli in vivo in AS patients.

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Section: Discussionmentioning

confidence: 56%

Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

et al. 2017

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“…The etiology of systematic osteoporosis and insufficiency fracture in RA is multifactorial and includes excessive production of proinflammatory cytokines,28, 29 immobility,30–32 weight loss,1, 30 glucocorticoids use,1, 3 and risk of falling 33. Proinflammatory cytokines activate osteoclasts while impeding osteoblasts such that bone resorption is favored over bone formation 34. The degree of inflammation is related to the magnitude of local or systematic osteoporosis 35.…”

Section: Discussionmentioning

confidence: 99%

Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case-control study

Zhu

Griffith

Qin

et al. 2012

Journal of Bone and Mineral Research

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The purpose of this work was to investigate the volumetric bone mineral density (vBMD), bone microstructure, and mechanical indices of the distal radius in female patients with rheumatoid arthritis (RA). We report a cross-sectional study of 66 middle-aged female RA patients and 66 age-matched healthy females. Areal BMD (aBMD) of the hip, lumbar spine, and distal radius was measured by dual-energy X-ray absorptiometry (DXA). High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed at the distal radius, yielding vBMD, bone microstructure, and mechanical indices. Cortical and trabecular vBMD were 3.5% and 10.7% lower, respectively, in RA patients than controls, despite comparable aBMD. Trabecular microstructural indices were -5.7% to -23.1% inferior, respectively, in RA patients compared to controls, with significant differences in trabecular bone volume fraction, separation, inhomogeneity, and structural model index. Cortical porosity volume and percentage were 128% and 93% higher, respectively, in RA patients, with stress being distributed more unevenly. Fourteen RA patients had exaggerated periosteal bone apposition primarily affecting the ulnovolar aspect of the distal radius. These particular patients were more likely to have chronic and severe disease and coexisting wrist deformity. The majority of the differences in density and microstructure between RA patients and controls did not depend on menstrual status. Recent exposure to glucocorticoids did not significantly affect bone density and microstructure. HR-pQCT provides new insight into inflammation-associated bone fragility in RA. It detects differences in vBMD, bone microstructure, and mechanical indices that are not captured by DXA. At the distal radius, deterioration in density and microstructure in RA patients involved both cortical and trabecular compartments. Excessive bone resorption appears to affect cortical more than trabecular bone at distal radius, particularly manifested as increased cortical porosity. Ulnovolar periosteal apposition of the distal radius is a feature of chronic, severe RA with wrist deformity. ß

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“…Pathological changes that occur with natural aging and through a variety of disease processes lead to compositional and structural changes in the bone, including loss of mineral mass in osteoporosis (Kanis et al, 1994), non-enzymatic glycation of collagen in type 1 diabetes (Saito and Marumo, 2010; Silva et al, 2009; Tang and Vashishth, 2011; Vashishth, 2007), or concomitant deterioration in the mineral and organic phases of the bone matrix in inflammatory diseases such as RA (Abdulghani et al, 2009; David and Schett, 2010; Lacativa and Farias, 2010; Li and Schwarz, 2003; Romas, 2005; Takahata et al, 2012). These changes invariably affect bone strength and toughness, which cannot be noninvasively measured or reliably predicted with current clinical technologies.…”

Section: Introductionmentioning

confidence: 99%

Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis

Inzana

Maher

Takahata

et al. 2013

Journal of Biomechanics

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Clinical prediction of bone fracture risk primarily relies on measures of bone mineral density (BMD). BMD is strongly correlated with bone strength, but strength is independent of fracture toughness, which refers to the bone’s resistance to crack initiation and propagation. In that sense, fracture toughness is more relevant to assessing fragility-related fracture risk, independent of trauma. We hypothesized that bone biochemistry, determined by Raman spectroscopy, predicts bone fracture toughness better than BMD. This hypothesis was tested in tumor necrosis factor-transgenic mice (TNF-tg), which develop inflammatory-erosive arthritis and osteoporosis. The left femurs of TNF-tg and wild type (WT) littermates were measured with Raman spectroscopy and micro-computed tomography. Fracture toughness was assessed by cutting a sharp notch into the anterior surface of the femoral mid-diaphysis and propagating the crack under 3 point bending. Femoral fracture toughness of TNF-tg mice was significantly reduced compared to WT controls (p=0.04). A Raman spectrum-based prediction model of fracture toughness was generated by partial least squares regression (PLSR). Raman spectrum PLSR analysis produced strong predictions of fracture toughness, while BMD was not significantly correlated and produced very weak predictions. Raman spectral components associated with mineralization quality and bone collagen were strongly leveraged in predicting fracture toughness, reiterating the limitations of mineralization density alone.

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Biomechanical effects of inflammatory diseases on bone-rheumatoid arthritis as a paradigm

Cited by 15 publications

References 22 publications

Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

Ankylosing Spondylitis Patients Have Impaired Osteoclast Gene Expression in Circulating Osteoclast Precursors

Structure and strength of the distal radius in female patients with rheumatoid arthritis: A case-control study

Bone fragility beyond strength and mineral density: Raman spectroscopy predicts femoral fracture toughness in a murine model of rheumatoid arthritis

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