Local and generalized bone loss in rheumatoid arthritis

The article presents a review of cross-sectional studies and long-term prospective observations dedicated to changes in bone mineral density (BMD) in patients with rheumatoid arthritis (RA) and factors influencing it. The relationship between local bone loss (erosion count) and generalized BMD loss was noted. It is indicated that existing RA treatment strategies are aimed at suppressing inflammation rather than preventing bone resorption. There is evidence that anti-inflammatory therapy using glucocorticoids, methotrexate, and biologic DMARDs in combination with antiresorptive drugs (bisphosphonates and denosumab) helps prevent BMD loss and the progression of erosions. It is emphasized that osteoporosis in RA, which belongs to the immune-mediated secondary osteopathies, is one of the most frequent and serious complications of RA, which determine the unfavorable course and prognosis of the underlying disease.

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SAT0034 CLINICAL SIGNIFICANCE OF ANTI-CARBAMYLATED PROTEIN ANTIBODIES IN PREMENOPAUSAL RHEUMATOID ARTHRITIS WOMEN: RELATION TO DISEASE ACTIVITY AND BONE LOSS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.637 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 947.2-947

Author(s):

R. Elnemr ◽

R. Bastawy ◽

R. Ghazala ◽

M. Abdelrazek ◽

N. Elsawy

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Bone Mineral Density ◽

Body Mass Index ◽

Serum Level ◽

Bone Loss ◽

Disease Activity ◽

Bone Mineral ◽

Mineral Density ◽

Local Bone

Background:Anti carbamylated protein anti carP are present in patients with Rheumatoid Arthritis RA and are associated with erosions. However their association with systemic or local bone loss in RA patients is still not confirmed.Objectives:The purpose of this study was to measure the serum level of anti carP in premenopausal women with RA and determine its relation to disease activity and bone loss.Methods:This case control study was conducted on forty eight RA premenopausal female patients diagnosed according to 2010 ACR/EULAR criteria and forty eight ages and body mass index matched healthy premenopausal females. RA patients with other autoimmune diseases, viral hepatitis malignancy or erosive joint disease and systemic diseases that affect bone quality were excluded from the study. All RA women were subjected to history taking, clinical examination, assessment of disease activity using disease activity score-28 DAS28 and clinical disease activity index CDAI functional assessment using health assessment questionnaire HAQ physical activity assessment using international physical activity questionnaire short form IPAQ fatigue assessment using modified fatigue impact scale MFIS, routine laboratory investigations, serological tests as well as Anti carP using ELISA kit. Moreover the bone mineral density was measured by a lunar Prodigy Advanced DEXA scanner system and plain x-ray of both hands and wrists in the anteroposterior view was done to assess the juxta articular osteopenia and erosions.Results:Anti carP level was significantly higher in RA patients than in healthy controls table 1. The serum level of anti carP had a significant positive correlation with RA DAS, CDAI, HAQ, IPAQ, MFIS and erosion and joint space narrowing in original sharp score. Also the anti carP had a significant negative correlation with the bone mineral density BMD of spine. The AUC of anti carP level showed a high level of accuracy AUC 0.857 figure 1 and the calculated cutoff value >65 can precisely discriminate subjects with RA from those without RA with 85.42% sensitivity and 85.11% specificity.Table 1.Comparison between the patient and healthy groups according to anti carp levelAnti-carpRA patientsHealthy controlUpMin – Max15.0 – 90.01.0 – 78.50322.0*<0.001*Mean ± SD71.24 ± 14.7045.99 ± 21.99Median (IQR)72.75 (70.5–78.3)55.0 (32.5–61.5)Figure 1.ROC curve for anti carP to diagnose RA patients from healthy subjectsConclusion:Anti carbamylated antibodies were higher in premenopausal RA women compared to ages and body mass index matched healthy women. Anti carP are associated with higher RA disease activity, increased disability and decreased physical activity. Moreover anti carP are associated with systemic trabecular bone loss manifested by decreased bone mineral density of the spine as well as local bone loss as manifested by increased number of joint erosions in premenopausal RA women.References:[1] Regueiro C, Ortiz AM, Boveda MD, Castañeda S, Gonzalez-Alvaro I, Gonzalez A. Association of high titers of anti-carbamylated protein antibodies with decreased bone mineral density in early arthritis patients. PLoS ONE 2018; 13(8):e0202583.Disclosure of Interests:None declared

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Osteoimmunology: Major and Costimulatory Pathway Expression Associated with Chronic Inflammatory Induced Bone Loss

Journal of Immunology Research ◽

10.1155/2015/281287 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 55

Author(s):

Tania N. Crotti ◽

Anak A. S. S. K. Dharmapatni ◽

Ekram Alias ◽

David R. Haynes

Keyword(s):

Rheumatoid Arthritis ◽

Bone Loss ◽

Chronic Inflammation ◽

Bone Erosion ◽

Adaptor Proteins ◽

Periprosthetic Osteolysis ◽

Related Factors ◽

Local Bone ◽

Immune Mediated ◽

Pathway Expression

The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA). Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM) signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR).

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Immuno-biological Assessments of Temporomandibular Joint Disease in Patients with Immune-mediated Rheumatic Conditions. A cross sectional study of 273 cases

Revista de Chimie ◽

10.37358/rc.17.12.6023 ◽

2018 ◽

Vol 68 (12) ◽

pp. 2987-2991

Author(s):

Cristina Iordache ◽

Bogdan Vascu ◽

Eugen Ancuta ◽

Rodica Chirieac ◽

Cristina Pomirleanu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Psoriatic Arthritis ◽

Temporomandibular Joint ◽

Final Analysis ◽

Cross Sectional Study ◽

Joint Disease ◽

Sectional Study ◽

Cross Sectional ◽

Immune Parameters ◽

Immune Mediated

Temporomandibular joint (TMJ) is commonly involved in various immune-mediated rheumatic disorders accounting for significant disability and impaired quality of life. The aim of our study was to assess inflammatory and immune parameters in patients with TMJ arthritis related to rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) and to identify potential relation with severity and dysfunction of TMJ pathology. We performed a cross-sectional study in a cohort of 433 consecutive RA, 32 JIA, 258 AS, and 103 PsA. Only patients presenting with clinically significant TMJ involvement (273) related to their rheumatic condition were included in the final analysis. TMJ involvement is traditionally described in chronic inflammatory rheumatic disorders, particularly in patients with higher levels of inflammation as detected in rheumatoid arthritis and psoriatic arthritis. Disease activity and severity, as well as biological and positive serological assessments (rheumatoid factor, anti-cyclic citrullinated peptide, IL-1) remain significant determinants of the severity of TMJ arthritis.

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Prevalence and risk factors for bone loss in rheumatoid arthritis patients from South China: modeled by three methods

BMC Musculoskeletal Disorders ◽

10.1186/s12891-021-04403-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zhuoran Hu ◽

Lei Zhang ◽

Zhiming Lin ◽

Changlin Zhao ◽

Shuiming Xu ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Lumbar Spine ◽

Bone Loss ◽

South China ◽

Serum Vitamin ◽

Tumor Necrosis Factor Inhibitor ◽

Healthy Controls ◽

Mineral Density ◽

Serum Vitamin D

Abstract Background To explore the prevalence of bone loss among patients with rheumatoid arthritis (RA) and healthy controls (HC) and further explored the risk factors for osteopenia and osteoporosis of RA patients. Methods A cross-sectional survey was undertaken in four hospitals in different districts in South China to reveal the prevalence of bone loss in patients. Case records, laboratory tests, and bone mineral density (BMD) results of patients were collected. Traditional multivariable logistic regression analysis and two machine learning methods, including least absolute shrinkage selection operator (LASSO) and random forest (RF) were for exploring the risk factors for osteopenia or osteoporosis in RA patients. Results Four hundred five patients with RA and 198 HC were included. RA patients had lower BMD in almost BMD measurement sites than healthy controls; the decline of lumbar spine BMD was earlier than HC. RA patients were more likely to comorbid with osteopenia and osteoporosis (p for trend < 0.001) in the lumbar spine than HC. Higher serum 25-hydroxyvitamin D3 level and using tumor necrosis factor inhibitor in the last year were protective factors; aging, lower body mass index, and increased serum uric acid might be risk factors for bone loss. Conclusions RA patients were more prone and earlier to have bone loss than HC. More attention should be paid to measuring BMD in RA patients aging with lower BMI or hyperuricemia. Besides, serum vitamin D and all three measurement sites are recommended to check routinely. TNFi usage in the last year might benefit bone mass.

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P129 Predictors of low bone mineral density in rheumatoid arthritis

Rheumatology ◽

10.1093/rheumatology/keab247.124 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Malika A Swar ◽

Marwan Bukhari

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Bone Mineral Density ◽

Family History ◽

Bone Loss ◽

Femoral Neck ◽

Bone Mineral ◽

Fragility Fracture ◽

Mineral Density ◽

History Of

Abstract Background/Aims Osteoporosis (OP) is an extra-articular manifestation of rheumatoid arthritis (RA) that leads to increased fracture susceptibility due to a variety of reasons including immobility and cytokine driven bone loss. Bone loss in other populations has well documented risk factors. It is unknown whether bone loss in RA predominantly affects the femoral neck or the spine. This study aimed to identify independent predictors of low bone mineral density (BMD) in patients RA at the lumbar spine and the femoral neck. Methods This was a retrospective observational cohort study using patients with Rheumatoid arthritis attending for a regional dual X-ray absorptiometry (DEXA) scan at the Royal Lancaster Infirmary between 2004 and 2014. BMD in L1-L4 in the spine and in the femoral neck were recorded. The risk factors investigated were steroid use, family history of osteoporosis, smoking, alcohol abuse, BMI, gender, previous fragility fracture, number of FRAX(tm) risk factors and age. Univariate and Multivariate regression analysis models were fitted to explore bone loss at these sites using BMD in g/cm2 as a dependant variable. . Results 1,527 patients were included in the analysis, 1,207 (79%) were female. Mean age was 64.34 years (SD11.6). mean BMI was 27.32kg/cm2 (SD 5.570) 858 (56.2%) had some steroid exposure . 169(11.1%) had family history of osteoporosis. fragility fracture history found in 406 (26.6%). 621 (40.7%) were current or ex smokers . There was a median of 3 OP risk factors (IQR 1,3) The performance of the models is shown in table one below. Different risk factors appeared to influence the BMD at different sites and the cumulative risk factors influenced BMD in the spine. None of the traditional risk factors predicted poor bone loss well in this cohort. P129 Table 1:result of the regression modelsCharacteristicB femoral neck95% CIpB spine95%CIpAge at scan-0.004-0.005,-0.003<0.01-0.0005-0.002,0.00050.292Sex-0.094-0.113,-0.075<0.01-0.101-0.129,-0.072<0.01BMI (mg/m2)0.0080.008,0.0101<0.010.01130.019,0.013<0.01Fragility fracture-0.024-0.055,0.0060.12-0.0138-0.060,0.0320.559Smoking0.007-0.022,0.0350.650.0286-0.015,0.0720.20Alcohol0.011-0.033,0.0 5560.620.0544-0.013,0.1120.11Family history of OP0.012-0.021,0.0450.470.0158-0.034,0.0650.53Number of risk factors-0.015-0.039,0.0080.21-0.039-0.075,-0.0030.03steroids0.004-0.023,0.0320.030.027-0.015,0.0690.21 Conclusion This study has shown that predictors of low BMD in the spine and hip are different and less influential than expected in this cohort with RA . As the FRAX(tm) tool only uses the femoral neck, this might underestimate the fracture risk in this population. Further work looking at individual areas is ongoing. Disclosure M.A. Swar: None. M. Bukhari: None.

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SAT0082 FRAX AND DAS IN MOROCCAN RHEUMATOID ARTHRITIS PATIENTS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4467 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 975.1-975

Author(s):

H. Azzouzi ◽

O. Lamkhanat ◽

I. Linda

Keyword(s):

Rheumatoid Arthritis ◽

Fracture Risk ◽

Disease Activity ◽

Descriptive Analysis ◽

Cross Sectional Study ◽

Fracture Probability ◽

Mineral Density ◽

Cross Sectional ◽

Risk Probability ◽

Fracture Assessment

Background:Rheumatoid Arthritis (RA) is one of the risk factors for the calculation of the 10 years fracture probability assessed by the FRAX tool.Objectives:The aim was to study the association of disease activity and the 10 year fracture risk probability by the FRAX tool in our RA patients and their impact on fracture prevalence.Methods:Cross-sectional study of the association FRAX and disease activity score (DAS 28 CRP) was designed. Patients with RA were included. Mean DAS was calculated for each patient adjusted on his follow-up duration. Data about patients (demographic, disease characteristics and fracture assessment) were collected. The 10 year fracture risk probability for major osteoporotic fracture was calculated with and without BMD (bone mineral density) using the FRAX tool for Morocco. Descriptive analysis and regressions were performed with SPSS.20. p<0.05 was considered significant.Results:One hundred and ninety nine RA patients were included with mean age of 55.5±12 years. Women represented 91% and 40.1% had osteoporosis. Remission was observed in 86.4% with 95.5% taking methotrexate. 17.1% had vertebral fractures. FRAX and DAS were associated (p=0.03), and both explained vertebral fracture (VF) prevalence. When adjusted on disease parameters, FRAX with and without BMD explained the vertebral prevalence (p=0.02, OR=1.09[1.01-1.19]). However, age remains the only predictor of VF when adjusted on osteoporosis factors (DAS28CRP, menopause, BMI, smoking, diabetes, gender, steroid use, HAQ) and FRAX BMD.Conclusion:Persistent disease activity was associated to high 10 year fracture risk probability calculated by the FRAX tool in RA.Disclosure of Interests:None declared

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β-Hydroxy-β-Methylbutyrate (HMB) Supplementation Prevents Bone Loss during Pregnancy—Novel Evidence from a Spiny Mouse (Acomys cahirinus) Model

International Journal of Molecular Sciences ◽

10.3390/ijms22063047 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3047

Author(s):

Ewa Tomaszewska ◽

Janine Donaldson ◽

Jakub Kosiński ◽

Piotr Dobrowolski ◽

Agnieszka Tomczyk-Warunek ◽

...

Keyword(s):

Articular Cartilage ◽

Bone Loss ◽

Young Modulus ◽

Compact Bone ◽

Second Trimester ◽

Mineral Density ◽

Tissue Quality ◽

Cross Sectional ◽

Acomys Cahirinus ◽

Trabecular Number

The aim of this study was to determine the effects of ß-hydroxy-ß-methylbutyrate (HMB) supplementation during pregnancy on postpartum bone tissue quality by assessing changes in trabecular and compact bone as well as in hyaline and epiphyseal cartilage. The experiment was carried out on adult 6-month-old female spiny mice (Acomys cahirinus) divided into three groups: pregnant control (PregCont), pregnant HMB-treated (supplemented with 0.02 g/kg b.w of HMB during the second trimester of pregnancy, PregHMB), and non-pregnant females (NonPreg). Cross-sectional area and cortical index of the femoral mid-shaft, stiffness, and Young modulus were significantly greater in the PregHMB group. Whole-bone mineral density was similar in all groups, and HMB supplementation increased trabecular number. Growth plate cartilage was the thinnest, while the articular cartilage was the thickest in the PregHMB group. HMB supplementation increased the content of proteoglycans in the articular cartilage and the percentage of immature collagen content in metaphyseal trabeculae and compact bone. In summary, dietary HMB supplementation during the second trimester of pregnancy intensifies bone metabolic processes and prevents bone loss during pregnancy.

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The role of Tai Chi Chuan exercise on osteoporosis prevention and treatment in postmenopausal women

Alternative Medicine Studies ◽

10.4081/ams.2011.e10 ◽

2011 ◽

Vol 1 (1) ◽

pp. 10

Author(s):

Haiyan Chen

Keyword(s):

Bone Loss ◽

Postmenopausal Women ◽

Tai Chi ◽

Weight Bearing ◽

Depression And Anxiety ◽

Osteoporosis Prevention ◽

Mineral Density ◽

Cross Sectional ◽

Tai Chi Chuan

Osteoporosis is a disease characterized by fragile bones and high susceptibility to low trauma fractures. Tai Chi, an ancient Chinese mind-body exercise that is reported to enhance muscle function, balance and flexibility, and to reduce pain, depression and anxiety, may safely and effectively be used to prevent or treat osteoporosis. The aim of this review is to evaluate the evidence for Tai Chi as an intervention to reduce rate of bone loss in postmenopausal women. A literature search on randomized controlled trials (RCTs), prospective cohort studies, and cross-sectional studies that included Tai Chi as an intervention, and had at least 1 outcome related to measurement of bone metabolism were identified in PubMed/Medline. Twenty-one controlled studies were identified in the database, which suggested Tai Chi slowed down the loss of bone mineral density in most postmenopausal women, improved balance and strength, relieves pain from arthritis, and improved mental strength so they can cope better with chronic diseases. Regular Tai Chi Chuan exercise is beneficial for retarding bone loss in the weight-bearing bones of postmenopausal women.

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Role of Secreted Frizzled-Related Protein 1 and Tumor Necrosis Factor-α (TNF-α) in Bone Loss of Patients with Rheumatoid Arthritis

International Journal of Rheumatology ◽

10.1155/2020/9149762 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Andi Raga Ginting ◽

Rudy Hidayat ◽

Sumariyono Sumariyono ◽

Sukamto Koesnoe

Keyword(s):

Rheumatoid Arthritis ◽

Bone Loss ◽

Cross Sectional Study ◽

Related Protein ◽

Cross Sectional ◽

Low Level ◽

Female Patients ◽

Premenopausal Female ◽

High Level ◽

Turn Over

Bone loss is one of the emerging extra-articular manifestations of rheumatoid arthritis. TNF-α is the main inflammatory cytokine that can directly increase bone resorption. However, its role in bone formation is still unknown, especially related to secreted frizzled-related protein 1 (SFRP-1), an osteoblast inhibitor. This study examines the correlation between TNF-α and SFRP-1, with a bone turn over marker (CTX and P1NP). This is a cross-sectional study with 38 subjects of premenopausal female patients with RA. This study found that 60.6% of the patients were in remission or low disease activity. The median of TNF-α was 10.6 pg/mL, mean of SFRP-1 was 9.29 ng/mL, mean of CTX was 2.74 ng/mL, and the median of P1NP was 34.04 pg/ml. There is positive correlation between TNF-α and P1NP (r=0.363, p=0.026), also between SFRP-1 and P1NP (r=0.341; p=0.036). A low level of TNF-𝛼, high level of SFRP-1, high level of CTX, and low level of P1NP in this study indicate a high bone turn over process, with dominant resorption activity in premenopausal female patients with RA.

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Bone Loss, Osteoporosis, and Fractures in Patients with Rheumatoid Arthritis: A Review

Journal of Clinical Medicine ◽

10.3390/jcm9103361 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3361

Author(s):

Patrice Fardellone ◽

Emad Salawati ◽

Laure Le Monnier ◽

Vincent Goëb

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Bone Loss ◽

Interleukin 1 ◽

Bone Destruction ◽

Fragility Fractures ◽

Systemic Effect ◽

Vertebral Fracture Assessment ◽

Mineral Density ◽

Accurate Treatment

Rheumatoid arthritis (RA) is often characterized by bone loss and fragility fractures and is a frequent comorbidity. Compared with a matched population, RA patients with fractures have more common risk factors of osteoporosis and fragility fractures but also risk factors resulting from the disease itself such as duration, intensity of the inflammation and disability, and cachexia. The inflammatory reaction in the synovium results in the production of numerous cytokines (interleukin-1, interleukin-6, tumor necrosis factor) that activate osteoclasts and mediate cartilage and bone destruction of the joints, but also have a systemic effect leading to generalized bone loss. Regular bone mineral density (BMD) measurement, fracture risk assessment using tools such as the FRAX algorithm, and vertebral fracture assessment (VFA) should be performed for early detection of osteoporosis and accurate treatment in RA patients.

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