Osteoporosis In Rheumatoid Arthritis Research Articles

Skeletal muscle index together with body mass index is associated with secondary osteoporosis in patients with rheumatoid arthritis

ObjectiveThe objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA).MethodsThe bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1–4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI.ResultsA total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p < 0.0001), and the prevalence of OP (36.1%, 160/443) and sarcopenia (65.2%, 288/443) in the RA patients were higher than those in the controls (12.7%, 20/158, p < 0.0001; 9.0%, 14/156, p < 0.0001). Significant differences in the BMD, FMI, SMI, mineral content, body fat percentage and skeletal muscle mass were found among the RA patients in the different BMI groups (p < 0.05). In RA patients with BMI < 18.5 kg/m2, the prevalence of OP in the RA patients with sarcopenia was similar to that in those without sarcopenia (44.4% vs. 66. 7%, χ2 = 0. 574, p = 0.449). In the RA patients with a normal BMI or who were overweight or obese, prevalence of OP in the RA patients with sarcopenia was significantly higher than that in the RA patients without sarcopenia (42.8% vs. 21.7%, χ2 = 10.951, p = 0.001; 61.1% vs. 13.0%, χ2 = 26.270, p < 0.0001). In the RA patients without sarcopenia, the prevalence of OP in the RA patients in the different BMI groups was different (p = 0.039). In the RA patients with sarcopenia, there was no significant difference in the prevalence of OP among the RA patients in the different BMI groups (p = 0. 128). The linear correlation analysis showed that the SMI in RA patients was positively correlated with the BMD of each site measured and BMI and FMI (p < 0.0001). However, there was a negative linear correlation between SMI and disease duration (p = 0.048). The logistic regression analysis found that SMI (OR = 0.569, p = 0.002, 95% CI 0.399–0.810), BMI (OR = 0.884, p = 0.01, 95% CI 0.805–0.971) and gender (1 = female, 2 = male) (OR = 0.097, p < 0.0001, 95% CI 0.040–0.236) were protective factors for OP in RA, while age (OR = 1.098, p < 0.0001, 95% CI 1.071–1.125) was the risk factor.ConclusionBMI and SMI are associated with the occurrence of OP in RA patients, and both SMI and BMI are important protective factors for OP secondary to RA.

Metabolomics-based analysis of plasma in postmenopausal women with normal bone mineral density, postmenopausal osteoporosis, and rheumatoid arthritis osteoporosis

This study aimed to examine metabolites in the plasma derived from postmenopausal women by untargeted metabolomics along with possible diagnostic markers for osteoporosis. From March 2020 through June 2020, 30 postmenopausal women with normal bone mineral density (BMD) were recruited in the N group, 30 postmenopausal women with postmenopausal osteoporosis were recruited in the postmenopausal osteoporosis (PMO) group, and 30 postmenopausal women with rheumatoid arthritis osteoporosis were recruited in the rheumatoid arthritis osteoporosis (RAOP) group. The height, weight, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), lumbar BMD, hip BMD, femoral neck BMD, and plasma metabolite levels were measured. Seven differential metabolites were observed between the PMO and N groups and recorded as metabolite set 1, and 38 differential metabolites were found between the RAOP and N groups and recorded as metabolite set 2. Six same metabolites were found between these two metabolite sets. The area under the curve (AUC) of the combined receiver operating characteristic (ROC) curves for the six metabolites was 0.900. In this study, six metabolites with a diagnostic value for osteoporosis were found in the plasma of postmenopausal women, and the combined diagnosis efficiency of these six metabolites was high. Key policy highlights A non-targeted metabolomics approach was used to find common diagnostic targets for postmenopausal osteoporosis and postmenopausal rheumatoid arthritis osteoporosis in this study. This study was a preliminary exploration of the examination of common diagnostic targets for primary and secondary osteoporosis.

Positive Effects of Biologics on Osteoporosis in Rheumatoid Arthritis.

Osteoporosis is a systemic skeletal disorder that causes vulnerability of bones to fracture owing to reduction in bone density and deterioration of the bone tissue microstructure. The prevalence of osteoporosis is higher in patients with autoimmune inflammatory rheumatic diseases, including rheumatoid arthritis (RA), than in those of the general population. In this autoimmune inflammatory rheumatic disease, in addition to known risk factors for osteoporosis, various factors such as chronic inflammation, autoantibodies, metabolic disorders, drugs, and decreased physical activity contribute to additional risk. In RA, disease-related inflammation plays an important role in local or systemic bone loss, and active treatment for inflammation can help prevent osteoporosis. In addition to conventional synthetic disease-modifying anti-rheumatic drugs that have been traditionally used for treatment of RA, biologic DMARDs and targeted synthetic DMARDs have been widely used. These agents can be employed more selectively and precisely based on disease pathogenesis. It has been reported that these drugs can inhibit bone loss by not only reducing inflammation in RA, but also by inhibiting bone resorption and promoting bone formation. In this review, the pathogenesis and research results of the increase in osteoporosis in RA are reviewed, and the effects of biological agents on osteoporosis are discussed.

Rapamycin regulates osteogenic differentiation through Parkin-mediated mitophagy in rheumatoid arthritis.

Varying degrees of bone destruction and bone loss occur in the development of rheumatoid arthritis (RA). Nevertheless, the mechanism underlying osteoporosis in the development of RA is not completely elucidated. Recent evidence indicates that mitophagy may play a vital role in regulating the differentiation and function of preosteoblast. Parkin is associated with mitophagy and various inflammatory diseases, but the precise role of Parkin in the treatment of osteoporosis in RA is unclear. In the present study, we found that the abnormal bone metabolism of RA is related to the activation of the mechanistic targets of mTORC1 pathway, and chronic inflammation which regulates the differentiation of preosteoblast through mitophagy. In this study, we found that Parkin was upregulated, and the mitochondrion was damaged in tumor necrosis factor alpha (TNF-α) stimulated preosteoblasts. Rapamycin (RAPA, an mTORC1 pathway blocker) upregulation of Parkin-mediated mitophagy tends to attenuate mitochondrial impairment caused by TNF-α in preosteoblasts. Theexperimentinvivo demonstrated that the combination therapy with TNF-α neutralizing antibody and RAPA significantly reduced osteoporosis in AIA mice. Drug inhibition of this pathway can be a potential treatment for osteoporosis in patients with RA.

Association of 25-Hydroxy Vitamin D with IL-17 Inflammatory Cytokines, and Osteoporosis in patients with Rheumatoid Arthritis in Kurdish nation / Iraq

Introduction: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Lower Vitamin D (Vit. D) levels correlate with more severe clinical manifestations in RA and other rheumatic diseases. IL-17A promotes inflammation by inducing various proinflammatory cytokines and chemokines. In this study, we evaluated the association between Vitamin. D and IL-17 in osteoporosis in Rheumatoid Arthritis in Kurdish nation / Iraq. Objective: Blood samples from rheumatoid arthritis (RA) patients were used to measure the levels of the inflammatory cytokine IL-17 and the Vit. D precursor 25(OH)D and bone loss in patients with RA in this study. Methods: In this study, 40 healthy controls were included in the research, which comprised 100 new cases of RA. ELISA was used to measure the level of serum 25(OH)D and IL-17. Moreover, DXA was used to assess average bone mineral density (BMD). Results: We discovered no difference between the two groups in terms of age or gender. This means that compared to the control group, the 25(OH)D serum levels in the RA group were lower (P 0.01; 16.85+8.7 nmol/l vs. 39.95 (-+9.8)). IL-17 serum levels were highly and negatively associated with 25(OH)D levels in arthritic patients. A comparison of 25(OH)D levels in patients with osteoporosis and osteopenia and those with BMD was also performed. Conclusion: Bone loss and IL-17 have been associated with reduced Vit. D levels in patients with rheumatoid arthritis; a lack of Vit. D may have a role in developing the disease, according to the data presented in this study.

Bone-sparing effects of tocilizumab in rheumatoid arthritis: a monocentric observational study.

Bone loss is a common feature in several autoimmune and chronic inflammatory diseases, such as rheumatoid arthritis (RA). Indeed, the high levels of pro-inflammatory cytokines seem to enhance bone resorption and to diminish bone formation, thus producing an uncoupling between osteoclast and osteoblast function and favoring the onset of juxtarticular as well as systemic osteoporosis. Many papers underline the high prevalence of osteoporosis in RA, as well as the negative correlation between interleukin 6 (IL-6) serum levels and bone mineral density (BMD). The aim of this study was to assess the effectiveness of one-year treatment with tocilizumab (TCZ), the first approved IL-6 receptor inhibitor, in reducing bone loss in RA. We enrolled 18 patients fulfilling 2010 ACR and EULAR criteria for RA from our arthritis outpatient clinic, assessing clinical and biochemical parameters during a 12-month period. The patients received TCZ 8 mg/kg i.v. every 4 weeks and underwent dual energy X-ray absorptiometry (DXA) for the measurement of bone mineral density (BMD) at baseline and at the end of study. Serum levels of C-reactive protein (CRP), erythrocytes sedimentation rate (ESR), IL-6, serum CrossLaps, osteoprotegerin (OPG), receptor activator of nuclear factor κβ ligand (RANK-L) and dickkopf-1 (DKK-1) were measured at baseline, at 6 months and 1 year. No significant difference in IL-6, RANK-L, DKK-1, OPG and serum CrossLaps levels between baseline, 6 months and 1 year were found. A significant increase of lumbar spine BMD was evidenced after 1 year of TCZ treatment. No difference in total body and femoral neck BMD was documented the end of the study. This study suggest the bone-sparing effect of TCZ in RA affected individuals.

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis.

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system’s and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures.

Correlation between vitamin D metabolites and rheumatoid arthritis with osteoporosis by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Our aim is to study the correlation between vitamin D metabolites and osteoporosis in rheumatoid arthritis (RA) by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). At the same time, other influencing factors and serum biomarkers of osteoporosis in patients with RA were studied. Patients with RA admitted from January 2020 to December 2020 were selected at our hospital. The subjects were divided into the normal bone mineral density (BMD), osteopenia, and osteoporosis groups. The differences of vitamin D (VD) metabolites among groups were compared. The Pearson correlation coefficient was used to analyze the relationship between BMD and various parameters. The relationship between BMD and influencing factors was studied by a multiple linear regression equation. A total of 287 patients with RA were included. RA patients with 25-hydroxy vitamin D [25(OH)D] deficiency accounted for 43.63% and 25(OH)D insufficient levels accounted for 31.37%. There were 31 cases (10.80%) in the normal BMD group, 161 cases (56.10%) in the osteopenia group, and 95 cases (33.10%) in the osteoporosis group. The BMD of L1-4 (T- score) was negatively correlated with age (P < 0.05), course of disease (P < 0.05), and erythrocyte sedimentation rate (ESR) (P < 0.05), and positively correlated with 25(OH)D3 (P < 0.05). The multiple linear regression model results showed that age and 25(OH)D3 were independent predictors of BMD; this explained 22.11% of the total variation. VD deficiency and insufficient are common in RA patients. RA patients can be appropriately supplemented with VD. VD3 may be a better choice.

AB0311 RHEUMATOID ARTHRITIS AND OSTEOPOROSIS: FREQUENCY AND ASSOCIATED FACTORS

BackgroundIn rheumatoid arthritis (RA), persistent systemic inflammation may cause bone and cartilage destruction and systemic osteoporosis (OP).ObjectivesWe conducted this study to determine the frequency of OP in RA patients and to focus on associated factors.MethodsThis is a retrospective descriptive and analytic study including consecutive RA patients. The epidemiological, clinical, biological data and the measurement of bone mineral density were collected from patients’ records. A statistical analysis was performed to study the clinico-biological profile of osteoporotic patients and determine factors associated with the development of OP in RA patients.ResultsSeventy-one of RA patients were recruited: 67 females (94.4%) and 4 males (5.6%) with a mean age of 54.28 years ± 11.09 [30-75]. OP was noted in 45.1% of cases (32 patients). The mean T-scores at the lumbar and femoral sites were -2.7 ± 0.6 SD and -1.3 ± 1 SD, respectively. Patients with OP were older (58.8 ± 7.6 years vs 50.5 ± 12.1 years; p &lt;0.01) and with a greater number of postmenopausal women than patients with normal bone density (68.7% vs 41%; p=0.02). Osteoporotic patients had RA duration longer than the other group (15.2 ± 12.5 years vs 11.9 ± 8.2 years; p=0.02) and more extra-articular manifestations associated with RA (100% vs 76.9%; p &lt; 0.01). Both groups were treated with corticosteroid drugs with similar frequency, although patients with normal bone density received biotherapy more frequently than patients with OP (23% vs 18.7%; p= 0.03). The two groups had almost similar disease activity DAS28 ESR (44,3 ± 34 vs 42.7 ± 30.7; p=0.2). The following parameters were not associated with the occurrence of OP in our series: gender, smoking, BMI, ESR, CRP, ACPA, RF, erosive and deforming character of RA.ConclusionOP is an extra-articular disease that must be systematically screened throughout the follow-up. In our study, there was no significant difference in disease activity at both groups of patients. However, patients with OP had longer duration of RA, more extra-articular manifestations and were less frequently treated with biotherapy.

Mapping Knowledge Structure and Themes Trends of Osteoporosis in Rheumatoid Arthritis: A Bibliometric Analysis.

Background: Rheumatoid arthritis is a chronic disabling disease characterized by chronic inflammation, articular cartilage destruction, and reduced bone mass. Multiple studies have revealed that the development of osteoporosis in rheumatoid arthritis (RA; ORA) patients could be led to a reduced quality of life and increased healthcare costs. Nevertheless, no attempt has been made to analyze the field of ORA research with the bibliometric method. This study aimed to provide a comprehensive overview of the knowledge structure and theme trends in the field of ORA research from a bibliometric perspective.Methods: Articles and reviews regarding ORA from 1998 to 2021 were identified from the Web of Science database. An online bibliometric platform, CiteSpace, and VOSviewer software were used to generate visualization knowledge maps including co-authorship, co-citation, and co-occurrence analysis. SPSS, R, and Microsoft Excel software were used to conduct curve fitting and correlation analysis, and to analyze quantitative indicators, such as publication and citation counts, h-index, and journal citation reports.Results: A total of 1,081 papers with 28,473 citations were identified. Publications were mainly concentrated in North America, Western Europe, and Eastern Asia. Economic strength is an important factor affecting scientific output. The United States contributed the most publications (213) with the highest h-index value (46) as of September 14, 2021. Diakonhjemmet Hospital and professor Haugeberg G were the most prolific institution and influential authors, respectively. Journal of Rheumatology was the most productive journal concerning ORA research. According to the burst references, “anti-citrullinated protein antibodies” and “preventing joint destruction” have been recognized as the hot research issues in the domain. The keywords co-occurrence analysis identified “teriparatide,” “interleukin-6,” “Wnt,” and “vertebral fractures” as the important future research directions.Conclusion: This was the first bibliometric study comprehensively summarizing the trends and development of ORA research. Our findings could offer practical sources for scholars to understand the key information in this field, and identify the potential research frontiers and hot directions in the near future.

Peficitinib improves bone fragility by recovering bone turnover imbalance in arthritic mice

Peficitinib, a pan-JAK inhibitor, is known to suppress the activation of fibroblast-like synoviocytes (FLSs) and thereby reduces joint inflammation associated with rheumatoid arthritis (RA). However, the effect on osteoporosis in RA remains to be elucidated. In this study, the effect of peficitinib or etanercept on joint inflammation, and consequently decreased bone mineral density (BMD) was evaluated in mice with collagen-induced arthritis (CIA). Additionally, the effect on RANKL production from osteoblasts differentiated from the mesenchymal stem cells of RA patients was evaluated. Administration of peficitinib for established CIA ameliorated arthritis and improved BMD in the femoral metaphysis, but not in the femoral diaphysis. Conversely, etanercept suppressed an increase in synovial inflammatory markers but did not improve arthritic conditions or the reduction of BMD in either region. All elevated bone formation and bone resorption markers were decreased with peficitinib but only partially decreased with etanercept. Furthermore, production of RANKL by human osteoblasts was suppressed by peficitinib but enhanced by etanercept. Unlike etanercept, peficitinib is thought to increase BMD by ameliorating the high bone turnover associated with RA states, resulting in improvement of bone fragility. Our data provide evidence that peficitinib would be expected to show efficacy for osteoporosis associated with RA.

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.

A Comparison of Demographics, Disease Activity, Disability, and Treatment Among Rheumatoid Arthritis Patients with and without Osteoporosis.

IntroductionOsteoporosis (OP) is one of the most common comorbidities associated with rheumatoid arthritis (RA). Literatures reported that the risk for developing OP was strongly associated with duration and severity of RA. We aim to elaborate on the consequences of OP on disease activity and management plan in patients with RA.Patients and MethodsA retrospective cohort study recruited 408 patients, including those with RA alone and with RA plus OP. The RA disease activity in the patients was assessed using disease activity score in 28 joints (DAS28-CRP). A statistical analysis was performed to compare data between the two groups of patients and determine any significant risk factor associated with the development of OP in RA patients.ResultsOf 408 patients who were included in this study, 353 patients (86.5%) had only RA, while 55 patients (13.5%) had RA with OP and showed significant difference (P = 0.04) concerning age categories. Patients diagnosed with RA and OP had RA duration longer than RA-only patients (independent t-test, P = 0.01). The two groups had almost similar disease activity at the three clinical visits, as well, had nearly similar disability at their first visit, whereas RA with OP patients had significant greater disability at their 2nd and 3rd visits (independent t-test, P = 0.001). Both groups were treated with the same biologic and non-biologic medication of similar frequency, although RA patients with OP received steroid more frequently than patients had RA only (61.7% vs. 41.7%, chi square test, P = 0.03).ConclusionThere was no significant difference in disease activity at both groups of patients. However, RA with OP group had longer duration of RA, were more frequently treated with steroids, and had greater disability. We recommend physicians focus on controlling RA disease activity, early screening for and treating of OP.

Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

Background Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. Methods Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. Results The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). Conclusion High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

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

BackgroundTo 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.MethodsA 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.ResultsFour 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.ConclusionsRA 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.

ADIPONECTIN LEVEL AND ITS RELATION TO OSTEOPOROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Background: Adiponectin possesses anti-inflammatory properties and also has pro-inflammatory aspects in some diseases. Adiponectin plays an important role in bone metabolism and osteoporosis (OP) pathophysiology, modulating bone formation and remodeling by selectively enhancing stem cell development between adipocyte and bone precursors in the bone marrow in response to reduced energy storage and metabolic needs.Aim of work: The aim of our study was to assess serum adiponectin level in rheumatoid arthritis (RA) patients and to study the possible role of adiponectin as a marker of osteoporosis in rheumatoid arthritis patients.Patient and Methods: The study included 30 premenopausal rheumatoid arthritis female patients. The age ranged from 26 to 46 years old and body mass index (BMI) ranged from 23 to 37.34 compared to 15 healthy controls. They were subjected to full history taking. Laboratory investigation was done to exclude other causes of osteoporosis. Serum level of adiponectin was measured by ELISA. They were also assessed radiologically by DEXA scan of lumbar spine to confirm osteoporosis.Results: In our study, we found that RA patients had statistically significant higher adiponectin level than healthy controls. Moreover, serum adiponectin was significantly higher in patients with both RA and OP compared to RA female patients only. Moreover, our results demonstrated that a serum adiponectin of 1400 μg/L or higher is capable of detecting osteoporosis among RA patients with a sensitivity of 100% and a specificity of 100%. Regarding predictive ability of adiponectin in detecting RA with osteoporosis, our findings showed that there was an inverse association between adiponectin level and bone density, and there was a significant negative correlation between adiponectin level and DEXA scores in RA group.Conclusion: There was a clinical usefulness of measuring serum adiponectin in predicting OP among RA premenopausal female patients. This was strongly suggest the possible utility of serum adiponectin as a marker to detect OP in patients with RA hand in hand with conventional parameters.

Osteoporosis in Rheumatoid Arthritis: Dangerous Liaisons.

Osteoporosis has been classically considered a comorbidity of rheumatoid arthritis (RA). However, recent advances in the pathogenesis of osteoporosis in RA have shown a close interplay between cells of the immune system and those involved in bone remodeling, introducing new actors into the classic route in which osteoclast activation is related to the RANK/RANKL/OPG pathway. In fact, the inflammatory state in early stages of RA, mediated by interleukin (IL)-1, IL-6, IL-8 and tumor necrosis factor (TNF)-α has the ability to activate and differentiate osteoclasts not only through their relationship with RANKL, but also through the Wnt/DKK1/sclerostin pathway, leading to bone loss. The role of synovial fibroblasts and activated T lymphocytes in the expression of the RANKL system and its connection to bone destruction is also depicted. In addition, autoantibodies such as rheumatoid factor and anti-citrullinated protein antibodies are other pathogenic mechanisms for the development of bone erosions and systemic osteoporosis in RA, even before the onset of arthritis. The aim of this review is to unravel the relationship between different factors involved in the development of osteoporosis in RA patients, both the classic factors and the most novel, based on the relationship of autoantibodies with bone remodeling. Furthermore, we propose that bone mineral density measured by different techniques may be helpful as a biomarker of severity in early arthritis patients.

Клиническая эффективность применения препаратов Остеомед, Остеомед Форте, Остео-Вит D3 у больных вторичным остеопорозом при ревматоидном артрите

Клиническая эффективность применения препаратов Остеомед, Остеомед Форте, Остео-Вит D3 у больных вторичным остеопорозом при ревматоидном артрите

Polymorphisms in TNF Receptor Superfamily 1B (TNFRSF1B:rs3397) are Linked to Mycobacterium avium paratuberculosis Infection and Osteoporosis in Rheumatoid Arthritis.

We previously discovered that single nucleotide polymorphisms (SNPs) in PTPN2/22 (T-cell negative-regulators) occur in 78% of rheumatoid arthritis (RA), along with Mycobacterium avium paratuberculosis (MAP) infection in 33% of patients. In Crohn’s disease, we reported that SNPs in TNFα and receptors (TNFRSF1A/TNFRSF1B) benefited intracellular MAP-survival, increased infection, and elevated inflammatory response mimicking the poor response to anti-TNFα treatment in some patients. Here, we studied the frequency and effects of SNPs in TNFα/TNFRSF1A/TNFRSF1B in RA including gene expression, MAP infection, and osteoporosis marker levels in blood (54 RA and 48 healthy controls). TNFα:rs1800629 (GA) was detected in 19/48 (40%) RA and 8/54 (15%) controls (p-value < 0.05, odds ratio (OR) = 3.6, 95% CI: 1.37–9.54). TNFRS1B:rs3397 (CT) was detected in 21/48 (44%) RA and 10/54 (19%) controls (p-value < 0.05, OR = 4.43, 95% CI: 1.73–11.33). In RA, rs3397 downregulated TNFRSF1B expression (CC > CT (0.34 ± 0.14) and CC > TT (0.27 ± 0.12)), compared to wildtype CC (0.51 ± 0.17), p-value < 0.05. MAP DNA was detected significantly in 17/48 (35.4%) RA compared to 11/54 (20.4%) controls (p-value < 0.05, OR = 2.14, 95% CI: 1.12–5.20). The average osteocalcin level was significantly lower (p-value < 0.05) in RA (2.70 ± 0.87 ng/mL), RA + MAP (0.60 ± 0.31 ng/mL), RA + TNFRSF1B:rs3397 (TT) (0.67 ± 0.35 ng/mL), compared to the healthy control (5.31 ± 1.39 ng/mL), and MAP-free RA (3.85 ± 1.31 ng/mL). Overall, rs3397 appears to downregulate TNFRSF1B, increase MAP infection, worsen inflammation, and cause osteocalcin deficiency and possibly osteoporosis in RA.

Pharmacological Management of Osteoporosis in Rheumatoid Arthritis Patients: A Review of the Literature and Practical Guide.

Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with increased localized and generalized osteoporosis (OP). Previous studies estimated that approximately one-third of the RA population experience bone loss. Moreover, RA patients suffer from a doubled fracture incidence depending on several clinical factors, such as disease severity, age, glucocorticoid (GC) use, and immobility. As OP fractures are related to impaired quality of life and increased mortality rates, OP has an enormous impact on global health status. Therefore, there is an urgent need for a holistic approach in daily clinical practice. In other words, both OP- and RA-related factors should be taken into account in treatment guidelines for OP in RA. First, to determine the actual fracture risk, dual-energy X-ray absorptiometry (DXA), including vertebral fracture assessment (VFA) and calculation of the 10-year fracture risk with FRAX®, should be performed. In case of high fracture risk, calcium and vitamin D should be supplemented alongside anti-osteoporotic treatment. Importantly, RA treatment should be optimal, aiming at low disease activity or remission. Moreover, GC treatment should be at the lowest possible dose. In this way, good fracture risk management will lead to fracture risk reduction in RA patients. This review provides a practical guide for clinicians regarding pharmacological treatment options in RA patients with OP, taking into account both osteoporotic-related factors and factors related to RA.