scholarly journals Effects of 1-year anti-TNF-α therapies on bone mineral density and bone biomarkers in rheumatoid arthritis and ankylosing spondylitis

2019 ◽  
Vol 39 (1) ◽  
pp. 167-175 ◽  
Author(s):  
Katalin Gulyás ◽  
Ágnes Horváth ◽  
Edit Végh ◽  
Anita Pusztai ◽  
Ágnes Szentpétery ◽  
...  

Abstract Objectives Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with generalized and localized bone loss. We conducted a comprehensive study using imaging (dual-energy X-ray absorptiometry, DXA) and laboratory biomarkers in order to determine bone health and to study the effects of anti-tumor necrosis factor (TNF) biologics in RA and AS. Patients and methods Thirty-six RA and 17 AS patients undergoing 1-year etanercept (ETN) or certolizumab-pegol (CZP) therapy were studied. Bone density was assessed by DXA at baseline and after 12 months. Serum C-reactive protein (CRP), calcium, phosphate, parathyroid hormone (PTH), vitamin D3, osteocalcin, procollagen type I N-propeptide (P1NP), C-terminal telopeptide (βCTX), osteoprotegerin, sclerostin (SOST), Dickkopf-1 (DKK-1), soluble receptor activator nuclear kappa B ligand (sRANKL), and cathepsin K (cathK) levels were determined at baseline and after 6 and 12 months. Results TNF-α inhibition was clinically effective. Anti-TNF-α halted further bone loss over 1 year. In general, anti-TNF therapy significantly increased P1NP, SOST levels, and the P1NP/βCTX ratios, while decreased DKK-1 and CathK production at different time points in most patient subsets. In the full cohort and in RA, baseline and/or 12-month bone mineral density (BMD) at multiple sites exerted inverse relationships with CRP and βCTX, and positive correlation with SOST. In AS, L2-4 BMD after 1-year biologic therapy inversely correlated with baseline βCTX, while femoral neck BMD rather showed inverse correlations with CRP. Conclusions Anti-TNF therapy slowed down generalized bone loss, in association with clinical improvements, in both diseases. TNF blockade may enhance bone formation and suppress joint destruction. Anti-TNF therapy may act inversely on DKK-1 and SOST. Independent predictors of BMD were SOST and βCTX in RA, whilst CRP in AS.Key Points• One-year anti-TNF therapy halted generalized bone loss in association with clinical improvement in arthritides.• Anti-TNF therapy may inversely act on DKK-1 and SOST.• Independent predictors of BMD were SOST and βCTX in RA, while CRP in AS.

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Malika A Swar ◽  
Marwan Bukhari

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.


2017 ◽  
Vol 36 (4) ◽  
pp. 431-438 ◽  
Author(s):  
Takeshi Mochizuki ◽  
Koichiro Yano ◽  
Katsunori Ikari ◽  
Kosei Kawakami ◽  
Ryo Hiroshima ◽  
...  

2015 ◽  
Vol 42 (8) ◽  
pp. 1413-1417 ◽  
Author(s):  
Haibo Li ◽  
Qiuxia Li ◽  
Xi Chen ◽  
Chen Ji ◽  
Jieruo Gu

Objective.To evaluate the effect of anti-tumor necrosis factor (TNF) therapy on bone mineral density (BMD) in patients with active ankylosing spondylitis (AS) with low BMD.Methods.Eighty-nine patients with active AS with low BMD were randomly divided into either a study group or a control group. The study group received etanercept (50 mg/week) or adalimumab (40 mg/2 week) subcutaneously for 1 year. BMD of lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry, and bone turnover markers serum C telopeptide of type-I collagen (sCTX) and serum procollagen type-I N propeptide (PINP) were detected by ELISA at baseline and at end of study.Results.After 1 year, compared with baseline, there was a significant increase in spine and femoral neck BMD by a mean ± SD of 14.9% ± 15.6% (p < 0.0001) and 4.7% ± 7.9% (p < 0.0001) in the study group. In the control group, there was a significant decrease in spine and femoral neck BMD by a mean ± SD of −8.6% ± 9.7% (p < 0.0001) and −9.8% ± 11.5% (p < 0.0001). Compared with baseline, sCTX was significantly decreased in the study group (−40% at 1 yr, p < 0.0001), but bone-specific alkaline phosphatase and PINP increased (45.6%, p < 0.0001 and 30.8%, p < 0.0001, respectively).Conclusion.In patients with active AS with low BMD, the spine and femoral neck BMD increased after anti-TNF therapy for 1 year, and it was accompanied by a significant decrease in bone resorption markers and an increase in bone formation markers.


2021 ◽  
Vol 2 (3) ◽  
pp. 116-121
Author(s):  
Aya N. Abdelrafee ◽  
Mohamed G. E. Zaki ◽  
Abeer K. El Zohiery ◽  
Manar A. Azab

Background: Rheumatoid Arthritis [RA] is a chronic systemic disease that affects the functional capacity of the hand due to inflammatory arthritis and joint destruction. RA patients have difficulties with everyday life activities and daily living activities. The prevalence of osteoporosis is estimated to be about twice that of the general population. Dual-energy X-ray absorptiometry (DEXA) is the most precise tool for detecting loss in bone mineral density in RA. Aim of the study: This study aims to investigate the relation between generalized bone mineral density (BMD) and each of hand joint destruction and hand function in order to find out its possible role in assessment of rheumatoid hand disability. Patients and Methods: Fifty patients diagnosed as RA based on the 2010 ACR Rheumatoid Arthritis Classification Criteria were included in this study. All patients were subjected to the following scores: Duruöz Hand Index (DHI), Grip Ability Test (GAT), Grip strength test, and Pinch strength tests for assessing the function of the dominant hand of each patient. The participants were also subjected to plain x-ray evaluated by van der Heijde-modified total Sharp score (vdH-S) to assess the damage of the joints of the dominant hand, and Dual-energy X-ray absorptiometry (DEXA) to assess the Bone Mineral Density. Results: The current study showed that wrist BMD was correlated with grip strength, pinch strength, GAT, and van der Heijde modified sharp score of the dominant hand. Moreover, X-ray joint findings were significantly correlated with each of total grip ability test, grip strength, and pinch strength as the hand disability manifested more with joint damage. Conclusion: In conclusion, Osteoporosis, hand function, and joint damage in RA are correlated suggesting related pathophysiological mechanisms. The Severity of RA could be related to osteoporosis as well as joint destruction and hand disability.


Author(s):  
Kusworini Handono ◽  
BP Putra Suryana ◽  
Sulistyorini Sulistyorini

Rheumatoid Arthritis (RA) is a systemic autoimmune disease accompanied by decreasing bone mass density and ultimately leads toosteoporosis. The cause of decreased bone mass density is still unknown, but the inflammation has been suspected as an important factor.The correlation between the severity of inflammation with the decrease in bone mass density in Indonesian RA patients has not been muchstudied. The purpose of this study was to know the assessment in the correlation between levels of C-reactive protein (CRP), Tumour NecrosisFactor-α (TNFα) and bone mineral density (BMD) with bone resorption marker CTx-1 β-Cross Laps in premenopausal RA patients.Thisobservational study using cross sectional design, was carried out in the Rheumatology Clinic and Central Laboratory of RSSA, Malang fromAugust 2009 until October 2010. All 47 RA patients were diagnosed according to revised of the 1997 American College of Rheumatology(ACR). Measurement of CRP levels uses turbidimetry method, TNF-α and CTX-1 β-Cross Laps levels using ELISA methods and the measurementof BMD using DEXA. The results of this study showed mean levels of CRP were 4.288±1.775 g/L, TNF-α were 322.077±275.248 pg/mLand CTX-1 β-Cross Laps were 0.588±0.139 ng mL. The correlation of CRP and TNF-α levels with CTX-1 β-Cross Laps level were r=0.5832,p=0.453 and r=0.615, p=0.041. Correlation of CTX-1 β-Cross Laps level and Femoral Neck BMD was r=–0.469, p=0.143 and r=0.248,p=0.799 for L average BMD. There was no correlation between CRP level and BMD results with bone resorption marker CTX-1 β-Cross Laps,but there is a significant correlation between high levels of TNFα with CTX-1 β-Cross Laps. It seems that TNF-α appears to be contributed tothe decrease of bone mass density in RA patients.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 947.2-947
Author(s):  
R. Elnemr ◽  
R. Bastawy ◽  
R. Ghazala ◽  
M. Abdelrazek ◽  
N. Elsawy

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


2017 ◽  
Vol 14 (4) ◽  
pp. 461-465 ◽  
Author(s):  
Takeshi Mochizuki ◽  
Koichiro Yano ◽  
Katsunori Ikari ◽  
Ryo Hiroshima ◽  
Yu Sakuma ◽  
...  

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