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Objectives: To investigate the changes of bone mineral density (BMD) and their relationship with some risk factors in female patients with rheumatoid arthritis (RA). Subjects and methods: A cross-sectional descriptive study on 49 female patients with RA, who had average age of 58.16 ± 7.15 years.
Journal of military pharmaco-medicine INVESTIGATION OF BONE MINERAL DENSITY IN FEMALE PATIENTS WITH RHEUMATOID ARTHRITIS Nguyen Minh Phuong*; Le Van Quyet**; Nguyen Ngoc Chau*** SUMMARY Objectives: To investigate the changes of bone mineral density (BMD) and their relationship with some risk factors in female patients with rheumatoid arthritis (RA) Subjects and methods: A cross-sectional descriptive study on 49 female patients with RA, who had average age of 58.16 ± 7.15 years BMD at lumbar spine and neck of femur were measured by a DEXA method (Hologic QDR4500 Elite) Tender and swollen joints were examined; also CRP, hemoglobin, anti-CCP levels, and erythrocyte sedimentation rates (ESR) were measured; then DAS28 CRP and DAS28 ESR were calculated Results: The mean of BMD of lumbar spine and neck of femur were 0.76 ± 0.12 and 0.59 ± 0.11 g/cm2, respectively; mean BMD and BMD of categories of age from 40 to 70 years old were lower than those of Vietnamese woman with the same age The results of multivariant regression analysis showed that there were corelations between BMD and age, BMI, DAS28 CRP, DAS28 ESR, and hemoglobin levels; however, among five variants, the corelation between BMD and age was the strongest, with R = 0.232, p = 0.013, and the age also was considered as an independent factor to predict BMD of neck of femur BMD of lumbar spine was insignificantly inversely associated with DAS28 CRP and hemoglobin levels BMD of neck of femur was also insignificantly inversely associated with DAS28 CRP Conclusion: These results suggested that BMD of lumbar spine and neck of femur reduces in female patients with RA There was a strongest correlation between BMD and age and the age could be an independent factor to predict BMD in neck of femur * Keywords: Rheumatoid arthritis; Bone mineral density; Osteoporosis INTRODUCTION Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly in synovium, causing destruction of the edge of joint bones, cartilage, soft tissue, leading to severe disability and premature mortality Decrease patients with with multiple have shown osteoporosis in BMD, osteoporosis in RA is a pathological state risk factors Some studies the relationship between and pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, since these cytokines play an important role in the pathogenesis of RA and bone destruction as well [7] In some epidemiological studies, it was founded that there was a positive correlation between osteoporosis and C-reactive protein (CRP) - a marker of inflammation [7] Other risk factors include age, female sex, menopause, low BMI, glucocorticoid therapy, high activity in RA, prolonged duration of RA, and reduced physical activity * Vietnam Military Medical University ** 103 Military Hospital Corresponding author: Nguyen Minh Phuong (phuongk21@gmail.com) Date received: 06/07/2017 Date accepted: 18/08/2017 164 Journal of military pharmaco-medicine In Vietnam, there are many studies on BMD among population without RA [2, 3, 4] However, there is not much published research on BMD in RA patients, recently Therefore, we conducted this study with aims as followed: - Evaluation of bone mineral density among female patients with RA - To investigate the relationship between BMD and some risk factors in female patients with RA SUBJECTS AND METHODS Subjects 49 female patients with RA who had been treated in the Department of Rheumatology and Endocrinology, 103 Military Hospital from May, 2013 to July, 2015 * Selection criteria: Female patients with diagnosis of RA fulfilled the ACR/EULAR 2010 RA classification criteria * Exclusion criteria: Patients have risk factors which may effect BMD such as current smoking, alcohol abuse (drinking over units of alcohol per day), causes of secondary osteoporosis (diabetes, osteogenesis imperfecta in adults, untreated hyperthyroidism, impaired sexual function, early menopause, chronic gastrointestinal disorders, chronic liver disease) Methods This study was designed as a prospective, descriptive, cross-sectional study * Study parameters: - Clinical parameters: number of pain joints, number of swollen joints (within 28 joints: shoulder joints, elbow joints, wrist joints, 10 hand-finger joints, knuckles near the hand, knuckles of thumbs, knee joints), VAS (Visual Analoge Score), Disease Activity Score 28 (C-reactive protein) - DAS28 (CRP), Disease Activity Score 28 (erythrocyte sedimentation rate ) - DAS (ESR) - Labolatory analysis: CRP (mg/L), erythrocyte sedimentation rate (mm/h), red blood cell (RBC) (T/L), hemoglobin (Hb) (g/L), anti-cyclic citrulinated peptides anti-CCP (U/mL), rheumatoid factor (RF) BMD was measured at lumbar spine and neck of femur using Hologic QDR4500 Elite Machine Data analysis using SPSS version 17.0 RESULTS Clinical and subclinical charateristics of patients with RA Table 1: Clinical and subclinical charateristics of patients with RA Parameters Mean ± SD Age (years) 58.16 ± 7.15 Disease duration (months) 22.18 ± 25.63 Number of pain joints 11.2 ± 8.31 Number of swollen joints 7.70 ± 6.21 Time of morning stiffness duration (minutes) 33.80 ± 32.44 VAS (cm) 6.78 ± 2.11 Parameters DAS28-CRP Using corticoid for a long time n (%) Recover (0) Low (2) Moderate 16 (32.7) High 32 (65.3) Yes 49 (100) No (0) 165 Journal of military pharmaco-medicine RBC (T/L) 4.10 ± 0.5 Hb (g/L) 113.7 ± 15.0 ESR (mm/h) 70.80 ± 45.0 CRP (mg/L) 56.76 ± 44.39 Anti-CCP (U/L) 112.32 ± 74.46 DAS28-ESR 5.64 ± 1.30 DAS28-CRP 6.06 ± 1.55 Chronic adrenal failure due to medication X-ray stage RF Yes 30 (61.2) No 19 (38.7) Steinbroker 22 (44.9) Steinbroker 13 (26.5) Steinbroker 13 (26.6) Steinbroker (2.0) Positive 35 (71.4) Negative 14 (28.6) The results in table showed that, the age of patients was between 43 and 75 years and the average age of 58.16 ± 7.15 years The average duration of patients with RA was 22.18 ± 25.63 months The majority of patients had moderate and severe disease activity, with an average DAS28-CRP of 5.64 ± 1.30; DAS28-ESR of 5.64 ± 1.30, in which the majority of patients had high disease activity level (65.3%) The changes in BMD in female patients with RA Table 2: The BMD and T-score in RA patiens (n = 49) Region BMD (g/cm ) T-score Lumbar spine 0.76 ± 0.12 -2.9 ± 0.4 Neck of femur 0.59 ± 0.11 -2.6 ± 0.6 The results in table showed that the mean BMD of lumbar spine and of the neck of femur were 0.76 ± 0.12 g/cm2 and 0.59 ± 0.11 g/cm2, respectively The T-score of lumbar sine and neck of femur were -2.9 ± 0.4 and -2.6 ± 0.6, respectively Relationship between diabetes and some risk factors in female patients with RA Figure 1: Corelation between BMD of lumbar spine and DAS28 CRP 166 Figure 2: Corelation between BMD of neck of femur and DAS28 CRP Journal of military pharmaco-medicine There are many risk factors affecting the BMD in female patients with RA In addition to age factors, nutrition, physical activity levels and the risk factors of RA are also associated with BMD in patients with RA The results in fig.1 and fig.2 showed that there were negative correlations between BMD of lumbar spine and neck of femur with DAS28-CRP DICUSSION Rheumatoid arthritis mainly occurs in middle age, prevalence usually begins to increase at the age of 25 then stabilizes and decreases after 75 years old [8] In our study, patients between the ages of 43 and 75 years and the average age of 58.16 ± 7.15 years were not excluded from this rule The use of glucocorticoid in the treatment of RA is an important issue, which helps to control inflammation rapidly in patients with RA Although the benefits of glucocorticoid in controlling disease activity and severity of RA are well understood, the safety of low-dose and long-acting of glucocorticoid for BMD remains inadequate clear The controversy exists as the use of glucocorticoid reduces the concentration of proinflammatory cytokines as well as increases the mobility of the patient, which is beneficial for bone strength Recently, there were some evidences supporting the point of view that osteoporosis in patients with RA is a disease which independently associated with disease activity of RA or glucocorticoid using In Vietnam, corticosteroid abuse has become an alarming problem An epidemiological study in Longan province showed that the rate of corticosteroid abuse was 39.4% [1] Therefore, using corticosteroid in RA treatment is no exception Our research results showed that 100% of patients using corticosteroids that can be used on their own or used in medicine in the form of tablets, solution, powder, thus negatively affecting the BMD, as well as can lead to chronic adrenal failure The results in table showed that 61.2% of patients with chronic adrenal failure due to medication Our results showed that among female patients with RA, the mean BMD of lumbar spine and of the neck of femur were 0.76 ± 0.12 g/cm2 and 0.59 ± 0.11 g/cm2, respectively When comparing the BMD of Vietnamese women in the same age in a study by Nguyen Thi Thanh Huong et al (2009) [3], we found that the BMD of female patients with RA at age from 40 to 70 years were lower than those in the Vietnamese population without RA (1.16 ± 0.13 g/cm2 at the lumbar spine 0.94 ± 0.11 g/cm2 at neck of femur) Moreover, female patients with RA were more likely to be suffered from osteoporosis in lumbar spine (T-score was -2.9 ± 0.4) than in neck of femur (T-score was -2.6 ± 0.6) According to Book C et al (2008) [5], the important risk factors for bone loss and predictable osteoporosis in RA patients are high disease activity along with motor dysfunction but not the situation of using steroids The authors found that the DAS28 was an independent predictor of changes in lumbar spine bone density (p = 0.003), and the HAQ index (Health Assessment Questionnaire) was the independent predictor of bone loss in neck of femur (p = 0.018) Our results 167 Journal of military pharmaco-medicine showed that there was a negative correlation between BMD of lumbar spine (fig 1) and neck of femur (fig 2) with DAS28-CRP However, the regression coefficient (β) and the correlation coefficient (R) were low and not statistically significant This may be due to the limited number of patients in our study, which does not yet show the predictive value of DAS28-CRP for BMD of lumbar spine and neck of femur in patients with RA Enhancing the activity of osteoclast and reducing the activity of osteoblasts is the mechanism of bone loss This process is mainly through the role of proinflammatory cytokines such as tumor necrosis factor (TNF-α), interleukin (IL) -1, IL-6, IL-17, and receptor activator of nuclear factor kappa B ligand (RANKL) [10, 11] Recently, chronic inflammation is therefore recognized as a potential risk factor for bone loss, osteoporosis, and osteoporotic fracture [12] Many studies had shown that high level of inflammation markers in the blood, such as CRP, IL-2, IL-6, and TNF-α are associated with these conditions [6, 7] In a research on 74 post-menopausal women with RA, the result showed that the disease activity increased along with elevated CRP, erythrocyte sedimentation rate as well as elevated IL-6 levels and were associated with extra-articular symptoms as well as systemic bone loss In our study, inflammatory index values such as elevated CRP and erythrocyte sedimentation rates were not significantly correlated with bone mineral density in lumbar spine and neck of femur The autoimmune process is common in RA patients and occurs many years before clinical manifestations of RA High 168 levels of RF and anti-CCP in the blood of RA patients Guler H et al (2008) [9] studied 80 RA patients, found that patients with high serum anti-CCP serum levels had low BMD in lumbar spine and neck of femur Anti-CCP levels positively correlate with the Sharp index, thus which is associated with bone loss situation that have seen in X-rays Therefore, the authors suggest that anti-CCP levels can predict bone loss in RA patients The results of our study showed that RF was positive in 71.4% of women with RA High anti-CCP levels, with mean values of 112.32 ± 74.46 U/mL, however, that have not been correlated with bone loss in RA We performed a multivariate regression analysis to assess the effects of factors such as age, BMI, DAS28-CRP, DAS28ESR, and hemoglobin concentration on BMD in lumbar spine and neck of femur We found that the five factors were not significantly correlated with BMD in lumbar spine (r = 0.512, p = 0.063), but these were significantly correlated with BMD in neck of femur (r = 0.583, p = 0.014) However, in individual analysis of each variable, there was only significantly negative correlation between age and BMD in neck of femur (p = 0.013) That means that only age was independent predictors of BMD in neck of femur with r = 0.232 CONCLUSION Study on BMD in 49 RA female patients with an average age of 58.16 ± 7.5 years, we found that: - BMD in lumbar spine and neck of femur decreased with mean values of 0.76 ± 0.12 g/m2 and 0.59 ± 0.10 g/m2, respectively Journal of military pharmaco-medicine - CRP level, erythrocyte sedimentation rate, DAS28 CRP, DAS28 ESR highly increased with the mean values of 56.76 ± 44.39 mg/L; 70.80 ± 45.0 mm/h; 6.06 ± 1.55; 5.64 ± 1.30, respectively - BMD in lumbar spine and neck of femur were not significantly correleted with DAS28 CRP - Multivariate regression analysis showed that BMD in neck of femur was significantly correlated with age, BMI, DAS28 CRP, DAS28 ESR and hemoglobin level, in which the age was significantly negative correlated with BMD in neck of femur and considered as a independent predictor of the change of BMD in neck of femur - There was not correlation between BMD and some inflammation indices such as CRP level, ESR, as well as autoimmuno indices in RA patients such as RF and anti-CCP REFERENCE Trần Ngọc Hữu Nghiên cứu đánh giá hoạt động chăm sóc sức khoẻ ban đầu tỉnh Long An đề xuất số biện pháp can thiệp Viện Vệ sinh Dịch tễ Trung ương Thư viện Quốc gia Việt Nam 2002 Ho Pham Thuc Lan, Nguyen S.C, Tran B et al Contributions of Caucasian-associated bone mass loci to the variation in bone mineral density in Vietnamese population Bone, 2015, 76, pp.18-22 ultrasonometer and data-derived T-scores J Bone Miner Metab 2003, 21 (2), pp.114-119 Book C, Karlsson M, Akesson K et al Disease activity and disability but probably not glucocorticoid treatment predicts loss in bone mineral density in women with early rheumatoid arthritis Scand J Rheumatol 2008, 37 (4), pp.248-254 Cauley J.A, Danielson M.E, Boudreau R.M et al Inflammatory markers and incident fracture risk in older men and women: the health aging and body composition study J Bone Miner Res 2007, 22 (7), pp.1088-1095 Ding C, Parameswaran V, Udayan R et al Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study J Clin Endocrinol Metab 2008, 93 (5), pp.1952-1958 Dr Fauci's et al Harrison's™ PRINCIPLES OF INTERNAL MEDICINE Eighteenth Edition Harrison's Online, Chapter 321 Rheumatoid Arthritis 2012 Guler H, Turhanoglu A.D, Ozer B et al The relationship between anti-cyclic citrullinated peptide and bone mineral density and radiographic damage in patients with rheumatoid arthritis Scand J Rheumatol 2008, 37 (5), pp.337-342 10 Herman S, Kronke G, Schett G Molecular mechanisms of inflammatory bone damage: emerging targets for therapy Trends Mol Med 2008, 14 (6), pp.245-253 Nguyen Thi Thanh Huong, von Schoultz B., Pham D.M et al Peak bone mineral density in Vietnamese women Arch Osteoporos, 2009, (1 - 2), pp.9-15 11 Hirayama T, Danks L, Sabokbar A et al Osteoclast formation and activity in the pathogenesis of osteoporosis in rheumatoid arthritis Rheumatology (Oxford) 2002, 41 (11), pp.1232-1239 Vu Thi Thanh Thuy, Chau T.T, Cong N.D et al Assessment of low bone mass in Vietnamese: comparison of QUS calcaneal 12 McLean R.R Proinflammatory cytokines and osteoporosis Curr Osteoporos Rep 2009, (4), pp.134-139 169 ... Clinical parameters: number of pain joints, number of swollen joints (within 28 joints: shoulder joints, elbow joints, wrist joints, 10 hand-finger joints, knuckles near the hand, knuckles of. .. this study with aims as followed: - Evaluation of bone mineral density among female patients with RA - To investigate the relationship between BMD and some risk factors in female patients with RA... change in bone mineral density and resorption in older adults: a longitudinal study J Clin Endocrinol Metab 2008, 93 (5), pp.1952-1958 Dr Fauci's et al Harrison's™ PRINCIPLES OF INTERNAL MEDICINE