Investigation of bone mineral density in female patients with rheumatoid arthritis

Nội dung text: Investigation of bone mineral density in female patients with rheumatoid arthritis

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