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.
Trang 1INVESTIGATION 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
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 in BMD, osteoporosis in
patients with RA is a pathological state
with multiple risk factors Some studies
have shown the relationship between
osteoporosis 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
Trang 2In 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
1 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 3 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)
2 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: 2 shoulder joints, 2 elbow joints,
2 wrist joints, 10 hand-finger joints,
8 knuckles near the hand, 2 knuckles of thumbs, 2 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
1 Clinical and subclinical charateristics of patients with RA
Table 1: Clinical and subclinical charateristics of patients with RA
DAS28-CRP
Time of morning stiffness
duration (minutes)
Using corticoid for a long time
Trang 3RBC (T/L) 4.10 ± 0.5 Yes 30 (61.2)
Chronic adrenal failure due to medication
X-ray stage
RF
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)
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/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
3 Relationship between diabetes and some risk factors in female patients with RA
Figure 1: Corelation between BMD of
lumbar spine and DAS28 CRP
Figure 2: Corelation between BMD of
neck of femur and DAS28 CRP
Trang 4There 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 1 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
Trang 5showed 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
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, CRP, DAS28-ESR, 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
Trang 6- 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.
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