Abstract
Introduction
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes chronic inflammation of the synovium with subsequent destruction and deformity of the joints. The etiology of RA remains unclear, but it is known to be associated with genetic and environmental factors. 1 The prevalence of RA is approximately 0.8% (0.3%–2.1%). 2
Osteoporosis is more common in patients with RA than in the general population. The prevalence of concurrent osteoporosis is 50%. Osteoporosis can cause pain and loss of height, and increases the risk of fractures after falling. 3 The chronic synovial inflammation in RA can promote osteoclastogenesis, leading directly to both focal and generalized bone loss and increased risk of fractures. In addition, many indirect factors associated with inflammatory arthritis contribute to the risk of osteoporosis. These include immobility, weight loss, and use of medications known to promote bone loss, such as glucocorticoids. 4
The International Society for Clinical Densitometry (ISCD) and National Osteoporosis Foundation (NOF) has recommended dual-energy x-ray absorptiometry (DEXA) testing for all adults RA patients, as well as women over 65 years old, those who sustain fractures after the age of 50 years or suffer a fragility fracture, those on chronic glucocorticoids therapy, and anyone at high risk of low bone mass, bone loss, or fracture. 5 The aim of this study was to evaluate changes in bone mineral density (BMD) in patients with recent-onset RA (less than 12 months) and its correlation, if any, with RA disease activity and radiological joint damage scores.
Methods
Study Population
This was a cross-sectional case control study that included 30 patients with recent onset RA (<12 months) and 20 healthy age and sex matched volunteers as controls. All patients fulfilled the American College of Rheumatology/European League Against Rheumatism EULAR/ACR criteria for RA. 6 They were either inpatients in the Internal Medicine and Rheumatology Department or were attending the rheumatology outpatient clinic for regular follow-up at Ain Shams University Hospital. Informed consent was obtained from participants.
All participants underwent full history-taking and a thorough physical examination, including a detailed musculoskeletal assessment. Using the modified DAS-28 score to evaluate RA disease activity, a score ≤ 2.6 was considered to be disease remission, 2.6–3.2 as low disease activity, 3.3–4.9 as moderate disease activity, and >5.1 as severe disease activity. 7 We determined the DAS cutoff value according to the median DAS score for our patients. Functional class assessment was done using a validated Arabic version of the health assessment questionnaire (HAQ). 8
Laboratory investigations were performed, including a full blood count (CBC), erythrocyte sedimentation rate (ESR, mm/hour) in the first hour, C-reactive protein (CRP, mg/dL), and complete urine analysis, with full blood chemistry, including renal and liver function tests. Rheumatoid factor (RF IgM, U/L) was measured using the Biotec RA factor latex agglutination slide for qualitative determination of RF in serum.
All RA patients underwent plain X-ray films on the hands, feet and wrists joints, with calculation of radiological damage using SENS. The x-ray films were examined by an expert radiologist. The SENS cutoff value was determined according to the median SENS score for the RA patients. 9
BMD was measured for all RA patients at the Radiodiagnosis Department using DEXA at the proximal femur, lumbar spine (L1–L4), and distal radius. A trained technician performed all scans using the same Lunar DEXA machine. The threshold for establishing a diagnosis of osteoporosis was based on the World Health Organization (WHO) definition, ie, BMD ≥2.5 standard deviations below the young adult mean (or T score ≤ –2.5). Osteopenia was defined as BMD ≤ –1.0 SD and > –2.5 SD from this mean, with low bone mass including all participants with osteopenia or osteoporosis. 10
Statistical Analysis
Analysis of data was done using the Statistical Program for Social Sciences version 12 (SPSS Inc, Chicago, IL). Values are expressed as mean ± standard deviation differences in values between the two groups and were analyzed using the unpaired
The Mann–Whitney test was used for nonparametric data. The Kruskal-Wallis test (F) was used to compare more than two groups with regard to quantitative variables for nonparametric data. The difference was considered nonsignificant if
Results
Demographic data, DAS-28 score, HAQ score, SENS score, and ESR for the study subjects are summarized in Table 1. The 30 patients with RA (group 1) comprised 20 females and 10 males, aged 23–54 (35.7 ± 7.6) years with a mean disease duration of 8.6 ± 3.6 months. The 20 controls (group 2) comprised 17 (85%) females and three (15%) males aged 23–50 (mean 35.7 ± 7) years. Six (20%) patients in group 1 were smokers and two (10%) people in group 2 were smokers. Seventeen patients (56.6%) received non steroidal anti-inflammatory drugs (NSAIDs) alone and 13 (43.3%) received steroids with disease-modifying antirheumatic drugs (DMARDS), with 12 receiving methotrexate and one receiving leflunamide.
Demographic, clinical, and laboratory data in 30 patients with rheumatoid arthritis versus controls.
Using a modified DAS-28, it was found that 5/30 RA patients (16.6%) were in remission, one patient (3.3%) was in a low disease activity, 17/30 patients (56.6%) were in a moderate disease activity, and 7/30 patients (23.3%) were in a high disease activity (Table 1). HAQ scores showed that 24/30 (80%) of the RA patients had mild functional disability (score 0–1), 5/30 (16.7%) had moderate disability (score 1–2), and one patient (3.3%) had severe disability (score 2–3, Table 1).
Radiological assessment of joint damage in RA patients showed a SENS score of 0–31.4 (11.7 ± 9.7), Table 1. On DEXA scanning, 15 (50%) RA patients had osteopenia and four (13.3%) had osteoporosis at the lumbar spine. In the control group, two (10%) had osteopenia at the lumbar spine, and none had osteoporosis. Fisher's Exact test showed that RA patients had a significantly higher frequency of osteoporosis and osteopenia than controls (
Comparison of bone mineral density at three anatomical sites between patients with rheumatoid arthritis and controls.
Comparison of risk factors for osteoporosis between patients and controls revealed no statistically significant (
Osteoporosis was significantly more common in males than in females (
Comparison of BMD between patients with rheumatoid arthritis having low versus high DAS score, HAQ, SENS, CRP.
By HAQ score, 3/4 (75%) RA patients with osteoporosis had severe disability (HAQ 3), while 7/15 (46.7%) patients with osteopenia had moderate disability (HAQ 2). Furthermore, 11/30 RA patients had normal BMD, of whom four with mild disability (HAQ 1), seven had moderate disability, and none had severe disability. This indicates that there was significant disability (increased HAQ score) consistent with lower BMD in subgroups of RA patients according to HAQ score and the difference was statistically significant (
Four out of 19 CRP-positive RA patients had osteoporosis and no none of the CRP-negative RA patients had osteoporosis. Seven of the 19 CRP-positive patients were found to be osteopenic, ie, BMD was lower in CRP-positive RA patients than in CRP-negative patients, and the difference was statistically significant (
There was no statistically significant correlation was found between disease duration, ESR, DAS-score and BMD at any anatomical site (

Comparison of bone mineral density between patients with rheumatoid arthritis and controls.

Significant negative correlation between t score at lumbar spine and SENS in patients with rheumatoid arthritis (r = –0.54,
Correlations between t scores, z scores, and various clinical parameters in patients with rheumatoid arthritis.
Discussion
Osteoporosis and fragility-related fractures are one of the most common complications seen in patients with RA and dramatically affect quality of life. 11 The present study was designed to evaluate BMD changes in patients with recent-onset RA, as well as the effect of inflammation, mobility, and drugs (steroids and DMARDS) on these changes.
Our results support the association between early RA and osteoporosis. We found that 13.3% of our patients with early RA had osteoporosis, 50% had osteopenia, and 36.7% had normal BMD, while none of the control subjects had osteoporosis. Only two controls (10%) had osteopenia, and 18 control subjects (90%) had normal BMD. These findings are in agreement with those of Brand et al 12 who reported that patients with RA have a higher risk of low BMD than normal age- and gender-matched populations. Similarly, a study reported by Kim et al 13 showed an increased risk of osteoporotic fractures in RA patients in all age groups, regardless of gender, and at various anatomical sites compared with individuals without RA. In contrast, Curtis et al 14 found that the proportion of their RA patients meeting t score criteria for osteoporosis (t score ≤ –2.5 at either the lumbar spine or femoral neck) was only 4%, and Yoon et al 15 reported that 52% of their patients with early-onset RA had osteoporosis and 39% were classified as having osteopenia.
In the present study, we found that the most common site for osteoporosis in our RA patients was the lumbar spine (four patients [13.3%]), followed by the femur (two patients [6.6%]), with involvement of the forearm in only one patient (3.3%). We also found that only two of 20 (10%) control subjects had osteopenia which affected the lumbar spine. These findings are consistent with those of Güler-Yüksel et al 16 who reported that the most common site for osteoporosis in patients with early RA was the spine (9%), followed by the total hip (4%), with 11% of cases occurring at either the spine or the hip. The proportion of patients with decreased BMD was 19% for the spine, 14% for the hip, and 25% for either the spine or the hip. Yoon et al 15 showed that osteoporosis was slightly more prevalent at the lumbar spine than at the femur in women with RA who were younger than 60 years of age, but the difference was not statistically significant.
We found that 22/30 (73.3%) of our RA patients had normal BMD at the femoral neck, six (20%) had osteopenia, and two (6.6%) had osteoporosis. These findings are similar to that reported by Curtis et al 14 who found that the majority of their RA patients had normal t scores at the femoral neck (t score > –1.0) while the remainder had femoral neck t scores < –1.0 but > –2.0, and none had osteoporosis. In our RA cohort, 43.3% had normal BMD, 43.3% had osteopenia, and 13.3% had osteoporosis at the lumber spine. Zhang et al 17 found that 38.6% of their subjects had either osteopenia or osteoporosis at the lumbar spine, and 44.9% had either osteopenia or osteoporosis at the femoral neck.
Interestingly, in the present study, osteoporosis was more common in RA men (40%) than in women (0%) with RA, and this difference was highly statistically significant (
Furthermore, our RA patients with osteoporosis were older and had a longer disease duration than those without osteoporosis, but the difference was not statistically significant (
In the present study, we found a significantly lower BMD in RA patients who received steroids and DMARDS compared with those who received NSAIDS alone (
Additionally, we found that osteoporosis in RA patients was more common in smokers than in nonsmokers, but the difference was not statistically significant (
We have also found that osteoporosis was significantly more common in CRP-positive than in CRP-negative RA patients (
Regarding HAQ score, we have found that most of RA patients with osteoporosis have severe functional disability (HAQ 3) (
In our study RA patients with osteoporosis were found to have a higher SENS, indicative of radiological damage than non osteoporotic RA patients In another way significantly lower BMD was found in RA patients with higher SENS than in those with a lower SENS (
We found a higher incidence of osteoporosis in patients with a high DAS-28 score compared with those with a low DAS-28 score, but the difference was not statistically significant (
Moreover, we found that there was no correlation between ESR and BMD at different sites (lumbar spine, r = –0.09; radius, r = –0.007; femur, r = –0.12,
In our study, we found a statistically significant inverse correlation between SENS and BMD only- at the lumbar spine (r = –0.54,
Finally, we found that there was a significant positive correlation between HAQ and DAS-28 (
We concluded that BMD changes do occur early in patients with RA, they are not necessarly correlated with clinical disease activity, as it can occur in patients with mild disease activity. There was a significant correlation between radiographic damage and reduced bone mass. DEXA is an important diagnostic tool for detecting osteoporosis in patients with early RA, serving as a promising supplement to x-ray scoring methods.
Disclosures
Author(s) have provided signed confirmations to the publisher of their compliance with all applicable legal and ethical obligations in respect to declaration of conflicts of interest, funding, authorship and contributorship, and compliance with ethical requirements in respect to treatment of human and animal test subjects. If this article contains identifiable human subject(s) author(s) were required to supply signed patient consent prior to publication. Author(s) have confirmed that the published article is unique and not under consideration nor published by any other publication and that they have consent to reproduce any copyrighted material. The peer reviewers declared no conflicts of interest.
