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The Egyptian Rheumatologist xxx (2018) xxx–xxx

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The Egyptian Rheumatologist


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Original Article

Risk factors associated with bone loss and occurrence of fragility


fractures in rheumatoid arthritis patients
Hamdi Wafa, Alaya Raja ⇑, Kaffel Dhia, Boughanmi Nada, Zouche Imene, Kchir Mohamed Montacer
Rheumatology Department, Mohamed Kassab Orthopaedic Institute, Faculty of Medicine, Tunis el Manar University, Tunisia

a r t i c l e i n f o a b s t r a c t

Article history: Aim of the work: To investigate the bone mineral density (BMD) in rheumatoid arthritis (RA) Tunisian
Received 3 January 2018 patients, to identify the risk factors associated with its decrease and to assess the fracture risk.
Accepted 21 January 2018 Patients and methods: The study included 173 patients and 173 matched healthy controls. BMD was
Available online xxxx
assessed by the dual-energy X-ray absorptiometry. The risk of hip fracture (HF) and major osteoporotic
fracture (MOF) were assessed using the fracture risk assessment tool (FRAX). The disease activity, radio-
Keywords: logical severity and functional status were investigated.
Rheumatoid arthritis
Results: The mean age of patients was 54.1 ± 11.04 years and 141 were females; 71.6% menopausal.
Osteoporosis
Fracture
Disease duration was 8.2 ± 8 years and disease activity score was 5.54 ± 1.26. Sharp van-der-Heijde
FRAX (SvdH) score was 113.9 ± 106.8, health assessment questionairre (HAQ) score 1.03 ± 0.9. The BMD was
Bone mineral density significantly reduced in 138 (79.8%) patients and FRAX was higher compared to control (p < .001). The
frequency of osteoporosis (48% vs. 18.5%), the risk of MOF (1.8 ± 2.6 vs. 0.6 ± 0.3) and HF (0.7 ± 1.7 vs.
0.08 ± 0.1) were significantly higher in RA patients than in controls. Bone loss in RA was significantly
associated with age, low body mass index (BMI), longer disease duration, rheumatoid factor, SvdH,
atlantoaxial subluxation and corticosteroids use. Menopause, low calcium intake, erythrocyte sedimen-
tation rate and HAQ were risk factors for reduced BMD. The risk of MOF and HF was associated with
age, menopause, calcium intake, BMI, disease duration, HAQ, SvdH, cumulative dose and duration of cor-
ticosteroids.
Conclusion: bone loss and fragility fracture are frequent in RA and related to disease severity, function
impairment and corticosteroids use.
Ó 2018 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction anti-citrullinated protein antibodies (ACPAs) have been reported to


strongly influence the development of osteoporosis and bone loss
Rheumatoid arthritis (RA) is a multifactorial autoimmune dis- in Moroccan RA patients [9]. Bone loss is enhanced by general risk
ease that primarily affects the joint synovium [1]. Reduced bone factors of osteoporosis and factors related to RA [10].
mineral density and fracture risk have been previously reported This study aimed to compare the bone mineral density (BMD) in
in patients with other rheumatic diseases as systemic lupus ery- Tunisian patients with RA and matched healthy controls and to
thematosus [2], systemic sclerosis [3], ankylosing spondylitis [4], assess the risk factors associated with bone loss and fracture risk.
osteoarthritis [5] and juvenile idiopathic arthritis [6]. Pro-
inflammatory cytokines play an important role in the development
of reduced bone mineral density in RA since they are directly 2. Patients and methods
involved in the initiation and perpetuation of inflammation. They
also interact with bone cells promoting osteoarticular destruction This cross-sectional study was performed during the period
and bone loss [1,7]. Osteoprotegerin and receptor activator of the from June 2012 till June 2013 and included 173 RA patients who
nuclear factor jB ligand (RANKL) may also contribute to the bone fulfilled the 2010 RA classification criteria [11]. They were consec-
loss and generation of osteoporosis in RA patients [8]. Furthermore, utively enrolled from the in-patient or the Rheumatology outpa-
tient clinic of Mohamed Kassab Orthopaedic Institute, Faculty of
Peer review under responsibility of Egyptian Society of Rheumatic Diseases. Medicine, Tunis el Manar University. Another 173 age and sex
⇑ Corresponding author. matched healthy controls were considered. None of patients was
E-mail address: alayaraja@yahoo.fr (A. Raja). receiving any anti-osteoporotic medications at inclusion. An

https://doi.org/10.1016/j.ejr.2018.01.004
1110-1164/Ó 2018 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Wafa H et al. Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients.
The Egyptian Rheumatologist (2018), https://doi.org/10.1016/j.ejr.2018.01.004
2 H. Wafa et al. / The Egyptian Rheumatologist xxx (2018) xxx–xxx

informed consent was provided by the patients and the study man- years (17–74 years) and the mean disease duration 8.2 ± 8 years.
agement approved by the university ethical committee. The mean DAS28 was 5.54 ± 1.26 and a high disease activity was
All BD patients and controls were subjected to full history tak- found in 59.5% of patients. Only 1.7% of patients were in remission.
ing, clinical examination and laboratory investigations. The risk The average HAQ score was 1.03 ± 0.9. The mean modified Sharp
factors for osteoporosis were evaluated. Rheumatoid factor and score was 113.9 ± 106.8. The RF was positive in 125 (72.3%)
ACPAs [12] were measured and the disease activity score patients and ACPA in 128 (74%).
(DAS28) [13] was calculated for each patient. The joint destruction Disease modifying antirheumatic drugs (DMARDs) were dis-
and severity were assessed using of the Sharp van der Heijde pensed in all cases; methotrexate in 167 (96.5%) and leflunomide
(SvdH) score [14]. The functional impact was evaluated by the in 24 (13.9%) while biologics were prescribed in 32 (18.5%); etan-
health assessment questionairre (HAQ) score [15]. Dual-energy ercet 14 (8.1%), infliximab 8 (4.6%), adalimumab 5 (2.9%), tocilizu-
X-ray absorptiometry (DXA) was used to measure the BMD of mab 3 (1.7%) and rituximab in 2 (1.2%). Corticosteroids were used
the lumbar spine and the femoral neck. The diagnosis of osteoporo- in 125 (72.3%) of patients. The mean daily dose was 6.3 ± 4.6 mg.
sis was based on the World Health Organization criteria [16] where The mean duration of use of corticosteroid was 22.7 ± 13.1 months
osteoporosis was defined as a T score  2.5 SD and reduced BMD and cumulative dose was 7.4 ± 4.4 g. The mean daily dietary cal-
as T score  1 SD. The risk of hip fracture (HF) and major osteo- cium intake was 495.2 ± 147.7 mg/j. The mean BMD was signifi-
porotic fracture (MOF) over 10 years using the Fracture Risk cantly lower in 138 (79.8%) RA patients both in the lumbar spine
Assessment Tool (FRAX) [17] which was recently adapted for the and femoral neck compared to 58% of the controls (p < .001). The
Tunisian population [18] were also calculated. Patients using other frequency of osteoporosis (48% vs. 18.5%), the risk of MOF (1.8 ±
treatment than those used for RA or whose clinical examination or 2.6 vs. 0.6 ± 0.3) and HF (0.7 ± 1.7 vs. 0.08 ± 0.1) were significantly
laboratory assessment have detected a disorder that might have an higher in RA patients than in controls. RA patients were 1.38 times
impact on BMD such as endocrinopathy, osteomalacia or malig- more at risk of bone loss than controls (OR = 1.4; CI95% [1.2–1.6]).
nant tumors were excluded. This risk was higher among both men (OR = 2.3; CI95% [1.5–3.7])
Statistical analysis was performed by SPSS, version 13. Bivariate and women (OR = 1.3; CI95% [1.1–1.5]) compared to control. The
comparisons of demographic, disease activity, and disease severity risk of MOF and HF was significantly higher in RA patients (p <
measures between patients with and without reduced BMD were .001) (Table 1).
performed, using two sided t tests for continuous variables and Bone loss in RA patients was significantly associated with age,
Chi 2 tests for percentage. The same tests were also used to com- low BMI and menopause (Table 2), dietary calcium intake, disease
pare BMD and FRAX of patients with RA and healthy controls. duration, RF, erythrocyte sedimentation rate (ESR), SvdH,
The correlation between continuous variables has been evaluated atlantoaxial subluxation (AAL), HAQ and corticosteroids use. There
by the calculation of the r coefficient of Pearson. The possible pre- was no association between reduced BMD and gender (Table 3),
dictors of bone loss were subsequently entered into a logistic smoking, vitamin D levels, age at onset, DAS28, C-reactive protein
regression analysis applying low bone mass as dependent variable. (CRP), ACPA and the use of MTX and biologics. The MOF and HF
To assess independent predictors of bone loss we performed mul- FRAX correlated with age, menopause, dietary calcium intake,
tivariate analysis. Variables showing p < 0.15 when we compared BMI, disease duration, HAQ, SvdH, cumulative dose and duration
patients with and without low BMD was dichotomised. The level of corticosteroids (Table 4). Independent risk factors for bone loss
of significance was set at p < 0.05 in all analysis. revealed by the multiple regression analysis were menopause,
low calcium intake (<500 mg/day), ESR (55 mm/1st h), and HAQ
score (0.25)(Table 5).
3. Results

The mean age of the RA patients was 54.1 ± 11.04 years (29–78 4. Discussion
years) and 141 (81.5%) were females; 71.6% of them were meno-
pausal. Osteoporotic fracture history in the first-degree relatives Osteoporosis is actually considered as an extra-articular feature
was found in 5 (2.9%) of patients. 9 (5.2%) of cases were under- of RA. In addition to usual risk factors of osteoporosis, other ones
weight and 28 (16.2%) were smokers. The control consisted in related to RA may be involved. Indeed, inflammation, functional
141 (81.5%) females (49.7% were menopausal). Their mean age impairment, disease duration and treatment are all factors to take
was 53.7 ± 11.2 years (29–80 years) and 20 (11.6%) were smokers. into account to identify RA patients at high risk of osteoporosis
In the RA patients the mean age at disease onset was 45.6 ± 12.9 [19]. Several cross-sectional studies have demonstrated a reduced

Table 1
Comparison of the bone mineral density and fracture risk assessment tool (FRAX) in rheumatoid arthritis patient and control.

Variable RA patients Control p


mean ± SD (n = 173) (n = 173)
BMD T score Lumbar spine F 0.97 ± 0.01 1.04 ± 0.01 <0.001
M 0.93 ± 0.03 1.15 ± 0.03 <0.001
All 0.96 ± 0.18 1.06 ± 0.18 <0.001
Femoral neck F 0.85 ± 0.01 0.93 ± 0.01 <0.001
M 0.82 ± 0.02 1.00 ± 0.03 <0.001
All 0.84 ± 0.16 0.94 ± 0.15 <0.001
FRAX MOF F 1.84 ± 0.21 0.59 ± 0.02 <0.001
M 1.81 ± 0.42 0.04 ± 0.03 0.002
All 1.84 ± 2.56 0.56 ± 0.27 <0.001
HF F 0.73 ± 0.14 0.08 ± 0.01 <0.001
M 0.77 ± 0.27 0.08 ± 0.02 0.014
All 0.74 ± 1.67 0.08 ± 0.14 <0.001

RA: rheumatoid arthritis, F: females (n = 141), M: males (n = 32), BMD: bone mineral density, FRAX fracture risk assessment tool, MOF: major osteoporotic fracture, HF: hip
fracture. Bold values are significant at p < .05.

Please cite this article in press as: Wafa H et al. Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients.
The Egyptian Rheumatologist (2018), https://doi.org/10.1016/j.ejr.2018.01.004
H. Wafa et al. / The Egyptian Rheumatologist xxx (2018) xxx–xxx 3

Table 2 patients compared to corresponding controls (51.7 to 102.3% vs.


Association between the bone mineral density and menopause in rheumatoid 14.3 to 27%) [24]. The risk was estimated at 2.05 by GulerYuksel
arthritis patients.
et al. [20] and at 1.38 in this study. In the current study, the age
n (%) Menopausal in RA patients (n = p and disease duration were identified as risk factors of bone loss
141) in RA. Other studies have confirmed this negative relation between
yes (n = 101) no (n = 40) age, disease duration and bone loss [1,2,25,26]. Heidary et al. [27],
BMD Normal 13 (12.9) 19 (47.5) <.001 demonstrated that a significant decrease of BMD (-10.9% in femoral
Reduced 88 (87.1) 21 (52.5) neck and -10.4% in lumbar spine) occurs after 10 years of disease
RA: rheumatoid arthritis, BMD: bone mineral density. Bold values are significant at
onset.
p < .05. The association between low calcium intake and reduced BMD
has not been confirmed [28,29]. However, in this work a daily cal-
cium intake <500 mg was an independent risk factor for bone loss.
That could be explained by the poor calcium diet in the current
Table 3
Comparison of bone mineral density and T score according to the gender in
patients compared to the >500 mg/day reported in the other
rheumatoid arthritis patients. studies.
Data regarding the association between sex and bone loss are
Variable RA patients (n = 173) p
mean ± SD or n(%)
still controversial and need to be confirmed on large series
Female (n = 141) Male (n = 32) [1,20,25,26]. In our study, the risk of bone loss seems to be more
T score important in male than in female with RA compared to controls.
Lumbar spine 1.70 ± 0.13 1.96 ± 0.25 0.39 Although smoking has recently been identified as an indepen-
Femoral neck 1.48 ± 0.11 1.42 ± 0.16 0.82
dent risk factor for femoral bone loss in RA [30], in the present
BMD study it had no influence. This could be explained by the low expo-
Normal 32 (22.7) 3 (9.3) 0.09
sure of our population to this risk factor.
Reduced 109 (77.3) 29 (90.6)
High ESR was an independent risk factor of bone loss. This was
RA: rheumatoid arthritis, BMD: bone mineral density. concordant with the study of Tourinho et al. [31] and Hauser et al.
[32]. However, the disease activity did not correlate with bone loss
as in the study of Ben Abdelghani et al. [20]. This could be
BMD in RA. This bone loss concerned cortical and trabecular bone explained by the high disease activity in the most of our patients.
and the prevalence of bone loss ranged from 11 to 88.3% in at least Rheumatoid factor and ACPA are predictive factors of joint
one measurement site [1,2,20,21]. This wide range of frequency of destruction and severity of RA Muraviu et al. [33] revealed an
bone loss in RA could be explained by heterogeneity of the study increased bone loss in seropositive RA patients. In this work, this
population caused by different definition used of bone loss, vari- correlation has been confirmed with RF but not with ACPA.
able disease severity and duration and design of studies. In a lon- Most studies have demonstrated a decrease in BMD directly
gitudinal study, Shenstone et al. followed 67 cases of early RA related to functional disability assessed by HAQ in RA
getting no corticosteroid therapy for 12 months and reported a sig- [20,30,34,35]. Kvien et al. [10], estimated that the risk of bone loss
nificant decrease in bone density at the femoral neck compared to was increased 1.62 times in the lumbar spine and 1.86 in the
controls ( 3.9 vs. 0.8%)[22]. In the present study, a reduced BMD femoral neck in patients with high HAQ scores. The association
was observed in 79.9% of RA. Similar results had been found in between the structural damage in RA measured by the Sharp Van
another Tunisian study (71%) [23]. der Heijde score and reduced BMD was demonstrated in a study
To quantify the relative risk of bone loss in RA patients, studies on 218 cases of recent onset RA [36]. This association was also
have been conducted; Macovei et al., found that the variation on confirmed in patient with long disease duration as in this study
BMD at one year was significantly higher in postmenopausal RA and in another [37].

Table 4
The relationship between reduced bone mineral density and fracture risk assessment tool with demographic characteristics, laboratory and clinical disease activity criteria in
patients with rheumatoid arthritis.

Rheumatoid arthritis patients (n = 173)


Risk factors Patients with reduced BMD (n = 138) FRAX
mean ± SD
Mean ± SD Lumbar spine Femoral neck MOF HF
r (p)
Age (year) 59.4 ± 0.9 0.4 (<0.001) 0.5 (<0.001) 0.3 (<0.001) 0.3 (<0.001)
Dis. Dur. (year) 9.1 ± 0.7 0.2 (0.002) 0.3 (<0.001) 0.3 (<0.001) 0.4 (<0.001)
BMI 28.1 ± 0.7 0.3 (<0.001) 0.2 (<0.001) 0.1 (0.12) 0.2 (0.03)
Menop. (year) 10.5 ± 8.5 0.4 (<0.001) 0.4 (<0.001) 2.6 (<0.001) 1.1 (<0.001)
Cal. intake (mg/d) 465.7 ± 11.3 0.5 (<0.001) 0.47 (<0.001) 0.3 (<0.001) 0.2 (0.001)
ESR (mm/1st hr) 50.3 ± 2.3 0.2 (0.003) 0.15 (0.03) 0.2 (0.87) 0.1 (0.7)
RF n (%) 104 (83.2) 1.9 (0.047) 1.6 (0.04) 1.6 (0.15) 0.7 (0.15)
AAL n (%) 25 (96.1) 1.2 (0.27) 2.14 (0.02) 6.5 (0.31) 0.02 (0.7)
SvdH score 138.4 ± 106.8 0.5 (<0.001) 0.5 (<0.001) 0.4 (<0.001) 0.3 (0.007)
HAQ score 1.3 ± 0.1 0.7 (<0.001) 0.7 (<0.001) 0.4 (<0.001) 0.3 (0.004)
DAS28 5.5 ± 0.1 0.1 (0.19) 0.09 (0.21) 0.04 (0.65) 0.02 (0.79)
Corticosteroids
Cumulative dose 6.6 ± 9.1 0.2 (0.002) 0.33 (<0.001) 0.3 (<0.001) 0.2 (0.003)
Daily dose (mg/d) 7.3 ± 4 0.3 (<0.001) 0.3 (<0.001) 0.2 (0.17) 0.1 (0.09)
Duration of use 18.9 ± 27.8 0.2 (<0.001) 0.28 (<0.001) 0.2 (0.005) 0.2 (0.04)

RA: rheumatoid arthritis, BMD: bone mineral density, MOF major osteoporotic fracture, HF hip fracture, Dis. Dur.: disease duration, BMI: bone mineral density, Menop:
menopausal, Cal: calcium, ESR: erythrocyte sedimentation rate, RF: rheumatoid factor, AAL: atlantoaxial subluxation, SvdH: Sharp van der Heijde, HAQ: health assessment
questionnaire, DAS28: disease activity score in 28 joints. Bold values are significant at p < .05.

Please cite this article in press as: Wafa H et al. Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients.
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Table 5 [6] Alkady EA, Rashad SM, Khedr TM, Mosad E, Abdel-Wahab N. Early predictors of
Multivariate regression analysis of risk variables for the development of low bone increased bone resorption in juvenile idiopathic arthritis: OPG/RANKL ratio, as
mineral density. a key regulator of bone metabolism. Egypt Rheumatol 2011;33(4):217–23.
[7] Korayem HK, Rezk MM, Hassan MM, El-Tawab SS, Elsaid NA. Relation between
Factors RA patients (n = 173) serum IL-17 level and risk of osteoporotic fracture in premenopausal
rheumatoid arthritis patients: clinical, radiological and laboratory studies.
Adjusted OR (95% CI) p
Egypt Rheumatol 2016;38(2):85–90.
Age 0.27 (0.02–2.7) 0.26 [8] Fadda S, Hamdy A, Abulkhair E, Elsify HM, Mostafa A. Serum levels of
BMI 3.45 (0.6–18.5) 0.14 osteoprotegerin and RANKL in patients with rheumatoid arthritis and their
Menopause duration 15.57 (1.3–181.6) 0.02 relation to bone mineral density and disease activity. Egypt Rheumatol
Disease duration 1.33 (0.12–14.2) 0.81 2015;37(1):1–6.
[9] Ghozlani I, Mounach A, Ghazi M, Kherrab A, El Maghraoui A. Influence of anti-
Calcium intake < 0.5 g/d 6.26 (1.2–33.9) 0.03
cyclic citrullinated peptide on disease activity, structural severity, and bone
ESR  55 mm/h 11.04 (1.11–109.02) 0.04
loss in Moroccan women with rheumatoid arthritis. Egypt Rheumatol 2017.
HAQ score  0.25 17.6 (1.7–185.9) 0.01
epub ahead of print.
SvdH 7.3 (0.9–60.7) 0.06 [10] Kvien TK, Haugeberg G, Uhlig T, Falch JA, Halse JI, Lems WF, et al. Data driven
Steroids (Cum. dose) 5.29 (0.8–35.04) 0.08 attempt to create a clinical algorithm for identification of women with
rheumatoid arthritis at high risk of osteoporosis. Ann Rheum Dis
BMI: body mass index, ESR: erythrocyte sedimentation rate, HAQ: score health
2000;59:805–11.
assessment questionnaire, SvdH: Sharp van der Heijde, Cum: cummulative. Bold [11] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham 3rd CO, et al.
values are significant at p < .05. 2010 Rheumatoid arthritis classification criteria: an american college of
rheumatology/European league against rheumatism collaborative initiative.
Concerning the fracture risk, several studies confirmed in accor- Arthritis Rheum 2010;62(9):2569–81.
dance with our study that the incidence of fracture is higher in RA [12] Taylor P, Gartemann J, Hsieh J, Creeden J. A systematic review of serum
biomarkers anti-cyclic citrullinated peptide and rheumatoid factor as tests for
patients than in controls [38–40]. The risk of fracture is associated rheumatoid arthritis. Autoimmun Dis 2011. 815038.
particularly to disease duration [39], disease activity (DAS28) [13] Prevoo ML, van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van
[41,42], biological inflammation (CRP), HAQ [43], disease severity Riel PL. Modified disease activity scores that include twenty-eight joints
counts development and validation in a prospective longitudinal study of
as assessed by RF [42] and Sharp score [44] as well as the use of
patients with rheumatoid arthritis. Arthritis Rheum 1995;38:44–8.
corticosteroids [45]. [14] Van der Heijde D. How to read radiographs according to the Sharp/van der
As there are no available guidelines in the management of Heijde method. J Rheumatol 2000;27:261–3.
osteoporosis in RA patients, some recommendation seems to be [15] El Miedany Y, Youssef S, El Gaafary M, Ahmed I. Evaluating changes in health
status: sensitivity to change of the modified arabic health assessment
useful and appropriate in this situation. Thus it would be better questionnaire in patients with rheumatoid arthritis. Joint Bone Spine
to screen osteoporosis at the disease onset and during the 2003;70(6):509–14.
follow-up. Afterward, associated risk factors of osteoporosis should [16] WHO. Assessment of fracture risk and its application to screening for
postmenopausal osteoporosis. Report of a WHO Study Group. World Health
be controlled such as: using the lowest effective dose of corticos- Organization technical report series 1994;843:1–129.
teroids, prescription of effective DMARD, supplementation in vita- [17] Watts NB, Lewiecki EM, Miller PD, Baim S. National Osteoporosis Foundation
min D and calcium, prevention of falls by an adequate 2008 Clinician’s Guide to Prevention and Treatment of Osteoporosis and the
World Health Organization Fracture Risk Assessment Tool (FRAX): what they
rehabilitation and occupational therapy. Treatment of osteoporosis mean to the bone densitometrist and bone technologist. J Clin Densitom.
should be indicated in patients with a high rating FRAX and/or 2008;11(4):473–7.
reduced BMD with a fragility fracture. [18] Zrour-Hassen S, Jguirim M, Guezguez M, Mnif H, Younes M, Bejia I, et al. The
fracture risk assessment tool (FRAXTM), where are we in Tunisia? Tunis Med
In conclusion, bone loss and fragility fracture are frequent in RA 2011;89(2):136–41.
and related to disease severity, function impairment and corticos- [19] Nolla JM, Fiter J, Gómez-Vaquero C, Alegre JJ, Valverde J, Roig-Escofet D. Value
teroids use. In order to establish a preventive strategy, recognition of clinical factors in selecting postmenopausal women with rheumatoid
arthritis for bone densitometry. Ann Rheum Dis 2001;60:799–801.
of the risk factors of bone loss should be assessed as soon as the } ler-Yu
} ksel M, Bijsterbosch J, Goekoop-Ruiterman YP, De Vries-Bouwstra JK,
[20] Gu
disease is diagnosed. Patients at a high risk of osteoporosis should Ronday HK, Peeters AJ, et al. Bone mineral density in patients with recently
benefit of an early and adequate management. diagnosed, active rheumatoid arthritis. Ann Rheum Dis 2007;66:1508–12.
[21] Gheita T, Fawzy S, Rizk A, Hussein H. Impaired bone formation and
osteoporosis in postmenopausal elderly onset rheumatoid arthritis patients.
Conflict of interest Egypt Rheumatol 2011;33:155–62.
[22] Chen J, Liu Q, Lin Q, Chen L, Yin J, Huang H. Vitamin D deficiency and low bone
mineral density in native Chinese rheumatoid arthritis patients. Int J Rheum
None. Dis 2014;17:66–70.
[23] Ben Abdelghani K, Slouma M, Souabni L, Kassab S, Chekili S, Laater A, et al. Risk
Funding factors associated with osteoporosis among Tunisian women suffering from
rheumatoid arthritis. Rev Med Internet 2013;34:A83.
[24] Macovei L, Ancuta C, Belibou C, Chirieac R. Bone mineral density in patients
This research did not receive any specific grant from funding with rheumatoid arthritis. Rev Med Chir Soc Med Nat Iasi 2011;115:723–30.
agencies in the public, commercial, or not-for-profit sectors. [25] Senstone BD, Mahmoud A, Woodward R, Elvins D, Palmer R, Ring F, et al. Bone
mineral density in nonsteroid treated early rheumatoid arthritis. Ann Rheum
Dis 1994;53:681–4.
References [26] Keller C, Hafstrӧm I. Svensson B; BARFOT study group. Bone mineral density in
women and men with early rheumatoid arthritis. Scan. J Rheumatol
[1] Lodder MC, de Jong Z, Kostense PJ, Molenaar ET, Staal K, Voskuyl AE, et al. Bone 2001;30:213–20.
mineral density in patients with rheumatoid arthritis: relation between [27] Heidar B, Jalali F. Bone densitometry in patients with rheumatoid arthritis.
disease severity and low bone mineral density. Ann Rheum Dis Acta Med Iran 2005;43:99–104.
2004;63:1576–80. [28] Kroger H, Hobkanen R, Saarikoski S, Alhava E. Decreased axial bone mineral
[2] Hafez EA, ElBakry SA, Ibrahim SI, Morad CS, Abd El-Khalik DM. Assessment of density in perimenopausal women with rheumatoid arthritis: a population
fracture risk in a cohort of Egyptian female Systemic Lupus erythematosus based study. Ann Rheum Dis 1994;53:18–23.
patients. Egypt Rheumatol 2017. epub ahead of print. [29] Sarkis KS, Salvador MB, Pinheiro MM, Silva RG, Zerbini CA, Martini LA.
[3] Shahin AA, Zayed HS, Sayed S, Gomaa W. Bone mineral density in patients with Association between osteoporosis and rheumatoid arthritis in women: a cross-
systemic sclerosis and its association with hand involvement. Egypt sectional study. Sao Paulo Med J 2009;127:216–22.
Rheumatol 2013;35(4):233–8. [30] Haugeberg G, Helgetveit KB, Forre O, Garen T, Sommerseth H, Proven A.
[4] Sayed S, Darweesh H, Fathy K, Mourad A. Clinical significance of bone mineral Generalized bone loss in early rheumatoid arthritis patients followed for ten
density in Ankylosing Spondylitis patients: relation to disease activity and years in the biologic treatment era. BMC Musculoskelet Disord 2014;15:289.
physical function. Egypt Rheumatol 2015;37(1):35–9. [31] Tourinho TF, Stein A, Castro JA, Brenol JC. Rheumatoid arthritis: evidence for
[5] Elwakil WA, Mohasseb D, Elkaffash D, Elshereef S, Elshafey M. Serum leptin bone loss in premenopausal women. J Rheumatol 2005;32:1020–5.
and osteoporosis in postmenopausal women with primary knee osteoarthritis. [32] Hauser D, Riches P, Ralston S. Predictors of osteoporosis in rheumatoid
Egypt Rheumatol 2016;38(3):209–15. arthritis: retrospective cohort study. Bone 2012;50:S135.

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The Egyptian Rheumatologist (2018), https://doi.org/10.1016/j.ejr.2018.01.004
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[33] Murariu RV, Macovei LA, Brujbu IC. Osteoporosis in rheumatoid arthritis. Rev [40] Terpos E, Fragiadaki K, Konsta M, Bratengeier C, Papatheodorou A, Sfikakis PP.
Med Chir Soc Med Nat Iasi 2013;117:394–403. Early effects of IL-6 receptor inhibition on bone homeostasis: a pilot study in
[34] Sivas F, Barça N, Onder M, Ozoran K. The relation between joint erosion and women with rheumatoid arthritis. Clin Exp Rheumatol 2011;29:921–5.
generalized osteoporosis and disease activity in patients with rheumatoid [41] Cheng CK, McDonald-Blumer H, Boire G, Pope JE, Haraoui B, Hitchon CA, et al.
arthritis. Reumatol Int 2006;26:896–9. Care gap in patients with early inflammatory arthritis with a high fracture risk
[35] Coulson KA, Reed G, Gilliam BE, Kremer JM, Pepmueller PH. Factors influencing identified using FRAX. J Rheumatol 2010;37:2221–5.
fracture risk, T score, and management of osteoporosis in patients with [42] Filho JC, Pinheiro MM, De Moura Castro CH, Szejnfeld VL. Prevalence and risk
rheumatoid arthritis in the consortium of rheumatology researchers of North factors associated with low-impact fractures in men with rheumatoid
America (CORRONA) registry. J Clin Rheumatol 2009;15:155–60. arthritis. Clin Rheumatol 2014;33:1389–95.
[36] Güler-Yüksel M, Bijsterbosch J, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, [43] Furuya T, Kotake S, Inoue E, Nanke Y, Yago T, Hara M, et al. Risk factors
Hulsmans HM, de Beus WM, et al. Changes in hand and generalised bone associated with incident fractures in Japanese men with rheumatoid arthritis:
mineral density in patients with recent-onset, active rheumatoid arthritis. Ann a prospective observational cohort study. J Bone Miner Metab
Rheum Dis 2008;67:823–8. 2008;26:4999–5505.
[37] Shankar S, Handa R, Aneja R, Marwaha V, Ammini AC, Aprajita V. Bone mineral [44] El Maghraoui A, Rezqi A, Mounach A, Achemlal L, Bezza A, Ghozlani I.
density in Indian women with rheumatoid arthritis. Rheumatol Int Prevalence and risk factors of vertebral fractures in women with rheumatoid
2009;29:377–81. arthritis using vertebral fracture assessment. Rheumatology (Oxford)
[38] Kim SY, Schneeweiss S, Liu J, Daniel GW, Chang CL, Garneau K, et al. Risk of 2010;49:1303–10.
osteoporotic fracture in a large population-based cohort of patients with [45] Majumdar SR, Morin SN, Lix LM, Leslie WD. Influence of recency and duration
rheumatoid arthritis. Arthritis Res Ther 2010;12:R154. of glucocorticoid use on bone mineral density and risk of fractures:
[39] Van Staa TP, Geusens P, Bijlsma JW, Leufkens HG, Cooper C. Clinical population-based cohort study. Osteoporos Int 2013;24:2493–8.
assessment of the long-term risk of fracture in patients with rheumatoid
arthritis. Arthritis Rheum 2006;54:3104–12.

Please cite this article in press as: Wafa H et al. Risk factors associated with bone loss and occurrence of fragility fractures in rheumatoid arthritis patients.
The Egyptian Rheumatologist (2018), https://doi.org/10.1016/j.ejr.2018.01.004

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