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Oh, Park, Seo, and Park: Meta-analysis on the Risk Factors for Fracture in Patients with Rheumatoid Arthritis
Original Article

J Korean Rheum Assoc 2010;17(1):23-35.

Published online: 23 March 2010

DOI: https://doi.org/10.4078/jkra.2010.17.1.23

Meta-analysis on the Risk Factors for Fracture in Patients with Rheumatoid Arthritis

Hyun Soo Oh1, Won Park2, Wha Sook Seo1, Jong Suk Park3

Department of Nursing, Inha University

Division of Rheumatology, School of Medicine, Inha University, Inha University Hospital

Graduate Student, Department of Nursing, Inha University, Inha University Hospital, Surgical Intensive Care Unit

Received 25 November 200929 January 2010       Accepted 4 February 2010

Copyright © 2010 The Korean Rheumatism Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

This study was conducted by using a meta-analysis to calculate the mean effect sizes of the risk factors for fracture of patients with rheumatoid arthritis (RA) and to perform tests for the significance of the calculated mean effect sizes.

Methods

Eleven studies that directly examined the relationships between fracture and risk factors were selected from 179 related studies identified from PubMed, MEDLINE, COCHRAN and CINHAL with the key words being ‘rheumatoid arthritis’, ‘fracture’ and ‘risk factors’.

Results

The mean effect size of age on fracture was significant. The mean effect sizes of steroid use and the duration of RA on fracture were also significant. However, all of these effect sizes (age, the use of steroid and the duration of disease) were small (bar D=0.15, 0.16 and 0.12, respectively). The mean effect size of the BMD at the lumbar spine was significant and the effect of the BMD at the L-spine was of medium size (bar D=0.47). The mean effect sizes of the other risk factors such as disability, disease activity, the BMD at the femur neck, BMI and a smoking habit were not significant.

Conclusion

From the study results, it was noted that the efforts to prevent fracture of RA patients should focus on patients with an older age, the patients who used steroid, the patients with a longer duration of RA and the patients who present with low BMD at the lumbar spine.

Keywords: Rheumatoid arthritis, Fracture, Risk factor

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Fig. 1.
Effect size of individual study for risk factors on fracture of rheumatoid arthritis patients. (A) Effect size of age on fracture, (B) Effect size of steroid on fracture, (C) Effect size of disability on fracture, (D) Effect size of duration on fracture, (E) Effect size of disease activity on fracture, (F) Effect size of L-spine BMD on fracture, (G) Effect of Femur BMD on fracture, (H) Effect of BMI on fracture, (I) Effect of smoking on fracture.
jkra-17-23f1a.tifjkra-17-23f1b.tif
Table 1.
The sample size, sample characteristics, fracture site, BMD site, and results, and the quality score of the reviewed studies
Author 1. Sample size
2. Subjects' characteristics
3. Study design∗		 1. Fracture site
2. BMD sites		 1. % of fracture patients
2. Risk factors and statistics† 		Quality score
1. Spector, et al. (1) 1. 191
2. Menopaused RA women		 1. Spine fx
2. Femur neck, L1-4 		1. 12.1%
2. 1) Age: p=0.02, 2) Duration of disease: p=0.37, 3) ESR: t=-0,10, 4) HAQ: t=0.04, 5) Disability: p=0.14, 6) Duration of disease: t=0.99, 7) Menopaused age: p=0.60, 8) BMI: p=0.41, 9) Use of steroid: Z=–0.58, 10) BMD: L (t=–0.6), femur (t=–1.75), 11) Smoking: p=0.04		 4
2. Peel, et al. (27) 1. 76
2. Menopaused RA women (duration: 90%, 15 years; steroid: 85%, > 10 years)		 1. Vertebral fx
2. Lumbar, femur		 1. 27.6% (vertebral deformity)
2. 1) L: t=–0.75, 2) Femur: t=–0.5		 4
3. de Nijs, et al. (8) 1. 500
2. RA patients		 1. Spine
2. –		 1. 19.0%
2. 1) Use of steroid: Z=3.0 (vetebral fracture)		 4
4. Perez-Edo, et al. (9) 1. 66
2. RA patients		 1. Spine fx
2. Radius, Lumbar		 1. 30%
2. Age: p=0.04		 2
5. Arai, et al. (7) 1. 117
2. Menopaused RA women (Japan)		 1. Vertebral fx
2. Lumbar (L2-L4)		 1. 21%
2. 1) Use of steroid: Z=2.75, 2) BMD: Z=3.91, 3) Age: Z=3.5		 3
6. Kay, et al. (4) 1. 36
2. RA patients		 1. Stress fx
2. Femur, lumbar		 1. 0.8%
2. 1) Age: p=0.41, 2) Duration of disease: p=0.37, 3) RF: p=0.18, 4) Disability: p=0.14, 5) Arthroplasty: p=0.73, 6) Menopaused age: p=0.60, 7) BMI: p=0.41, 8) Use of steroid: p=0.32, 9) BMD: Lumbar (p=0.77), femur (p=0.59), 10) Smoking: p=0.81		 2
7. Michel, et al. (24) 1. 395
2. RA patients (mean age: 49 years, duration: 9.3 years)		 1. Fracture all over the body
2. –		 1. 13.2%
2. 1) Steroid: p=0.026, 2) Duration: p=0.083		 4
8. Furuya, et al. (6) 1. 1,635
2. RA women above 50 years old		 1. Fracture all over the body (spine, wrist, hip, pelvis, ribs)
2. –		 1. 17.6%
2. Selected only vertebral fracture 1) Age: t=–1.08, 2) BMI: t=0.11, 3) Smoking: Z=0.33, 4) Alcohol: Z=–0.83, 5) Duration of disease: t=–0.80, 6) RF: t=–0.53, 7) ESR: t=–0.64, 8) Pain: t=–0.74, 9) HAQ-J: t=–1.52, 10) Prior fx: Z=1.25, 11) Orthopedic surgery: Z=0.44, 12) Use of steroid: Z=2.44		 4
9. Michel, et al. (22) 1. 1,110
2. RA patients (mean age: 54, mean duration of disease: 8.4 years)		 1. Fracture all over the body
2. –		 1. 20.4%
2. 1) Duration of steroid use: Z=6.0, 2) Grip power: Z=3.67, 3) Disability: Z=5.0, 4) Duration: Z=3.75, 5) BMI: Z=4.58, 6) Age: Z=4.4		 4
10. Nampei, et al. (28) 1. 209
2. RA outpatients		 1. Vertebral+non vertebral+insufficiency fx
2. –		 1. 11.5%
2. Only vertebra fx (multivariate analysis)
1) Steroid: p=0.032		 3
11. Coulson, et al. (29) 1. 8,419
2. RA female patients		 1. Spine, hip, nonspine (wrist, ribs, pelvis, other)
2. L-spine, femur		 1. 431/8,419(5.1%) subjects with fracture (spine: 99, hip: 77, others: 326)
2. Spine fracture
1) Postmenopausal: p=0.15, 2) BMI: p=0.38, 3) Marial status: p=0.86, 4) HAQ: p=0.77, 5) Steroid: 0.52, 6) TNF: p=0.08, 7) TNF+MTX: p=0.51, 8) DMARDS: p=0.35, 9) MTX-DMARDS: p=0.62		 3

∗A11 of the studies included in this meta-analysis adopted a non-experimental correlational research design, †If Z or t ≥ 1.96, p≤0.05; if Z or t≥2.54, p≤0.01

Table 2.
The results of the meta-analyses for the fracture risk factors of rheumatoid arthritis patients
Domain Parameters n $DM∗(95% CI) Sig.† U (p) $RM‡ Homogeneity§ Q (p) nfs||
Age 6 0.15 (0.08 ~ 0.22) 17.68 (<0.001) 0.08 4.53 (0.211) 2.18
Medication Use of steroid treatment 7 0.16 (0.08 ~ 0.24)∗∗ 16.24 (<0.001) 0.08 10.83 (0.060) 1.23
Disability Health assessment Questionnaire-disability index 6 0.03 (–0.007 ~ 0.007) 2.65 (0.100) 0.02 5.54 (0.242) 4.21
Duration of disease 5 0.12 (0.05 ~ 0.18) 11.76 (0.011) 0.06 6.06 (0.200) 2.08
Disease activity ESR (mm/hr), Rheumatoid factor (U/ml) 4 0.03 (–0.03 ~ 0.10) 0.83 (0.362) 0.02 0.67 (0.881) 3.39
Bone mineral Lumbar spine BMD (%) 4 0.47 (0.21 ~ 0.74)†† 12.60 (<0.001) 0.23 4.57 (0.102) 4.17
Density Femur BMD (%) 3 0.20 (–0.03 ~ 0.42) 2.92 (0.092) 0.10 0.42 (0.813) 1.00
Body weight Body mass index (kg/m2) 4 0.01 (–0.03 ~ 0.05) 0.11 (0.741) 0.003 0.04 (0.982) 2.90
Health habit Smoking status (smoker vs non smoker) 3 0.04 (–0.05 ~ 0.13) 0.94 (0.333) 0.02 2.96 (0.231) 2.34

∗Mean effect size the analysis was done by using the mata-analysis SAS program developed by Song HH (14) >, †Significant test for $DM, ‡Mean effect size r, §Similarity test among studies, ||Fail safe numbers (the magnitude of the publication bias), 5 results were included in calculating the mean effect size (1 was excluded because of violation for homogeneity), ∗∗6 results were included in calculating the mean effect size (one study was excluded because of violation for homogeneity), ††3 results were included in calculating the mean effect size (one study was excluded because of violation for homogeneity)

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