Rheumatoid Factor Positivity is Associated with Lower Bone Mass in Korean Male Health Examinees without Clinically Apparent Arthritis

Jiwon Hwang; Joong Kyong Ahn; Jaejoon Lee; Eun-Mi Koh; Hoon-Suk Cha

doi:10.4078/jrd.2019.26.1.31

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Hwang, Ahn, Lee, Koh, and Cha: Rheumatoid Factor Positivity is Associated with Lower Bone Mass in Korean Male Health Examinees without Clinically Apparent Arthritis

Original Article

J Rheum Dis 2019;26(1):31-40.

Published online: 31 January 2019

DOI: https://doi.org/10.4078/jrd.2019.26.1.31

Rheumatoid Factor Positivity is Associated with Lower Bone Mass in Korean Male Health Examinees without Clinically Apparent Arthritis

Jiwon Hwang¹, Joong Kyong Ahn^2,^*, Jaejoon Lee³, Eun-Mi Koh³, Hoon-Suk Cha^3,^*

¹Department of Internal Medicine, National Police Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

²Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

³Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding to: Hoon-Suk Cha http://orcid.org/0000-0001-5391-5376 Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea. E-mail: hoonsuk.cha@samsung.com Joong Kyong Ahn http://orcid.org/0000-0003-3246-4435 Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwang University of School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea. E-mail: mdahnjk@skku.edu *These authors contributed equally to this work.

^* These authors contributed equally to this work.

Received 31 May 201824 August 2018 Accepted 18 September 2018

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

This cross-sectional study aimed to investigate the association between rheumatoid factor (RF) positivity and bone mineral density (BMD) in male Korean subjects without any history of joint disease.

Methods

Of 84,344 males who had under-gone a comprehensive health checkup program in 2012, 1,390 male health examinees were recruited, whose BMD and RF results were available. A RF titer ≥20 IU/mL was considered positive. BMD was measured at lumbar spine (L1∼ L4) or hip (femoral neck and total hip) by dual-energy X-ray absorptiometry.

Results

The association between RF positivity and BMD was assessed by multiple linear regression analysis. The mean age was 52.7±10.9 years (range 19∼88 years), and RF was detected in 64 subjects (4.6%). Demographics and laboratory data were not different between RF-positive and -negative subjects except hepatitis B surface antigen (HBsAg), which was more frequently seen in RF-positive subjects (15.6% vs. 4.3%, p=0.001). RF-positive subjects had significantly lower BMD compared to RF-negative subjects in lumbar spine but not in total hip regardless of the existence of HBsAg (1.17±0.16 g/cm² vs. 1.10±0.18 g/cm², p=0.002 in total subjects; 1.17±0.16 g/cm² vs. 1.10±0.18 g/cm², p=0.004 in HBsAg-negative subjects). After adjusting for multiple confounders, RF positivity was negatively associated with lumbar spine BMD (B=−0.088 and standard error=0.035, p=0.011).

Conclusion

Our results show that the presence of RF could have an unfavorable impact on bone density in apparently normal males. Additional studies to elucidate the osteoimmunological mechanism of rheumatoid factor are warranted.

Keywords: Rheumatoid factor, Bone density, Male, Men's health

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Figure 1.

Selection of subjects. BMD: bone mineral density, RF: rheumatoid factor.

Figure 2.

Mean BMD and the proportion of low bone mass in lumbar spine along RF titers. (A) and (C) drawn for total subjects, and (B) and (D) for HBsAg-negative subjects. (A, B) RF titers were grouped into four categories, and each rhombus dot represents the mean estimated value (±95% CI) of lumbar BMD in the corresponding RF titer group. The imaginary connecting line between the dots demonstrates the decreasing tendency of BMD as the RF titers increase on one-way ANOVA testing (p=0.015 in A) and p=0.027 in B, respectively). (C, D) Each column represents the percentage of subjects with osteopenia (dark gray) and osteoporosis (light gray). Across the four groups, low bone mass frequency increases as RF titers increase (p for trend ＜0.001, both). BMD: bone mineral density, RF: rheumatoid factor, HBsAg: hepatitis B surface antigen, CI: confidence intervals.

Table 1.

General characteristics by RF positivity in men (n=1,390)

	RF(−)(n=1,326)	RF(+)(n=64)	p-value
Age (yr)	52.7±10.9	55.0±10.7	0.093
Body mass index (kg/m²)	24.3±2.9	24.1±2.7	0.654
Obesity (≥30.0 kg/m²)	43 (3.2)	3 (4.7)	0.639
Current smoker (n=1,093)	394 (37.6)	20 (43.5)	0.665
Pack-years of smoking (n=1,063)	16.5±16.7	17.6±15.1	0.421
Alcohol intake (g/wk) (n=1,235)	30.2±43.9	27.8±41.2	0.777
Vigorous exercise (times/wk) (n=1,275)	1.27±1.9	0.88±1.6	0.092
Hypertension	316 (23.8)	9 (14.1)	0.098
Coronary artery disease	42 (3.2)	4 (6.2)	0.158
Fasting glucose (mg/dL)	98.6±14.7	97.3±14.0	0.487
Total cholesterol (mg/dL)	200.8±35.3	198.3±37.6	0.580
High density lipoprotein cholesterol (mg/dL)	52.9±13.9	53.8±14.4	0.579
Calcium (mg/dL)	9.4±0.3	9.4±0.4	0.787
Phosphorus (mg/dL)	3.4±0.4	3.4±0.5	0.455
Total vitamin D (mg/dL)	19.3±7.9	21.1±9.3	0.202
Uric acid (mg/dL)	5.9±1.2	6.0±1.3	0.633
HBsAg(+)	57 (4.3)	10 (15.6)	0.001
HCV Ab(+) (n=1,389)	6 (0.5)	0	1.000
eGFR (mL/min/1.73 m²)	87.5±20.0	84.3±15.5	0.118
CRP (mg/dL)	0.06 (0.02∼0.12)	0.08 (0.02∼ 0.19)	0.229
RF titer (IU/mL)	8.00 (4.95∼9.70)	34.2 (26.3∼77.2)	＜0.001

Values are presented as mean±standard deviation, number of subjects with percentages or median (interquartile range). RF: rheumatoid factor, HBsAg: hepatitis B virus surface antigen, HCV Ab: antibody against hepatitis C virus, eGFR: estimated glomerular filtration rate, CRP: C-reactive protein. p-values were determined by Chi-square test for categorical variables, and Student's t-test or Mann-Whitney U-test which was for skewed continuous variables.

Table 2.

Bone mineral density values in total subjects

Variable	Lumbar spine			Variable	Total hip
Variable	RF(−)(n=1,140)	RF(+)(n=54)	p-value	Variable	RF(−)(n=249)	RF(+)(n=12)	p-value
BMD (g/cm²)	1.17±0.16	1.10±0.18	0.002	BMD (g/cm²)	0.97±0.15	0.94±0.23	0.537
(n=1,194)*				(n=261)*
T-score (n=1,194)*	−0.05±1.33	−0.64±1.52	0.009	T-score (n=261)*	0.17±1.19	−0.07±1.76	0.116
Category based on			＜0.001	Category based on			0.683
spine T-score				total hip T-score
(n=1,386)*				(n=307)*
Normal	1,043 (78.9)	47 (73.4)		Normal	246 (83.4)	9 (75.0)
Osteopenia	241 (18.2)	9 (14.1)		Osteopenia	47 (15.9)	3 (25.0)
Osteoporosis	38 (2.9)	8 (12.5)		Osteoporosis	2 (0.7)	0

Values are presented as mean±standard deviation or number of subjects with percentages. RF: rheumatoid factor, HBsAg: hepatitis B surface antigen, BMD: bone mineral density.

^* The discrepancy of the numbers was due to the missing values between the L1∼ L4 BMD results and the category, and the category was determined by the lowest T-score. p-values were determined by Chi-square test for categorical variables, and Student's t-test or Mann-Whitney U-test for skewed continuous variables.

Table 3.

Bone mineral density values in subjects without HBsAg*

Variable	Lumbar spine			Variable	Total hip
Variable	RF(−)(n=1,090)	RF(+)(n=54)	p-value	Variable	RF(−)(n=240)	RF(+)(n=10)	p-value
BMD (g/cm²)	1.17±0.16	1.10±0.18	0.004	BMD (g/cm²)	0.97±0.15	0.96±0.24	0.922
(n=1,135)^†				(n=250)^†
T-score (n=1,135)^†	−0.06±1.32	−0.64±1.47	0.004	T-score (n=250)^†	0.17±1.19	−0.15±1.85	0.951
Category based on			0.026	Category based on			0.769
spine T-score				total hip T-score
(n=1,319)^†				(n=262)^†
Normal	1,002 (79.2)	39 (72.2)		Normal	215 (85.0)	7 (77.8)
Osteopenia	227 (17.9)	9 (16.7)		Osteopenia	36 (14.2)	2 (22.2)
Osteoporosis	36 (2.8)	6 (11.1)		Osteoporosis	2 (0.8)	0

Values are presented asmean±standard deviation or number of subjects with percentages. RF: rheumatoid factor, HBsAg: hepatitis B surface antigen, BMD: bone mineral density. p-values were determined by Chi-square test for categorical variables, and Student's t-test or Mann-Whitney U-test for skewed continuous variables.

^* This analysis was performed on HBsAg-negative subjects.

^† The discrepancy of the numbers was due to the missing values between the L1∼ L4 BMD results and the category, and the category was determined by the lowest T-score.

Table 4.

Multiple linear regression analysis of the association between the RF positivity and lumbar spine BMD*

BMD (g/cm²)	B	SE	p-value	R²
Model 1	−0.065	0.023	0.005	0.101
Model 2	−0.069	0.028	0.014	0.084
Model 3	−0.088	0.035	0.011	0.147

Model 1: adjusted for age, body mass index. Model 2: as for Model 1 plus: alcohol intake (g/week), smoking (pack-years), history of hypertension, and history of coronary artery disease. Model 3: as for Model 2 plus: fasting glucose, alanine aminotransferase, estimated glomerular filtration rate, uric acid, triglyceride, high density lipoprotein, homocysteine, ferritin, total vitamin D, and serum concentration of calcium and phosphorus. RF: rheumatoid factor, BMD: bone mineral density, B: unstandardized coefficient means the degree of change in lumbar spine BMD values (g/cm²) along the presence of RF, SE: standard error, R2: coefficient of multiple determination.

^* This analysis was performed on HBsAg-negative subjects.

Supplementary Table 1.

Correlation between variables of model 2 in multiple regression analysis for the association of RF positivity with the lumbar spine BMD

Variable	L1∼L4 BMD	Age	BMI	Alcohol intake (g/wk)	Smoking (pack-years)	History of hypertension	History of coronary artery disease	HBsAg	RF
L1∼L4 BMD Age	1.000 −0.023 (0.253)	1.000
BMI	0.265 (＜0.001)	−0.058 (0.044)	1.000
Alcohol intake (g/wk)	0.063 (0.031)	−0.097 (0.002)	0.071 (0.019)	1.000
Smoking (pack-years)	0.017 (0.313)	0.279 (＜0.001)	0.066 (0.027)	0.096 (0.002)	1.000
History of hypertension	0.037 (0.142)	0.319 (＜0.001)	0.186 (＜.001)	0.044 (0.100)	0.086 (0.006)	1.000
History of coronary artery disease	−0.002 (0.480)	0.134 (＜0.001)	0.011 (0.375)	0.009 (0.396)	0.065 (0.029)	0.131(＜0.001)	1.000
HBsAg	0.026 (0.223)	−0.027 (0.212)	0.019 (0.293)	−0.035 (0.152) −	−0.053 (0.061) −	−0.044 (0.099)	0.034 (0.162)	1.000
RF	−0.078 (0.011)	0.037 (0.139)	−0.033 (0.165)	−0.001 (0.491)	0.020 (0.280) −	−0.025 (0.236)	0.037 (0.142)	0.101 (0.001)	1.000

Values represent correlation coefficient (p-value). RF: rheumatoid factor, BMD: bone mineral density, BMI: body mass index, HBsAg: hepatitis B virus surface antigen.

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