Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily affects the axial skeleton. Although it is characterized by new bone formation, which leads to the formation of syndesmophytes and ankylosis of the spine and sacroiliac joints [
It is well-known that, as a secosteroid hormone, vitamin D is crucial in maintaining bone health. Many studies have shown that vitamin D participates in the regulation of the body’s immune system, so it is helpful to obtain adequate vitamin D in the patients with rheumatic diseases. The pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a specific component of type I collagen, only generated from damaged mature bone matrix, and can represent a sensitive indicator of bone resorption in vivo. Till now, lots of researches on ICTP have been done worldwide, but most of them were about its relationship with malignant bone metastases. It was reported that there was a positive correlation between serum ICTP activity and pathological bone resorption [
The aim of this study was to elucidate the alteration of serum ICTP and vitamin D level in patients with AS and to further investigate the relations between ICTP, vitamin D, disease activity (CRP, BASDAI), and BMD in these patients.
From June 2012 to April 2013, 150 AS patients, from both the out-patients and in-patients registered in the Rheumatology Department of the Third Affiliated Hospital, were included in this study. The age ranged from 18 years to 50 years, with a mean disease duration of 8.4 years. All the patients fulfilled the modified New York criteria for AS [
Patients with the concomitant presence of inflammatory bowel disease, chronic renal or hepatic disease, diabetes mellitus, parathyroid or thyroid disease, recent fractures, malnutrition, or drug intake affecting bone metabolism (bisphosphonates, glucocorticoids, anticonvulsants, coumarin derivatives, or diuretics) were excluded, and postmenopausal, pregnant, and breast-feeding women were also excluded in this research. The study was approved by the local ethical committee, and all patients included in our study were provided with written informed consent to participate in this study. All the patients had received conventional treatment which included nonsteroidal anti-inflammatory drugs (NSAIDs) and/or sulfasalazine, but no one received anti-tumor necrosis factor alpha(anti-TNF
Laboratory assessment included complete blood count, C-reactive protein (CRP), liver and kidney function tests, HLA-B27, and serum levels of 25(OH)D and ICTP. The blood specimens of all the patients were taken after an overnight fasting. CRP was measured using the nephelometric method, and ELISA was used to detect serum HLA-B27, 25(OH)D, and ITCP. Vitamin D deficiency was defined as 25(OH)D serum level less than 12 ng/mL (50 nmol/L), vitamin D insufficiency as 25(OH)D at a level of 12–32 ng/mL (50–80 nmol/L), and vitamin D sufficiency at a level higher than 32 ng/mL (80 nmol/L) [
Clinical assessment included collection of demographic data, disease duration, medication history (NSAIDS, sulfasalazine, and calcium and vitamin D supplements), and visual analogue scale (VAS) of patients assessment of pain and disease activity. Disease activity was evaluated by ESR, CRP, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [
Statistical analysis was performed with SPSS 20.0 software. In independent-sample
150 AS patients involved 127 males and 23 females (Male : female = 5.52 : 1) and the mean age of the patients was 29.83 years (SD ±8.94); 168 controls included 128 males and 40 females (male : female = 3.20 : 1), and mean age of the controls was 31.83 years (SD ± 9.97). The differences of age and gender between AS group and healthy control subjects were not significant (
Comparison of indicators between AS and control groups.
Factor | AS | Controls |
|
---|---|---|---|
|
150 | 168 | |
Age (years) | 29.19 ± 8.94 | 31.83 ± 9.97 |
|
Gender (male/female) | 127/23 | 128/40 |
|
25(OH)D (nmol/L) | 57.92 ± 24.42 | 91.24 ± 42.02 |
|
ICTP (ug/L) | 5.72 ± 3.88 | 3.69 ± 1.26 |
|
Note: we compared means using
25-Hydroxyvitamin D (25(OH)D); pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP); ankylosing spondylitis (AS).
The AS patients were divided into different groups according to gender, age, disease duration, HLA, CRP, 25(OH)D, and BASDAI, and the comparisons were as follows (Table
Comparison of biochemical index and BMD in different groups (AS patients were divided into groups according to different clinical factor).
AS group |
|
25(OH)D (nmol/L) | ICTP (ug/L) | Lumbar spine BMD ( |
Hip BMD ( |
---|---|---|---|---|---|
Gender | |||||
Male | 127 | 56.81 ± 22.79 | 6.07 ± 4.05 | −1.64 ± 1.24 | −0.90 ± 0.94 |
Female | 23 | 64.08 ± 31.90 | 3.84 ± 1.96** | −1.51 ± 1.69 | −1.01 ± 0.86 |
Clinical type | |||||
AAS | 134 | 58.90 ± 25.19 | 5.27 ± 3.65 | −1.58 ± 1.35 | −0.88 ± 0.90 |
JAS | 16 | 49.78 ± 14.81 | 9.52 ± 3.79** | −1.96 ± 1.03 | −1.21 ± 1.08 |
Disease duration | |||||
>4 y | 100 | 58.44 ± 27.58 | 5.78 ± 4.05 | −1.54 ± 1.36 | −1.02 ± 0.91 |
≦4 y | 50 | 56.88 ± 16.56 | 5.62 ± 3.55 | −1.79 ± 1.23 | −0.71 ± 0.93 |
HLA-B27 | |||||
Positive | 129 | 56.98 ± 25.25 | 5.95 ± 4.03 | −1.60 ± 1.34 | −0.93 ± 0.93 |
Negative | 21 | 63.72 ± 17.96 | 4.32 ± 2.37 | −1.78 ± 1.36 | −0.82 ± 0.92 |
CRP (mg/L) | |||||
>6 | 109 | 58.00 ± 21.65 | 5.94 ± 3.96 | −1.71 ± 1.40 | −0.99 ± 0.94 |
≦6 | 41 | 57.72 ± 30.92 | 5.16 ± 3.66 | −1.37 ± 1.03 | −0.72 ± 0.88 |
25(OH)D (nmol/L) | |||||
>50 | 91 | 4.75 ± 2.23 | −1.53 ± 1.35 | −0.75 ± 0.86 | |
≦50 | 59 | 7.23 ± 5.21** | −1.77 ± 1.26 | −1.18 ± 0.97** | |
BASDAI | |||||
>4 | 29 | 50.93 ± 17.25 | 6.70 ± 5.47 | −2.21 ± 1.42 | −1.31 ± 0.86 |
≦4 | 121 | 59.60 ± 25.62 | 5.49 ± 3.38 | −1.51 ± 1.27* | −0.82 ± 0.92* |
Note: independent-sample
Values are in means ± SD.
C-reactive protein (CRP), bone mineral density (BMD), Bath AS Disease Activity Index (BASDAI), 25-hydroxyvitamin D (25(OH)D); pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP).
The comparison between the two groups.
By partial correlation analysis, we found some correlations in different clinical biochemical indexes and BMD. Serum levels of 25(OH)D were inversely associated with ICTP (
A multiple regression model was built to assess how biochemical index, disease activity, and clinical assessments could predict the variation of hip BMD in AS patients. ICTP, BASDAI, disease duration, and 25(OH)D contributed independently and significantly to the hip BMD
Multiple linear regression model analysis for hip BMD.
Coefficientsa | |||||
---|---|---|---|---|---|
Model | Unstandardized coefficients | Standardized coefficients |
|
Sig. | |
|
Std.Error | Beta | |||
(Constant) | −0.523 | 0.265 | −1.971 | 0.051 | |
ICTP | −0.053 | 0.018 | −0.220 | −2.852 | 0.005 |
BASDAI | −0.106 | 0.035 | −0.224 | −3.008 | 0.003 |
Disease duration | 0.033 | 0.012 | −0.208 | −2.795 | 0.006 |
25(OH)D | 0.007 | 0.003 | 0.180 | 2.332 | 0.021 |
Multiple linear regression model analysis for 25(OH)D.
Coefficientsb | |||||
---|---|---|---|---|---|
Model | Unstandardized coefficients | Standardized coefficients |
|
Sig. | |
|
Std.Error | Beta | |||
(Constant) | 71.315 | 3.552 | 20.077 | 0.000 | |
ICTP | −1.526 | 0.506 | −0.242 | −3.017 | 0.003 |
Multiple linear regression model analysis for ICTP.
Coefficientsc | |||||
---|---|---|---|---|---|
Model | Unstandardized coefficients | Standardized coefficients |
|
Sig. | |
|
Std.Error | Beta | |||
(Constant) | 8.990 | 0.922 | 9.755 | 0.000 | |
CRP | 0.087 | 0.017 | 0.627 | 5.155 | 0.000 |
25(OH)D | −0.042 | 0.011 | −0.262 | −3.641 | 0.000 |
Vitamin D is a secosteroid hormone which is produced in the skin under adequate exposure to sunlight or obtained from the diet. It is metabolized by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1 alpha-hydroxylase into the vitamin D hormone calcitriol. Due to its stability and relatively long half-life, the serum 25(OH)D level is the best indicator to assess vitamin D situation in the body [
Previous studies have showed the relation between a biochemical marker of type I collagen degradation (urinary CTX-I, reflecting bone resorption) and lower BMD at the hip [
So far, there have been few studies on evaluating the vitamin D and ICTP levels and their relationship to BMD in AS patients. This study showed that patients with AS were more likely to have lower serum 25(OH)D level and higher ICTP level compared to healthy individuals, and there was a common situation of 25(OH)D lacking and bone loss in AS patients. Our study revealed that about 84% AS patients were vitamin D deficient or insufficient in 25(OH)D serum level, which meant less than 32 ng/mL (80 nmol/L), and about 46.7% patients were diagnosed with osteopenia or osteoporosis whose hip BMD
Recent studies have found low level of vitamin D in AS patients is extremely common due to high disease activity [
No significant correlations were found between BMD (lumbar spine or proximal femur bone) and turnover markers (such as serum carboxyterminal cross-linked telopeptide of type I collagen (CTX), osteocalcin (OC)) in a cohort study [
A few studies have found increased bone turnover and disease activity and decreased vitamin D levels were associated with AS-related osteoporosis in AS patients [
The main limitations of our study are the fact that it is a cross-sectional study. No investigation was made to monitor 25(OH)D level at different periods of disease, and there was no data on the radiographic aspect of the spine and its scores. Also, other bone turnover markers such as osteocalcin, procollagen type I N-terminal peptide (PINP), pyridinoline, N-telopeptide, and bone specific alkaline phosphatase (BALP) were not taken into consideration. We could not properly assess the influence of drugs intake, dietary calcium supply, and seasonal differences during the study period.
In conclusion, this study indicates that there is a high incidence of vitamin D inadequacy in AS patients. As an indicator of bone resorption, serum ICTP level was elevated in AS, especially in JAS and male patients. 25(OH)D and ICTP seem to be valuable markers to detect bone loss in AS; the serum levels of vitamin D and ICTP may play an important role in the pathophysiology of AS-related osteoporosis, which needs further research on its pathogenesis.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Pingping Zhang and Qiuxia Li contributed equally.
This work is supported by the 985 Subject of Sun Yat-Sen University (900033283407) and National Natural Science Foundation of China Grant (31070806).