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INTRODUCTION
Spondyloarthritis (SpA) is a systemic rheumatic disease group that causes inflammation in the skin, eyes and gastrointestinal system as extra-articular involvement, as well as with sacroiliitis, spondylitis, oligoarthritis and enthesitis [1,2]. SpA may be predominantly axial SpA (ax-SpA) or predominantly peripheral phenotype. Ax-SpA is classified as radiographic axSpA (r-axSpA) or ankylosing spondylitis (AS) with at least bilateral grade 2 sacroiliitis or unilateral grade 3 sacroiliitis according to radiographic involvement, and non-r-axSpA (nr-axSpA), which may have radiographic changes in sacroiliac (SI) joints but do not fulfill the modified New York criteria for AS [3].
As a frequent congenital anomaly of the lumbosacral spine, lumbosacral transitional vertebra (LSTV) involves either the complete or partial joining of the lowest lumbar vertebra’s transverse process to the sacrum, known as sacralization (or partial sacralization) of L5. Also, LSTV can manifest as the first sacral vertebra being distinct from the sacrum, termed lumbarized S1 [4].
LSTV can be a cause of low back pain in young people by disrupting the spine biomechanics [5]. Its prevalence in the normal population varies widely, from 3.9% to 35.6% [6]. Maintaining motion in the lower lumbar segments improves patient comfort and function during activities of daily living, but increased proximal segment load during sitting after lower lumbar fusion in the presence of LSTV may cause discomfort and segmental degeneration in some patients [7].
The frequency of LSTV was tried to be determined in two studies conducted on a patient population with inflammatory low back pain and suspected ax-SpA. The prevalence of LSTV and the distribution of LSTV types were found to be similar to those reported in the general population [8]. While one study found that a correlation between a LSTV and bone marrow edema adjacent to the SI joints was unlikely, meaning that a LSTV did not alter the magnetic resonance imaging (MRI) manifestation of ax-SpA [9], in the other, the relationship between LSTV and sacroiliitis may be related to changes in mechanical loads caused by pseudo-articulation and/or fusion between the transverse process and sacrum [8]. This situation created difficulties in the diagnosis of ax-SpA and it was stated that further studies in healthy individuals are needed to determine whether the association reflects an accidental or pathophysiological mechanism [8].
While the presence of LSTV and its effect on the diagnosis of ax-SpA were studied in patients with suspected ax-SpA, no study was found that evaluating the frequency of LSTV in patients with ax-SpA, and the relationship between the presence of LSTV and disease burden. In this study, we aimed to evaluate the frequency of LSTV in patients with ax-SpA and to explore the relationship of the presence of LSTV with disease activity, quality of life, functionality and spinal mobility.
MATERIALS AND METHODS
Patients
This prospective study included 177 adult patients (18~65 years) who met the ASAS (Assessment of Spondyloarthritis International Society) criteria for ax-SpA, who consecutively applied to the Selçuk University Medical Faculty outpatient clinic and volunteered to participate in the study [10]. Selçuk University Faculty of Medicine Dean’s Office, Local Ethics Committee approval was obtained for this study (approval no. E.203850), all patients were informed about the study protocol and their written consent was obtained.
A questionnaire including age, sex, height, weight, educational status (primary school, high school or university), occupation, smoking status (non-smoker, ex-smoker, current smoker) and alcohol use, low back pain characteristics, presence of SpA features, comorbidities, history of surgery, systemic and anti-rheumatic drug use was filled in patients diagnosed with ax-SpA. The C-reactive protein (CRP) and erythrocyte sedimentation rate values and HLA-B27 status of the patients were recorded in the evaluation form. ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with CRP) [11] and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) [12,13] scores were used to evaluate the disease activities of the patients. The health assessment questionnaire (HAQ) [14] to assess disability and the EQ-5D-3L scale [15] to assess quality of life were also administered to the patients. BASFI (Bath Ankylosing Spondylitis Functional Index) was used to evaluate functional aspects [16]. Clinical measurements in BASMI (Bath Ankylosing Spondylitis Metrology Index) were also performed to determine spinal mobility [17]. Studies have also emphasized that the Türkish version of the BASDAI [13], BASFI [18] and HAQ [19] scales has good reliability and validity features and is a practical and useful scale for SpA patients in the Türkish society.
Radiographic evaluation
The radiographs of the patients were evaluated by a rheumatologist and a physiatrist with at least 10 years of experience in musculoskeletal diseases, blinded to the clinical information of the patients. The presence of definite sacroiliitis (bilateral grade ≥2 or unilateral grade ≥3 according to modified New York criteria) was decided by consensus on pelvic X-rays. Patients without definite sacroiliitis on pelvic X-ray were defined as nr-axSpA, and patients with definite sacroiliitis on pelvic X-ray were defined as r-axSpA or AS (r-axSpA/AS). To evaluate LSTV, we analyzed front-view X-rays of the pelvis and lower spine, looking at both sides of the lumbar and sacral vertebrae for enlarged transverse processes, pseudoarticulation between these processes and the sacrum, and their fusion. The findings were then classified using the Castellvi system [6], and its frequency was determined. Patients with LSTV were named group 1 and patients without LSTV were named group 2. Subtypes were determined in patients with LSTV.
Statistical analysis
The number of patients to be included in the study was determined to determine the frequency of LSTV in patients with ax-SpA. For an estimated prevalence of 8% and a maximum ±4% difference with this estimated prevalence (precision) [5,6,20], it was determined that at least 177 patients should be included in the study with a confidence interval of 95%. In the calculation of the sample size, the Epitools website (https://epitools.ausvet.com.au/samplesize) was used.
Data entry and statistical analysis PASW Statistics for Windows version 18.0 (IBM Co., Armonk, NY, USA) was made using the package program. The suitability of the data for normal distribution was examined using visual (histogram and probability graphs) and analytical methods (Kolmogrorov–Smirnov/Shapiro–Wilk tests). In the evaluation of numerical data, arithmetic mean, standard deviation, median [interquartile range, per 25~75]; frequency distributions and percentiles were used in summarizing the categorical data. Chi-square (χ2) test and Fischer’s exact test were used to compare categorical data. The comparison of categorical data with non-normally distributed numerical data was evaluated with the Mann–Whitney U-test. The type I error level was accepted as 5% for statistical significance.
RESULTS
A total of 177 patients with ax-SpA were enrolled in this study. Within this cohort, 55.9% (n=99) were classified as having r-axSpA, and 44.1% (n=78) as having nr-axSpA. The demographic and clinical characteristics of the patients with r-axSpA/AS and nr-axSpA are detailed in Table 1. The mean age for the r-axSpA group was 40.01 (±10.86) years, and for the nr-axSpA group, it was 38.18 (±11.76) years (p=0.320). In terms of sex, the ratio of male patients was higher in r-axSpA (n=60, 60.6%) than in nr-axSpA (n=31, 39.7%) (p=0.006).
The frequency of LSTV was 28.8% (n=51) in the entire patient group. LSTV was present in 32.3% (n=32) of patients with r-axSpA and 24.4% (n=19) of patients with nr-axSpA (p>0.05). Of the 51 patients with LSTV, 27.5% (n=14) had type IA, 35.3% (n=18) had type IB, 11.8% (n=6) had type IIA, 2.0% (n=1) had type IIB, 3.9% (n=2) had type IIIA, 11.8% (n=6) had type IIIB, and 7.8% (n=4) had type IV LSTV. Thirty-two (62.7%) patients with LSTV were r-axSpA, and 19 (37.3%) patients with LSTV were nr-axSpA (p=0.245) (Table 2).
The demographic and clinical data of the patients according to the presence of LSTV in patients with ax-SpA are shown in Table 3. The age, sex, educational status, marital status, body mass index, smoking and alcohol use characteristics of patients with or without LSTV were similar (p>0.05). In patients with or without LSTV, chronic low back pain starting under the age of 40, night pain, low back pain that does not improve with rest, low back pain that improves with movement, morning stiffness, insidious onset, inflammatory low back pain presence rates and the age of first complaint onset, median age of diagnosis, HLA-B27 positivity rates were similar (p>0.05). The median duration of illness of patients with LSTV (3.00 years) was statistically significantly higher than the median duration of illness of patients without LSTV (1.00 years) (p=0.035).
Patients with and without LSTV were compared in terms of available treatments. Systemic drug use rates were similar (p=0.812). Likewise, the rate of use of anti-rheumatic drugs and use of biological agents were found to be similar between patients with and without LSTV (p>0.05).
The clinical activity indices of patients with and without LSTV are given in Table 4. In terms of pain severity values, the patient global health score and the doctor global health score evaluations were similar (p>0.05). The median scores of the groups obtained from sedimentation, CRP, ASDAS-CRP values, VAS (visual analogue scale), BASDAI total, BASFI, HAQ, and EQ-5D-3L general quality of life scale were similar (p>0.05).
DISCUSSION
Firstly, the prevalence of LSTV in patients with axSpA was 28.8% and there was no statistically significant difference in terms of presence of LSTV in patients with r-axSpA and nr-axSpA in this study. Secondly, no differences were found between patients with LSTV and patients without LSTV in terms of pain scores, disease activity indices, functionality and spinal mobility in patients with ax-SpA.
According to Tang et al. [21] in a population-based study conducted by, the prevalence of LSTV was determined as 15.8%, 11.6% [22] in a retrospective cohort study, and 35.6% [23] in a prevalence study involving 211 people. The prevalence of LSTV is observed in a wide range and high frequency in society. In our study, the prevalence of LSTV was also high at 28.8%, similar to the general population.
In a study investigating the relationship between LSTV and both radiographic and MRI sacroiliitis in patients with suspected ax-SpA and described inflammatory low back pain, LSTV was detected in 29.1% of patients. Type 1 accounted for the majority of all patients, including 18.8%. There was a 56.5% higher male sex ratio in the group with LSTV [8]. de Bruin et al. [9] examined the prevalence of LSTV, its clinical potential association with ax-SpA manifestations, in a cohort of young patients with suspected ax-SpA. Patients were divided into three groups as non-axSpA, possible ax-SpA and definite ax-SpA according to the condition of meeting the ax-SpA criteria in comparing the presence of LSTV. The prevalence of LSTV was found to be 25% in all patients with suspected ax-SpA and 28.6%, the most common type 1, similar to our study in patients with a definite ax-SpA diagnosis [9].
As far as we know, we investigated the frequency of LSTV for the first time in patients diagnosed with ax-SpA. In our study, the frequency of LSVT was also found to be 28.8%. Type 1 LSVT had a higher prevalence of 18.0% compared to other types, and the male sex was higher in those with LSTV compared to those without LSTV by 62.7% and 46.8%. However, this difference did not reach statistical significance. This ratio was similar to the frequency and type of LSTV with the other two studies mentioned above. When evaluated in terms of biologic drug use, we found no difference between the group with LSTV and the group without LSTV. This suggests that the presence of LSTV does not affect the transition to a biological drug.
According to Carvajal Alegria et al. [8]’s study, morning stiffness, inflammatory low back pain, and buttock pain were questioned in the symptom interrogation. Inflammatory low back pain was found in 89.0% and 87.7% of the groups with and without LSTV, respectively. LSTV was observed in about 30% of 71 patients with inflammatory low back pain. No significant difference was found between BASDAI, BASFI, BASMI, ASDAS-CRP values from disease activity scores in the group with LSVT and without LSTV [8]. de Bruin et al. [9] on the other hand, pain score and modified schober test, lateral spinal flexion measurement from clinical tests were applied to ax-SpA suspicious patients and it was concluded that there is no difference in these parameters in the presence of LSTV.
In our study, inflammatory low back pain was similarly in high prevalence regardless of the presence of LSTV. LSTV was detected in 33 of 128 patients with inflammatory low back pain, and this rate was found to be 25%. In our study, disease activity (BASDAI and ASDAS-CRP) and functionality (BASFI) were similar when patients diagnosed with ax-SpA who had LSTV and not LSTV were compared. Again, when spinal mobility was examined (BASMI, occiput-wall distance and chest expansion measurement), it was shown for the first time in the literature that it was similar. Therefore, the effect of the presence of LSTV on the burden of disease in patients with ax-SpA could not be demonstrated.
The limitations of the study are that; firstly, the cross-sectional design constrains the capability to deduce causality between the presence of LSTV and several clinical parameters evaluated. Secondly, although the sample of 177 axSpA patients is sufficient for identifying certain associations, it could be inadequate for detecting subtler relationships or variations between subgroups. A larger sample would enhance statistical power, leading to more reliable subgroup analyses. Thirdly, the recruitment of our study population from a solitary institution may constrain the generalizability of the outcomes to other populations exhibiting distinct demographic and clinical profiles. Future research involving multiple centers is warranted to validate these findings within a wider scope. Lastly, the lack of a healthy control group in our study design precluded the comparison of LSTV frequency between our study population and healthy individuals from the same geographical area with comparable sociocultural and genetic backgrounds. The interpretation of this study necessitates consideration of the heterogeneous nature of axSpA, as well as the demographic and clinical characteristics of the patient population included in our investigation.
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