Associations between trabecular bone score and vertebral fractures in patients with axial spondyloarthritis

Associations between trabecular bone score and vertebral fractures in patients with axial... Abstract Objectives To compare trabecular bone scores (TBS) between axial SpA (axSpA) patients with and without vertebral fractures and investigate associations between TBS and vertebral fractures. Methods Two hundred and fifty-five patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. TBS and BMD were assessed using dual-energy X-ray absorptiometry. Vertebral fracture of the thoracic and lumbar spine was defined according to the Genant criteria. Osteoporosis risk factors, inflammatory markers, DAS and spinal structural damage were also assessed. Univariate logistic regression analysis was performed to identify factors associated with vertebral fractures. Results There were 31 vertebral fractures in 28/255 axSpA patients (11%). The mean (s.d.) TBS was 1.39 (0.11) and 1.30 (0.13) in patients without and with vertebral fractures, respectively (P < 0.001). BMD in the femoral neck was lower in patients with vertebral fractures (P = 0.027), but BMDs in the lumbar spine and total hip were not. Univariate logistic regression analyses identified old age (⩾50 years), TNF inhibitor treatment, the presence of syndesmophytes and a low TBS (<1.23) as associated with prevalent vertebral fractures [odds ratio (95% CI): 6.9 (2.0, 24.4), 2.4 (1.0, 5.5), 5.5 (2.2, 13.5) and 5.3 (2.0, 14.1), respectively]. TBS has a better discriminatory value than BMD at the total hip for prediction of vertebral fractures in axSpA patients (P = 0.034). Conclusion Similar to individuals with primary osteoporosis, axSpA patients with vertebral fractures have a lower TBS. This suggests that TBS has the potential to predict future vertebral fractures in patients with axSpA. axial spondyloarthritis, vertebral fracture, trabecular bone score, bone mineral density, bone microarchitecture Rheumatology key messages The trabecular bone score is lower in axial SpA patients with vertebral fractures. The trabecular bone score has the potential to predict future vertebral fractures in axial SpA. Introduction Axial SpA (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton, including the sacroiliac joints. AxSpA includes both the early inflammatory phase of the disease in which there is no structural damage in the sacroiliac joints (non-radiographic disease) and the later stages in which structural damage is visible on X-ray scans of the sacroiliac joints as erosion, sclerosis or bony bridges. This later stage is known as radiographic disease or AS [1]. Chronic inflammation of the spine leads to disease symptoms such as pain and stiffness, and structural damage to the bone tissue [2]. Bony overgrowth leading to ankylosis of axial joints and vertebral spaces is the typical structural damage occurring in axSpA, while osteoporosis also frequently develops in the vertebral bodies. The bone tissue directly exposed to inflammation (osteitis) in axSpA is the trabecular bone of the vertebrae, and consequently, vertebral osteoporosis and resorption of trabecular bone are increased in axSpA [2]. Inflammatory infiltration in the bone marrow of SpA patients can be detected as spondylitis on MRI scans. Indeed, histologic examinations of bone sections from the spines of patients with AS show an accumulation of osteoclasts in the bone marrow and the formation of inflammatory infiltrates [3, 4]. The combination of spinal rigidity (resulting from syndesmophytes or ankyloses) and osteoporosis within the trabecular bone contributes to the development of vertebral fractures [5], which AS patients are known to be at increased risk of [6–8]. These vertebral fractures often do not come to clinical attention, yet their presence is diagnostic of osteoporosis and helps to predict the risk of future fractures [9]. Therefore, to reduce the incidence of future fractures, an accurate and clinically available tool is required for the discrimination of patients with vertebral fractures. To date, it is unclear which imaging approach is most useful for diagnosing and monitoring osteoporosis in axSpA. Most data related to osteoporosis in axSpA are based on BMD measurements using DXA, but this technique has some limitations. BMD in axSpA can be overestimated due to the presence of syndesmophytes or other structural lesions such as an ankylosed posterior arch and periosteal bone formation. Additionally, active or past coxitis can impair the internal rotation of the lower limb, which is mandatory for an accurate hip BMD assessment [10]. Furthermore, BMD only partially takes into account information on bone microarchitecture. Therefore, any additional information on microarchitecture can help to reduce the substantial overlap that exists between those patients with and without a truly increased risk of fracture [11]. The trabecular bone score (TBS) is a novel tool used to evaluate bone microarchitecture. It is a textural index that evaluates pixel grey-level variations in the lumbar spine DXA image, thereby providing an indirect index of trabecular microarchitecture [12]. It is obtained via re-analysis of DXA scans and can be directly compared with BMD because both evaluate the same region of bone. In a previous study using TBS, axSpA patients showed poor bone quality compared with matched controls [13]. However, it is not yet known whether TBS is associated with vertebral fractures in axSpA. The aims of the present study were to compare TBS bone quality assessments between axSpA patients with and without vertebral fractures, and to investigate the associations between TBS and vertebral fractures in axSpA patients. Methods Study population Between August 2013 and February 2017, consecutive axSpA patients from Incheon St Mary’s Hospital (Incheon, Korea) were recruited to this analysis. All enrolled patients fulfilled the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria [14]. All patients were aged between 20 and 67 years. Exclusion criteria included patients with thyroid or parathyroid disorders, the presence of chronic renal or liver disease, use of corticosteroids, cancer or concurrent RA. TBS, BMD and lateral radiographs of the thoracic and lumbar spine were assessed at the time of enrolment. At the time of TBS assessment, demographic data were collected and osteoporosis risk factors were assessed (smoking status and alcohol consumption). All participants provided written consent according to the Declaration of Helsinki, and the study was approved by the ethics committee at Incheon St Mary’s Hospital (study number: OC16OISI0138). Clinical data Disease-related data and DAS were collected. Clinical data included the time after symptom onset, the presence of HLA B27, family history, the use of medications such as anti-inflammatory drugs, SSZ, TNF inhibitors, calcium, bisphosphonate and vitamin D at the time of DXA measurements. Measures of disease activity were collected using the BASDAI [15]. All scores were recorded on a visual analogue scale from 0 to 10. The BASFI [16] and patient global assessment scores were also recorded. The Ankylosing Spondylitis Disease Activity Score was calculated as described previously [17]. ESR and CRP were also measured. BMD assessment BMD of the lumbar spine and left hip was assessed using DXA (Lunar Prodigy densitometer, Madison, WI, USA). All measurements were taken by experienced operators using the same machine and standardized procedures for participant positioning. BMD was measured at the lumbar spine using an anteroposterior projection at L1–L4 and at the left hip from the femoral neck and total proximal femur, and was expressed as the number of grams of bone mineral per square centimetre (g/cm2), calculated as T scores using the manufacturer’s reference. According to the World Health Organization criteria, osteopaenia is defined as a T score between −1 and −2.5, and osteoporosis is defined as a T score −2.5 or less [18]. TBS assessment TBS was analysed using DXA images of the lumbar spine (L1–L4). Lumbar spine DXA images were reanalysed in an operator-independent automated manner using TBS iNight® software version 2.1 (Med-Imaps, Merignac, France). The software uses the posterior-anterior images, including the BMD region of interest and edge detection; thus, the TBS is calculated over exactly the same region as the lumbar BMD assessment. Patients were divided into three TBS groups according to the risk of fracture, as identified in a recent meta-analysis: high risk: TBS <1.23; intermediate risk: TBS 1.23–1.31; low risk: TBS >1.31 [19]. Low TBS was defined as a TBS ⩽1.31. Radiographic scoring For all patients, radiographs of the cervical, thoracic and lumbar spine were obtained at the time of the TBS assessment. Lateral views of the cervical and lumbar spine were scored according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) [20]. The mSASSS was scored by a single trained expert who was blinded to the patient characteristics. The total scores ranged from 0 to 72. The number of syndesmophytes was assessed using the mSASSS. Assessment of vertebral fractures Two independent trained readers (K.Y.K. and I.J.K.) scored lateral radiographs of the thoracic and lumbar spine for vertebral fractures using the standardized semi-quantitative method described by Genant et al. [21], which involves evaluating the fourth thoracic vertebra (T4) to the fourth lumbar vertebra (L4). A vertebral fracture was defined as a ⩾20% reduction in any vertebral height. Vertebral fractures were divided into grades of 0–3: grade 0 (normal), <20% height reduction; grade 1 (mild), 20–25% reduction; grade 2 (moderate), 25–40% reduction; and grade 3 (severe), >40% reduction. If the measurement was complicated because of new bone formation or erosions at the corners of the vertebral bodies, a lengthened imaginary line representing the original edge of the vertebral body was used. There were few discrepancies between the two independent trained readers, but when they did occur, the two investigators reached a consensus. The inter-observer variability was calculated using Cohen’s kappa value (κ = 0.72). Statistical analysis Continuous data are expressed as the mean (s.d.) and categorical data are expressed as percentages. Clinical variables were compared using an independent t-test, and the chi-squared test was used to compare categorical variables between axSpA patients with and without vertebral fractures. Univariate logistic regression analyses were performed to investigate the association between clinical variables, DAS, BMD and TBS and vertebral fractures. The accuracy of TBS and BMD for the discrimination of prevalent vertebral fractures was assessed by determining the area under the receiving operator characteristics (ROC) curves. P ⩽ 0.05 were considered statistically significant. Statistical analysis was performed with IBM SPSS Statistics version 18. Results Data from 255 patients (80% male) were analysed. The mean age was 38 (11) years (range, 20–67), and the mean symptom duration and time after diagnosis of axSpA were 10 (9) and 5 (7) years, respectively. A total of 92 patients (36%) were current smokers and 222 (87%) were HLA-B27 positive. In all, 222 (87%) fulfilled the modified New York criteria for AS [22]. Among the 255 patients, 28 (11%) had morphometric vertebral fractures (a total of 31). Of these fractures, 21 (68%) were defined as mild (grade 1), 9 (29%) as moderate (grade 2) and 1 (3%) as severe (grade 3), as shown in Fig. 1. The most common location of vertebral fractures was T11 (16%). Fig. 1 View largeDownload slide Locations and numbers of vertebral fractures VF: vertebral fractures; T: thoracic vertebra; L: lumbar vertebra. Fig. 1 View largeDownload slide Locations and numbers of vertebral fractures VF: vertebral fractures; T: thoracic vertebra; L: lumbar vertebra. Comparisons between patients with and without vertebral fractures are shown in Table 1. Patients with vertebral fractures were significantly older than patients without them. There were no differences between the two groups in terms of BMI, social habits, symptom duration, history of previous fractures, HLA-B27 positivity and DAS. Patients with vertebral fractures scored higher in the mSASSS and had more syndesmophytes. The use of TNF inhibitors was more common in patients with vertebral fractures than in those without vertebral fractures. The mean TBS was 1.39 (0.11) for patients without vertebral fractures and 1.30 (0.13) for those with vertebral fractures (P < 0.001). BMD data for the lumbar spine and total hip did not differ between the two groups. The mean BMD at the femoral neck was lower in patients with vertebral fractures (P = 0.027). Table 1 Characteristics of the axSpA patients stratified according to vertebral fractures Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Values are given as mean (s.d.) unless otherwise stated. ASDAS: Ankylosing Spondylitis Disease Activity Score; axSpA: axial SpA; mSASSS: modified Stoke Ankylosing Spondylitis Spinal Score; TBS: trabecular bone score. Table 1 Characteristics of the axSpA patients stratified according to vertebral fractures Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Values are given as mean (s.d.) unless otherwise stated. ASDAS: Ankylosing Spondylitis Disease Activity Score; axSpA: axial SpA; mSASSS: modified Stoke Ankylosing Spondylitis Spinal Score; TBS: trabecular bone score. The proportions of patients meeting the TBS high (TBS <1.23) and intermediate fracture risks (1.23–1.3) were 8.8 and 10.1%, respectively, in patients without vertebral fractures and 28.6 and 21.4%, respectively, in those with vertebral fractures (P = 0.001; Fig. 2A). According to the BMD measurements, osteoporosis (T score −2.5 or less) and osteopaenia (T score −2.5 to −1.0) were more frequent in patients with vertebral fractures; however, the difference was not statistically significant (Fig. 2B). Fig. 2 View largeDownload slide TBS and BMD in axSpA patients according to vertebral fractures (A) Frequency of low, intermediate and high fracture risk TBS groups among patients without or with a vertebral fracture. (B) Frequency of osteoporosis, osteopaenia and normal BMD. AxSpA: axial SpA; TBS: trabecular bone score; VF: vertebral fractures. Fig. 2 View largeDownload slide TBS and BMD in axSpA patients according to vertebral fractures (A) Frequency of low, intermediate and high fracture risk TBS groups among patients without or with a vertebral fracture. (B) Frequency of osteoporosis, osteopaenia and normal BMD. AxSpA: axial SpA; TBS: trabecular bone score; VF: vertebral fractures. Table 2 shows the results of univariate logistic regression analyses of factors associated with vertebral fractures. The results show that older age (⩾50 years old), TNF inhibitor treatment, the presence of syndesmophytes and a lower TBS value (<1.23) were associated with vertebral fractures [odds ratio (OR) (95% CI): 6.9 (2.0, 24.4), 2.4 (1.0, 5.5), 5.5 (2.2, 13.5) and 5.3 (2.0, 14.1), respectively]. Male sex showed a moderate association [OR (95% CI): 3.7 (0.8, 16.0)]. Table 2 Univariate analyses of factors associated with vertebral fractures in patients with axSpA Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 AxSpA: axial spondyloarthritis; OR: odds ratio; TBS: trabecular bone score. Table 2 Univariate analyses of factors associated with vertebral fractures in patients with axSpA Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 AxSpA: axial spondyloarthritis; OR: odds ratio; TBS: trabecular bone score. The discriminative values of TBS and hip BMD for vertebral fracture were calculated by determining the area under the ROC curve (Fig. 3). The ROC curve showed an inflection point for a sensitivity value of 68% and a specificity of 68%, representing a TBS of 1.359. TBS showed a higher area under the curve than hip BMD for the detection of prevalent vertebral fractures (0.713 and 0.577, respectively, P = 0.033). The area under the curve for TBS was also higher than that of the femoral neck BMD, although the difference was not statistically significant. Fig. 3 View largeDownload slide ROC curves of TBS and BMD for the discrimination of vertebral fractures (A) Comparison between TBS at L1–L4 and BMD at the femoral neck in the discrimination of vertebral fractures. (B) Comparison between TBS and hip BMD in the discrimination of vertebral fractures. TBS: trabecular bone score; ROC: receiver operating characteristic; L: lumbar vertebra. Fig. 3 View largeDownload slide ROC curves of TBS and BMD for the discrimination of vertebral fractures (A) Comparison between TBS at L1–L4 and BMD at the femoral neck in the discrimination of vertebral fractures. (B) Comparison between TBS and hip BMD in the discrimination of vertebral fractures. TBS: trabecular bone score; ROC: receiver operating characteristic; L: lumbar vertebra. The distribution of vertebral fractures in the non-osteoporotic patients (n = 237) according to the TBS values is shown in Table 3. Among the 237 patients, 24 had vertebral fractures. Of these 24 non-osteoporotic patients with vertebral fractures, 13 (54%) showed normal TBS and 11 (46%) low TBS (<1.31). Low TBS was more frequent in patients with vertebral fractures than in those without vertebral fractures (P = 0.003). Table 3 Vertebral fracture discrimination by TBS in non-osteoporotic AxSpA patients (N = 237) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) AxSpA: axial spondyloarthritis; TBS: trabecular bone score. Table 3 Vertebral fracture discrimination by TBS in non-osteoporotic AxSpA patients (N = 237) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) AxSpA: axial spondyloarthritis; TBS: trabecular bone score. Discussion This observational study of patients with axSpA revealed that TBS was associated with prevalent vertebral fractures. The TBS was lower in axSpA patients with vertebral fractures than in those without. The results also showed that TBS was superior to hip BMD for discrimination of vertebral fractures in axSpA patients. Increased vertebral fractures in axSpA are considered to be the result of poor bone quality in combination with biomechanical factors, such as hyperkyphosis and vertebral fusion. Decreased bone density and poor bone microarchitecture [23] can lead to the slow progressing collapse of vertebral bodies, without major trauma. Additionally, spinal structural damage, such as syndesmophytes and vertebral bridging, is associated with a reduction in spinal flexibility. This increased rigidity means that a simple fall or minor trauma can result in vertebral fractures [23]. Hyperkyphosis resulting from spinal ankyloses, calcification of the ligaments and previous vertebral fractures [24] leads to an increased mechanical loading, which results in an increased risk of vertebral fractures. In a previous study, we observed that TBS was lower in AS patients with lumbar spinal fractures than in those without them [25]. This suggests that low TBS may be related to the risk of vertebral fractures in AS patients. However, this previous study analysed only the lumbar spine, and included only young male AS patients. To the best of our knowledge, this is the first study showing that TBS is associated with vertebral fractures in axSpA. This finding is consistent with earlier studies among the general population. A recent study showed that a low TBS is useful as a determinant of fracture risk, independently of BMD [26]. Additionally, TBS can predict fractures in the general population independently of the fracture probability predicted using the Fracture Risk Assessment Tool (FRAX) algorithm [27]. In axSpA, inflammation has a direct effect on the trabecular bone of the vertebrae, but not on the cortical bone [2]. TBS has an advantage in that it directly assesses the microarchitecture of trabecular bone at the spine, which is the main area of involvement in axSpA patients. Theoretically, as the TBS value is influenced by the trabecular pattern, it should also be influenced by inflammation known to affect bone microarchitecture. Therefore, in comparison with BMD, TBS could be a better reflection of osteoporotic change resulting from inflammation in axSpA. The results of the present study showed that spinal structural damage was also associated with vertebral fractures. This association between vertebral fractures and spinal damage has also been found in previous studies [6, 7, 28, 29]. Our results were consistent with earlier findings, in that the presence of syndesmophytes was associated with vertebral fractures. Spinal structural damage may contribute to the development of vertebral fractures due to the biomechanical effects resulting from poor spinal mobility and hypokyphosis. Stiffening of the spine in axSpA contributes to the vertebral fracture risk by reducing biomechanical competence. Also, as syndesmophytes are characteristic of the spinal structural damage resulting from inflammation in axSpA, they could reflect cumulative inflammation in the spine. In our previous study, spinal structural damage was found to be associated with low TBS [13]. This finding implies that spinal structural damage may result in an increased risk of vertebral fractures due to the poor bone quality resulting from chronic inflammation, as well as biomechanical factors. We found that TNF inhibitor treatment was also associated with vertebral fractures. It is possible that this may be related to more severe inflammatory disease activity in patients receiving TNF inhibitor, rather than to a problem with TNF inhibitor itself. The EULAR taskforce made a series of recommendations with respect to the use of imaging for the management of SpA. These propose that in patients with axSpA without syndesmophytes in the lumbar spine on conventional radiography, osteoporosis should be assessed using hip DXA and anterior-posterior spine DXA, while in patients with syndesmophytes in the lumbar spine on conventional radiography, osteoporosis should be assessed using hip DXA supplemented by either spine DXA (lateral projection) or possibly quantitative CT (QCT) of the spine [30]. In this study, BMD at the femoral neck was lower in patients with vertebral fractures than in those without, but we found no difference in BMD at the lumbar spine and total hip. Also, we did not find an association between BMD values (according to World Health Organization criteria) [18] and vertebral fractures. This result suggests that BMD alone is not enough to assess the risk of fracture in axSpA patients. BMD measured by DXA has been considered to be the most important predictor of fragile fractures [31], but previous studies on the association between BMD and fracture in AS patients have been inconsistent [29, 32–34]. This finding may be related to the limitations of BMD measurement in axSpA. One limitation of spinal BMD assessment is that the presence of overlying calcifications, such as osteophytes or syndesmophytes, can erroneously elevate the resulting measurement [35]. Although lateral spinal DXA is recommended in patients with syndesmophytes, it is known to have poor precision due to the difficulty in positioning. Also, as the last rib and iliac crest overlap, only L3 can be measured in some cases [36, 37]. Furthermore, BMD is known to account for only 60–80% of bone strength. Bone quality, which is determined by bone microarchitecture, cannot be assessed by BMD [38]. This means that BMD may insufficiently reflect changes in the quality of trabecular bone caused by chronic inflammation. To overcome this problem, QCT and high resolution peripheral QCT have been used to investigate the bone microarchitecture changes resulting from inflammation in axSpA [23, 39]. QCT and high resolution peripheral QCT were developed to measure bone microarchitecture and assess bone quality. Although evidence suggests that these methods can predict fracture, the high radiation exposure, cost and limited access to such devices means that they are not routinely available in practice [35]. Therefore, a new non-invasive technology for the accurate clinical evaluation of bone microarchitecture in axSpA is needed. The data presented herein show that TBS may be a valuable alternative tool for assessment of the vertebral fracture risk in patients with axSpA. A point of note is that the mean value for TBS in axSpA patients with vertebral fractures was 1.30, which corresponds to the tertile for intermediate risk defined in a recent meta-analysis of TBS [19]. Another point of note in the present study is that TBS showed a superior predictive ability for vertebral fracture discrimination in axSpA in comparison with BMD values at the hip. Our results also showed that about half of the non-osteoporotic patients with vertebral fractures had low TBS. This means that TBS assessment may have an added value to BMD measurement. Furthermore, TBS has the advantage that it is not affected by bony artefacts. Osteophytes in cases of spinal osteoarthritis increase the overall BMD value in the lumbar spine, whereas TBS is not affected by such artefacts [37]. A recent study also showed that TBS in axSpA is not affected by the presence of syndesmophytes [40]. Therefore, inclusion of bone microarchitecture assessment by TBS, as well as bone density measurement using DXA, may improve the predictive value for the development of new vertebral fractures. This study has some limitations. We did not investigate whether TBS can predict the development of incident vertebral fractures because this study was of a cross-sectional design. Longer prospective longitudinal studies are needed to examine whether TBS is predictive of vertebral fractures in axSpA. Additionally, we have no data available on vitamin D level, which is related to fracture risk. Also, we defined vertebral fractures using the Genent method, so fractures of the spinal process or pseudoarthrosis were not included. This may be related to the underestimation of vertebral fractures in these data from axSpA patients. Lastly, the number of vertebral fractures was relatively small when considered alongside the total number of axSpA patients; therefore, the regression analysis could be under powered. In addition, this study included a large percentage of grade 1 vertebral fractures. The inter- and intra-observer variability for grade 1 fracture was limited; therefore, the association between TBS, BMD and vertebral fractures in axSpA should be confirmed by further studies of larger cohorts. In conclusion, the TBS value is lower in axSpA patients with vertebral fractures than in those without vertebral fractures. Low TBS was associated with vertebral fractures in axSpA. TBS has a superior predictive value to BMD at the hip in the discrimination of prevalent vertebral fractures. This finding suggests that TBS has the potential to predict future vertebral fractures in patients with axSpA. 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Associations between trabecular bone score and vertebral fractures in patients with axial spondyloarthritis

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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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1462-0324
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1462-0332
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10.1093/rheumatology/key027
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Abstract

Abstract Objectives To compare trabecular bone scores (TBS) between axial SpA (axSpA) patients with and without vertebral fractures and investigate associations between TBS and vertebral fractures. Methods Two hundred and fifty-five patients fulfilling the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria were enrolled. TBS and BMD were assessed using dual-energy X-ray absorptiometry. Vertebral fracture of the thoracic and lumbar spine was defined according to the Genant criteria. Osteoporosis risk factors, inflammatory markers, DAS and spinal structural damage were also assessed. Univariate logistic regression analysis was performed to identify factors associated with vertebral fractures. Results There were 31 vertebral fractures in 28/255 axSpA patients (11%). The mean (s.d.) TBS was 1.39 (0.11) and 1.30 (0.13) in patients without and with vertebral fractures, respectively (P < 0.001). BMD in the femoral neck was lower in patients with vertebral fractures (P = 0.027), but BMDs in the lumbar spine and total hip were not. Univariate logistic regression analyses identified old age (⩾50 years), TNF inhibitor treatment, the presence of syndesmophytes and a low TBS (<1.23) as associated with prevalent vertebral fractures [odds ratio (95% CI): 6.9 (2.0, 24.4), 2.4 (1.0, 5.5), 5.5 (2.2, 13.5) and 5.3 (2.0, 14.1), respectively]. TBS has a better discriminatory value than BMD at the total hip for prediction of vertebral fractures in axSpA patients (P = 0.034). Conclusion Similar to individuals with primary osteoporosis, axSpA patients with vertebral fractures have a lower TBS. This suggests that TBS has the potential to predict future vertebral fractures in patients with axSpA. axial spondyloarthritis, vertebral fracture, trabecular bone score, bone mineral density, bone microarchitecture Rheumatology key messages The trabecular bone score is lower in axial SpA patients with vertebral fractures. The trabecular bone score has the potential to predict future vertebral fractures in axial SpA. Introduction Axial SpA (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton, including the sacroiliac joints. AxSpA includes both the early inflammatory phase of the disease in which there is no structural damage in the sacroiliac joints (non-radiographic disease) and the later stages in which structural damage is visible on X-ray scans of the sacroiliac joints as erosion, sclerosis or bony bridges. This later stage is known as radiographic disease or AS [1]. Chronic inflammation of the spine leads to disease symptoms such as pain and stiffness, and structural damage to the bone tissue [2]. Bony overgrowth leading to ankylosis of axial joints and vertebral spaces is the typical structural damage occurring in axSpA, while osteoporosis also frequently develops in the vertebral bodies. The bone tissue directly exposed to inflammation (osteitis) in axSpA is the trabecular bone of the vertebrae, and consequently, vertebral osteoporosis and resorption of trabecular bone are increased in axSpA [2]. Inflammatory infiltration in the bone marrow of SpA patients can be detected as spondylitis on MRI scans. Indeed, histologic examinations of bone sections from the spines of patients with AS show an accumulation of osteoclasts in the bone marrow and the formation of inflammatory infiltrates [3, 4]. The combination of spinal rigidity (resulting from syndesmophytes or ankyloses) and osteoporosis within the trabecular bone contributes to the development of vertebral fractures [5], which AS patients are known to be at increased risk of [6–8]. These vertebral fractures often do not come to clinical attention, yet their presence is diagnostic of osteoporosis and helps to predict the risk of future fractures [9]. Therefore, to reduce the incidence of future fractures, an accurate and clinically available tool is required for the discrimination of patients with vertebral fractures. To date, it is unclear which imaging approach is most useful for diagnosing and monitoring osteoporosis in axSpA. Most data related to osteoporosis in axSpA are based on BMD measurements using DXA, but this technique has some limitations. BMD in axSpA can be overestimated due to the presence of syndesmophytes or other structural lesions such as an ankylosed posterior arch and periosteal bone formation. Additionally, active or past coxitis can impair the internal rotation of the lower limb, which is mandatory for an accurate hip BMD assessment [10]. Furthermore, BMD only partially takes into account information on bone microarchitecture. Therefore, any additional information on microarchitecture can help to reduce the substantial overlap that exists between those patients with and without a truly increased risk of fracture [11]. The trabecular bone score (TBS) is a novel tool used to evaluate bone microarchitecture. It is a textural index that evaluates pixel grey-level variations in the lumbar spine DXA image, thereby providing an indirect index of trabecular microarchitecture [12]. It is obtained via re-analysis of DXA scans and can be directly compared with BMD because both evaluate the same region of bone. In a previous study using TBS, axSpA patients showed poor bone quality compared with matched controls [13]. However, it is not yet known whether TBS is associated with vertebral fractures in axSpA. The aims of the present study were to compare TBS bone quality assessments between axSpA patients with and without vertebral fractures, and to investigate the associations between TBS and vertebral fractures in axSpA patients. Methods Study population Between August 2013 and February 2017, consecutive axSpA patients from Incheon St Mary’s Hospital (Incheon, Korea) were recruited to this analysis. All enrolled patients fulfilled the imaging arm of the Assessment of SpondyloArthritis International Society axSpA criteria [14]. All patients were aged between 20 and 67 years. Exclusion criteria included patients with thyroid or parathyroid disorders, the presence of chronic renal or liver disease, use of corticosteroids, cancer or concurrent RA. TBS, BMD and lateral radiographs of the thoracic and lumbar spine were assessed at the time of enrolment. At the time of TBS assessment, demographic data were collected and osteoporosis risk factors were assessed (smoking status and alcohol consumption). All participants provided written consent according to the Declaration of Helsinki, and the study was approved by the ethics committee at Incheon St Mary’s Hospital (study number: OC16OISI0138). Clinical data Disease-related data and DAS were collected. Clinical data included the time after symptom onset, the presence of HLA B27, family history, the use of medications such as anti-inflammatory drugs, SSZ, TNF inhibitors, calcium, bisphosphonate and vitamin D at the time of DXA measurements. Measures of disease activity were collected using the BASDAI [15]. All scores were recorded on a visual analogue scale from 0 to 10. The BASFI [16] and patient global assessment scores were also recorded. The Ankylosing Spondylitis Disease Activity Score was calculated as described previously [17]. ESR and CRP were also measured. BMD assessment BMD of the lumbar spine and left hip was assessed using DXA (Lunar Prodigy densitometer, Madison, WI, USA). All measurements were taken by experienced operators using the same machine and standardized procedures for participant positioning. BMD was measured at the lumbar spine using an anteroposterior projection at L1–L4 and at the left hip from the femoral neck and total proximal femur, and was expressed as the number of grams of bone mineral per square centimetre (g/cm2), calculated as T scores using the manufacturer’s reference. According to the World Health Organization criteria, osteopaenia is defined as a T score between −1 and −2.5, and osteoporosis is defined as a T score −2.5 or less [18]. TBS assessment TBS was analysed using DXA images of the lumbar spine (L1–L4). Lumbar spine DXA images were reanalysed in an operator-independent automated manner using TBS iNight® software version 2.1 (Med-Imaps, Merignac, France). The software uses the posterior-anterior images, including the BMD region of interest and edge detection; thus, the TBS is calculated over exactly the same region as the lumbar BMD assessment. Patients were divided into three TBS groups according to the risk of fracture, as identified in a recent meta-analysis: high risk: TBS <1.23; intermediate risk: TBS 1.23–1.31; low risk: TBS >1.31 [19]. Low TBS was defined as a TBS ⩽1.31. Radiographic scoring For all patients, radiographs of the cervical, thoracic and lumbar spine were obtained at the time of the TBS assessment. Lateral views of the cervical and lumbar spine were scored according to the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) [20]. The mSASSS was scored by a single trained expert who was blinded to the patient characteristics. The total scores ranged from 0 to 72. The number of syndesmophytes was assessed using the mSASSS. Assessment of vertebral fractures Two independent trained readers (K.Y.K. and I.J.K.) scored lateral radiographs of the thoracic and lumbar spine for vertebral fractures using the standardized semi-quantitative method described by Genant et al. [21], which involves evaluating the fourth thoracic vertebra (T4) to the fourth lumbar vertebra (L4). A vertebral fracture was defined as a ⩾20% reduction in any vertebral height. Vertebral fractures were divided into grades of 0–3: grade 0 (normal), <20% height reduction; grade 1 (mild), 20–25% reduction; grade 2 (moderate), 25–40% reduction; and grade 3 (severe), >40% reduction. If the measurement was complicated because of new bone formation or erosions at the corners of the vertebral bodies, a lengthened imaginary line representing the original edge of the vertebral body was used. There were few discrepancies between the two independent trained readers, but when they did occur, the two investigators reached a consensus. The inter-observer variability was calculated using Cohen’s kappa value (κ = 0.72). Statistical analysis Continuous data are expressed as the mean (s.d.) and categorical data are expressed as percentages. Clinical variables were compared using an independent t-test, and the chi-squared test was used to compare categorical variables between axSpA patients with and without vertebral fractures. Univariate logistic regression analyses were performed to investigate the association between clinical variables, DAS, BMD and TBS and vertebral fractures. The accuracy of TBS and BMD for the discrimination of prevalent vertebral fractures was assessed by determining the area under the receiving operator characteristics (ROC) curves. P ⩽ 0.05 were considered statistically significant. Statistical analysis was performed with IBM SPSS Statistics version 18. Results Data from 255 patients (80% male) were analysed. The mean age was 38 (11) years (range, 20–67), and the mean symptom duration and time after diagnosis of axSpA were 10 (9) and 5 (7) years, respectively. A total of 92 patients (36%) were current smokers and 222 (87%) were HLA-B27 positive. In all, 222 (87%) fulfilled the modified New York criteria for AS [22]. Among the 255 patients, 28 (11%) had morphometric vertebral fractures (a total of 31). Of these fractures, 21 (68%) were defined as mild (grade 1), 9 (29%) as moderate (grade 2) and 1 (3%) as severe (grade 3), as shown in Fig. 1. The most common location of vertebral fractures was T11 (16%). Fig. 1 View largeDownload slide Locations and numbers of vertebral fractures VF: vertebral fractures; T: thoracic vertebra; L: lumbar vertebra. Fig. 1 View largeDownload slide Locations and numbers of vertebral fractures VF: vertebral fractures; T: thoracic vertebra; L: lumbar vertebra. Comparisons between patients with and without vertebral fractures are shown in Table 1. Patients with vertebral fractures were significantly older than patients without them. There were no differences between the two groups in terms of BMI, social habits, symptom duration, history of previous fractures, HLA-B27 positivity and DAS. Patients with vertebral fractures scored higher in the mSASSS and had more syndesmophytes. The use of TNF inhibitors was more common in patients with vertebral fractures than in those without vertebral fractures. The mean TBS was 1.39 (0.11) for patients without vertebral fractures and 1.30 (0.13) for those with vertebral fractures (P < 0.001). BMD data for the lumbar spine and total hip did not differ between the two groups. The mean BMD at the femoral neck was lower in patients with vertebral fractures (P = 0.027). Table 1 Characteristics of the axSpA patients stratified according to vertebral fractures Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Values are given as mean (s.d.) unless otherwise stated. ASDAS: Ankylosing Spondylitis Disease Activity Score; axSpA: axial SpA; mSASSS: modified Stoke Ankylosing Spondylitis Spinal Score; TBS: trabecular bone score. Table 1 Characteristics of the axSpA patients stratified according to vertebral fractures Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Variables, N (%) No vertebral fractures (N = 227) Vertebral fractures (N = 28) P-value Age, years 37 (11) 46 (13) 0.001 Male, n (%) 177 (78) 26 (93) 0.046 BMI, kg/m2 24.0 (3.6) 23.5 (3.6) 0.520 Current smoking, n (%) 78 (34) 14 (50) 0.080 Alcohol ≥3 U/day, n (%) 4 (2) 0 (0) 0.626 Symptom duration, years 10 (9) 12 (13) 0.246 Family history of axSpA, n (%) 31 (14) 3 (11) 0.468 Previous fractures, n (%) 27 (12) 6 (21) 0.135 HLA B27-positive, n (%) 199 (90) 23 (92) 0.286 ESR, mm/h 23.1 (21.3) 22.0 (24.5) 0.808 CRP, mg/l 8.4 (13.5) 11.5 (24.4) 0.522 Patient global assessment 4.7 (2.6) 4.1 (2.6) 0.282 BASDAI score, range 0–10 4.2 (2.3) 3.4 (2.2) 0.070 BASFI score 2.0 (2.3) 2.0 (2.2) 0.867 ASDAS-ESR 2.7 (1.1) 2.4 (1.2) 0.156 ASDAS-CRP 2.4 (1.3) 2.0 (1.4) 0.131 mSASSS 10.6 (18.8) 24.0 (23.3) 0.006 Number of syndesmophytes 3.6 (7.0) 7.7 (8.4) 0.018 Presence of syndesmophytes, n (%) 80 (35) 21 (75) <0.001 Patients on NSAIDs, n (%) 209 (92) 28 (100) 0.114 Patients on SSZ, n (%) 65 (29) 4 (14) 0.078 Patients on TNF inhibitors, n (%) 43 (19) 10 (36) 0.041 Patients on bisphosphonate, n (%) 8 (4) 2 (7) 0.302 Patients on calcium, n (%) 16 (7) 5 (18) 0.064 Patients on vitamin D, n (%) 3 (1) 1 (4) 0.374 TBS, L1–L4 1.39 (0.11) 1.30 (0.13) <0.001 BMD, g/cm2     Lumbar spine 1.19 (0.20) 1.18 (0.35) 0.879     Femoral neck 0.94 (0.14) 0.88 (0.16) 0.027     Total hip 0.98 (0.14) 0.94 (0.18) 0.197 Values are given as mean (s.d.) unless otherwise stated. ASDAS: Ankylosing Spondylitis Disease Activity Score; axSpA: axial SpA; mSASSS: modified Stoke Ankylosing Spondylitis Spinal Score; TBS: trabecular bone score. The proportions of patients meeting the TBS high (TBS <1.23) and intermediate fracture risks (1.23–1.3) were 8.8 and 10.1%, respectively, in patients without vertebral fractures and 28.6 and 21.4%, respectively, in those with vertebral fractures (P = 0.001; Fig. 2A). According to the BMD measurements, osteoporosis (T score −2.5 or less) and osteopaenia (T score −2.5 to −1.0) were more frequent in patients with vertebral fractures; however, the difference was not statistically significant (Fig. 2B). Fig. 2 View largeDownload slide TBS and BMD in axSpA patients according to vertebral fractures (A) Frequency of low, intermediate and high fracture risk TBS groups among patients without or with a vertebral fracture. (B) Frequency of osteoporosis, osteopaenia and normal BMD. AxSpA: axial SpA; TBS: trabecular bone score; VF: vertebral fractures. Fig. 2 View largeDownload slide TBS and BMD in axSpA patients according to vertebral fractures (A) Frequency of low, intermediate and high fracture risk TBS groups among patients without or with a vertebral fracture. (B) Frequency of osteoporosis, osteopaenia and normal BMD. AxSpA: axial SpA; TBS: trabecular bone score; VF: vertebral fractures. Table 2 shows the results of univariate logistic regression analyses of factors associated with vertebral fractures. The results show that older age (⩾50 years old), TNF inhibitor treatment, the presence of syndesmophytes and a lower TBS value (<1.23) were associated with vertebral fractures [odds ratio (OR) (95% CI): 6.9 (2.0, 24.4), 2.4 (1.0, 5.5), 5.5 (2.2, 13.5) and 5.3 (2.0, 14.1), respectively]. Male sex showed a moderate association [OR (95% CI): 3.7 (0.8, 16.0)]. Table 2 Univariate analyses of factors associated with vertebral fractures in patients with axSpA Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 AxSpA: axial spondyloarthritis; OR: odds ratio; TBS: trabecular bone score. Table 2 Univariate analyses of factors associated with vertebral fractures in patients with axSpA Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 Univariate analysis Variables OR (95% CI) P-value Age, years <0.001     20–29 1.0 (Reference)     30–39 0.9 (0.2–3.7) 0.930     40–49 1.4 (0.3–5.2) 0.676     50–59 6.9 (2.0–24.4) 0.003     60–69 10.2 (2.0–51.4) 0.005 BMI, kg/m2 0.640     <18.5 1.0 (Reference)     18.5–22.9 0.5 (0.1–2.0) 0.297     23.0–24.9 0.4 (0.1–1.9) 0.259     25.0–29.9 0.7 (0.2–2.9) 0.637     ≥30.0 0.3 (0.0–2.9) 0.282 Male sex 3.7 (0.8–16.0) 0.08 HLA B27-positive 1.5 (0.5–4.4) 0.414 Current smoking 1.9 (0.9–5.2) 0.108 Previous fracture 2.0 (0.7–5.4) 0.166 Patients on SSZ 0.4 (0.1–1.2) 0.116 Patients on TNF inhibitors 2.4 (1.0–5.5) 0.045 Presence of syndesmophytes 5.5 (2.2–13.5) <0.001 TBS 0.002     Low risk (>1.31) 1.0 (Reference)     Intermediate risk (1.23–1.31) 3.4 (1.2–9.8) 0.021     High risk (<1.23) 5.3 (2.0–14.1) 0.001 BMD 0.110     Normal (T ≥ −1.0) 1.0 (Reference)     Osteopaenia (−2.5 to −1.0) 1.9 (0.8–4.5) 0.133     Osteoporosis (T ≤ −2.5) 3.3 (0.9–11.7) 0.061 AxSpA: axial spondyloarthritis; OR: odds ratio; TBS: trabecular bone score. The discriminative values of TBS and hip BMD for vertebral fracture were calculated by determining the area under the ROC curve (Fig. 3). The ROC curve showed an inflection point for a sensitivity value of 68% and a specificity of 68%, representing a TBS of 1.359. TBS showed a higher area under the curve than hip BMD for the detection of prevalent vertebral fractures (0.713 and 0.577, respectively, P = 0.033). The area under the curve for TBS was also higher than that of the femoral neck BMD, although the difference was not statistically significant. Fig. 3 View largeDownload slide ROC curves of TBS and BMD for the discrimination of vertebral fractures (A) Comparison between TBS at L1–L4 and BMD at the femoral neck in the discrimination of vertebral fractures. (B) Comparison between TBS and hip BMD in the discrimination of vertebral fractures. TBS: trabecular bone score; ROC: receiver operating characteristic; L: lumbar vertebra. Fig. 3 View largeDownload slide ROC curves of TBS and BMD for the discrimination of vertebral fractures (A) Comparison between TBS at L1–L4 and BMD at the femoral neck in the discrimination of vertebral fractures. (B) Comparison between TBS and hip BMD in the discrimination of vertebral fractures. TBS: trabecular bone score; ROC: receiver operating characteristic; L: lumbar vertebra. The distribution of vertebral fractures in the non-osteoporotic patients (n = 237) according to the TBS values is shown in Table 3. Among the 237 patients, 24 had vertebral fractures. Of these 24 non-osteoporotic patients with vertebral fractures, 13 (54%) showed normal TBS and 11 (46%) low TBS (<1.31). Low TBS was more frequent in patients with vertebral fractures than in those without vertebral fractures (P = 0.003). Table 3 Vertebral fracture discrimination by TBS in non-osteoporotic AxSpA patients (N = 237) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) AxSpA: axial spondyloarthritis; TBS: trabecular bone score. Table 3 Vertebral fracture discrimination by TBS in non-osteoporotic AxSpA patients (N = 237) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) Normal TBS (N = 188), N (%) Low TBS (N = 49), N (%) P-value No vertebral fractures (N = 213) 175 (82) 38 (18) 0.003 Vertebral fractures (N = 24) 13 (54) 11 (46) AxSpA: axial spondyloarthritis; TBS: trabecular bone score. Discussion This observational study of patients with axSpA revealed that TBS was associated with prevalent vertebral fractures. The TBS was lower in axSpA patients with vertebral fractures than in those without. The results also showed that TBS was superior to hip BMD for discrimination of vertebral fractures in axSpA patients. Increased vertebral fractures in axSpA are considered to be the result of poor bone quality in combination with biomechanical factors, such as hyperkyphosis and vertebral fusion. Decreased bone density and poor bone microarchitecture [23] can lead to the slow progressing collapse of vertebral bodies, without major trauma. Additionally, spinal structural damage, such as syndesmophytes and vertebral bridging, is associated with a reduction in spinal flexibility. This increased rigidity means that a simple fall or minor trauma can result in vertebral fractures [23]. Hyperkyphosis resulting from spinal ankyloses, calcification of the ligaments and previous vertebral fractures [24] leads to an increased mechanical loading, which results in an increased risk of vertebral fractures. In a previous study, we observed that TBS was lower in AS patients with lumbar spinal fractures than in those without them [25]. This suggests that low TBS may be related to the risk of vertebral fractures in AS patients. However, this previous study analysed only the lumbar spine, and included only young male AS patients. To the best of our knowledge, this is the first study showing that TBS is associated with vertebral fractures in axSpA. This finding is consistent with earlier studies among the general population. A recent study showed that a low TBS is useful as a determinant of fracture risk, independently of BMD [26]. Additionally, TBS can predict fractures in the general population independently of the fracture probability predicted using the Fracture Risk Assessment Tool (FRAX) algorithm [27]. In axSpA, inflammation has a direct effect on the trabecular bone of the vertebrae, but not on the cortical bone [2]. TBS has an advantage in that it directly assesses the microarchitecture of trabecular bone at the spine, which is the main area of involvement in axSpA patients. Theoretically, as the TBS value is influenced by the trabecular pattern, it should also be influenced by inflammation known to affect bone microarchitecture. Therefore, in comparison with BMD, TBS could be a better reflection of osteoporotic change resulting from inflammation in axSpA. The results of the present study showed that spinal structural damage was also associated with vertebral fractures. This association between vertebral fractures and spinal damage has also been found in previous studies [6, 7, 28, 29]. Our results were consistent with earlier findings, in that the presence of syndesmophytes was associated with vertebral fractures. Spinal structural damage may contribute to the development of vertebral fractures due to the biomechanical effects resulting from poor spinal mobility and hypokyphosis. Stiffening of the spine in axSpA contributes to the vertebral fracture risk by reducing biomechanical competence. Also, as syndesmophytes are characteristic of the spinal structural damage resulting from inflammation in axSpA, they could reflect cumulative inflammation in the spine. In our previous study, spinal structural damage was found to be associated with low TBS [13]. This finding implies that spinal structural damage may result in an increased risk of vertebral fractures due to the poor bone quality resulting from chronic inflammation, as well as biomechanical factors. We found that TNF inhibitor treatment was also associated with vertebral fractures. It is possible that this may be related to more severe inflammatory disease activity in patients receiving TNF inhibitor, rather than to a problem with TNF inhibitor itself. The EULAR taskforce made a series of recommendations with respect to the use of imaging for the management of SpA. These propose that in patients with axSpA without syndesmophytes in the lumbar spine on conventional radiography, osteoporosis should be assessed using hip DXA and anterior-posterior spine DXA, while in patients with syndesmophytes in the lumbar spine on conventional radiography, osteoporosis should be assessed using hip DXA supplemented by either spine DXA (lateral projection) or possibly quantitative CT (QCT) of the spine [30]. In this study, BMD at the femoral neck was lower in patients with vertebral fractures than in those without, but we found no difference in BMD at the lumbar spine and total hip. Also, we did not find an association between BMD values (according to World Health Organization criteria) [18] and vertebral fractures. This result suggests that BMD alone is not enough to assess the risk of fracture in axSpA patients. BMD measured by DXA has been considered to be the most important predictor of fragile fractures [31], but previous studies on the association between BMD and fracture in AS patients have been inconsistent [29, 32–34]. This finding may be related to the limitations of BMD measurement in axSpA. One limitation of spinal BMD assessment is that the presence of overlying calcifications, such as osteophytes or syndesmophytes, can erroneously elevate the resulting measurement [35]. Although lateral spinal DXA is recommended in patients with syndesmophytes, it is known to have poor precision due to the difficulty in positioning. Also, as the last rib and iliac crest overlap, only L3 can be measured in some cases [36, 37]. Furthermore, BMD is known to account for only 60–80% of bone strength. Bone quality, which is determined by bone microarchitecture, cannot be assessed by BMD [38]. This means that BMD may insufficiently reflect changes in the quality of trabecular bone caused by chronic inflammation. To overcome this problem, QCT and high resolution peripheral QCT have been used to investigate the bone microarchitecture changes resulting from inflammation in axSpA [23, 39]. QCT and high resolution peripheral QCT were developed to measure bone microarchitecture and assess bone quality. Although evidence suggests that these methods can predict fracture, the high radiation exposure, cost and limited access to such devices means that they are not routinely available in practice [35]. Therefore, a new non-invasive technology for the accurate clinical evaluation of bone microarchitecture in axSpA is needed. The data presented herein show that TBS may be a valuable alternative tool for assessment of the vertebral fracture risk in patients with axSpA. A point of note is that the mean value for TBS in axSpA patients with vertebral fractures was 1.30, which corresponds to the tertile for intermediate risk defined in a recent meta-analysis of TBS [19]. Another point of note in the present study is that TBS showed a superior predictive ability for vertebral fracture discrimination in axSpA in comparison with BMD values at the hip. Our results also showed that about half of the non-osteoporotic patients with vertebral fractures had low TBS. This means that TBS assessment may have an added value to BMD measurement. Furthermore, TBS has the advantage that it is not affected by bony artefacts. Osteophytes in cases of spinal osteoarthritis increase the overall BMD value in the lumbar spine, whereas TBS is not affected by such artefacts [37]. A recent study also showed that TBS in axSpA is not affected by the presence of syndesmophytes [40]. Therefore, inclusion of bone microarchitecture assessment by TBS, as well as bone density measurement using DXA, may improve the predictive value for the development of new vertebral fractures. This study has some limitations. We did not investigate whether TBS can predict the development of incident vertebral fractures because this study was of a cross-sectional design. Longer prospective longitudinal studies are needed to examine whether TBS is predictive of vertebral fractures in axSpA. Additionally, we have no data available on vitamin D level, which is related to fracture risk. Also, we defined vertebral fractures using the Genent method, so fractures of the spinal process or pseudoarthrosis were not included. This may be related to the underestimation of vertebral fractures in these data from axSpA patients. Lastly, the number of vertebral fractures was relatively small when considered alongside the total number of axSpA patients; therefore, the regression analysis could be under powered. In addition, this study included a large percentage of grade 1 vertebral fractures. The inter- and intra-observer variability for grade 1 fracture was limited; therefore, the association between TBS, BMD and vertebral fractures in axSpA should be confirmed by further studies of larger cohorts. In conclusion, the TBS value is lower in axSpA patients with vertebral fractures than in those without vertebral fractures. Low TBS was associated with vertebral fractures in axSpA. TBS has a superior predictive value to BMD at the hip in the discrimination of prevalent vertebral fractures. This finding suggests that TBS has the potential to predict future vertebral fractures in patients with axSpA. 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RheumatologyOxford University Press

Published: Mar 9, 2018

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