In this large survey of VFs in 390 men and women with SpA, we found >10 % prevalence of moderate to severe VFs, already before the age of 30 years and within 5 years of symptoms.
The pathophysiology of VFs in SpA is complex [13, 24–26]. In AS, markers of bone resorption are increased in active disease and are related to low BMD and bone loss in the femoral neck and in the spine [27, 28]. Markers of bone formation are mostly normal in AS and not correlated with BMD . Low BMD and bone loss have been documented in the spine [by DXA and quantitative computed tomography (QCT)] and in the hip (by DXA) [29, 30]. Later in the course of AS, BMD is decreased in the hip (as shown by DXA) and within the vertebrae (by QCT), but not in the lumbar spine (by DXA). This is due to intervertebral syndesmophyte formation, periosteal bone formation with squaring of the vertebrae, ankylosis of the facet joints, and calcification of the perivertebral ligaments (by QCT) [29, 30].
Using high-resolution peripheral QCT, it has been shown that patients with AS who have osteoporosis also have a decrease in bone volume density and in cortical thickness in the distal radius and distal tibia, which correlated with trabecular volumetric BMD in the lumbar spine using QCT . These studies suggest that patients with AS have a generalized loss of trabecular bone density. The clinical consequence is that this low BMD and bone loss are measurable by DXA in the spine and hip early in the disease, but only in the hip later in the disease course [24, 25].
Interestingly, in this study, the presence of VF was related to mSASSS and marginally to BMD measured by DXA in the femoral neck. This indicates that, in addition to a low BMD, an altered biomechanical performance of the vertebrae by the stiffening of the spine contributes to the occurrence of VF [13, 24, 25]. These results further support the European League Against Rheumatism (EULAR) recommendations on imaging in SpA, which state that in patients with axial SpA without syndesmophytes in the lumbar spine visualized by conventional Rx, osteoporosis should be assessed by hip DXA and anteroposterior spine DXA. In patients with syndesmophytes in the lumbar spine visualized by conventional Rx, osteoporosis should be assessed by hip DXA supplemented by either spine DXA in lateral projection or possibly QCT of the spine .
VFs do not occur uniformly along the spine, but, as shown in postmenopausal and senile osteoporosis, they occur more often in the midthoracic and thoracolumbar regions than elsewhere [33, 34], which is likely attributable to biomechanical factors. Apart from loading (body height, weight, muscle forces, movements such as bending), other factors play a role in VF, such as spinal curvature and the heterogeneity of BMD between vertebrae . Furthermore, a wedged thoracic VF increases the biomechanical stresses in other vertebrae . In view of the relationship between VF and mSASSS in this and other studies , stiffening of the spine in SpA also could contribute to VF risk. Segmental or generalized syndesmophyte formation (bamboo spine) transforms the flexible spine in a long stiff bone (with intravertebral osteoporosis as shown with computed tomography) with decreased biomechanical competence. Stiffening of the spine in AS can also explain why VFs in AS occur at unusual locations (cervical spine) with unusual characteristics (e.g., transdiscal and horizontal transvertebral fractures and fractures of the dorsal arch structures of the vertebrae, which was reported by one of our patients) and with severe neurologic deficits, which occurred in three patients (0.8 %) .
Patients with a VF more often had a history of acute and chronic back pain after trauma than did patients without a VF. However, this occurred only in a minority of patients with a VF (one of six patients), suggesting that most VFs in SpA are not the result of trauma. The clinical consequence is that a history of trauma helps to identify only a limited number of patients with a VF. According to the ASAS/EULAR recommendations, imaging of the spine is advocated in AS in cases of a significant change in the course of the disease [15, 16]. However, on the basis of the high prevalence of subclinical VFs, this recommendation could need adaption, as VFs can be diagnosed only when imaging of the spine is performed and can be present without a history of trauma or typical signs and symptoms of an acute fracture.
The agreement between digitized Rx and VFA in diagnosing VFs, as well as the high NPV [17–19], is of clinical interest. VFA missed six (12.5 %) of the radiographic VFs. This indicates that in the majority of patients with SpA, VFA will enable diagnosis of VFs using a much lower level of radiation than Rx. Earlier studies showed less congruent results, but this could have been due to measuring vertebral heights using a less reliable magnification loop on plain radiographic films instead of electronic aids on digitized radiographs in this study [18, 19].
In view of its high NPV, VFA allows selection of patients who will or who will not need Rx for diagnosing VFs [17–19, 23]. A prevalent VF is a strong predictor of future VFs and non-VFs. No fracture prevention studies are available in SpA. It is therefore indicated that patients with SpA and early bone loss, osteoporosis, and/or a prevalent VF should be considered candidates for antiresorptive drugs to prevent fractures.
The strength of this study is the large sample collection and the representativeness of the patient group in a peripheral non-academic rheumatology center, including a broad range of ages and representing both sexes. Interestingly, we found the overall prevalence of SpAs to be as common in women as in men. The dominant male prevalence in AS is well accepted. However, the gender distribution in our survey is in line with the finding that, in recent years, the gender ratio approached 1:1 in an AS patient survey in Germany  and in a population survey in the south of Sweden for SpAs . This finding has been included in the ASAS mission statement on epidemiology of AS . The reported data regarding prevalence of PsA according to gender is conflicting . The incidence of Crohn’s disease is similar between women and men, but the prevalence of IBD with SpA is unknown .
The finding that VFA using DXA has high sensitivity, specificity, PPV, and NPV compared with Rx is another strength with possible clinical consequences for screening. It indicates that VFA can be used as a prescreening tool for the presence of a VF in SpA, limiting the use of radiographs to patients with a VF on VFA, or when VFA is not of adequate quality to evaluate VFs.
A limitation of the study is the small number of patients with PsA and IBD. Furthermore, we chose only VFs with a deformity >25 % and not smaller deformities, as this would have increased sensitivity but decreased specificity for diagnosing a VF . Therefore, the prevalence of VFs is even higher in this population when mild deformities are also included . Last, the relationship between a history of trauma and the presence of VF should be interpreted with caution, as there is a possibility of recall bias of traumas.