Abstract: Ankylosing spondylitis (As) is often associated with osteoporosis, with an incidence of 50%. 92%, in addition to calcification and bony ankylosis of the intervertebral disc fibular ring and adjacent ligaments. In osteoporosis, the most common form of fracture is vertebral fracture, but vertebral fractures caused by osteoporosis alone have different characteristics from vertebral fractures secondary to As, and how to assess their fracture risk is an important issue. In this paper, we review the progress of risk assessment methods for osteoporosis and vertebral fractures caused by As. Keywords: vertebral compression fracture; ankylosing spondylitis; osteoporosis Ankylosing spondylitis (AS) is a chronic inflammatory disease that primarily invades the spine and involves almost all of the sacroiliac joints and, to varying degrees, the peripheral joints. In addition to calcification and bony ankylosis of the intervertebral disc fibular ring and its adjacent ligaments, it is often associated with osteoporosis. Recent studies have shown that osteoporosis or reduced bone mass is prevalent in patients with AS, with an incidence of 50% to 92%. It has been reported in the literature that vertebral bone mineral density (BMD) decreases in patients with early As and that the hip is a susceptible site for the development of osteoporosis in patients with late As. The pathogenesis of osteoporosis due to AS is unknown and may be related to the role of hormonal imbalance, immune inflammation, and exercise restriction. In osteoporosis, the most common form of fracture is vertebral fracture, but vertebral fractures caused by osteoporosis alone have different characteristics than vertebral fractures secondary to As. This paper reviews the progress of risk assessment of osteoporosis caused by AS and its related complications, in order to provide reference for the proper management of osteoporosis caused by AS and other related problems in clinical work. 1. Diagnosis of vertebral fractures 1.1 Imaging diagnosis Vertebral fractures due to osteoporosis are often difficult to diagnose in patients with AS because the patients themselves have back pain and spinal deformity. In general, vertebral fractures in patients with AS. It is only after multiple fractures have occurred (usually 3 to 4 vertebrae) that they are more easily noticed. Furthermore, some studies have shown that even when fractures have occurred and imaging has been performed, the fractures are easily overlooked because in the thoracic back, images of the vertebral body often do not show well and overlap with the soft tissues and ribs, resulting in misinterpretation of the images, which, together with the preconceived impression of AS, makes the reading of the films subjective. Although there is agreement on many aspects of the imaging definition of vertebral fracture, there is still much disagreement, and there is no widely accepted gold standard for what level of deformity can be considered a fracture, especially in patients under 50 years of age, and the lack of epidemiologic data on vertebral body morphology in young and middle-aged adults has become a major obstacle to determining vertebral fracture. Currently, the risk of vertebral fracture is assessed by knowing the deformation of the vertebral body (e.g., anterior, middle, or posterior compression height loss greater than 20%), the number and severity of vertebral fractures (whether silent or clinically symptomatic), and these indicators can indicate a relatively high risk of future fracture and the possibility of re-fracture in the short term. A 20% loss of vertebral height is associated with at least a 20% loss of bone volume on micro CT. Furthermore, the risk of vertebral re-fracture, regardless of BMD, is largely dependent on the current state of vertebral fracture. Therefore, the use of vertebral height loss to assess the risk of future vertebral fractures in patients with AS has some practical value. One study showed that the OR for vertebral fracture in AS patients reached an average of 7.7, and in the long term, men had a higher risk of vertebral fracture than women with AS (OR 10.7 for men and 4.2 for women), and this risk increased progressively during the first 5 years of the disease course. The different opinions on diagnostic imaging indicators reduce the credibility of the diagnosis of the same patient for fracture by different physicians, which can only be solved with the help of further investigations, such as radionuclide scans and MRI. However, it is often due to economic conditions and long cognitive. The diagnostic process causes a delay in diagnostic treatment. However, it is important to note that endplate erosion lesions due to problems with AS itself are often accompanied by non-infectious discitis, often leading to deformed H-dissection of the vertebral body on imaging, which can potentially lead to misdiagnosis of the fracture. 1.2 Diagnosis of physical signs After a vertebral fracture, two main symptomatic manifestations are usually produced, one is acute back pain, and the other is that the patient himself is unaware and goes into silence. Therefore, the common clinical kyphosis can be used not only as a clinical sign, but actually indicates the possibility of wedge compression fractures. Fractures in specific sites or forms, such as cervical fractures and dislocations, often result in more severe functional impairment or even death, which is very different from fractures caused by postmenopausal osteoporosis. The injuries accompanying these fractures include spinal cord injuries, strain injuries to nerve roots, paravertebral hematomas, and so on. And due to the As themselves, the weakened bone healing ability after fracture may cause posterior arching of the vertebrae to form a pseudo-joint, thus causing spinal instability. In order to avoid secondary spinal cord and nerve injury due to fracture, treatment can be performed by internal fixation, but internal fixation needs to take into account the presence of osteoporosis in the vertebral body. 2. Vertebral fracture risk assessment methods 2.1 Comprehensive analysis For patients with As, in addition to fractures caused by problems such as reduced mobility, which can easily lead to falls, structural problems of the bone itself are also the main cause of easy fracture. However, this approach is becoming increasingly limited due to the interference of peripheral ossification of bone fragments, so other factors need to be taken into account to make a comprehensive diagnosis. Extensive bone fragmentation, disease activity, peripheral joint involvement, and spinal functional limitations. 2.2 Risk of falls The increased risk of falls in postmenopausal osteoporotic fractures is the main cause of fractures by factors such as vision, hearing, balance, and decreased muscle strength, unlike the risk of falls in AS, which is not supported by definitive research data, however, in terms of the bony destruction and fusion that exists in the spine itself, even minor external forces may cause serious injury, so future in-depth studies on the role of external injury risk factors in the assessment of fracture risk in patients with As appear to be very important. 2.3 Low BMD and its correct assessment method In the early stages of AS, there is a reduction in BMD and persistent bone loss. However, the current BMD detection method of dual-energy x-rays is less accurate for the reduced vertebral BMD caused by AS due to the influence of paravertebral bone fragments and subperiosteal ossification. A study snapped1 showed that the BMD of the lumbar spine, femoral neck, triangle, and ramus in AS patients with normal spine function was significantly lower compared to healthy controls, but in patients with advanced As there was no significant difference in the BMD of the lumbar spine compared to healthy controls, while the BMD of the femoral neck, triangle, and ramus differed significantly from controls, mainly due to the increase in lumbar vertebral bone redundancy as the disease progressed in As making the BMD measured by dual-energy x-ray BMD of the lumbar spine produced a pseudo-increase. Therefore, the detection of osteoporosis or bone loss in patients with AS requires consideration of the effect of the duration of the disease and the location of the examined site on the results. In patients with juvenile AS, it is more appropriate to measure BMD in the femoral neck than in the lumbar spine. In conclusion, BMD results detected by dual-energy X-rays of the hip can support the determination of osteoporosis, and its value is proportional to the risk of vertebral fracture. Early low BMD is not associated with spinal mobility and exercise, and the presence of reduced BMD can be determined by the analysis of scores of bone redundancy, the stage of disease activity and indicators of bone resorption. The study showed that the anti-tartaric acid phosphatase (TRAP) in AS patients varied with blood sedimentation (ESR), C-reactive protein (CRP), BathAS disease activity index (BASDAI), gender, and disease duration, and the largest OR value was found for BASDAI in multivariate analysis. thus, it was concluded that in addition to fractures caused by problems such as falls caused by bone in AS patients, the structural nature of the bone itself problems are also the main cause of ease of fracture. However, this approach is increasingly limited by the interference of peripheral ossification of the bone, so it needs to be combined with other factors, specifically, gender (more males than females), age, low body weight, low BMD, duration of disease, and vertebral fracture. extensive intervertebral bone formation, degree of peripheral joint involvement in disease activity status, and functional limitations of the spine. 2.4 Analysis of microstructural damage As early histological studies of the lesion showed that bone formation in the iliac spine and ribs began to slow down, serum tests would show increased bone resorption indexes and decreased bone formation indexes, leading to an imbalance between bone formation and bone resorption, especially during the active phase of the disease, bone resorption would increase significantly. The resulting accumulation of bone-like material and thinning of bone trabeculae are related to vitamin D metabolism oldo, which suggests that we need to pay attention to vitamin D-related treatment for patients with As. With the onset of hyperostosis, processes such as bone mineralization are affected, resulting in stress concentration in the trabeculae and causing microdamage to the bone. The structure of the vertebral body is characterized by a large amount of cancellous bone and a small amount of dense bone, resulting in a lightweight but ductile and strong material. Damage to the trabeculae occurs early in AS, resulting in microfractures that accumulate over time and gradually result in compression fractures of the vertebral body, and the resulting difference in the hardness of the vertebral material increases the chance of fracture of the adjacent vertebral body, as has been confirmed. In the advanced stages of the disease, the ankylosis of the joints and the formation of paravertebral bones cause the otherwise flexible spine to fuse together to form a structure resembling a long bone, but the weakening of the trabeculae within the vertebral body makes the cortex act as a shell that has difficulty withstanding the external load, resulting in fractures, nerve damage, and other injuries. In conclusion, vertebral fractures due to osteoporosis in patients with As need to be taken seriously, and their early diagnosis can help in early treatment and assessment of disease progression. This suggests the need for effective assessment of osteoporosis status along with spinal function, serum indices and imaging indices when receiving AS. Care needs to be taken to rule out the influence of structural problems in the spine itself on the BMD results. Priority can be given to BMD testing of the hip joint, and the presence of problems with bone microstructure can be determined indirectly by testing bone metabolic indicators. If persistent back pain is present, further imaging, such as MRI, can be considered to avoid misdiagnosis. Treatment of osteoporosis is required along with the treatment of As. Especially in patients with established osteoporosis, supplemental anti-osteoporosis treatment along with the treatment of As is better than symptomatic treatment alone. In order to minimize the increased risk of osteoporosis due to the treatment of AS, the dose and duration of hormones during the treatment of As need to be appropriately controlled, e.g., the duration of prednisone use should not exceed six months and should be controlled to less than 15 mg/day.