Diffuse idiopathic skeletal hyperostosis (DISH) is an easily overlooked systemic disease characterized by ossification or calcification of spinal ligaments and entheses (1). Predominantly affecting the lower thoracic and thoracolumbar regions of the spine, DISH can also extend to the peripheral skeleton, causing hyperplastic joint changes and a decrease in mobility (2).The cause of DISH remains obscure and is suspected to involve a combination of genetic factors, metabolic processes, and inflammatory mechanisms (1, 3). The hallmark of this disease is the development of new bone, partly in entheses (3).

Forestier and Rotes-Querol initially characterized DISH in 1950, referring to it as “ankylosing hyperostosis” (4). Subsequently, Resnick and colleagues established diagnostic criteria for DISH, which include the presence of calcification along the anterolateral aspects of at least four consecutive vertebral bodies, maintenance of the intervertebral disc space, and absence of sacroiliac and apophyseal joint fusion or erosion (5). A definitive diagnosis of DISH is confirmed through the identification of these specific spinal morphological changes on imaging studies ( Figure 1 ). Since DISH is predominantly asymptomatic and many individuals are not cognizant of its early presence, it has not been widely studied by medical professionals. However, in recent years, more and more evidence has shown that DISH is an indicator for a variety of pathological states, such as diabetes, hyperinsulinemia, dyslipidemia, and hyperuricemia have been reported (6–9). Furthermore, the bone formation associated with DISH may result in alterations to the musculoskeletal system’s biomechanics and the development of obstructive cervical masses (10, 11). Additionally, several studies have identified a correlation between DISH and incidents of vertebral fractures and cerebrovascular events (12, 13).

There is a scarcity of data regarding the worldwide incidence of DISH. Consequently, we conducted a systematic review and meta-analysis of existing literature with the aims: (1) to determine the global prevalence of DISH among both the general population and clinical patients; (2) to investigate the prevalence in relation to potential correlates, including publication year, geographical region, gender, age distribution, and race.

To our knowledge, this systematic review and meta-analysis represents the inaugural effort to assess the worldwide prevalence of DISH among both the general population and clinical patients. Within this study, we examined the global prevalence of DISH across various spatial, temporal, and demographic dimensions. The findings revealed an overall estimated prevalence of DISH of 11.92% within the general population and 14.30% among clinical patients. Additionally, this research indicates that men exhibit a higher prevalence of DISH in comparison to women. It mainly affects people aged 50 and over, and it tends to increase with age. In addition, the prevalence of DISH in black race is lower than that in white and Asian race. However, the number of studies in black race was limited, and more research was needed to enhance reliability. No statistical association was observed between the prevalence of DISH and year of publication. Due to the high heterogeneity of the included studies, which may be attributed to differences in study design, population characteristics, and diagnostic criteria, our findings should be interpreted with caution.

There is high heterogeneity among studies on the prevalence of DISH for several possible reasons. First, because DISH is, for the most part, an asymptomatic disease, most patients do not seek medical help, and the diagnosis of this disease is usually established during an examination of other disorders. Therefore, it is difficult to reliably estimate the prevalence of DISH in the population, which inevitably involves chance factors. In addition, the criteria for establishing the diagnosis of DISH are not always uniformly applied. The Resnick and Niwayama criteria of 1976 called for a “bone bridge” connecting at least 4 adjacent vertebrae, or ossification of the anterior longitudinal ligament, while maintaining intervertebral height, with no spondyloarthritis or sacroiliac joint changes (5). On the basis of the former, some scholars also lowered the standard to three adjacent vertebral bodies or there may be incompletely connected bone bridges between vertebral bodies (50). In addition, some scholars have also included factors such as the influence of surrounding bones, because the manifestations of DISH are not limited to the spine, and peripheral joints and joint capsules are often affected (51). Indeed, ossification and/or calcification near peripheral joints, such as tendons, ligaments, and joint capsules, can be observed in patients with DISH (52, 53). What’s more, some diseases that manifest as excessive bone formation and bone involvement can easily confuse the diagnosis (54), such as ankylosing spondylitis, ossification of the anterior longitudinal ligament, etc. These diseases all have a tendency to ossify ligaments or joints, and it is not always easy to distinguish these diseases. In addition, the choice of imageological examination also has an impact, such as choosing X-ray or CT examination, choosing thoracic spine or whole spine (34). In previous reports, the prevalence of DISH identified only by x-ray was lower than that using CT (42). Finally, methodological heterogeneity should also be taken into account, as the prevalence data came from different study designs with different levels of methodological quality. Examples include different study populations, sampling methods and coverage of samples, sample size, imageological examinations, data collection, participant collaboration, and examiner expertise, resulting in differences between studies.

Overall, our study found a higher prevalence in clinical patients than in the general population. As previously described, DISH is in most cases an asymptomatic disease that can be difficult to detect without appropriate testing. Another reason is that DISH disease has been found to be significantly associated with metabolic diseases (such as diabetes, obesity, and hyperuricemia), fractures, and low back pain, and because the effects of these diseases are detected at the time of care, clinical patients have a relatively higher prevalence than the general population. Our study also found that, according to different populations, races, ages, sexes, and imaging studies, the prevalence of DISH varied greatly among different studies ( Tables 1 , 2 ).

Subgroup analysis by sex showed a higher prevalence of DISH in men than in women, unlike many types of arthritis. One of the reasons for this discrepancy may be related to manual labor. DISH, similar to osteophyte formation, is considered to be a response of the bone to stress or repeated microtrauma, and it is mainly seen in manual laborers, especially men (55). Julkunen et al. (32) analyzed the occupation of their patients and found that heavy physical labor may increase the chance of disease, however, further research is still needed to fully understand the underlying mechanisms. Subgroup analysis by age showed that DISH diseases mainly affected people aged 50 years and over, and there was an increasing trend with age. One of the reasons may be related to the continuous development of the formation of DISH. The onset process of DISH begins in early life, but it takes decades for the disease to fully develop and meet the diagnostic criteria (3). Another possible reason is related to multiple metabolic factors, which are widely recognized as key determinants in patients with DISH. Known risk factors such as obesity, diabetes and hormones themselves are also associated with aging. Obesity is closely associated with DISH as well as other widespread musculoskeletal disorders (56, 57), and the role of adipokines in the pathogenesis of DISH has been proposed because they affect bone metabolism and promote the number and activity of osteoblasts (58, 59). Several studies analyzing the link between DISH and diabetes have suggested that a possible pathogenesis is that high levels of insulin or insulin-like growth factor stimulate new bone formation (60). In fact, insulin is a peptide that promotes bone growth (61) and is considered a key player in the pathophysiology of DISH and other spinal inflammatory and degenerative diseases (62). In addition, hormones or growth factors are also involved in the pathogenesis of DISH because they act on fibroblasts, chondrocytes, and collagen fibers of cartilage to promote bone regeneration (63).

Subgroup analysis by race showed that the Black race has a lower incidence of DISH than the White race and the Asian race. This may be because the Black race possesses some specific gene sequences or gene expression patterns, which influence physiological processes related to the pathogenesis of DISH, such as bone metabolism and cell signaling pathways. Certain genes may endow the bones of Black individuals with a stronger resistance to the pathological processes leading to DISH, reducing the tendency of bone spur formation and ligament calcification, thus decreasing the occurrence of DISH. Another reason is that Black people may face a shortage of healthcare resources, which may lead to a relatively higher rate of missed diagnosis or misdiagnosis of DISH. Some early-stage or mildly symptomatic DISH cases may not be detected and diagnosed in a timely manner. In addition, due to their relatively disadvantaged socioeconomic status and the relative scarcity of medical facilities, the conduct of clinical research is limited. Considering cultural and ideological factors as well, there is relatively less research on the Black race compared to the White and Asian races.

At present, the pathogenesis of DISH is still unclear. It is increasingly recognized that the development of DISH disease is progressive continuously (64). From the microscopic level, the most important feature in the early stage is the formation of new bone, which progressively forms a bony bridge from one vertebral body to the adjacent vertebral body, accompanied by biomechanical changes (65). According to Wolff’s law, bone is continuously remodeled under the influence of biomechanical loading (66). Over time, under long-term gravitational loading, the bone bridge may gradually integrate the upper and lower vertebral bodies. New bone is mainly formed in the epiphysis, and local fibroblasts, chondrocytes, collagen fibers, and calcified matrix can promote the formation of new bone, but it is affected by genetic, vascular, metabolic, and mechanical factors (67). In addition, diseases related to modern lifestyles, such as obesity and type 2 diabetes, have been associated with the development of DISH (56, 60), which has emerged in Western European countries such as the United Kingdom. As DISH is frequently found to be comorbid with metabolic disorders, DISH may be driven at least in part by biochemical pathways shared with metabolic disorders such as hyperlipidemia and hyperglycemia (19). In addition, it is also related to genetics. Sethi et al. (68) identified 10 DISH-related loci through genetic association analysis, including multiple genes related to bone remodeling, such as osteogenesis master regulator RUNX2, BMP signaling pathway (CHRDL2, NOG, GDFS), wnt signaling pathway (ROR2) and ILI1 etc., implying that overactive osteogenesis plays an important role in the disease development of DISH.

In clinical practice, it has been found that DISH has a direct correlation with fractures (13, 69). Continuously fused spinal segments in patients with DISH resemble long bones, and the number of fused segments determines the length of the “lever arm” over which traumatic forces can act. Longer lever arms can cause severely displaced spinal fractures after relatively minor trauma, such as a fall from standing or sitting position or a low-speed motor vehicle crash (39). On the other hand, it is well known that the reduction of intravertebral bone mineral density is inversely proportional to the extravertebral bone hyperplasia over time (70). When attempting to assess bone mineral density using dual-energy X-ray absorptiometry (DEXA), the occurrence of extravertebral hyperostosis can lead to markedly increased bone density, making it difficult to assess intravertebral osteoporosis.

Therefore, this may hamper the appropriate treatment of osteoporosis in DISH patients, making patients more prone to spinal fractures. As mentioned above, many of the problems associated with DISH observed in the spine have been noted so far, but few large epidemiological investigations of this disease have been reported. Knowledge of the epidemiology and associated clinical and radiological features of DISH may help improve awareness among rheumatologists, radiologists, and their associated clinicians, and allow proper recognition and reporting of the condition. In addition, we also expect that by comparing the incidence rates of populations with different exposure factors, we can identify potential causative agents and risk factors, providing data support for the rational allocation of healthcare resources and the formulation of health policies. Although the excessive bone formation in DISH is unlikely to be reversed, it may be prevented with increased knowledge. Therefore, it is necessary to conduct a large-scale epidemiological study of the disease to understand the clinical characteristics of DISH and its prevalence, natural process and outcome, which will help pave the way for more targeted and effective treatments in the future.

This study determined the global prevalence of DISH in terms of spatial, temporal and population distribution. We estimated the overall prevalence of DISH to be approximately 11.92% (95%CI, 8.68%-15.59%) in the general population and 14.30% (95% CI, 10.10%-19.09%) in clinical patients. In addition, it was also found that the prevalence of DISH was higher in men compared with women. It mainly affects people aged 50 and over, and it tends to increase with age. Black race has a lower incidence of DISH than white race and Asian race. Due to the high heterogeneity of the included studies, our findings should be considered with caution.