Background: Computed tomography (CT) analyses have reported that the prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in Japan is 8.7–27.1%. However, these data were obtained using chest-abdominal CT, and no evaluations of sagittal, coronal, and axial images using whole-spine CT have been reported. The aim of this study was to investigate the prevalence and characteristic of DISH by whole spinal CT. Methods: Participants were patients who had experienced trauma who had undergone whole-spine CT scanning based on the initial clinical practice guidelines for trauma in our institute from April 2015 to February 2018. The subjects were > 20 years old and 1479 were included in the analysis. The presence and distribution of DISH and clinical parameters such as age and sex were reviewed retrospectively according to the location of DISH. Results: The overall prevalence of DISH was 19.5% (n = 289). Subjects with DISH were older than those without. DISH was located in the thoracic spine in 65.1% and thoracolumbar spine in 24.2% of patients. More than 80% of ligamentous ossifications associated with DISH occurred at T8 (n = 255, 88%), T9 (n = 262, 91%), and T10 (n = 247, 85%). Most of the ossification occurred to the right anterior of the vertebral body, and there were few ossifications in the areas in contact with the artery and vein. Conclusions: The prevalence of DISH based on whole-spine CT was 19.5%. Ossification was noted more often at T8, T9, and T10, and to the right anterior of the vertebral body. It is for the first time report that we have studied the location of ossification in detail using the axial images of whole spine CT. We hope this study will enhance the understanding of the characteristics of DISH. Keywords: Diffuse idiopathic skeletal hyperostosis (DISH), Computed tomography (CT), Prevalence, Thoracic spine Background etiology is not easily identified. In Japan, which is experi- Recently, much attention has focused on vertebral encing an aging society, the prevalence of minor paraly- fractures accompanying diffuse idiopathic skeletal hyper- sis caused by trauma is on the rise. ostosis (DISH). That is, an ankylosed spine tends to frac- Proposed by Resnick et al. in 1975, DISH is a degen- ture as result of minor injuries such as falling because of erative disease in which the spinal longitudinal ligaments stress concentration. Such fractures can cause reverse and entheses gradually become ossified . The patho- chance fractures that can lead to spinal paralyses, and genetic mechanisms responsible for DISH are poorly are often resistant to conservative treatment [1–3]. Like understood, but genetic, metabolic, endocrine, anatomic, other conditions with ligament ossification, DISH is environmental, and toxic factors may contribute to its’ thought to result from a multifactorial process whose development [5, 6]. Moreover, DISH is a condition of the elderly and is rarely seen before middle age. It is more common in males than in females with male/fe- * Correspondence: firstname.lastname@example.org Department of Orthopaedic Surgery, Tokai University School of Medicine, male ratios ranging between 2:1 and 7:1 [7, 8]. The 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Hiyama et al. BMC Musculoskeletal Disorders (2018) 19:178 Page 2 of 7 criteria most often used to diagnose DISH was first re- Table 1 Distribution of study population according to sex ported by Resnick and Niwayama in 1976 , before Age group, yrs Male Female ALL computed tomography (CT) was available as a diagnos- 20–39 286 93 379 tic tool. However, when examining the prevalence of 40–49 167 60 227 DISH, the problem is that the criteria also differs 50–59 160 46 206 according to the article [9, 10]. 60–69 167 70 237 The prevalence of DISH reported both in Japan and 70–79 162 98 260 internationally varies widely between 3.8–25% [8, 9, 11–15]. It is considered to occur more frequently in Caucasians 80–89 70 77 147 than in people of Asian and Black ethnicity. However, 90- 11 12 23 some groups have suggested that this considerable vari- 1023 456 1479 ation could be attributed to the incomplete diagnosis of DISH based on X-ray alone. CT provides far more detailed imaging of the intervertebral disc spaces and bridging ligamentous ossification in ≥4 contiguous vertebrae of ossifications, but there are only a few reports on CT-based the spine, with preserved intervertebral disc space, and diagnosis of DISH. Analyses using CT have reported that the absence of inflammatory changes in the apophyseal the prevalence of DISH in Japan averages 8.7% (13% for joints or the sacroiliac region. The reconstructed CT males, 2.5% for females) and may be as high as 27.1% sagittal, coronal, and axial images (Fig. 1) were used (38.7% for males, 13.9% for females) [12, 16]. However, rather than X-ray to evaluate the continuous ligament these data were obtained using chest-abdominal CT, and ossification. All CT data were evaluated by authors. For evaluations using sagittal, coronal, and axial whole-spine testing the reliability of diagnoses, the testers read the CT have not been reported. Most of the patients surveyed same images of 20 patients to check inter-observer so far have been older than 40 years and, therefore, the agreement. We also used intra-observer error at differ- true prevalence is unknown. The purpose of this study ent time points, and the interval was found to be longer was to use whole-spine CT to investigate the prevalence than one month by the first author. Differences were and characteristics of DISH in trauma patients examined settled by consensus to minimize intra- and inter-observer in an emergency critical care setting. In addition, we hope bias and errors. Finally all images were reviewed by the this study will enhance the understanding of the charac- first author. teristics of DISH. Statistical analysis Methods Statistical analysis was performed using SPSS software Our institution is a tertiary emergency medical facility for Windows (v. 20.0; IBM Corp., Armonk, NY, USA). that treats over 800 patients with severe trauma a year. All values are expressed as mean ± standard deviation. The patients included in this study were those who had We studied statistical differences between the group undergone whole-spine CT scanning during the period with and without DISH. Analysis of DISH prevalence in between April 2015 to February 2018 based on the males and females was performed using the chi-squared clinical practice guidelines for trauma patients at our test. Analysis of variance with a post hoc test (Mann– institute. The patients were aged over 20 years and their Whitney U test) was used for comparisons. P-values mean age was 54.7 years. < 0.05 were considered significant. A total of 1479 subjects were included in the analysis: 1023 males and 456 females. The presence and distribu- Results tion of DISH, and their clinical parameters such as age The Kappa coefficient of inter- and intra-observer agree- and sex were reviewed retrospectively and classified ments were 0.79 and 0.89, respectively. according to the location of DISH. The numbers of The demographics of the subjects included in this subjects in the age groups 20–39, 40–49, 50–59, 60–69, study are shown in Table 2. The prevalence of DISH was 70–79, 80–89, and ≥90 years were described in Table 1. 19.5% (289/1479). The subjects with DISH were signifi- cantly older than those without: 71.7 and 50.6 years, re- Computed tomography (CT) examination spectively (P < 0.001). The prevalence of DISH increased All CT scans were performed on a multidetector CT with age. The prevalence of DISH in subjects aged ≥70 (120 kV, 380 mA, 0.6 mm slice; SOMATOM Definition years was 40.9% (176/430), indicating that one in two AS; Siemens Healthcare, Forchheim, Germany) equipped people ≥70 years had DISH. In addition, the prevalence with a 128-slice multidetector array. The diagnosis of of DISH increased with age in both males and females DISH was based on whole-spine CT according to the (Fig. 2a). The results showed that the prevalence rates criteria proposed by Resnick and Niwayama : flowing classified by age groups 20–39, 40–49, 50–59, 60–69, Hiyama et al. BMC Musculoskeletal Disorders (2018) 19:178 Page 3 of 7 Fig. 1 CT images of a patient with DISH. Reconstructed CT of sagittal (a), axial (b), coronal (c) and 3D (d) views in a patient with DISH 70–79, 80–89, and ≥90 years were 0.3, 4.8, 18.1, 32.3, We classified DISH into six types according to 50.0, 51.4, and 63.6% in male and 0, 3.3, 10.9, 20.0, 19.4, location in which ossification along the aspect of ≥4 36.4, and 41.7% in female, respectively. There were a sig- contiguous vertebral bodies was observed: (1) cervical— nificantly greater number of subjects with DISH in their ossification only in the cervical region (C1–C7); (2) cer- 70s using the chi-squared test. vicothoracic—ossification only in the cervicothoracic Among the 289 subjects with DISH, 216 (prevalence region (C1–T12); (3) thoracic—ossification only in the 216/1023 = 21.1%) were male and 73 (73/456 = 16.0%) thoracic region (T1–T12); (4) thoracolumbar—ossifica- were female (Fig. 2b). This tendency for a higher fre- tion only in the thoracolumbar region (T1–L5); (5) quency in male was a significant (P < 0.05). In addition, lumbar—ossification only in the lumbar region (L1–L5); when analyzed with subjects ≥40 years as in previous and (6) whole spine—ossification in the entire spine reports, the prevalence of DISH in 737 males and 363 (C1–L5). Figure 3 shows the prevalence of DISH classi- females was 29.2% (215/737) and 20.1% (73/363), fied by location in the spine: 65.1% were thoracic, and respectively, also showing a significant sex difference 24.2% were thoracolumbar. The prevalence of cervical (P < 0.01) (data not shown). and lumbar spine involvement was low. Evaluation of the fused segments from the cervical to lumbar spine for all subjects revealed that the eighth Table 2 Distribution of study population according to DISH(+) thoracic (T8) to the 10th thoracic (T10) levels were the or (−) levels most involved, with more than 80% of the liga- DISH (+) DISH (−) ALL mentous ossifications associated with DISH located at Sex N N N (%) T8 (n = 255segments/289subjects, 88%), T9 (n = 262seg- Male 216 807 1023 (69.2) ments/289subjects, 91%), or T10 (n = 247segments/ 289subjects, 85%) (Fig. 3). Of the 233 cases with Female 73 383 456 (30.8) consecutive ossification at T8–T10, the apex of thor- Male to Female 3.0: 1 2.1: 1 2.3: 1 acic kyphosis was located at T8–T10 in 142 subjects Age, Mean 71.7 50.6 54.7 (60.9%) (Table 3). Age group, yrs N (%) N (%) N Axial images of the ossification lesions at T9 (Fig. 4a) 20–39 1 (0.3) 378 (99.7) 379 were studied further focusing on the location of the 40–49 10 (4.4) 217 (95.6) 227 ossification, revealing that the ossification at T9 was observed in almost all cases in area 1, which is the right 50–59 34 (16.5) 172 (83.5) 206 anterior region of the vertebra (98.3%) (Fig. 4b). As age 60–69 68 (28.7) 169 (71.3) 237 increased, ossification in the left anterior region also ap- 70–79 100 (38.5) 160 (61.5) 260 peared (Table 4). In a few subjects, the ossification was 80–89 64 (43.5) 83 (56.5) 147 observed in the area in contact with the aorta and the 90- 12 (52.2) 11 (47.8) 23 azygous vein (Fig. 4c). The average number of vertebral Total (%) 289 (19.5) 1190 (80.5) 1479 bodies continuously bridged by ossification of the anter- DISH diffuse idiopathic skeletal hyperostosis, N number ior longitudinal ligament was 7.9, and involvement of Hiyama et al. BMC Musculoskeletal Disorders (2018) 19:178 Page 4 of 7 Fig. 2 Prevalence of DISH detected by CT. a Age distribution of the prevalence of DISH detected by CT. The prevalence of DISH increased with age in both males and females. b Comparison of the prevalence of DISH between male and female ≥12 vertebrae was seen in 47 of the 289 patients (16.3%). would exclude the effects of race and genetic factors, has The average numbers of ossified vertebrae according been reported to range from 8.7 to 27.1% [12, 13, 16]. to the age groups 20–49 (n = 11), 50–59 (n = 34), Based on chest X-rays of 1363 patients, Weinfeld et al. 60–69 (n = 68), 70–79 (n = 100), 80–89 (n =64), and showed that the prevalence differed between ethnic ≥90 (n = 12) years were 6.8 ± 2.0, 6.8 ± 2.6, 7.4 ± 3.2, groups . They reported DISH to be less common in 8.3 ± 3.5, 8.3 ± 4.2, and 9.4 ± 3.6, respectively, showing the black, Native-American and Asian populations. that the number of vertebrae with ligamentous ossifi- The prevalence of DISH may differ between past and cation increased with age. present reports because of advances in diagnostic imaging (Additional file 1). In past reports, DISH was Discussion identified by X-ray alone, which resulted in lower preva- DISH is a common condition in the elderly, but DISH is lence than that identified by recent reports of DISH still insufficiently investigated and understood. In this identified through examination of chest CT. Hirasawa et study, CT images of the whole spine were used to al. compared the prevalence of DISH evaluated by re- determine the prevalence of DISH in 1479 patients aged constructed CT of the chest to pelvis against plain radi- > 20 years. While the prevalence of DISH has been ography of the chest and abdomen , and found that reported to vary widely from 3.8 to 25%, it was 19.5% in the prevalence of DISH based on CT was 27.1% and that these subjects. Factors that may affect the prevalence of based on X-ray was 17.6%. Mori et al. reported that the DISH include differences in ethnic and genetic back- prevalence of DISH was 8.7% using chest CT performed ground, diagnostic imaging methods, patient age, and for investigation of pulmonary disease , which was lifestyle habits. The prevalence of DISH in Japan, which smaller than that reported by Hirasawa et al. . The Fig. 3 Prevalence of DISH classified by location in the spine. The levels of fused segments are shown from the cervical to lumbar spine, and involved mainly T8–10 Hiyama et al. BMC Musculoskeletal Disorders (2018) 19:178 Page 5 of 7 Table 3 Among 233 subjects who had consecutive ossification for the differences from the study by Hirasawa et al. in T8 - T10, 142 subjects were found at the apex of the thoracic . Our findings and those of previous reports indicate kyphosis at T8 - T10 that most cases of DISH occur in the middle and lower Apex of kyphosis N % thoracic spine. This means that when making the diag- T5 1 0.4 nosis, evaluation using whole-spine CT will be more effective than X-ray [12, 16]. On the accuracy of DISH T6 11 4.7 diagnosis by CT, intra- and inter-observer error by re- T7 37 15.9 view of CT was also less than that of X-ray . From T8 68 29.2 these data, we think that CT may be a most suitable T9 47 20.2 142 (60.9%) modality for the evaluation of DISH. Thus, analysis of T10 27 11.6 the prevalence of DISH and its characteristics from the T11 25 10.7 analysis using CT is considered to be useful for analyz- ing the treatment and pathology. T12 11 4.7 Another possible reason for the difference in preva- L1 5 2.1 lence of DISH is age of the study population. Most L3 1 0.4 previous reports only included people older than 40 years with an average of 65 years [8, 13, 17], whereas in this N number study, we included younger patients (> 20 years) for an average age of 54.7 years old. differences in prevalence between these studies may re- One limitation of our study is that the patients’ past late to the sample size: that Mori et al. evaluated a large history was not analyzed; in particular, the presence of number of subjects (3013 cases), but was a patient-based metabolic disease, because the distribution of these and not a population-based study . They acknowl- patients may affect the prevalence of DISH. Although edged that the relationship between pulmonary disease the pathogenesis of DISH has not been fully elucidated, and ossification of the spinal ligaments, including DISH, DISH may be related to modern lifestyle-related diseases could have affected the prevalence data. Moreover, the such as obesity and metabolic syndrome, and the preva- study by Mori et al. included only chest CT and was not lence rate of DISH may be higher in those with meta- based on CT of the chest to pelvis, which may account bolic disease. Some have suggested that its prevalence Fig. 4 Axial (AX) image of the areas showing ossification at T9. a A 58-year-old man presented with DISH between T7–11. The vertebral body was divided into 4 areas from the AX image of T9. In this case ossification was observed in area 1 (arrow). b Location of ossification on vertebral body: Area 1, right anterior; Area 2, left anterior; Area 3, right posterior; Area 4, left posterior. c Ossification was rarely found in vertebral bodies contacting with the aorta and the azygous vein Hiyama et al. BMC Musculoskeletal Disorders (2018) 19:178 Page 6 of 7 Table 4 Axial image of the lesion of ossification at the T9 level ossification occurred to the right anterior of the verte- among 233 subjects who had consecutive ossification in T8 - T10 bral body, and there were few ossifications in the area in T9 Lesion T9 Lesion contact with the arteries and veins. Previous study also demonstrated that the location of ossification was 12 34 1 2 3 4 termed as anteolateral or right-sided hyperostosis . Age, yrs N % Arterial blood flow and blood pressure may be affecting 20–39 110 00 100 0 0 0 the ossification progress of DISH. Unfortunately we do 40–49 7 6 1 3 1 85.7 14.3 42.9 14.3 not know about this mechanism from this study. How- 50–59 24 24 3 18 1 100.0 12.5 75.0 4.2 ever, it is for the first time report that we have studied 60–69 54 52 6 24 3 96.3 11.1 44.4 5.6 the location of ossification in detail using the axial im- 70–79 86 85 25 56 10 98.8 29.1 65.1 11.6 ages of whole spine CT. To date, the current knowledge on the pathogenesis of 80–89 51 51 29 35 18 100.0 56.9 68.6 35.3 DISH is very limited. Some groups have reported that the 90- 10 10 7 8 4 100.0 70.0 80.0 40.0 pathogenesis of DISH is based on the excess of growth 233 229 71 144 37 98.3 30.5 61.8 15.9 factors that might induce transformation of mesenchymal N number cells into fibroblasts and osteoblasts [20–22]. We think that it is need further analysis of these molecular mecha- may increase in the coming decades because of the rela- nisms, which is important to clarify the etiology of DISH tionship between DISH and such modern lifestyle-related in the future. Okada et al. reported that the thoracolumbar diseases [5, 6, 18, 19]. We could not investigate any pos- junction (T11–L2) was the most frequently fractured level sible associations between such factors and DISH because (54.8%) in patients with DISH . The fact that vertebral no clinical background information except for age and sex body fractures associated with DISH are more frequent in were available in our retrospective study. the thoracolumbar junction may be related to the fact that Other studies have reported a higher prevalence of most of DISH occurs from T8 to T10. However, in this DISH in males than in females. The Research on Osteo- cross-sectional study, it was impossible to evaluate arthritis/Osteoporosis Against Disability (ROAD) study of whether DISH occurred first in the thoracic spine and Kagotani et al. investigated the prevalence of DISH in then secondarily in the cervical or lumbar spine. 1647 people who underwent whole-spine X-ray . Their This study has some limitations. First, we did not have logistic regression analysis revealed that the prevalence of access to clinical data such as the presence of diabetes, DISH was associated with male sex (odds ratio (OR): 5.55) which is a risk factor associated with DISH. This was a and presence of severe lumbar spondylosis (OR: 5.50). It retrospective study and it was not possible to investigate appears that male tend to be more likely to develop DISH all subjects. Second, there may have been selection bias in than female regardless of ethnicity or genetic factors. In the inclusion of subjects due to the fact that they were all our study, there was a tendency for the prevalence of trauma patients, but we did not have access to data about DISH to be higher in males than in females, but the differ- each patient before their trauma. DISH patients are ence was small than in previous studies. It is possible that usually asymptomatic, and health checks of the general this result may have been affected by the inclusion of population will be an excellent way to evaluate the preva- younger patients than in previous studies. lence of DISH. Finally, the radiation exposure experienced The most common site of DISH is the thoracic spine. in whole-spine CT imaging in normal subjects is a health We found that most of the ossification occurred in the risk that must be considered. Some researchers agree that, middle and lower thoracic spine: T8 (88%), T9 (91%), when used correctly, such scans can save lives. However, and T10 (85%). It is interesting that DISH occurs at according to some estimates, the radiation exposure a these sites. Hirasawa et al. and Kagotani et al. also found patient receives from a full-body CT scan is often 500 that DISH frequently occurred at T7–10 [12, 13]. times that of an X-ray. Despite these limitations, our data Hirasawa et al. reported that more than 80% of DISH suggest that the prevalence of DISH in Japan is larger than occurred at T8/9 or T9/10, which may reflect an ana- in past reports. We believe that prospective multicenter tomical effect; these vertebrae are susceptible to com- studies are needed to determine the prevalence and patho- pressive mechanical stress because T8 is located almost genesis of DISH. at the peak of the physiological spinal kyphosis. Accord- ingly, DISH seems to arise mainly from the thoracic Conclusions spine and may extend to the cervical and/or lumbar The prevalence of DISH based on whole-spine CT was spine because of mechanical stress. Similar results were 19.5%, which is similar to that reported by other studies. obtained in this study when the peak of spinal kyphosis Most ossification occurred at levels T8–10 and in the was evaluated by supine CT. Interestingly, most of the right anterior region of the vertebral body. Hiyama et al. BMC Musculoskeletal Disorders (2018) 19:178 Page 7 of 7 Additional file 10. Mata S, Chhem RK, Fortin PR, Joseph L, Esdaile JM. Comprehensive radiographic evaluation of diffuse idiopathic skeletal hyperostosis: development and interrater reliability of a scoring system. Semin Arthritis Additional file 1: Previous of DISH in each investigative modality. N: Rheum. 1998;28(2):88–96. number, Xp: x-ray, AP: anterior-posterior, PA: posterior-anterior, CT: 11. Cassim B, Mody GM, Rubin DL. The prevalence of diffuse idiopathic skeletal computed tomography. (DOC 47 kb) hyperostosis in African blacks. Br J Rheumatol. 1990;29(2):131–2. 12. Hirasawa A, Wakao N, Kamiya M, Takeuchi M, Kawanami K, Murotani K, Matsuo T, Deie M. The prevalence of diffuse idiopathic skeletal hyperostosis Abbreviations in Japan - the first report of measurement by CT and review of the CT: Computed tomography; DISH: Diffuse idiopathic skeletal hyperostosis; literature. J Orthop Sci. 2016;21(3):287–90. ROAD: Research on Osteoarthritis/Osteoporosis Against Disability 13. Kagotani R, Yoshida M, Muraki S, Oka H, Hashizume H, Yamada H, Enyo Y, Nagata K, Ishimoto Y, Teraguchi M, et al. Prevalence of diffuse idiopathic Funding skeletal hyperostosis (DISH) of the whole spine and its association with Non financial associations that may be relevant or seen as relevant to the lumbar spondylosis and knee osteoarthritis: the ROAD study. J Bone Miner submitted manuscript. Metab. 2015;33(2):221–9. 14. Weinfeld RM, Olson PN, Maki DD, Griffiths HJ. The prevalence of diffuse Availability of data and materials idiopathic skeletal hyperostosis (DISH) in two large American Midwest Data available upon request from corresponding author. metropolitan hospital populations. Skelet Radiol. 1997;26(4):222–5. 15. Westerveld LA, van Ufford HM, Verlaan JJ, Oner FC. The prevalence of Authors’ contributions diffuse idiopathic skeletal hyperostosis in an outpatient population in the All authors have read and approved the manuscript. AH conceived and Netherlands. J Rheumatol. 2008;35(8):1635–8. designed the study and interpreted the results; HK analyzed the data and 16. Mori K, Kasahara T, Mimura T, Nishizawa K, Nakamura A, Imai S. Prevalence interpreted the results; DS acquired the data and interpreted the results; MS of thoracic diffuse idiopathic skeletal hyperostosis (DISH) in Japanese: results acquired the data and interpreted the results; MT analyzed and acquired the of chest CT-based cross-sectional study. J Orthop Sci. 2017;22(1):38–42. data; MW conceived and designed the study and interpreted the results. 17. Oudkerk SF, de Jong PA, Attrach M, Luijkx T, Buckens CF, Mali WP, Oner FC, Resnick DL, Vliegenthart R, Verlaan JJ. Diagnosis of diffuse idiopathic skeletal Ethics approval and consent to participate hyperostosis with chest computed tomography: inter-observer agreement. This investigation was designed as a single-center retrospective comparative Eur Radiol. 2017;27(1):188–94. study and was approved by the Committee on Ethics and the Institutional 18. Laroche M, Moulinier L, Arlet J, Arrue P, Rousseau H, Cantagrel A, Mazieres Review Board of Tokai University School of Medicine (17R239). We have B. Lumbar and cervical stenosis. Frequency of the association, role of the obtained informed consent form with opt-out method from patients. ankylosing hyperostosis. Clin Rheumatol. 1992;11(4):533–5. 19. Sarzi-Puttini P, Atzeni F. New developments in our understanding of DISH Competing interests (diffuse idiopathic skeletal hyperostosis). Curr Opin Rheumatol. 2004;16(3): The authors AH, HK, DS, MS, MT and MW declare that they have no 287–92. competing interests. 20. Iwasawa T, Iwasaki K, Sawada T, Okada A, Ueyama K, Motomura S, Harata S, Inoue I, Toh S, Furukawa KI. Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif Publisher’sNote Tissue Int. 2006;79(6):422–30. Springer Nature remains neutral with regard to jurisdictional claims in 21. Denko CW, Malemud CJ. Body mass index and blood glucose: correlations published maps and institutional affiliations. with serum insulin, growth hormone, and insulin-like growth factor-1 levels in patients with diffuse idiopathic skeletal hyperostosis (DISH). Rheumatol Received: 4 February 2018 Accepted: 22 May 2018 Int. 2006;26(4):292–7. 22. Eckertova M, Krskova K, Penesova A, Radikova Z, Zlnay D, Rovensky J, Zorad S. Impaired insulin secretion and uptake in patients with diffuse idiopathic References skeletal hyperostosis. Endocr Regul. 2009;43(4):149–55. 1. Okada E, Tsuji T, Shimizu K, Kato M, Fukuda K, Kaneko S, Ogawa J, Watanabe K, Ishii K, Nakamura M, et al. CT-based morphological analysis of spinal fractures in patients with diffuse idiopathic skeletal hyperostosis. J Orthop Sci. 2017;22(1):3–9. 2. Balling H, Weckbach A. Hyperextension injuries of the thoracolumbar spine in diffuse idiopathic skeletal hyperostosis. Spine. 2015;40(2):E61–7. 3. Rustagi T, Drazin D, Oner C, York J, Schroeder GD, Vaccaro AR, Oskouian RJ, Chapman JR. Fractures in spinal ankylosing disorders: a narrative review of disease and injury types, treatment techniques, and outcomes. J Orthop Trauma. 2017;31(Suppl 4):S57–74. 4. Resnick D, Shaul SR, Robins JM. Diffuse idiopathic skeletal hyperostosis (DISH): Forestier's disease with extraspinal manifestations. Radiology. 1975; 115(3):513–24. 5. Littlejohn GO. Insulin and new bone formation in diffuse idiopathic skeletal hyperostosis. Clin Rheumatol. 1985;4(3):294–300. 6. Vezyroglou G, Mitropoulos A, Antoniadis C. A metabolic syndrome in diffuse idiopathic skeletal hyperostosis. A controlled study. J Rheumatol. 1996;23(4): 672–6. 7. Julkunen H, Heinonen OP, Knekt P, Maatela J. The epidemiology of hyperostosis of the spine together with its symptoms and related mortality in a general population. Scand J Rheumatol. 1975;4(1):23–7. 8. Kim SK, Choi BR, Kim CG, Chung SH, Choe JY, Joo KB, Bae SC, Yoo DH, Jun JB. The prevalence of diffuse idiopathic skeletal hyperostosis in Korea. J Rheumatol. 2004;31(10):2032–5. 9. Resnick D, Niwayama G. Radiographic and pathologic features of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). Radiology. 1976;119(3):559–68.
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Published: May 30, 2018
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