The prevalence of vertebral fractures in diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis: A systematic review and meta-analysis.

Background: Subjects with ankylosing spinal disorders, including diffuse idiopathic skeletal hyperostosis (DISH) and ankylosing spondylitis (AS) are more prone to vertebral fractures and frequently present with neurological deficit compared to the patients without an ankylosed spine. Moreover, prevalent vertebral fractures are an important predictor for subsequent fracture risk. However, the pooled fracture prevalence for DISH is unknown and less recent for AS. We aimed to systematically investigate the prevalence and risk of vertebral fractures in DISH and AS populations. Methods: Publications in Medline and EMBASE were searched from January 1980 until July 2023 for cohort studies reporting vertebral fractures in AS and DISH. Data on prevalence were pooled with random effects modeling after double arcsine transformation. Heterogeneity was assessed with I2 statistics and we performed subgroup analysis and meta-regression to explore sources of heterogeneity. Results: We included 7 studies on DISH (n = 1,193, total fractures = 231) with a pooled vertebral fracture prevalence of 22.6% (95%CI: 13.4%-33.4%). For AS, 26 studies were included (n = 2,875, total fractures = 460) with a pooled vertebral fracture prevalence of 15.2% (95%CI: 11.6%-19.1%). In general, fracture prevalence for AS remained similar for several study-level and clinically relevant characteristics, including study design, diagnostic criteria, spine level, and patient characteristics in subgroup analysis. AS publications from 2010 to 2020 showed higher fracture prevalence compared to 1990 to 2010 (18.6% vs. 11.6%). Fractures in DISH were most common at the thoracolumbar junction, whereas for AS, the most common location was the mid-thoracic spine. Conclusions: Vertebral fractures are prevalent in AS and DISH populations. Differences in fracture distribution along the spinal axis exist between the 2 disorders. Additional longitudinal studies are needed for incident fracture assessment in patients with ankylosing spinal disorders.

Diffuse idiopathic skeletal hyperostosis of the cervical spine causing dysphagia and airway obstruction: an updated systematic review.

BACKGROUND AND CONTEXT: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by growing ossifications of spinal entheses and tendons, which may cause trachea and esophagus compression when located anteriorly in the cervical spine. PURPOSE: Our previous systematic review on the epidemiological and clinical knowledge of dysphagia and airway obstruction caused by cervical DISH was updated, with a focus on (surgical) treatment and outcomes. STUDY DESIGN: A systematic review of the literature was performed. METHODS: Publications in Medline and EMBASE from July 2010 to June 2021 were searched. Two investigators performed data extraction and study specific quality assessment. RESULTS: A total of 138 articles (112 case reports and 26 case series) were included, describing 419 patients with dysphagia and/or airway obstruction. The mean age of the patient group was 67.3 years (range: 35-91 years), and 85.4% was male. An evident increase of published cases was observed within the last decade. Surgical treatment was chosen for 66% of patients with the anterolateral approach most commonly used. The total complication rate after surgery was 22.1%, with 12.7% occurring within 1 month after intervention. Improvement of dysphagia was observed in 95.5% of operated patients. After a mean follow-up of 3.7 years (range: 0.4-9.0 years), dysphagia recurred in 12 surgically treated patients (4%), of which five patients had osteophyte regrowth. CONCLUSIONS: The number of published cases of dysphagia in patients with DISH has doubled in the last decade compared to our previous review. Yet, randomized studies or guidelines on the treatment or prevention on recurrence are lacking. Surgical treatment is effective and has low (major) complication rates. Common trends established across the cases in our study may help improve our understanding and management of dysphagia and airway obstruction in cervical DISH.

Visceral Adipose Tissue and Different Measures of Adiposity in Different Severities of Diffuse Idiopathic Skeletal Hyperostosis.

BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with both obesity and type 2 diabetes. Our objective was to investigate the relation between DISH and visceral adipose tissue (VAT) in particular, as this would support a causal role of insulin resistance and low grade inflammation in the development of DISH. METHODS: In 4334 patients with manifest vascular disease, the relation between different adiposity measures and the presence of DISH was compared using z-scores via standard deviation logistic regression analyses. Analyses were stratified by sex and adjusted for age, systolic blood pressure, diabetes, non-HDL cholesterol, smoking status, and renal function. RESULTS: DISH was present in 391 (9%) subjects. The presence of DISH was associated with markers of adiposity and had a strong relation with VAT in males (OR: 1.35; 95%CI: 1.20-1.54) and females (OR: 1.43; 95%CI: 1.06-1.93). In males with the most severe DISH (extensive ossification of seven or more vertebral bodies) the association between DISH and VAT was stronger (OR: 1.61; 95%CI: 1.31-1.98), while increased subcutaneous fat was negatively associated with DISH (OR: 0.65; 95%CI: 0.49-0.95). In females, increased subcutaneous fat was associated with the presence of DISH (OR: 1.43; 95%CI: 1.14-1.80). CONCLUSION: Markers of adiposity, including VAT, are strongly associated with the presence of DISH. Subcutaneous adipose tissue thickness was negatively associated with more severe cases of DISH in males, while in females, increased subcutaneous adipose tissue was associated with the presence of DISH.

Diffuse idiopathic skeletal hyperostosis: Etiology and clinical relevance.

Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic bone-forming condition characterized by the presence of at least three bony bridges at the anterolateral spine. The aim of this review was to address the present state of pathophysiological knowledge, the clinical relevance, and diagnosis of DISH. The pathogenesis of DISH is currently unknown. The presence of DISH has been associated with older age, male sex, obesity, hypertension, atherosclerosis, and diabetes mellitus. Because the new bone forms mainly at entheseal sites, local fibroblasts, chondrocytes, collagen fibers, and calcified matrix are probably influenced by genetic, vascular, metabolic, and mechanical factors. Diagnosing the presence of DISH is of clinical importance, because the risk of a spinal fracture increases and associations with the metabolic syndrome, coronary and aortic disease, and respiratory effects are strong. Unravelling the pathogenesis of DISH can impact the field of regenerative medicine and bone tissue regeneration.

Clinical, radiological, and patient-reported outcomes 13 years after pedicle screw fixation with balloon-assisted endplate reduction and cement injection.

PURPOSE: In management of traumatic thoracolumbar burst fractures, short-segment pedicle screw fixation with balloon-assisted endplate reduction (BAER) and cement injection is a safe, feasible, and effective technique to maintain radiological alignment with minimum spinal segments involved. However, 20% of patients report daily discomfort despite good spinal alignment and fusion after this technique. This study provides clinical, radiological, and patient-reported outcomes after a minimum 13 years of follow-up. METHODS: Eighteen patients were invited at the outpatient clinic for clinical/radiological examinations. The cohort (originally 20 patients) was treated 13-14 years earlier with pedicle screw fixation, BAER, and cement injection for traumatic thoracolumbar burst fractures. Patient-reported outcome measures were obtained at time of examinations. Current data were compared with data obtained at 6 years of follow-up. RESULTS: Seventeen patients (median age 50; range 32-80) cooperated. No/minimal back pain was reported by 15 patients, and 12 patients returned to their previous heavy labor work. Median visual analog score of health (80%; 50-100%) was similar to results at 6 years (80%; 60-100% p = 0.259). An Oswestry Disability Index score of less than 20% (reflecting minimal disability) was reported by 14 patients, compared with 15 patients at 6 years of follow-up. No significant differences were found in wedge or Cobb angle between the time points. Intravertebral cement resorption was not observed. CONCLUSION: Results from this study suggest that, 13 years after pedicle screw fixation with BAER and cement injection for traumatic thoracolumbar burst fractures, functional performance, pain and radiological outcomes of the current cohort were stable or had slightly improved. These slides can be retrieved under Electronic Supplementary Material.

Diffuse Idiopathic Skeletal Hyperostosis in Smokers and Restrictive Spirometry Pattern: An Analysis of the COPDGene Cohort.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by bony proliferation at sites of tendinous and ligamentous insertions in the spine. Spinal mobility is reduced in DISH and may affect movement in the thorax, potentially leading to restrictive pulmonary function. This study investigated whether DISH is associated with restrictive spirometric pattern (RSP) in former and current smokers. METHODS: Participants (n = 1784) with complete postbronchodilator spirometry who did not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) at time of enrollment in the COPDGene study were included in this study. Subjects were classified as RSP if they had forced expiratory volume in 1 s(FEV1) to forced vital capacity (FVC) ratio > 0.7 with an FVC < 80%. Computed tomography (CT) scans were scored for the presence of DISH in accordance with the Resnick criteria. Chest CT measures of interstitial and alveolar lung disease, clinical symptoms, health surveys, and 6-min walking distance were recorded. Uni- and multivariable analyses were performed to test the association of DISH with RSP. RESULTS: DISH was present in 236 subjects (13.2%). RSP was twice as common in participants with DISH (n = 90/236, 38.1%) compared to those without DISH (n = 301/1548, 19.4%; p < 0.001). In multivariable analysis, DISH was significantly associated with RSP (OR 1.78; 95% CI 1.22-2.60; p = 0.003) after adjusting for potential confounders. The RSP group with and without DISH had significantly worse spirometry, dyspnea, St. George's Respiratory Questionnaire score, BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity), and Medical Outcomes Study Short Form-36 questionnaire score. CONCLUSION: In heavy smokers with an FEV1/FVC ratio > 0.70, DISH is associated with RSP after adjustment for intrinsic and extrinsic causes of restrictive lung function. (Clinical trial registration number: NCT00608764.).

Criteria for Early-Phase Diffuse Idiopathic Skeletal Hyperostosis: Development and Validation.

Background Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by the formation of new bone along the anterolateral spinal column at four adjacent vertebral bodies. Purpose To propose and validate criteria for the early phase of DISH by using CT data from two large-scale retrospective cohorts, each with 5-year follow-up. Materials and Methods For this retrospective study, CT data at baseline and follow-up in 1367 patients (cohort I) from 2004 to 2011 were evaluated by two observers to define no DISH, early-stage DISH, and definite DISH on the basis of interval development of consecutive complete or incomplete bone bridges. An independent group of 2267 participants from the COPDGene cohort from 2008 to 2016 was used to validate the early DISH criteria (cohort II). The sensitivity and specificity of early DISH criteria were based on findings in the last CT study as the reference standard by using a nested case-control design. κ Values were calculated between seven readers and with a 3-month interval for one reader. Results Cohort I consisted of 100% men, with a mean age of 60.0 years ± 5.6 (standard deviation) and a mean time between baseline and follow-up CT of 5.0 years ± 1.1. Cohort II consisted of 51% men, with a mean age of 59.9 years ± 8.6 and a mean time between baseline and follow-up CT of 5.4 years ± 0.5. In the derivation cohort, 55 patients comprised the early DISH group. Early DISH was defined as the presence of a spinal segment with a complete bone bridge with an adjacent segment of at least a near-complete bone bridge and another adjacent segment with at least the presence of newly formed bone or when three or more adjacent segments were recorded as showing a near-complete bone bridge. In the validation cohort, sensitivity for early DISH (vs no DISH) was 96% (99 of 103 participants; 95% confidence interval [CI]: 90%, 99%). The corresponding specificity was 83% (1695 of 2034 participants; 95% CI: 82%, 85%). The Fleiss κ for interrater reliability was 0.78 (95% CI: 0.77, 0.78), and the κ for intrarater reliability was 0.89 (95% CI: 0.82, 0.96). Conclusion Early diffuse idiopathic skeletal hyperostosis (DISH) criteria had high sensitivity and specificity for predicting the development of DISH. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Block in this issue.

Simultaneous occurrence of ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis: a systematic review.

Objectives: AS and DISH are both spinal ankylosing conditions with a 4-fold increased risk of spinal fractures. The most commonly used criteria for DISH were designed to exclude radiographic signs of spondyloarthritis. However, case reports describing the presence of both conditions exist. In this study, the co-occurrence of AS and DISH were reviewed in the literature to explore the potential need to revise the criteria for DISH. Methods: A search was conducted in Pubmed, Embase, Web of Science and the Cochrane library using the terms 'spondyloarthritis' and 'DISH' and their matching synonyms. Full-text articles describing the coexistence of both conditions in the same patient were included. A quality assessment was performed, and the case descriptions were extracted. Results: Twenty articles describing simultaneous occurrence of AS and DISH in 39 cases were retrieved. All articles were case reports or series of moderate quality. Back or neck pain was present in 97% of the patients (mean age 61.2 years, 90% male) and HLA-B27 was positive in 9/27 documented measurements. Radiographic abnormalities were described in the SI joint (82% AS, 13% DISH) and in the spine (49% AS, 100% DISH). Conclusion: Simultaneous occurrence of AS and DISH has been reported in the literature in at least 39 cases. AS and DISH should not be seen as mutually exclusive. If the results of the current study are confirmed in a large observational study, revision of the current criteria to include the co-existence of both conditions should be considered.

Bone mineral density changes over time in diffuse idiopathic skeletal hyperostosis of the thoracic spine.

Diffuse idiopathic skeletal hyperostosis (DISH) is an increasingly prevalent ankylosing condition. Patients with DISH have an increased risk of spinal fractures, hypothetically the result of biomechanical changes in the spine. The aim of this study was to analyze the occurrence of biomechanical stress shielding in patients with DISH. To do this, bone mineral density (BMD) was measured longitudinally in the vertebral bodies of subjects with and without DISH and in the newly formed bone of subjects with DISH. The presence of DISH was evaluated using Resnick criteria on two chest computed tomography (CT) scans taken at least 2.5 years apart from subjects over 50 years of age. Three groups were identified: pre-DISH (individuals who developed DISH after the first CT scan), definite DISH (individuals who had DISH on both CT scans), and controls (individuals with no DISH). Hounsfield units (HU) were measured in the newly formed bone and in predefined anterior and posterior portions of the involved vertebral bodies. Mean BMD of the newly formed bone increased significantly (mean ΔHU 137.5; p < 0.01) during a mean interval of 5 years in the cranial, middle, and caudally involved vertebral segments of both DISH groups. Mean BMD of the vertebral bodies in the ankylotic segments in the DISH groups did not significantly differ from that of the non-ankylotic vertebral bodies of the same subject. In contrast to our hypothesis, the HU value of the vertebral body decreased more in the control group than in the DISH groups; however, statistical significance was only reached at the cranial level in the anterior part of the vertebral body (p = 0.048). Our data suggest that 1) vertebral BMD is not influenced by the presence of DISH and 2) increased spinal stiffness may play a more important role than vertebral BMD in the increased fracture risk of and the typical fracture patterns observed in individuals with DISH.

The Natural Course of Diffuse Idiopathic Skeletal Hyperostosis in the Thoracic Spine of Adult Males.

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by flowing bony bridges on the right side of the spine. Knowledge of the development of these spinal bridges is limited. The current longitudinal computed tomography (CT) study was designed to bridge this gap. METHODS: Chest CT scans from elderly males with 2 scans (interval ≥ 2.5 yrs) were retrospectively included. Using the Resnick criteria, a pre-DISH group and a definite DISH group were identified. A scoring system based on the completeness of a bone bridge (score 0-3), extent of fluency, and location of the new bone was created to evaluate the progression of bone formation. RESULTS: In total, 145 of 1367 subjects were allocated to the DISH groups with a mean followup period of 5 years. Overall prevalence of a complete bone bridge increased in the pre-DISH group (11.3% to 31.0%) and in the definite DISH group (45.0% to 55.8%). The mean bridge score increased significantly in both the pre-DISH and definite DISH group (p < 0.001). The new bone gradually became more flowing and expanded circumferentially. CONCLUSION: Over the mean course of 5 years, the new bone developed from incomplete, pointy bone bridges to more flowing complete bridges. This suggests an ongoing and measurable bone-forming process that continues to progress, also in established cases of DISH.

Anterior longitudinal ligament in diffuse idiopathic skeletal hyperostosis: Ossified or displaced?

Diffuse idiopathic skeletal hyperostosis (DISH) is often theorized to be an ossification of the anterior longitudinal ligament (ALL). Using computed tomography (CT) imaging and cryomacrotome sectioning, we investigated the spatial relationship between the ALL and newly formed bone in DISH to test this hypothesis. In the current study, four human cadaveric spines diagnosed with DISH using CT imaging were frozen and sectioned using a cryomacrotome. Photographs were obtained of the specimen at 125 µm intervals. Manual segmentations of the ALL on cryomacrotome photographs were projected onto the three-dimensional reconstructed CT scans. The presence and location of newly formed bone were assessed in relationship to the location of the ALL. The ALL could be identified and segmented on the photographs at all levels. The ALL was located at the midline at levels where no new bone had formed. At the locations where new bone had abundantly formed, the ALL was displaced towards to the contralateral side and not replaced by bony tissue. The displacement of the-morphologically normal appearing-ALL away from the newly formed bone implies that newly formed bone in DISH may not originate from the ALL. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 36:2491-2496, 2018.

Morphological characteristics of diffuse idiopathic skeletal hyperostosis in the cervical spine.

OBJECTIVES: Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by anterior ossification of the spine and can lead to dysphagia and airway obstruction. The morphology of the newly formed bone in the cervical spine is different compared to the thoracic spine, possibly due to dissimilarities in local vascular anatomy. In this study the spatial relationship of the new bone with the arterial system, trachea and esophagus was analyzed and compared between subjects with and without DISH. METHODS: Cervical computed tomography (CT) scans were obtained from five patients with dysphagia and DISH and ten control subjects. The location of the vertebral and carotid arteries, surface area of the hyperostosis and distance between the vertebral body and the trachea and esophagus was assessed in the axial view. RESULTS: The surface area of the newly formed bone was located symmetrically anterior to the vertebral body. The ossifications were non-flowing in the sagittal view and no segmental vessels were observed. Substantial displacement of the trachea/esophagus was present in the group with DISH compared to the controls. CONCLUSIONS: The hyperostosis at the cervical level was symmetrically distributed anterior to the vertebral bodies without a flowing pattern, in contrast to the asymmetrical flowing pattern typically found in the thoracic spine. The hypothesis that the vascular system acts as a natural barrier against new bone formation in DISH could be further supported with these findings. The significant ventral displacement of the trachea and esophagus may explain the mechanism of dysphagia and airway obstruction in DISH.

Classification criteria for diffuse idiopathic skeletal hyperostosis: a lack of consensus.

Objectives: DISH is a condition characterized by flowing ossifications of the spine with or without ossifications of entheses elsewhere in the body. Studies on the prevalence and pathogenesis of DISH use a variety of partly overlapping combinations of classification criteria, making meaningful comparisons across the literature difficult. The aim of this study was to systematically summarize the available criteria to support the development of a more uniform set of diagnostic/classification criteria. Methods: A search was performed in Pubmed, Embase, Cochrane Library and Web of Science using the term DISH and its synonyms. Articles were included when two independent observers agreed that the articles proposed a new set of classification criteria for DISH. All retrieved articles were evaluated for methodological quality, and the presented criteria were extracted. Results: A total of 24 articles met the inclusion criteria. In all articles, spinal hyperostosis was required for the diagnosis of DISH. Peripheral, extraspinal manifestations were included as a (co-)requirement for the diagnosis DISH in five articles. Most discrepancies revolved around the threshold for the number of vertebral bodies affected and to defining different developmental phases of DISH. More than half of the retrieved articles described a dichotomous set of criteria and did not consider the progressive character of DISH. Conclusion: This systematic review summarizes the available different classification criteria for DISH, which highlights the lack of consensus on the diagnosis of (early) DISH. Consensus criteria, including consecutive phases of new bone formation that characterize DISH, can be developed based upon established diagnostic/classification criteria.

Histological characteristics of diffuse idiopathic skeletal hyperostosis.

Diffuse idiopathic skeletal hyperostosis (DISH) is a predominantly radiographic diagnosis and histological knowledge of DISH is limited. The aim of this study was to describe the histological characteristics of DISH in the spinal column and to study the relation between DISH and intervertebral disc (IVD) degeneration. Therefore, 10 human cadaveric spines with fluoroscopic evidence of DISH were compared with 10 controls. Plain radiographs and computed tomography (CT) scans were obtained and tissue blocks were resected from three predefined levels of all specimens. The microscopic sections were scored by two blinded observers using a newly developed scoring system specific for characteristics of DISH and a validated scoring system for IVD degeneration. Maximum IVD height was measured on the CT scans. Analyses were performed using Fisher's exact test and Student's t-test. When compared to controls, the right sided sections from DISH specimens showed partial or complete bone bridges, consisting of cortical woven bone, accompanied by morphological changes in the adjoining part of the IVD. Using the histological scoring system for DISH, all parameters were significantly different between the DISH and control group (p < 0.01). The contralateral location did not show differences between the groups. The overall degree of IVD degeneration and height of IVD was comparable for the two groups. The histopathological changes observed in spines with DISH corresponded to the fluoroscopic images and CT scans. The degree of IVD degeneration and IVD height was comparable for both groups, suggesting a limited role for IVD degeneration in the pathogenesis of DISH. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:140-146, 2017.