A narrative review

Publisher Copyright: Copyright © 2022 Couto, Parreira, Power, Pinheiro, Madruga Dias, Novofastovski, Eshed, Sarzi-Puttini, Pappone, Atzeni, Verlaan, Kuperus, Bieber, Ambrosino, Kiefer, Khan, Mader, Baraliakos and Bruges-Armas.Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.publishersversionpublishe

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

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

Morphological characteristics of diffuse idiopathic skeletal hyperostosis in the cervical spine

<div><p>Objectives</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p></div

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

Graphical illustration of the measurements on the CT images.

<p>In (A) the CT scan is shown of a control subject with corresponding illustration (B). The parallel lateral lines are presented in light blue and carotid and vertebral arteries in red. CT scan (C) represents a male subject with DISH (72 years old) and matches illustrations (D and E). The parallel lateral lines (light blue) and the midsagittal anteroposterior (MAP) line (dark blue) were used to compare the different surface areas of newly formed bone (light/dark grey). CT scan (F) shows a male subject with DISH (61 years old) and corresponds to illustrations (G and H). The green lines demonstrate the distances between the center of the vertebral body and the trachea and esophagus, respectively.</p

Graphical illustration of the planes used for the measurements.

<p>Measurements were performed at three levels in the C4, C5 and C6 vertebral bodies. The axial CT images were reconstructed to planes parallel to the endplate. (A) Sagittal CT image from a 69 year old male. The illustration (B) shows the three levels (C4, C5, C6) and three transverse locations at C5 (1, 2, 3) that were used for the measurements in the axial plane. The dashed line 1 shows the level adjacent to the cranial endplate, line 2 the mid-vertebral level and line 3 the level adjacent to the caudal endplate. The same approach (using the three lines for the transversal levels) was also used for the C4 and C6 vertebral body.</p

Results of the four different types of measurements.

<p>The location of the major arteries in the cervical spine was in all cases and at all levels lateral to the parallel lateral lines for the DISH and control group as shown in (A). The median total surface area of the newly formed bone per cervical level was significantly larger at the anterior location compared to the lateral location (B). There was no statistical difference between the left and right side of the MAP line (C). The distance between the center of the vertebral body and the trachea/esophagus was significantly larger in the group with DISH compared to the control group (D). The asterisk represents a p-value ≤ 0.05 and the triple asterisk represents a p-value ≤ 0.001. The error bars represent the standard error. VB–Vertebral body.</p

Typical examples of newly formed bone due to DISH in the cervical and thoracic spine.

<p>(A) Plain lateral radiograph shows a 69 year old male with DISH in the cervical spine. A solid formation of new bone is extending over at least four vertebral bodies. (B) Computed tomography (CT) visualizes the thoracic spine of a 72 year old male in the sagittal view. The scan shows a flowing ossification of the anterolateral spine with bridging over more than four contiguous vertebral bodies. The intervertebral discs and apophyseal joints are relatively intact in both images. (C + D) The CT scans in axial view demonstrate the differences in position of the new bone formation depending on the region. (C) The CT scan of the cervical spine corresponds to the radiographic image (A) and demonstrates symmetrical hyperostosis (yellow) anterior to the vertebral body and possible displacement of the trachea. (D) The axial CT of the mid thoracic spine in a 58 year old male with DISH shows the newly formed bone on the right anterolateral side with the aorta clearly located on the left anterolateral side.</p

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. k 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 k for interrater reliability was 0.78 (95% CI: 0.77, 0.78), and the k 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