• Open Access

    Diffuse idiopathic skeletal hyperostosis, beyond the musculoskeletal system

    Fabiola Atzeni 1*
    Alessandra Alciati 2,3
    Shay Brikman 4
    Reuven Mader 4

    Explor Musculoskeletal Dis. 2023;1:216–227 DOI: https://doi.org/10.37349/emd.2023.00024

    Received: March 30, 2023 Accepted: September 15, 2023 Published: December 04, 2023

    Academic Editor: Vivien Hsu, Rutgers Robert Wood Johnson Medical School, USA

    This article belongs to the special issue Diffuse Idiopathic Skeletal Hyperostosis- A common but neglected disease


    It has been suggested that diffuse idiopathic skeletal hyperostosis (DISH), a skeletal disease characterized by the ligamentous ossification of the anterolateral spine, is a radiological entity with no clinical implications; however, many patients suffer from chronic back pain, decreased spinal mobility, and postural abnormalities. Additionally, the pathological new bone formation at the cervical and thoracic levels may mainly produce dysphagia and breathing disturbances. Over the last 20 years, a close association between DISH, obesity, diabetes mellitus (DM), and metabolic syndrome (MS) has emerged. However, a causal relationship has not yet been established. It has been suggested that the longer life expectancy and the growing incidence of MS in Western populations, associated with the tendency of DISH to manifest in later life, may increase the DISH prevalence rates in the following decades. Future investigations should focus on the early DISH phase to clarify pathogenetic mechanisms and identify targeted therapies.


    Diffuse idiopathic skeletal hyperostosis, cardiovascular disease, diagnostic criteria, extra-spinal involvement, metabolic syndrome


    Diffuse idiopathic skeletal hyperostosis (DISH) is a skeletal disease of unknown etiology characterized by ligamentous ossification of the anterolateral spine that Forestier and Rotes-Querol first described more than 50 years ago [1]. The main targets of the disease process are entheses, which are subsequently thickened, calcified and/or ossified. It has also been suggested that DISH may be just a radiological entity, but many patients manifest significant clinical symptoms, complications, and comorbidities.

    DISH is often classified as a form of osteoarthritis (OA). However, although it often co-exists with OA, the two conditions differ in terms of prevalence in the general population, gender distribution, the primarily involved anatomical site, and the type of involvement and distribution in the spine and peripheral joints [2, 3]; DISH is, therefore, a distinct clinical entity [3]. Although the disease may be asymptomatic, some patients experience chronic back pain [47], decreased spinal mobility, and postural abnormalities that resemble those associated with long-standing advanced ankylosing spondylitis [810]. Furthermore, the sites of ossification and the subsequent production of large osteophytes may cause severe clinical manifestations that include dysphagia [6], quadriplegia [7], esophageal obstruction [3], dyspnea and hoarseness [11], atlanto-axial subluxation [12] and others, especially when the cervical spine is affected.

    Validated diagnostic criteria are not yet available. However, four classification criteria can be described. One of them is the Resnick and Niwayama’s [13] classification, requiring the involvement of at least four contiguous thoracic vertebrae with preserved intervertebral disc space, and the absence of inflammatory changes to the apophyseal or sacroiliac joints. The Arlet and Mazières’s [14] classification defines its sufficient requirements for a diagnosis of DISH as the involvement of three contiguous vertebral bodies at a lower thoracic level. Julkunen et al.’s [15] requirement is the presence of flowing anterolateral osteophytes that connect two vertebral bodies in at least two thoracic spine sections.

    The peripatellar ligaments, Achilles tendon insertion, plantar fascia, and olecranon might also be affected [6] despite being ignored by all three classifications above.

    The fourth classification is that of Utsinger [16], who added the presence of peripheral enthesopathies to the diagnostic measures and defined three categories: A (definite DISH), B (probable DISH), and C (possible DISH). However, these criteria are limited because other peripheral sites may be involved, such as the metacarpophalangeal joints, shoulders, ribs, and pelvis [17]; furthermore, peripheral joint involvement is often associated with hypertrophic changes, enthesopathies, and entheseal calcifications and ossifications in other sites.

    Some authors have described patients with DISH in the thoracic region as suffering from displaced spinal fractures with neurological deficits after minor trauma, such as a fall from a standing position or a low-speed car collision [18, 19]. Extraspinal manifestations of DISH have also been described. For instance, the ossification of tendons and insertions reducing both active and passive joint mobility [3], reduced chest expansion [20], and bone proliferations [21]. This supports the idea of inadequacy of the currently available criteria, with the potential of making diagnostic mistakes [22].

    The reported prevalence of DISH varies widely, probably because of differences in the studied populations. The only general population-based study found a prevalence of 3.8% in males and 2.6% in females, but these percentages rose to 10.1% and 6.7% in subjects aged 70 years or more [15]; however, it has also been reported to be 2.9% in Korea and up to 25% in the USA [23, 24]. DISH is more common in people aged over 50, among whom its prevalence in the USA is 25% in men and 15% in females, rising to 35% and 26% in those aged over 70 [24].

    The causative factors are not known yet, although the attention has been drawn to various genetic, metabolic, endocrine, and environmental factors [25, 26]. These two studies have been focused on the genetic factors associated with DISH and ossification of the posterior longitudinal ligament (OPLL), a condition often associated with DISH. Complex genetic analyses conducted to discover common genetic variants contributing to the risk of developing DISH have identified several genes involved in bone remodeling, supporting the hypothesis that overactive osteogenesis is involved in the pathogenesis of DISH [27]. A review suggested that biallelic pathogenic variants of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), dentin matrix protein 1 (DMP1), and hemizygous or heterozygous phosphate regulating endopeptidase homolog, X-linked (PHEX) mutations are genetic factors that place patients at risk for DISH and OPLL [28]. As ENPP1, DMP1, and PHEX all induce fibroblast growth factor 23 (FGF23)-related hypophosphatemia, it can be hypothesized that common pathophysiological mechanisms may favor spinal ligament ossifications.

    Over the last two decades, DISH has been strictly associated with DM and the metabolic syndrome (MS), which lead to several metabolic abnormalities. However, their direct or causal relationships have not been defined yet [29]. Nowadays, the only recognized comorbidity is the association between DISH and a higher body mass index (BMI) [30].

    The frequency of obesity, DM and MS—an acknowledged risk factor for coronary artery disease, also associated with increased mortality and morbidity [31]—has significantly increased in the western world. Not unexpectedly, two studies have shown that DISH patients have a higher incidence of risk factors for stroke and future coronary events [31, 32]. If the presumed association between DISH, an aging population, and the increasing incidence of MS is confirmed, the prevalence of DISH can be expected to rise proportionally, thus making it endemic in elderly people.

    To describe the clinical complexity of DISH, this review has been focused on its extraspinal features.

    Conditions associated with DISH:

    • Non-insulin-dependent DM.

    • Obesity.

    • High waist circumference (WC) ratio.

    • Dyslipidemia.

    • Hypertension (HTS).

    • Hyperuricemia.

    • Hyperinsulinemia.

    • Elevated insulin-like growth factor-1 (IGF-1).

    • Lung disease.

    • Dysphagia.

    MS and cardiovascular risk

    The MS, characterized by impaired glucose/insulin regulation, obesity/abnormal abdominal fat distribution, dyslipidemia, and HTS [33], represents a crucial risk factor for the development of type II DM, and cardiovascular disease (CVD) [34, 35].

    In 1996, Vezyroglou et al. [36] compared patients with DISH to patients without DISH, matched on age, sex, and BMI. This study showed that the rate of metabolic diseases including DM, dyslipidemia, and hyperuricemia was higher in patients with DISH than in those without DISH. Moreover, a significantly higher prevalence of obesity and first-degree relatives with DM or HTS was found in patients in the early phase of DISH (younger than 50 years of age) compared to patients of similar age with OA [29]. These patients were also more likely to develop DM during follow-up [29]. Serum IGF-1, insulin, and growth hormone (GH) levels are significantly higher in patients with DISH than in normal controls [37, 38]. Notably, basal serum insulin levels were significantly elevated in DISH patients with a BMI > 28 kg/m2, with a strong positive correlation between BMI values and serum insulin concentrations but not with basal serum GH or IGF-1 levels [39]. Corticosteroids and/or non-steroidal anti-inflammatory drug-related improvement of DISH symptoms (reduction in muscle pain and joint stiffness, increase in spinal range of motion) resulted in lower serum GH levels, but IGF-1 levels were unchanged, suggesting that elevated GH, and not IGF-1, contributed to the progression of clinical symptoms in DISH [37].

    In support of the role of endocrine-metabolic abnormalities in DISH, a retrospective study of whole spine computed tomography (CT) scans from 1,815 polytrauma patients recently confirmed that DISH is associated with obesity, DM, HTS, and aortic calcification [40].

    In line with these results, a vast body of studies supported the finding that patients with DISH, compared with non-DISH patients, express higher BMI and/or WC [41, 42].

    Increased body fat, mainly visceral adipose tissue (VAT) surrounding the intra-abdominal organs, has been associated with impaired glucose/insulin regulation and dyslipidemia [43, 44] and represents a major predictor for cardiovascular events [45].

    CT examination of abdominal fat surface area, a known marker for MS, revealed that they are significantly larger in DISH subjects than in controls [46].

    VAT may be a possible contributor to the pathogenesis of the spinal calcifications characteristic of DISH through the expression of inflammatory mediators. Studies consistently demonstrated that VAT produces bioactive polypeptides, collectively named “adipokines”, such as leptin and adiponectin (ADP), and inflammatory molecules, including tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) [47]. It has been hypothesized that adipokines could play a role in the pathogenesis of DISH, as animal studies demonstrate that leptin promotes osteoblast numbers and activity in mice [48]. Moreover, hereditary obese rats showed an altered leptin receptor gene associated with the ossification of spinal ligaments (OSL), a condition similar to DISH [49]. More recently, two studies evaluated the adipokine levels in patients with DISH [50, 51]. Tenti et al. [50] detected significantly higher serum leptin levels in DISH patients (with or without diabetes) compared with patients affected by lumbar OA (P < 0.0001 and P < 0.005, respectively). Furthermore, a significant decrease in ADP was observed in patients with DISH associated with diabetes vs. OA patients (P < 0.05). Mader et al. [51] found that serum ADP values negatively correlated with serum insulin and insulin resistance levels. In addition, in the same group of DISH patients, higher ADP values positively associated with serum cholesterol and low-density lipoprotein (LDL) levels and with the extent of bony bridges (r = 0.245, P = 0.02).

    The first study designed to assess the risk of MS in patients with DISH diagnosed by using accepted criteria (Resnick and Niwayama’s [13] classification), was published by Mader et al. [30] in 2009. MS was significantly more prevalent in DISH patients than in the control group (age and sex-matched; P = 0.001 and P = 0.007, respectively). The odds ratio (OR) for patients with DISH diagnosed according to the World Health Organization (WHO)-MS [52] was 3.61, and for DISH diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP)-MS criteria [53] was 3.88. DISH patients showed a higher risk to develop coronary heart disease (CHD; as per Framingham risk scoring system; P = 0.004), conferring a higher 10-year CHD risk relative to patients without DISH (P = 0.007) [30].

    A 10-year follow-up evaluation of participants without known CVD disease enrolled in the previous study cohort showed that the incidence of myocardial infarction (MI) was significantly higher in the DISH group (P = 0.005) than in the control non-DISH group [54]. It should be noted that CVD incidence was higher than expected. Specifically, using the Framingham score, 28.6% of the DISH patients were expected to develop CVD after ten years, while the study demonstrated that nearly 39% of them really developed CVD at the end of a 10-year follow-up period. The finding of a higher-than-expected actual MI incidence suggests that DISH may be an independent CVD risk factor. Further support to this hypothesis came from the study of Oudkerk et al. [55], who demonstrated that subjects with DISH had a significantly higher risk of having coronary artery calcifications compared to subjects without DISH [OR 1.37, 95% confidence interval (CI) = 1.05–1.78, P = 0.019; OR 1.27, CI = 1.05–1.78, P = 0.019] after correction for age, gender, race, chronic obstructive pulmonary disease (COPD) and atherosclerotic risk factors.

    A large retrospective cohort study in Taiwan found significantly higher prevalence rates of stroke, HTS, diabetes, and hyperlipidemia in patients with DISH compared with age- and sex-matched controls. In particular, DISH conferred a 1.68 times higher risk of developing stroke independently of the presence of HTS [56].

    In line with this result, a prospective cohort study including 4,624 individuals demonstrated that DISH was associated with a 55% increase in ischaemic stroke after correction for age, sex, and cardiovascular risk factors. No other independent relationships were found between DISH and MI, vascular death, or all-cause mortality [57]. In the same cohort, individuals with DISH have more thoracic aortic calcification (TAC), which may help to explain how DISH relates to ischaemic stroke [58]. It was hypothesized that TAC can influence arterial stiffness and hence the normal compressive (Windkessel) function of the aorta that converts the phasic systolic inflow produced by ventricular ejection into a more continuous outflow to peripheral vessels.

    The association between MS and DISH has been recently confirmed by a retrospective analysis of clinical data from 327 consecutive subjects undergoing health medical checkup examinations [59]. This study demonstrated that MS was more frequently detected in the DISH group (28.9%) than in the non-DISH group (16.0%; P = 0.045) with an OR of 2.0 (95% CI = 1.0–3.7; P = 0.004).

    Accordingly, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) [60]—a large population-based cohort study of older Icelanders comprising 5,321 participants aged 68–96—highlights the association between DISH and MS [OR 2.12; 95% CI = 1.69–2.64; P = 3.9 × 10−11] also in elderly individuals.


    The pathological new bone formation, mainly involving the anterior longitudinal ligament of the spine, may cause dysphagia, perceived as difficulty swallowing, sometimes associated with foreign body sensation, odynophagia, salivary stasis, and dysphonia [61]. The most common level of spine involvement in producing dysphagia is C5–C6, with C2–C3 less commonly affected [62].

    The estimated incidence of cervical dysphagia due to DISH is around 7:100,000 inhabitants per year [63]. A recently updated systematic review of 138 articles (112 case reports and 26 case series) described 419 patients with dysphagia and/or airway obstruction caused by cervical DISH. Patients mainly were males, 85.4% and had a mean age of 67.3 years [64].

    In addition to the direct mechanical obstruction due to the bone proliferation in the anterior part of the cervical spine, the inflammation of the soft tissue adjacent to the esophagus, together with esophageal and pharyngeal muscle spasm [65], and recurrent nerve palsies elicited by the hyperostosis, may also contribute to the development of dysphagia [66].

    Plain radiographs are usually sufficient to make a DISH diagnosis. Still, in DISH-related dysphagia, CT and magnetic resonance imaging (MRI) help to evaluate the extent of the hyperostosis, its location relative to the esophagus, and the presence of spinal stenosis with compression and myelomalacia [66].

    Treatment for DISH is based on symptomatic relief of symptoms, while anterior cervical resection of osteophyte may be considered in patients with airway obstruction and/or dysphagia, in whom a conservative approach was ineffective [67].

    The complication rate after surgery was 22.1%, and 12.7% occurred within 1 month after intervention [64]. Esophageal injury due to large osteophytes and esophagus adhesion to other cervical fascia produced by the local inflammation may be a surgery complication. The dysphagia improved in 95.5% of surgically treated patients but recurred in 4% of them after a mean follow-up of 3.7 years [64].

    Respiratory disturbances

    The bony bridges between vertebral bodies and the involvement of the sternocostal and costochondral junctions can lead to a limited expansion of the thoracic cage that may affect ventilation.

    In support of this hypothesis, a study recruiting a cohort of lung cancer screening participants demonstrated that individuals with DISH diagnosed on CT scans presented lower CT-measured lung volumes [68].

    The same authors studied 1,784 former and current smokers who, after a complete post-bronchodilator spirometry, did not meet the spirometric criteria for the diagnosis of COPD [69]. A restrictive spirometric pattern (RSP) was described if patients had a forced expiratory volume in 1s (FEV1) to forced vital capacity (FVC) ratio > 0.7 with an FVC < 80%. The results showed that DISH was significantly associated with RSP (OR 1.78; 95% CI = 1.22–2.60; P = 0.003) after adjusting for potential intrinsic and extrinsic causes of restrictive lung function [69].

    Dyspnea is associated with dysphagia in 14% patients with anterior cervical osteophytosis [70], while the literature reports only a few cases of patients with dyspnea without associated dysphagia [71].

    Aspiration pneumonia, usually associated with dysphagia, is rare but can be life-threatening. Of five patients with dysphagia caused by DISH, three showed bolus aspiration into the airways, mainly in the post-swallowing phase. The pathogenetic alterations affecting swallowing mechanisms were compression of the pharyngeal lumen with abnormal epiglottic tilt, incomplete openings of the upper esophageal sphincter, and epiglottic/vallecula stasis [72].

    Neurological symptoms

    DISH neurological complications are uncommon, being seen in around 0.4% of the patients [73]. A retrospective analysis of 74 cases of DISH [74] revealed that 11 patients had presented with progressive spinal cord or cauda equina compression. The neurological complication occurred in nine cases due to the OPLL and in two cases due to the ossification of the ligamentum flavum (OLF). The thoracic spinal cord and nerve root compression may lead to numbness, extreme weakness, and even paralysis in the lower extremities. Of note, the association of bladder and/or bowel loss of control requires immediate therapeutic interventions. The thoracic spinal stenosis slowly progresses, mainly driven by the stimulation of mechanical stress [75]. Unlike other types of spinal conditions, thoracic spinal stenosis often does not respond well to non-surgical treatment, while decompressing surgery is an effective treatment approach. The recent study of Dong et al. [76] suggested that posterior decompression and fusion surgery could achieve satisfactory clinical outcomes, which were comparable between DISH and non-DISH patients. Although ossification in DISH occurs primarily in the anterior longitudinal ligament, the involvement of the posterior longitudinal ligament in the cervicothoracic spine can result in ankylosis, which definitely changes the biomechanics of the spine. This spinal imbalance increases susceptibility to injury, even low-energy trauma, leading to fractures with an increased risk of neurological sequelae and difficulty with tracheal intubation if required.

    Cervical myelopathy can occur due to spinal canal narrowing caused by OPLL or OLF compression and manifests with difficulty in walking and weakness in all four limbs [77]. Early surgical intervention helps to achieve a better outcome in patients with neurodeficiency and prevents further complications.

    Finally, a cross-sectional study identified an association between DISH and lumbar spinal stenosis requiring surgery, a condition characterized by neurological deficits in the lower extremities, intolerable leg pain, and bladder or bowel dysfunction [78].


    DISH is a systemic disease characterized by progressive calcification and ossification of ligaments and entheses along the spine and with extra-spinal involvement. This disease often goes unnoticed among the affected individuals, and for this reason it has not yet been studied so in depth. DISH may suggest the presence of underlying metabolic imbalances and associated CVD. The prevalence of DISH in Western countries is set to increase due to the widespread presence of its risk factors: increased life expectancy, obesity, DM, and HTS. DISH involves the spine, peripheral joints and entheses, causing entheseal ossification and/or calcification around peripheral joints, in particular of tendons, ligaments, and joint capsules. Several complications of the disease such as higher cardiovascular risk, complex spinal fractures, post-surgical heterotopic ossifications, difficult intubation, aspiration pneumonia, and dysphagia have been described. Unfortunately, the current DISH classification criteria allow identifying the diagnostic feature late in the illness course. Research and clinical advantage may derive from identifying initial disease phases by detecting the early inflammatory changes around and within the axial and peripheral skeleton with MRI. Focusing on individuals with MS or increased VAT as at-risk populations may help clarify possible causal relationships and early pathogenetic mechanisms to implement targeted therapies.





    body mass index


    computed tomography


    cardiovascular disease


    diffuse idiopathic skeletal hyperostosis


    diabetes mellitus


    growth hormone




    insulin-like growth factor-1


    myocardial infarction


    metabolic syndrome




    ossification of the posterior longitudinal ligament


    odds ratio


    visceral adipose tissue



    We would like to thank our mentor Professor Reuven Mader who passed away during the article preparation. Professor Mader passed away in March 2023.

    Author contributions

    FA and RM: Conceptualization, Writing—original draft, Writing—review & editing, Supervision. AA: Writing—original draft, Writing—review & editing. SB: Writing—review & editing, Supervision. All authors, except Professor Mader read and approved the submitted version.

    Conflicts of interest

    The authors declare that they have no conflicts of interest.

    Ethical approval

    Not applicable.

    Consent to participate

    Not applicable.

    Consent to publication

    Not applicable.

    Availability of data and materials

    Not applicable.


    Not applicable.


    © The Author(s) 2023.


    Forestier J, Rotes-Querol J. Senile ankylosing hyperostosis of the spine. Ann Rheum Dis. 1950;9:32130. [DOI] [PubMed] [PMC]
    Sarzi-Puttini P, Atzeni F. New developments in our understanding of DISH (diffuse idiopathic skeletal hyperostosis). Curr Opin Rheumatol. 2004;16:28792. [DOI] [PubMed]
    Mader R. Diffuse idiopathic skeletal hyperostosis: a distinct clinical entity. Isr Med Assoc J. 2003;5:5068. [PubMed]
    Beyeler C, Schlapbach P, Gerber NJ, Sturzenegger J, Fahrer H, van der Linden S, et al. Diffuse idiopathic skeletal hyperostosis (DISH) of the shoulder: a cause of shoulder pain? Br J Rheumatol. 1990;29:34953. [DOI] [PubMed]
    Schlapbach P, Beyeler C, Gerber NJ, van der Linden S, Bürgi U, Fuchs WA, et al. The prevalence of palpable finger joint nodules in diffuse idiopathic skeletal hyperostosis (DISH). A controlled study. Br J Rheumatol. 1992;31:5314. [DOI] [PubMed]
    Littlejohn GO, Urowitz MB. Peripheral enthesopathy in diffuse idiopathic skeletal hyperostosis (DISH): a radiologic study. J Rheumatol. 1982;9:56872. [PubMed]
    Resnick D, Shaul SR, Robins JM. Diffuse idiopathic skeletal hyperostosis (DISH): Forestier’s disease with extraspinal manifestations. Radiology. 1975;115:51324. [DOI] [PubMed]
    Olivieri I, D’Angelo S, Palazzi C, Padula A, Mader R, Khan MA. Diffuse idiopathic skeletal hyperostosis: differentiation from ankylosing spondylitis. Curr Rheumatol Rep. 2009;11:3218. [DOI] [PubMed]
    Fahrer H, Barandum R, Gerber NJ, Friederich NF, Burkhardt B, Weisman MH. Pelvic manifestations of diffuse idiopathic skeletal hyperostosis (DISH): are they clinically relevant? Rheumatol Int. 1989;8:25761. [DOI] [PubMed]
    Olivieri I, D’Angelo S, Cutro MS, Padula A, Peruz G, Montaruli M, et al. Diffuse idiopathic skeletal hyperostosis may give the typical postural abnormalities of advanced ankylosing spondylitis. Rheumatology (Oxford). 2007;46:170911. [DOI] [PubMed]
    Mader R. Diffuse idiopathic skeletal hyperostosis: isolated involvement of cervical spine in a young patient. J Rheumatol. 2004;31;620–1. [PubMed]
    Mader R. Clinical manifestations of diffuse idiopathic skeletal hyperostosis of the cervical spine. Semin Arthritis Rheum. 2002;32:1305. [DOI] [PubMed]
    Resnick D, Niwayama G. Radiographic and pathologic features of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). Radiology. 1976;119:55968. [DOI] [PubMed]
    Arlet J, Mazières B. The hyperostotic disease. Rev Med Interne. 1985;6:55364. French. [DOI] [PubMed]
    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;4:237. [PubMed]
    Utsinger PD. Diffuse idiopathic skeletal hyperostosis. Clin Rheum Dis. 1985;11:32551. [PubMed]
    Mader R, Sarzi-Puttini P, Atzeni F, Olivieri I, Pappone N, Verlaan JJ, et al. Extraspinal manifestations of diffuse idiopathic skeletal hyperostosis. Rheumatology (Oxford). 2009;48:147881. [DOI] [PubMed]
    Laroche M, Moulinier L, Arlet J, Arrue P, Rousseau H, Cantagrel A, et al. Lumbar and cervical stenosis. Frequency of the association, role of the ankylosing hyperostosis. Clin Rheumatol. 1992;11:5335. [DOI] [PubMed]
    Paley D, Schwartz M, Cooper P, Harris WR, Levine AM. Fracture of the spine in diffuse idiopathic skeletal hyperostosis. Clin Orthop Relat Res. 1991:2232. [PubMed]
    Mata S, Fortin PR, Fitzcharles MA, Starr MR, Joseph L, Watts CS, et al. A controlled study of diffuse idiopathic skeletal hyperostosis clinical features and functional status. Medicine (Baltimore). 1997;76:10417. [DOI] [PubMed]
    Olivieri I, D’Angelo S, Borraccia F, Padula A. Images in rheumatology. Heel enthesopathy of diffuse idiopathic skeletal hyperostosis resembling enthesitis of spondyloarthritis. J Rheumatol. 2010;37:1923. [DOI] [PubMed]
    Mader R. Diffuse idiopathic skeletal hyperostosis: time for a change. J Rheumatol. 2008;35:3779. [PubMed]
    Cassim B, Mody GM, Rubin DL. The prevalence of diffuse idiopathic skeletal hyperostosis in African blacks. Br J Rheumatol. 1990;29:1312. [DOI] [PubMed]
    Weinfeld RM, Olson PN, Maki DD, Griffiths HJ. The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in two large American Midwest metropolitan hospital populations. Skeletal Radiol. 1997;26:2225. [DOI] [PubMed]
    Kiss C, Szilágyi M, Paksy A, Poór G. Risk factors for diffuse idiopathic skeletal hyperostosis: a case-control study. Rheumatology (Oxford). 2002;41:2730. [DOI] [PubMed]
    Littlejohn GO. Insulin and new bone formation in diffuse idiopathic skeletal hyperostosis. Clin Rheumatol. 1985;4:294300. [DOI] [PubMed]
    Sethi A, Ruby JG, Veras MA, Telis N, Melamud E. Genetics implicates overactive osteogenesis in the development of diffuse idiopathic skeletal hyperostosis. Nat Commun. 2023;14:2644. [DOI] [PubMed] [PMC]
    Kato H, Braddock DT, Ito N. Genetics of diffuse idiopathic skeletal hyperostosis and ossification of the spinal ligaments. Curr Osteoporos Rep. 2023;21:55266. [DOI] [PubMed] [PMC]
    Mader R, Lavi I. Diabetes mellitus and hypertension as risk factors for early diffuse idiopathic skeletal hyperostosis (DISH). Osteoarthritis Cartilage. 2009;17:8258. [DOI] [PubMed]
    Mader R, Novofestovski I, Adawi M, Lavi I. Metabolic syndrome and cardiovascular risk in patients with diffuse idiopathic skeletal hyperostosis. Semin Arthritis Rheum. 2009;38:3615. [DOI] [PubMed]
    Mader R, Dubenski N, Lavi I. Morbidity and mortality of hospitalized patients with diffuse idiopathic skeletal hyperostosis. Rheumatol Int. 2005;26:1326. [DOI] [PubMed]
    Atzeni F, Sarzi-Puttini P, Bevilacqua M. Calcium deposition and associated chronic diseases (atherosclerosis, diffuse idiopathic skeletal hyperostosis, and others). Rheum Dis Clin North Am. 2006;32:41326, viii. [DOI] [PubMed]
    Lemieux I, Després JP. Metabolic syndrome: past, present and future. Nutrients. 2020;12:3501. [DOI] [PubMed] [PMC]
    Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112:306672. [DOI] [PubMed]
    Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49:40314. [DOI] [PubMed]
    Vezyroglou G, Mitropoulos A, Antoniadis C. A metabolic syndrome in diffuse idiopathic skeletal hyperostosis. A controlled study. J Rheumatol. 1996;23:6726. Erratum in: J Rheumatol. 1997;24:1665. [PubMed]
    Denko CW, Boja B, Malemud CJ. Growth hormone and insulin-like growth factor-I in symptomatic and asymptomatic patients with diffuse idiopathic skeletal hyperostosis (DISH). Front Biosci. 2002;7:a3743. [DOI] [PubMed]
    Denko CW, Boja B, Moskowitz RW. Growth promoting peptides in osteoarthritis and diffuse idiopathic skeletal hyperostosis--insulin, insulin-like growth factor-I, growth hormone. J Rheumatol. 1994;21:172530. [PubMed]
    Denko CW, Malemud CJ. Body mass index and blood glucose: correlations with serum insulin, growth hormone, and insulin-like growth factor-1 levels in patients with diffuse idiopathic skeletal hyperostosis (DISH). Rheumatol Int. 2006;26:2927. [DOI] [PubMed]
    Ahmed O, Ramachandran K, Patel Y, Dhanapaul S, Meena J, Shetty AP, et al. Diffuse idiopathic skeletal hyperostosis prevalence, characteristics, and associated comorbidities: a cross-sectional study of 1815 whole spine CT scans. Global Spine J. 2022;[Epub ahead of print]. [DOI] [PubMed]
    Chaput CD, Siddiqui M, Rahm MD. Obesity and calcification of the ligaments of the spine: a comprehensive CT analysis of the entire spine in a random trauma population. Spine J. 2019;19:134653. [DOI] [PubMed]
    Harlianto NI, Westerink J, Foppen W, Hol ME, Wittenberg R, van der Veen PH, et al.; On Behalf Of The Ucc-Smart-Study Group. Visceral adipose tissue and different measures of adiposity in different severities of diffuse idiopathic skeletal hyperostosis. J Pers Med. 2021;11:663. [DOI] [PubMed] [PMC]
    Ritchie SA, Connell JM. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007;17:31926. [DOI] [PubMed]
    Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:3948. [DOI] [PubMed]
    Després JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126:130113. [DOI] [PubMed]
    Dan Lantsman C, Herman A, Verlaan JJ, Stern M, Mader R, Eshed I. Abdominal fat distribution in diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis patients compared to controls. Clin Radiol. 2018;73:910.e1520. [DOI] [PubMed]
    Foster MT, Pagliassotti MJ. Metabolic alterations following visceral fat removal and expansion: beyond anatomic location. Adipocyte. 2012;1:1929. [DOI] [PubMed] [PMC]
    Pillai S, Littlejohn G. Metabolic factors in diffuse idiopathic skeletal hyperostosis – a review of clinical data. Open Rheumatol J. 2014;8:11628. [DOI] [PubMed] [PMC]
    Li H, Jiang LS, Dai LY. Hormones and growth factors in the pathogenesis of spinal ligament ossification. Eur Spine J. 2007;16:107584. [DOI] [PubMed] [PMC]
    Tenti S, Palmitesta P, Giordano N, Galeazzi M, Fioravanti A. Increased serum letin and visfatin levels in patients with diffuse idiopathic skeletal hyperostosis: a comparative study. Scand J Rheumatol. 2017;46:1568. [DOI] [PubMed]
    Mader R, Novofastovski I, Schwartz N, Rosner E. Serum adiponectin levels in patients with diffuse idiopathic skeletal hyperostosis (DISH). Clin Rheumatol. 2018;37:283945. [DOI] [PubMed]
    Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA. Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol. 2002;156:10707. [DOI] [PubMed]
    Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA. 2001;285:248697. [DOI] [PubMed]
    Glick K, Novofastovski I, Schwartz N, Mader R. Cardiovascular disease in diffuse idiopathic skeletal hyperostosis (DISH): from theory to reality-a 10-year follow-up study. Arthritis Res Ther. 2020;22:190. [DOI] [PubMed] [PMC]
    Oudkerk SF, Mohamed Hoesein FAA, PThM Mali W, Öner FC, Verlaan JJ, de Jong PA, et al. Subjects with diffuse idiopathic skeletal hyperostosis have an increased burden of coronary artery disease: an evaluation in the COPDgene cohort. Atherosclerosis. 2019;287:249. [DOI] [PubMed] [PMC]
    Cheng YY, Lin CH, Tsai PY, Chen YH, Lin SY, Chang ST. Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study. Sci Rep. 2021;11:21349. [DOI] [PubMed] [PMC]
    Harlianto NI, Oosterhof N, Foppen W, Hol ME, Wittenberg R, van der Veen PH, et al.; UCC-SMART-Studygroup. Diffuse idiopathic skeletal hyperostosis is associated with incident stroke in patients with increased cardiovascular risk. Rheumatology (Oxford). 2022;61:286774. [DOI] [PubMed] [PMC]
    Harlianto NI, Westerink J, Hol ME, Wittenberg R, Foppen W, van der Veen PH, et al.; UCC-SMART Study Group. Patients with diffuse idiopathic skeletal hyperostosis have an increased burden of thoracic aortic calcifications. Rheumatol Adv Pract. 2022;6:rkac060. [DOI] [PubMed] [PMC]
    Okada E, Ishihara S, Azuma K, Michikawa T, Suzuki S, Tsuji O, et al. Metabolic syndrome is a predisposing factor for diffuse idiopathic skeletal hyperostosis. Neurospine. 2021;18:10916. [DOI] [PubMed] [PMC]
    Auðunsson AB, Elíasson GJ, Steingrímsson E, Aspelund T, Sigurdsson S, Launer L, et al. Diffuse idiopathic skeletal hyperostosis in elderly Icelanders and its association with the metabolic syndrome: the AGES-Reykjavik Study. Scand J Rheumatol. 2021;50:3148. [DOI] [PubMed] [PMC]
    Kmucha ST, Cravens RB Jr. DISH syndrome and its role in dysphagia. Otolaryngol Head Neck Surg. 1994;110:4316. [DOI] [PubMed]
    Hilding DA, Tachdjian MO. Dysphagia and hypertrophic spurring of the cervical spine. N Engl J Med. 1960;263:114. [DOI] [PubMed]
    García Callejo FJ, Oishi N, López Sánchez I, Pallarés Martí B, Rubio Fernández A, Gómez Gómez MJ. Incidence of diffuse idiopathic skeletal hyperostosis from a model of dysphagia. Acta Otorrinolaringol Esp (Engl Ed). 2020;71:7882. English, Spanish. [DOI] [PubMed]
    Harlianto NI, Kuperus JS, Mohamed Hoesein FAA, de Jong PA, de Ru JA, Öner FC, et al. Diffuse idiopathic skeletal hyperostosis of the cervical spine causing dysphagia and airway obstruction: an updated systematic review. Spine J. 2022;22:1490503. [DOI] [PubMed]
    Oga M, Mashima T, Iwakuma T, Sugioka Y. Dysphagia complications in ankylosing spinal hyperostosis and ossification of the posterior longitudinal ligament. Roentgenographic findings of the developmental process of cervical osteophytes causing dysphagia. Spine (Phila Pa 1976). 1993;18:3914. [PubMed]
    Lee JH, Paeng SH, Pyo SY, Kim ST, Lee WH. Swallowing difficulty in diffuse idiopathic skeletal hyperostosis with metabolic syndrome. Korean J Neurotrauma. 2020;16:908. [DOI] [PubMed] [PMC]
    Tran DDT, Nguyen QB, Truong VT, Truong TD, Do QV, Vo DP. Surgical intervention of dysphagia caused by ossification of anterior longitudinal ligament: a case report. Asian J Neurosurg. 2022;17:4858. [DOI] [PubMed] [PMC]
    Oudkerk SF, Buckens CF, Mali WP, De Koning HJ, Öner FC, Vliegenthart R, et al. Diffuse idiopathic skeletal hyperostosis is associated with lower lung volumes in current and former smokers. Am J Respir Crit Care Med. 2016;194:2412. [DOI] [PubMed]
    Oudkerk SF, Mohamed Hoesein FAA, Öner FC, Verlaan JJ, de Jong PA, Kuperus JS, et al. Diffuse idiopathic skeletal hyperostosis in smokers and restrictive spirometry pattern: an analysis of the COPDgene cohort. J Rheumatol. 2020;47:5318. [DOI] [PubMed] [PMC]
    Lecerf P, Malard O. How to diagnose and treat symptomatic anterior cervical osteophytes? Eur Ann Otorhinolaryngol Head Neck Dis. 2010;127:1116. [DOI] [PubMed]
    Souza S, Raggio B, Bareiss A, Friedlander P. Diffuse idiopathic skeletal hyperostosis of the cervical spine: a risk for acute airway obstruction. Ear Nose Throat J. 2021;100:921S3S. [DOI] [PubMed]
    Masiero S, Padoan E, Bazzi M, Ponzoni A. Dysphagia due to diffuse idiopathic skeletal hyperostosis: an analysis of five cases. Rheumatol Int. 2010;30:6815. [DOI] [PubMed]
    Terzi R. Extraskeletal symptoms and comorbidities of diffuse idiopathic skeletal hyperostosis. World J Clin Cases. 2014;2:4225. [DOI] [PubMed] [PMC]
    Sharma RR, Mahapatra A, Pawar SJ, Sousa J, Lad SD, Athale SD. Spinal cord and cauda equina compression in ‘DISH’. Neurol India. 2001;49:14852. [PubMed]
    Li B, Guo S, Qiu G, Li W, Liu Y, Zhao Y. A potential mechanism of dural ossification in ossification of ligamentum flavum. Med Hypotheses. 2016;92:12. [DOI] [PubMed]
    Dong Y, Li J, Yang K, Guo S, Zhai J, Zhao Y. Thoracic spondylotic myelopathy in diffuse idiopathic skeletal hyperostosis: a comparative study. J Orthop Surg Res. 2023;18:242. [DOI] [PubMed] [PMC]
    Mahajan NP, S PKG, Chandanwale AS, Sonawane DV, Patil OP, Yadav AK. Cervical myelopathy and lumbar spondylolisthesis in elderly patients with diffuse idiopathic skeletal hyperostosis (DISH) – a case series. J Orthop Case Rep. 2020;10 :4852. [DOI] [PubMed] [PMC]
    Yamada K, Satoh S, Hashizume H, Yoshimura N, Kagotani R, Ishimoto Y, et al. Diffuse idiopathic skeletal hyperostosis is associated with lumbar spinal stenosis requiring surgery. J Bone Miner Metab. 2019;37:11824. [DOI] [PubMed]