Key Points
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Diffuse idiopathic skeletal hyperostosis (DISH) is characterized by entheseal ossification and/or calcification involving mainly the thoracic spine
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Peripheral joints and adjacent entheses can also be involved
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The pathogenesis of DISH is not clear, but several factors may promote the differentiation of mesenchymal cells into bone-forming cells
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DISH is often associated with a variety of metabolic derangements, which may increase cardiovascular morbidity
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Patients with DISH also have an increased risk of complicated spinal fractures, with associated morbidities
Abstract
Diffuse idiopathic skeletal hyperostosis (DISH) is a systemic condition characterized by the ossification and calcification of ligaments and entheses. DISH is observed on all continents and in all races, but most commonly in men over 50 years of age. Although DISH is asymptomatic in most individuals, the condition is often an indicator of underlying metabolic disease, and the presence of spinal or extraspinal ossifications can sometimes lead to symptoms including pain, stiffness, a reduced range of articular motion, and dysphagia, as well as increasing the risk of unstable spinal fractures. The aetiology of DISH is poorly understood, and the roles of the many factors that might be involved in the development of excess bone are not well delineated. The study of pathophysiological aspects of DISH is made difficult by the formal diagnosis requiring the presence of multiple contiguous fully formed bridging ossifications, which probably represent advanced stages of DISH. In this Review, the reader is provided with an up-to-date discussion of the epidemiological, aetiological and clinical aspects of DISH. Existing classification criteria (which, in the absence of diagnostic criteria, are used to establish a diagnosis of DISH) are also considered, together with the need for modified criteria that enable timely identification of early phases in the development of DISH.
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References
Forestier, J. & Rotes-Querol, J. Senile ankylosing hyperostosis of the spine. Ann. Rheum. Dis. 9, 321–330 (1950).
Van der Merwe, A. E., Maat, G. J. & Watt, I. Diffuse idiopathic skeletal hyperostosis: Diagnosis in a palaeopathological context. Homo 63, 202–215 (2012).
Resnick, D. & Niwayama, G. Radiographic and pathologic features of spinal involvement in diffuse idiopathic skeletal hyperostosis (DISH). Radiology 119, 559–568 (1976).
Beyeler, C. et al. Diffuse idiopathic skeletal hyperostosis (DISH) of the elbow: A cause of elbow pain? A controlled study. Br. J. Rheumatol. 31, 319–323 (1992).
Mader, R., Novofestovski, I., Adawi, M. & Lavi, I. Metabolic syndrome and cardiovascular risk in patients with diffuse idiopathic skeletal hyperostosis. Semin. Arthritis Rheum. 38, 361–365 (2009).
Mader, R. et al. Extraspinal manifestations of diffuse idiopathic skeletal hyperostosis. Rheumatology 48, 1478–1481 (2009).
Verlaan, J. J., Boswijk, F. L., de Ru, J. A., Dhert, W. J. & Oner, F. C. Diffuse idiopathic skeletal hyperostosis of the cervical spine: an underestimated cause of dysphagia and airway obstraction. Spine J. 11, 1058–1067 (2011).
Weisz, G. M., Matucci-Cerinic, M., Lippi, D. & Albury, W. R. The ossification diathesis in the medici family: DISH and other features. Rheumatol. Int. 31, 1649–1652 (2011).
Verlaan, J. J., Oner, F. C. & Maat, G. J. Diffuse idiopathic skeletal hyperostosis in ancient clergymen. Eur. Spine J. 16, 1129–1135 (2007).
Chhem, R. K., Schmit, P. & Fauré, C. Did Ramesses II really have ankylosing spondylitis? A reappraisal. Can. Assoc. Radiol. J. 55, 211–217 (2004).
Crubézy, E. & Trinkaus, E. Shanidar 1: a case of hyperostotic disease (DISH) in the middle Paleolithic. Am. J. Phys. Anthropol. 89, 411–420 (1992).
Giuffra, V. et al. Diffuse idiopathic skeletal hyperostosis in the Medici, Grand Dukes of Florence (XVI century). Eur. Spine J. 19 (Suppl. 2), S103–S107 (2010).
Waldron, T. DISH at merton priory: evidence for a “new” occupational disease? BMJ 291, 1762–1763 (1985).
Rogers, J. & Waldron, T. DISH and the monastic way of life. Int. J. Osteoarchaeol. 11, 357–365 (2001).
Ullrich, H. [Goethe's skull and skeleton] 60, 341–368 (2002).
Kiss, C. et al. Prevalence of diffuse idiopathic skeletal hyperostosis in Budapest, Hungary. Rheumatology (Oxford) 41, 1335–1336 (2002).
Westerveld, L. A., van Ufford, H. M., Verlaan, J. J. & Oner, F. C. The prevalence of diffuse idiopathic skeletal hyperostosis in an outpatient population in the Netherlands. J. Rheumatol. 35, 1635–1638 (2008).
Weinfeld, R. M., Olson, P. N., Maki, D. D. & Griffiths, H. J. The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) in two large american midwest metropolitan hospital populations. Skeletal Radiol. 26, 222–225 (1997).
Holton, K. F. et al. Diffuse idiopathic skeletal hyperostosis and its relation to back pain among older men: The MrOS study. Semin. Arthritis Rheum. 41, 131–138 (2011).
Bray, G. A. & Bellanger, T. Epidemiology, trends, and morbidities of obesity and the metabolic syndrome. Endocrine 29, 109–117 (2006).
Mader, R. & Lavi, I. Diabetes mellitus and hypertension as risk factors for early diffuse idiopathic skeletal hyperostosis (DISH). Osteoarthritis Cartilage 17, 825–828 (2009).
Mader, R. Diffuse idiopathic skeletal hyperostosis: a distinct clinical entity. Isr. Med. Assoc. J. 5, 506–508 (2003).
Fornasier, V. L., Littlejohn, G. O., Urowitz, M. B., Keystone, E. C. & Smythe, H. A. Spinal entheseal new bone formation: the early changes of spinal diffuse idiopathic skeletal hyperostosis. J. Rheumatol. 10, 934–947 (1983).
Belanger, T. A. & Rowe, D. E. Diffuse idiopathic skeletal hyperostosis: musculoskeletal manifestations. J. Am. Acad. Orthop. Surg. 9, 258–267 (2001).
Mader, R. Clinical manifestations of diffuse idiopathic skeletal hyperostosis of the cervical spine. Semin. Arthritis Rheum. 32, 130–135 (2002).
Di Girolamo, C. et al. Intervertebral disc lesions in diffuse idiopathic skeletal hyperostosis (DISH). Clin. Exp. Rheumatol. 19, 310–312 (2001).
Hutton, C. DISH.... a state not a disease? [editorial]. Br. J. Rheumatol. 28, 277–280 (1989).
Utsinger, P. D. Diffuse idiopathic skeletal hyperostosis. Clin. Rheum. Dis. 11, 325–351 (1985).
Resnick, D. et al. Diffuse idiopathic skeletal hyperostosis (DISH) [ankylosing hyperostosis of Forestier and Rotes-Querol]. Semin. Arthritis Rheum. 7, 153–187 (1978).
Mata, S. et al. A controlled study of diffuse idiopathic skeletal hyperostosis. Clinical features and functional status. Medicine 76, 104–117 (1997).
Schlapbach, P. et al. Diffuse idiopathic skeletal hyperostosis (DISH) of the spine: A cause of back pain? A controlled study. Br. J. Rheumatol. 28, 299–303 (1989).
Mader, R. et al. Non articular tenderness and functional status in patients with diffuse idiopathic skeletal hyperostosis. J. Rheumatol. 37, 1911–1916 (2010).
Olivieri, I. et al. Diffuse idiopathic skeletal hyperostosis may give the typical postural abnormalities of advanced ankylosing spondylitis. Rheumatology 46, 1709–1711 (2007).
Baraliakos, X., Listing, J., Buschmann, J., von der Recke, A. & Braun, J. A comparison of new bone formation in patients with ankylosing spondylitis and patients with diffuse idiopathic skeletal hyperostosis. A retrospective cohort study over six years. Arthritis Rheum. 64, 1127–1133 (2012).
Belanger, T. A. & Rowe, D. E. Diffuse idiopathic skeletal hyperostosis: musculoskeletal manifestations. J. Am. Acad. Orthop. Surg. 9, 258–267 (2001).
Laroche, M. et al. Lumbar and cervical stenosis. Frequency of the association, role of the ankylosing hyperostosis. Clin. Rheumatol. 11, 533–535 (1992).
Liu, P. et al. Spinal trauma in mainland China from 2001 to 2007: An epidemiological study based on a nationwide database. Spine (Phila Pa 1976) 37, 1310–1315 (2012).
Caron, T. et al. Spine fractures in patients with ankylosing spinal disorders. Spine (Phila Pa 1976) 35, E458–E464 (2010).
Westerveld, L. A., Verlaan, J. J. & Oner, F. C. Spinal fractures in patients with ankylosing spinal disorders: A systematic review of the literature on treatment, neurological status and complications. Eur. Spine J. 18, 145–156 (2009).
Whang, P. G. et al. The management of spinal injuries in patients with ankylosing spondylitis or diffuse idiopathic skeletal hyperostosis: A comparison of treatment methods and clinical outcomes. J. Spinal Disord. Tech. 22, 77–85 (2009).
Westerveld, L. A., van Bemmel, J. C., Dhert, W. J., Oner, F. C. & Verlaan, J. J. Clinical outcome after traumatic spinal fractures in patients with ankylosing spinal disorders compared with control patients. Spine J. http://www.doi.org/10.1016/j.spinee.2013.06.038.
Littlejohn, J. O., Urowitz, M. B., Smythe, H. A. & Keystone, E. C. Radiographic features of the hand in diffuse idiopathic skeletal hyperostosis (DISH). Radiology 140, 623–629 (1981).
Beyeler, C. et al. Diffuse idiopathic skeletal hyperostosis (DISH) of the shoulder. A cause of shoulder pain? Br. J. Rheumatol. 29, 349–353 (1990).
Utsinger, P. D., Resnick, D. & Shapiro, R. Diffuse skeletal abnormalities in Forestier's disease. Arch. Intern. Med. 136, 763–768 (1976).
Schlapbach, P. et al. The prevalence of palpable finger joints nodules in diffuse idiopathic skeletal hyperostosis (DISH). A controlled study. Br. J. Rheumatol. 31, 531–534 (1992).
Littlejohn, J. O. & Urowitz, M. B. Peripheral enthesopathy in diffuse idiopathic skeletal hyperostosis (DISH): a radiologic study. J. Rheumatol. 9, 568–572 (1982).
Resnick, D., Shaul, S. R. & Robins, J. M. Diffuse idiopathic skeletal hyperostosis (DISH): Forestier's disease with extraspinal manifestations. Radiology 115, 513–524 (1975).
Haller, J. et al. Diffuse idiopathic skeletal hyperostosis: diagnostic significance of radiographic abnormalities of the pelvis. Radiology 172, 835–839 (1989).
Shehab, D., Elgazzar, A. H. & Collier, B. D. Heterotopic ossification. J. Nucl. Med. 43, 346–353 (2002).
Gorman, C., Jawad, A. S. M. & Chikanza, I. A family with diffuse idiopathic hyperostosis. Ann. Rheum. Dis. 64, 1794–1795 (2005).
Burges-Armas, J. et al. Ectopic calcification among families in the Azores: clinical and radiological manifestations in families with diffuse idiopathic skeletal hyperostosis and chondrocalcinosis. Arthritis Rheum. 54, 1340–1349 (2006).
Kranenburg, H. C. et al. The dog as an animal model for DISH? Eur. Spine J. 19, 1325–1329 (2010).
Havelka, S. et al. Are DISH and OPLL genetically related? Ann. Rheum. Dis. 60, 902–903 (2001).
Tsukahara, S. et al. COL6A1, the candidate gene for ossification of the posterior longitudinal ligament, is associated with diffuse idiopathic skeletal hyperostosis in Japanese. Spine 30, 2321–2324 (2005).
Shingyouchi, O., Nagahama, A. & Niida, M. Ligamentous ossification of the cervical spine in the late middle-aged Japanese men. Its relation to body mass index and glucose metabolism. Spine 21, 2474–2478 (1996).
Littlejohn, G. O. Insulin and new bone formation in diffuse idiopathic skeletal hyperostosis. Clin. Rheumatol. 4, 294–300 (1985).
Denko, C. W., Boja, B. & Moskowitz, R. W. Growth promoting peptides in osteoarthritis and diffuse idiopathic skeletal hyperostosis—insulin, insulin-like growth factor-I, growth hormone. J. Rheumatol. 21, 1725–1730 (1994).
Vezyroglou, G., Mitropoulos, A., Kyriazis, N. & Antoniadis, C. A metabolic syndrome in diffuse idiopathic skeletal hyperostos: A controlled study. J. Rheumatol. 23, 672–676 (1996).
Akune, T. et al. Insulin secretory response is positively associated with the extent of ossification of the posterior longitudinal ligament of the spine. J. Bone Joint Surg. 83A, 1537–1544 (2001).
Kiss, C., Szilagyi, M., Paksy, A. & Poor, G. Risk factors for diffuse idiopathic skeletal hyperostosis: a case control study. Rheumatology (Oxford) 41, 27–30 (2002).
Sarzi-Puttini, P. & Atzeni, F. New developments in our understanding of DISH (diffuse idiopathic skeletal hyperostosis). Curr. Opin. Rheumatol. 16, 287–292 (2004).
Miyazawa, N. & Akiyama, I. Diffuse idiopathic skeletal hyperostosis associated with risk factors for stroke. Spine 31, E225–E229 (2006).
Forestier, J. & Lagier, R. Ankylosing hyperostosis of the spine. Clin. Orthop. 74, 65–83 (1971).
Sencan, D., Elden, H., Nacitrahan, V., Sencan, M. & Kaptanoglu, E. The prevalence of diffuse idiopathic skeletal hyperostosis in patients with diabetes mellitus. Rheumatol. Int. 25, 518–521 (2005).
Denko, C. W. & Malemud, C. J. 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. 26, 292–297 (2006).
Littlejohn, G. O. & Smythe, H. A. Marked hyperinsulinemia after glucose challenge in patients with diffuse idiopathic skeletal hyperostosis. J. Rheumatol. 8, 965–968 (1981).
Eckertova, M. et al. Impaired insulin secretion and uptake in patients with diffuse idiopathic skeletal hyperostosis. Endocr. Regul. 43, 149–155 (2009).
Mueller, M. B. et al. Insulin is essential for in vitro chondrogenesis of mesenchymal progenitor cells and influences chondrogenesis in a dose-dependent manner. Int. Orthop. 37, 153–158 (2013).
Ohlsson, C., Bengtsson, B. A., Isaksson, O. G. P., Andereassen, T. T. & Slootweg, M. C. Growth hormone and bone. Endocrine Rev. 19, 55–79 (1998).
Vetter, U. et al. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth. J. Clin. Invest. 77, 1903–1908 (1986).
Denko, C. W., Boja, B. & Moskowitz, R. W. Growth factors, insulin-like growth factor-1 and growth hormone, in synovial fluid and serum of patients with rheumatic disorders. Osteoarthritis Cartilage 4, 245–249 (1996).
Denko, C. W., Boja, B. & Malemud, C. J. Intra-erythrocyte deposition of growth hormone in rheumatic diseases. Rheumatol. Int. 23, 11–14 (2003).
el Miedany, Y. M., Wassif, G. & el Baddini, M. Diffuse idiopathic skeletal hyperostosis (DISH): is it of vascular etiology? Clin. Exp. Rheumatol. 18, 193–200 (2000).
Nesher, G. & Zuckner, J. Rheumatologic complications of vitamin A and retinoids. Semin. Arthritis Rheum. 24, 291–296 (1995).
Abiteboul, M., Arlet J., Sarrabay, M. A., Mazières, B. & Thouvenot, J. P. Etude du metabolisme de la vitamine A au cours de la maladie hyperostosique de Forestier et Rote's-Querol. Rev. Rhum. Ed. Fr. 53, 143–145 (1986).
Ling, T. C., Parkin, G., Islam, J., Seukeran, D. C. & Cunliffe, W. J. What is the cumulative effect of long-term, low dose isotretinoin on the development of DISH? Br. J. Dermatol. 144, 630–632 (2001).
Aeberli, D., Schett, G., Eser, P., Seitz, M. & Villiger, P. M. Serum Dkk-1 levels of DISH patients are not different from healthy controls. Joint Bone Spine 78, 422–423 (2011).
Daoussis, D. & Andonopoulos, A. P. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin. Arthritis Rheum. 41, 170–177 (2011).
Senolt, L. et al. Low circulating Dickkopf-1 and its link with severity of spinal involvement in diffuse idiopathic skeletal hyperostosis. Ann. Rheum. Dis. 71, 71–74 (2012).
Mader, R. & Verlaan, J. J. Bone: Exploring factors responsible for bone formation in DISH. Nat. Rev. Rheumatol. 8, 10–12 (2011).
Kosaka, T., Imakiire, A., Mizuno, F. & Yamamoto, K. Activation of nuclear factor κB at the onset of ossification of the spinal ligaments. J. Orthop. Sci. 5, 572–578 (2000).
Inaba, T. et al. Enhanced expression of platelet-derived growth factor-β receptor by high glucose. Involvement of platelet-derived growth factor in diabetic angiopathy. Diabetes 45, 507–512 (1996).
Pfeiffer, A., Middelberg-Bisping, K., Drewes, C. & Schatz, H. Elevated plasma levels of transforming growth factor-β1 in NIDDM. Diabetes Care 19, 1113–1117 (1996).
Kon, T. et al. Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossification of the posterior longitudinal ligament. Calcif. Tissue Int. 60, 291–296 (1997).
Tanaka, H. et al. Involvement of bone morphogenic protein-2 (BMP-2) in the pathological ossification process of the spinal ligament. Rheumatology 40, 1163–1168 (2001).
Zebboudj, A. F., Imura, M. & Bostrom, K. Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2. J. Biol. Chem. 8, 4388–4394 (2002).
Tanno, M., Furukawa, K. I., Ueyama, K., Harata, S. & Motomura, S. Uniaxial cyclic stretch induces osteogenic differentiation and synthesis of bone morphogenetic proteins of spinal ligament cells derived from patients with ossification of the posterior longitudinal ligaments. Bone 33, 475–484 (2003).
Ohishi, H. et al. Role of prostaglandin I2 in the gene expression induced by mechanical stress in spinal ligament cells derived from patients with ossification of the posterior longitudinal ligament. J. Pharmacol. Exp. Ther. 305, 818–824 (2003).
Iwasawa, T. et al. Pathophysiological role of endothelin in ectopic ossification of human spinal ligaments induced by mechanical stress. Calcif. Tissue Int. 79, 422–430 (2006).
Kasperk, C. H. et al. Endothelin-1 is a potent regulator of human bone cell metabolism. Calcif. Tissue Int. 60, 368–374 (1997).
Carile, L., Verdone, F., Aiello, A. & Buongusto, G. Diffuse idiopathic skeletal hyperostosis and situs viscerum inversus. J. Rheumatol. 16, 1120–1122 (1989).
Smythe, H. A. The mechanical pathogenesis of generalized osteoarthritis. J. Rheumatol. 10 (Suppl. 9), 11–12 (1983).
Arlet, J. & Mazieres, B. La maladie hyperostosique. Rev. Mdd. Interne. 6, 553–564 (1985).
Mader, R. et al. Developing new classification criteria for diffuse idiopathic skeletal hyperostosis: back to square one. Rheumatology (Oxford) 52, 326–330 (2013).
Olivieri, I. et al. Diffuse idiopathic skeletal hyperostosis: differentiation from ankylosing spondylitis. Curr. Rheumatol. Rep. 11, 321–328 (2009).
Mader, R. Diffuse idiopathic skeletal hyperostosis: isolated involvement of cervical spine in a young patient. J. Rheumatol. 31, 620–621 (2004).
Al-Herz, A., Snip, J. P., Clark, B. & Esdaile, J. M. Exercise therapy for patients with diffuse idiopathic skeletal hyperostosis. Clin. Rheumatol. 27, 207–210 (2008).
Troyanovich, S. J. & Buettner, M. A structural chiropractic approach to the management of diffuse idiopathic skeletal hyperostosis. J. Manipulative Physiol. Ther. 26, 202–206 (2003).
Roberts, J. A., Tristy, M. & Wolfe, M. A. Chiropractic management of a veteran with lower back pain associated with diffuse idiopathic skeletal hypertrophy and degenerative disk disease. J. Chiropr. Med. 11, 293–299 (2012).
El Garf, A. & Khater, R. Diffuse idiopathic skeletal hyperostosis (DISH): a clinicopathological study of the disease pattern in Middle Eastern populations. J. Rheumatol. 11, 804–807 (1984).
Hochberg, M. C. et al. American College of Rheumatology recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee. Arthritis Care Res. 64, 465–474 (2012).
Roth, S. H. & Shainhouse, J. Z. Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial. Arch. Intern. Med. 164, 2017–2023 (2004).
Lithell, H. O. L. Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism. Diabetes Care 14, 203–209 (1991).
Carlson, M. L., Archibald, D. J., Graner, D. E. & Kasperbauer, J. L. Surgical management of dysphagia and airway obstruction in patients with prominent ventral cervical osteophytes. Dysphagia 26, 34–40 (2011).
Urrutia, J. & Bono, C. M. Long-term results of surgical treatment of dysphagia secondary to cervical diffuse idiopathic skeletal hyperostosis. Spine J. 9, e13–e17 (2009).
Guillemin, F., Mainard, D., Rolland, H. & Delagoutte, J. P. Antivitamin K prevents heterotopic ossification after hip arthroplasty in diffuse idiopathic skeletal hyperostosis: a retrospective study in 67 patients. Acta Orthop. Scand. 66, 123–126 (1995).
Knelles, D. et al. Prevention of heterotopic ossification after total hip replacement: a prospective, randomized study using acetylsalicylic acid, indomethacin and fractional or single-dose irradiation. J. Bone Joint Surg. Br. 79, 596–602 (1997).
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Mader, R., Verlaan, JJ. & Buskila, D. Diffuse idiopathic skeletal hyperostosis: clinical features and pathogenic mechanisms. Nat Rev Rheumatol 9, 741–750 (2013). https://doi.org/10.1038/nrrheum.2013.165
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DOI: https://doi.org/10.1038/nrrheum.2013.165
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