Diffuse idiopathic skeletal hyperostosis (DISH)

INTRODUCTION — Diffuse idiopathic skeletal hyperostosis (DISH), which has also been known as ankylosing hyperostosis, Forestier disease, and Forestier-Rotes-Querol disease, is a noninflammatory disorder principally characterized by calcification and ossification of spinal ligaments and entheses, the regions where tendons and ligaments attach to bone [1,2]. Symptoms of back and neck pain may be present, but radiographic changes characteristic of DISH may occur in the absence of any musculoskeletal symptoms.

The clinical manifestations, radiologic findings, diagnosis, and treatment of DISH are reviewed here. The evaluation of neck and back pain; the clinical features and treatment of osteoarthritis affecting the spine, including spinal stenosis; and the clinical manifestations, diagnosis, and treatment of spondyloarthritis are presented separately:

●Neck and back pain (see "Evaluation of the adult patient with neck pain" and "Evaluation of low back pain in adults" and "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment")

●Osteoarthritis of the spine (see "Clinical manifestations and diagnosis of osteoarthritis" and "Clinical manifestations and diagnosis of osteoarthritis", section on 'Facet joint' and "Lumbar spinal stenosis: Pathophysiology, clinical features, and diagnosis" and "Lumbar spinal stenosis: Treatment and prognosis" and "Cervical spondylotic myelopathy")

●Axial spondyloarthritis (see "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Diagnosis and differential diagnosis of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults" and "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults")

●Enthesopathy (see "Clinical manifestations and diagnosis of peripheral spondyloarthritis in adults", section on 'Musculoskeletal features' and "Overview of soft tissue musculoskeletal disorders")

ETIOLOGY AND PATHOGENESIS — While the cause of diffuse idiopathic skeletal hyperostosis (DISH) remains unknown, mechanical factors, dietary contributions, drugs, environmental exposures, and metabolic conditions have been hypothesized to be important. It is thought that the bone formation that is distinctive of DISH results from abnormal osteoblastic differentiation and activity at the enthesis.

Natural inhibitors of bone formation, such as matrix Gla protein and Dickkopf-1 (DKK1), may be deficient in DISH patients, contributing to hyperostosis [3,4]. An appropriate genetic background, as yet unidentified, external factors, or local or systemic factors may stimulate the abnormal osteoblastic differentiation.

A study of Wnt signaling antagonists in patients with DISH and other spinal disorders found that serum levels of osteocalcin were higher, but DKK1 levels were lower in DISH patients than those in the controls. Similarly, serum levels of secreted frizzled-related protein 1 and sclerostin were significantly higher in DISH patients than those in the controls [5].

Potentially important factors include:

●Mechanical factors – Bony bridging is usually more prominent on the right side of the thoracic spine in patients with DISH, but mechanical factors associated with the location of the aorta may affect the development of bony outgrowths [6]. In comparison with the usual right-sided prominence, those with DISH and dextrocardia or situs inversus have more extensive bony bridging on the left side of the thoracic spine.

In ossification of the posterior longitudinal ligament (OPLL) of the spine, a condition that can occur with DISH or as an independent entity, ligamentous stretching can increase prostaglandin I2 synthase, resulting in stimulation of osteogenic differentiation and suggesting a mechanism whereby mechanical forces may affect bone formation [7]. Circulating levels of DKK1, an inhibitor of osteoblastogenesis, may be reduced in DISH patients, contributing to hyperostosis [4].

A case-control study that reported no significant difference in the amount of heavy work performed by persons with DISH than by control individuals fails to support the mechanical hypothesis [8]. However, work as a measure of mechanical loading of bones and joints is notoriously difficult to accurately assess.

●Environmental factors and diet – Several known environmental causes of hyperostosis have been investigated as possible contributors to the development of DISH, including exposure to fluoride and to vitamin A. In one study, fluoride levels in both the water and air were measured in towns inhabited by 11 patients with DISH [9]. Based upon the levels of fluoride, chronic fluoride intoxication was unlikely to be causative.

The relationship between prolonged exposure to an excess of vitamin A and bone hyperostosis is established. However, while higher serum levels of retinol have been reported in DISH patients compared with normal controls [10,11], this has not been confirmed by all investigators [12].

●Medications – Selected medications may also drive hyperostosis. Long-term therapy of acne and other skin conditions with isotretinoin, a synthetic derivative of vitamin A, is associated with hyperostotic changes in the spine. Etretinate (no longer available for clinical use), acitretin, and other synthetic retinoids are associated with hyperostosis, particularly at extraspinal sites [13-15]. As noted in the previous section, however, increased exposure to vitamin A alone does not appear to be adequate to cause DISH.

●Metabolic conditions – Several growth factors may be involved in the pathogenesis of DISH, including insulin, insulin-like growth factor, and growth hormone. Insulin-like growth factor 1 stimulates osteoblasts, and growth hormone can induce the local production of insulin-like growth factor 1 in osteoblasts. It is believed that these factors are involved in the pathogenesis of the increased osteoblastic activity in DISH [3,16].

While individual studies evaluating levels of glucose, insulin, insulin-like growth factor 1, and growth hormone have produced conflicting results [17,18], some confirmation of their importance comes from clinical studies. As an example, the Pima people have a high frequency of DISH [19]. They also have a high prevalence of obesity, elevated blood pressure, adult-onset diabetes mellitus, and hyperinsulinemia.

Additionally, in White populations, the prevalence of DISH is increased in people with obesity and possibly in those with early obesity or diabetes mellitus, conditions in which increased levels of insulin are likely present [17,18,20,21]. Features of DISH are also found in up to 20 percent of those with acromegaly [22]. Elevated levels of insulin, insulin-like growth factor 1, and growth hormone have been reported in some studies of DISH patients [16,23].

Hypervascularity of ossified ligaments and involved vertebrae has been described. Whether this causes osteoblast proliferation or is a result of DISH is unclear [24].

Other growth factors and regulatory molecules may also play a role in DISH. Platelet-derived growth factor-BB and transforming growth factor-1-beta in ligament cells may lead to increased levels of nuclear factor kappa B in DISH. Nuclear factor kappa B can cause undifferentiated mesenchymal cells to differentiate into osteoblasts, providing a plausible mechanism for bony proliferation [25]. Matrix Gla protein likely inhibits bone formation. The apparently paradoxical finding of higher levels of matrix Gla in persons with DISH compared with controls suggests a possible role for this protein in the disease process [3].

EPIDEMIOLOGY — Diffuse idiopathic skeletal hyperostosis (DISH) is more common in males than females. The incidence varies by population and increases with age, rarely being diagnosed before the age of 40.

●In a population-based study of individuals over age 30 in Finland, the incidence was 0.7 and 0.4 per 100 person-years in males and females, respectively [26]. In another Finnish study, the prevalence in people over 40 years of age was 3.8 and 2.6 percent in males and females, respectively [27]. Among those over age 70, the prevalence was 10.1 and 6.8 percent. In a study in Hungary, the prevalence in those over 50 years was 4.9 percent in males and 1.4 percent in females [28].

●The Pima people in Arizona of the United States have a particularly high prevalence of DISH, occurring in 25 and 4.7 percent of males and females aged 15 years and over, respectively [19]; this rises to 48 and 12 percent in those over the age of 55 years.

●Black Americans may have a lower prevalence of DISH than White populations [1].

●Hospital-based studies may report a higher prevalence of disease than population-based studies, since DISH is more likely among those seeking or requiring hospital care. A hospital-based study of 1500 Black Africans found a radiographic prevalence of approximately 4 percent in both males and females over age 40 [29]. A similar study among a hospitalized Jewish population living in Jerusalem found a prevalence of 22.4 and 13.4 percent in males and females over age 40, respectively [30].

●In Japan, up to 4 percent of the general population have ossification of the posterior longitudinal ligament (OPLL), predominantly at the cervical spine, a prevalence that is nearly 80-fold that seen in Europe [31].

CLINICAL FEATURES — Patients with diffuse idiopathic skeletal hyperostosis (DISH) may experience musculoskeletal pain and stiffness in affected areas, including the neck, back, and sometimes the extremities; experience reduced spinal motion, especially in the thoracic spine, which is present in all patients in advanced cases; and demonstrate characteristic radiographic changes, including ossification of paravertebral ligaments and peripheral entheses. (See 'Symptoms' below and 'Physical findings' below and 'Radiographic findings' below.)

Laboratory findings are typically unremarkable, and whether DISH is associated with other musculoskeletal or systemic disorders is uncertain. (See 'Laboratory findings' below and 'Associated conditions' below.)

Because most reports of the clinical features of DISH are based upon clinic or hospital series, individuals evaluated in these studies are more likely to be symptomatic than those in population-based surveys.

Symptoms — Patients with DISH may have neck, thoracic spine, low back, and/or extremity pain and experience restricted spinal mobility. Dysphagia, airway obstruction, and other symptoms related to spinal involvement are also reported, as are myelopathy-related symptoms [32].

●Musculoskeletal symptoms – Spinal morning stiffness, a symptom usually associated with inflammatory disorders of the spine, is present in a large number of affected individuals (80 percent) [1]. Pain may be reported in the neck, mid- and low back, and the extremities. In one study in which the symptoms were compared among patients with either DISH or lumbar spondylosis and healthy controls, substantially higher levels of pain over the neck, thoracic spine, low back, and extremities were reported in those with DISH than in healthy persons [17].

Disability as assessed by the Health Assessment Questionnaire was also greater in those with DISH than in healthy subjects. In one study of community dwellers in southern California, those with DISH had 1.7-fold greater odds of self-reported difficulty bending, had worse grip strength, and males were less likely to complete five chair stands without using their arms [33].

Among those with DISH or symptomatic lumbar spondylosis, there were similar degrees of pain, disability, and diminution in global well-being. Radicular pain is not a feature of DISH itself, and its presence suggests the likelihood of an associated nerve impingement in the spine. Patients with DISH may also suffer from lumbar spinal stenosis unrelated to DISH.

The frequency of complaints among those with DISH varies by the site of discomfort. Pain in the thoracic spine, for example, has been reported to occur among 40 to 80 percent of patients [1,17]. By comparison, complaints of dysphagia and symptoms in the shoulder, elbow, and knee due to enthesopathy are less common, being reported in approximately 15 to 25 percent of patients. Stridor may rarely occur when large anterior osteophytes arise from C2 to C3; odynophagia and otalgia may result from pressure-induced hypopharyngeal ulceration [34].

Some patients complain of symptoms for years prior to diagnosis; some, but not all, studies suggest a link between radiologic findings at a particular site and the presence of symptoms attributed to the abnormality (see 'Radiographic findings' below). In one study of hospitalized patients, for example, a significant association was reported between shoulder hyperostosis and shoulder symptoms [35]. A near doubling of risk for elbow symptoms was also reported in those with elbow hyperostosis (but it did not reach statistical significance) [36]. However, unlike the studies cited earlier, no appreciable link was noted between axial hyperostosis and spinal pain [8].

In another study, a comparison of 56 patients with DISH and 43 patients with a history of chronic low back pain and moderate to severe radiographic lumbar spondylosis reported at least a fourfold increase in the frequency of medial epicondylitis, knee enthesitis, plantar fasciitis, and dysphagia in those with DISH [17]. However, none of these increases was statistically significant, each affecting only five to seven patients compared with a single affected spondylosis patient with each.

●Dysphagia and other symptoms with cervical involvement – An increase in the frequency of dysphagia has been noted in all series. This sometimes results from compression of the esophagus by large anterior cervical osteophytes [1,2,17,32]. Cervical involvement can also cause hoarseness, stridor, aspiration pneumonia, sleep apnea, atlantoaxial subluxation or pseudoarthrosis, and thoracic outlet syndrome [37].

●Neurologic manifestations – Neurologic complaints or findings may occur due to ossification of the posterior longitudinal ligament (OPLL), which can result in spinal cord compression and may lead to sensory or motor disturbances due to myelopathy. This condition may be more prevalent among Japanese patients with DISH. OPLL can cause cervical myelopathy with potentially devastating neurologic complications, including quadriparesis and quadriplegia [38]. Symptoms that should raise concerns for the development of cervical myelopathy include the development of sharp, shooting pain in the neck; the sudden loss of cervical spine motion; the presence of an unsteady gait and brisk reflexes; and the development of new sensory symptoms in the extremities.

Other complications that are rare include Horner's syndrome, recurrent laryngeal nerve palsy, and vertebral artery insufficiency [39].

Physical findings — Decreased range of spinal motion, particularly thoracic movement, is the most common finding upon physical examination. Although all spinal motion is diminished in DISH, the loss of thoracic lateral flexion is particularly notable. Palpable nodules may also be found at the entheses, with the elbow, knee, and Achilles region being the most common sites.

An increased prevalence of Bouchard and Heberden nodes in those with DISH compared with age- and sex-matched controls without DISH was noted in one study [40]; a similar finding relating to Heberden nodes was noted in a second report [17].

Radiographic findings — The hallmarks of DISH are radiographic abnormalities. DISH is characterized on imaging by the ossification of paravertebral ligaments and peripheral entheses [1,2,9,41-43].

Spinal involvement — The most common and characteristic radiographic findings involve the thoracic spine, but abnormalities may also be present in the cervical and lumbosacral spine.

●Thoracic – In the thoracic spine, the distinctive finding is flowing linear calcification and ossification along the anterolateral aspects of the vertebral bodies, which continue across the disc space. When present, a lucent area is noted between the anterior longitudinal ligament and the mid-portion of the vertebral body [41]. Thoracic involvement is usually more prominent on the right side of the spine (image 1) [2,42]. These findings may be more readily visualized on the lateral radiographic images.

●Cervical – In the cervical spine (image 2), hyperostosis occurs initially on the anterior surface of the vertebral body, particularly the inferior lip of the vertebra so that a downward-pointing spur arises. Changes are most common in the lower cervical spine.

The cervical spine hyperostosis is often symmetrically distributed anterior to the vertebral body, which may cause substantial displacement of the trachea and the esophagus. Unlike the thoracic spine, ossifications are nonflowing in the sagittal view [32].

●Lumbar – In the lumbar spine, the findings are similar to those of the cervical spine, except that there may be a tendency for the spurs to point upwards. Complete bridging of the lumbar disc space by bone is infrequent (image 3).

The flowing calcification observed in the thoracic region is much less common in the cervical and lumbar locations. Unlike the thoracic spine, in which disc narrowing is mild or nonexistent, disc narrowing can be present in the cervical and lumbar spine. However, marginal sclerosis of the vertebral body, vacuum phenomena, or disc calcification (which are seen in degenerative disc disease) are rare in any spinal region in DISH [2,41,42], unless there is a superimposed element of degenerative disc disease.

Calcification or ossification of the posterior longitudinal spinal ligament is a less common finding than involvement of the anterior counterpart. This arises almost solely in the cervical spine and occurs as a discrete disorder or in association with DISH, ankylosing spondylitis, or spondylosis (image 4).

Computed tomography (CT) is more sensitive than plain radiography for detecting posterior longitudinal ligamentous calcification [38]. A sequential CT imaging study of osteophyte progression in 26 patients with DISH observed two types of bridging patterns, with osteophyte fusion associated with a calcified anterior longitudinal ligament in two-thirds of patients and osteophyte fusion without apparent anterior longitudinal ligament calcification in one-third [44]. Both patterns were observed concomitantly in 15 patients. The authors noted that vertically oriented osteophytes were frequent and hypothesized that they may indicate an inflammatory pathogenesis, in contrast to horizontally oriented osteophytes that may be more characteristic of osteoarthritic change. The rate of change that was observed suggested that a full-flowing osteophyte forms in patients with DISH over a period of approximately 10 years.

In another study, which compared vertical and horizontal bone growth in patients with DISH to that in patients with ankylosing spondylitis, vertical growth (syndesmophyte formation) was more often found in ankylosing spondylitis, but also present in DISH, while horizontal growth (formation of osteophytes) was more often present in patients with DISH, although it was found in both conditions [45].

Extraspinal involvement — A high frequency of extraspinal involvement has been noted in patients with DISH. Whether DISH occurs in the absence of spinal involvement is uncertain, but it seems possible. Virtually any extraspinal osseous or articular site may be affected [2,46]. Radiographic changes in the appendicular skeleton are often symmetric. The following findings have been noted:

●Pelvic and hip involvement includes bony proliferation (also called whiskering), ligament ossification, and periarticular osteophytes (image 5). The whiskering can involve the iliac crest, ischial tuberosity, and trochanter. The iliolumbar and sacrotuberous ligaments can be calcified or ossified, and periarticular osteophytes may be seen at the inferior portion of the sacroiliac joint, the lateral acetabulum, and the superior pubic margins. Heterotopic bone formation may be seen following total hip replacement [47].

●Knees can be involved at the patella, at the insertion of the ligaments, and at the tibial tuberosity (image 6).

●Ankles and feet can have bony excrescences over the dorsal surface of the talus, the dorsal and medial tarsal navicular, the lateral and plantar aspects of the cuboid, and the base of the fifth metatarsal (image 7A-B).

●Shoulder involvement includes bony irregularity along the deltoid tuberosity, the inferior glenoid, and the inferior distal clavicle, as well as calcification and ossification of the coracoclavicular ligament.

●Elbow involvement includes bony irregularity over the olecranon surface that should not impede elbow joint range of motion [48].

●Hand changes include broadening and arrow heading of the phalangeal tufts, enlarged sesamoid bones, thickened cortical width of tubular bones, exostoses, new bone in the joint capsule, and striking proximal phalangeal enthesopathy [49].

●Hyperostosis frontalis interna, a thickening of the inner table of the frontal bones of the skull (usually an incidental radiologic finding of no clinical significance) is increased in DISH [42].

●Bone density is increased in DISH due to the artifact resulting from measurement in areas with substantial osteophytosis [50].

In patients in whom DISH coexists with another rheumatic disease, the presence of both disorders may result in an unusual radiographic appearance. As an example, when patients with rheumatoid arthritis and DISH were assessed radiographically, atypical features included a lack of juxtaarticular osteoporosis, the presence of bone sclerosis, and proliferative changes near erosions, osteophytosis, and bony ankyloses [51]. Flexion contractures of the elbows, wrists, ankles, or knees were also observed more frequently than expected for patients with rheumatoid arthritis alone.

Laboratory findings — There are no consistent laboratory abnormalities that are associated with DISH. The following are either normal or nondiagnostic: complete blood counts; erythrocyte sedimentation rate; serum levels of calcium, phosphorus, growth hormone, liver enzymes, parathyroid hormone, and fluoride; and the serum protein electrophoresis [1,9,17]. The frequency of human leukocyte antigen (HLA)-B27 is not increased [17,19].

Associated conditions — The coexistence of DISH with gout, rheumatoid arthritis, Paget disease, and chondrocalcinosis has been reported [51-54] but has not always been confirmed [12,17,55]. Additionally, patients with DISH have also been shown to have an elevated risk of the metabolic syndrome [56]. Given the very high prevalence of DISH in older adults, other diseases may coexist independently of any association.

As noted, however, the coexistence of DISH with other diseases, such as rheumatoid arthritis or gout, may alter the expected radiographic findings of these diseases (see 'Extraspinal involvement' above). In addition, DISH is associated with an increased risk of heterotopic bone formation following total hip replacement in most, but not all, studies [47]. (See "Complications of total hip arthroplasty", section on 'Heterotopic ossification'.)

DIAGNOSIS

When to suspect DISH — Diffuse idiopathic skeletal hyperostosis (DISH) should be suspected in a patient with a characteristic history and physical findings, particularly spinal stiffness and restricted motion of the thoracic spine (see 'Clinical features' above and 'Symptoms' above and 'Physical findings' above). Incidentally noted radiographic changes may sometimes suggest the diagnosis as well. Other clinical clues further supporting the possibility of DISH include the presence of one or more of the following (table 1) [1]:

●Palpable bony spurs (eg, of the calcaneus, olecranon, patella)

●Hyperostotic spurs at the olecranon (medial and lateral epicondyles) [48]

●Soft tissue mass adherent to quadriceps, patella, or Achilles tendon

●Generalized tenderness at peripheral entheses

●Recurrent Achilles tendinitis

●Recurrent shoulder "bursitis"

●Recurrent lateral or medial epicondylitis

●Dysphagia

●Myelopathy in patients with ossification of the posterior longitudinal ligament (OPLL)

Establishing the diagnosis — In patients in whom the disorder is suspected on the basis of suggestive symptoms or physical findings such as spinal stiffness and restricted motion of the thoracic spine (see 'Clinical features' above and 'When to suspect DISH' above), the diagnosis is made based upon the presence of the characteristic radiographic findings, including flowing linear calcification and ossification along the anterolateral aspects of the vertebral bodies, most often affecting the thoracic spine, which continue across the disc space (see 'Spinal involvement' above). At least two contiguous vertebrae should be involved and the disc space height in affected areas largely preserved.

Lateral radiographs of the thoracic spine should generally be obtained as the initial diagnostic test. In patients who have previous chest radiographs available for review, such studies may be sufficient to confirm the diagnosis. Additional radiographic studies may be necessary for those with clinical features suggesting cervical, lumbar, or extraspinal involvement. The incidental finding of spinal ligament calcification or ossification should alert the clinician to the possibility of a diagnosis of DISH.

Classification criteria — Classification criteria for DISH have been proposed by Resnick and Niwayama, and Utsinger has recommended different criteria for epidemiologic purposes (table 2) [1,41]. Despite the common use of elements of classification criteria as aids in diagnosis, such criteria sets have limitations when employed for that purpose [57]. As examples, the Resnick criteria rely solely upon axial radiographic findings (involvement of at least four contiguous vertebral bodies) and do not include changes present in the peripheral skeleton; the criteria of Utsinger rely comparatively less on radiographic changes (involvement of at least two contiguous vertebral bodies supports "probable DISH") and thus may be more suitable for identifying patients with earlier disease.

An important part of both sets of criteria is that the findings included have to be differentiated from those in other diseases. The absence of structural changes in the sacroiliac joints and of apophyseal joint bony ankyloses helps exclude typical ankylosing spondylitis, and the maintenance of intervertebral disc height helps to exclude typical of degenerative disc disease.

For screening or epidemiologic studies, a chest radiograph may be used, which will detect at least 75 percent of those with DISH as defined by Resnick's criteria. However, patients with less extensive radiographic disease but with skeletal changes consistent with DISH may remain undetected using these criteria [55].

DIFFERENTIAL DIAGNOSIS — A number of conditions may produce spinal bony excrescences similar to those observed with diffuse idiopathic hyperostosis (DISH) (table 3). Of these, the most commonly encountered are spondylosis deformans and ankylosing spondylitis:

●Spondylosis deformans – Spondylosis deformans (degenerative disc disease with osteophyte formation) is by far the most common of the disorders to be considered in the differential diagnosis of DISH. Although the spurs in the cervical and lumbar spine can resemble those seen in DISH, involvement of the anterior longitudinal ligament in the thoracic spine of DISH is not observed in spondylosis [9,41]. (See "Evaluation of the adult patient with neck pain", section on 'Cervical spondylosis'.)

●Ankylosing spondylitis – Ankylosing spondylitis shares some characteristics with DISH, such as a preponderance in males and an association with ligamentous ossification and syndesmophytes. In ankylosing spondylitis, however, the bony bridges are slender, vertical bony bridges that involve the outer margin of the annulus fibrosis and do not involve the anterior longitudinal ligament. In addition, erosions and bony ankylosis of the sacroiliac and apophyseal joints are not seen in DISH, although such changes can occur in patients with ankylosing spondylitis [9,41]. Another feature that may be seen on plain radiographs in patients with DISH, but not those with ankylosing spondylitis, is the finding of bony excrescences adjacent to peripheral joints such as the knee or elbow. (See "Clinical manifestations of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults".)

In one small study of 10 patients with DISH who had available magnetic resonance imaging (MRI) studies of the spine, bone marrow edema was identified in the anterior/posterior vertebral corners in five patients, and fat deposition in these corners was noted in eight patients, indicating that these findings are not specific for ankylosing spondylitis and suggesting that there may be overlapping pathogenetic mechanisms for new bone formation in these two disorders [58,59].

●Ossification of the posterior longitudinal ligament – Ossification of the posterior longitudinal ligament (OPLL) may be seen in up to 50 percent of patients with DISH [60] but occurs both independently and in association with other disorders, including ankylosing spondylitis and other spondyloarthropathies [61]. It is more commonly found in Japanese patients but can also be seen in other populations [38,62]. Unlike DISH, it occurs predominantly in the cervical spine, although thoracic and lumbar OPLL also occur [61]. Most symptomatic patients present with significant neurologic deficits such as myelopathy or radiculopathy, and surgery is frequently required. Some patients, especially those without myelopathy, do not have progressive disease requiring surgical intervention and may be managed conservatively [63].

TREATMENT

Treatment overview — Therapy of diffuse idiopathic skeletal hyperostosis (DISH) is symptomatic and generally similar to the treatment of mild chronic low back pain, including physical therapy, exercise, and symptomatic pain management [48]. No treatments have been documented to alter the disease course, and there have been no randomized trials examining the effectiveness of any interventions for the condition. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)

Patients with radiographic evidence of DISH but who are asymptomatic do not require any intervention or particular counseling, although all symptomatic patients (for example, describing pain or stiffness) should be referred for physical therapy, as should patients with findings of restricted spinal mobility. Patients with DISH can perform physical activities as tolerated.

Symptomatic management — We suggest symptomatic management of stiffness, the main symptom, and pain, which is usually mild, which is focused on physical measures, including formal physical therapy and regular exercise, with pharmacotherapy only as needed. The approach to treatment of pain in patients with DISH is generally similar to that in patients with subacute or chronic low back pain. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)

●Physical measures – Physical therapy and physical activity are usually beneficial in the author's experience, but have not been formally evaluated in patients with DISH. These include:

•Heat, ultrasound, gentle exercise, and modification of activities of daily living and of recreation can reduce pain

•Range of motion exercises and stretching help with stiffness

•Range of motion and functional exercise programs to strengthen can increase mobility

•Aerobic exercise programs will benefit endurance

•Daily swimming is an ideal exercise and can help with weight loss

•Orthotics help with painful heel spurs and assist with ambulation

●Pharmacotherapy (systemic and local) – Our approach to pharmacotherapy for the treatment of pain that has not adequately responded to physical measures is similar to that used for other causes of subacute and chronic low back pain. (See "Subacute and chronic low back pain: Nonpharmacologic and pharmacologic treatment".)

Points of particular relevance to DISH, in our experience, include the following, although the use of these medications in DISH has not been systematically evaluated [48]:

•We treat mild pain with acetaminophen (1000 to 2000 mg daily in divided doses), taken as needed. For many patients with mild pain this is sufficient analgesia.

•In patients with axial or peripheral joint pain inadequately relieved by acetaminophen, we use nonsteroidal antiinflammatory drugs (NSAIDs), although this has not been formally examined [48]. NSAIDS typically employed include naproxen (375 mg twice daily), ibuprofen (400 to 600 mg three to four times daily), or nabumetone (500 mg twice daily). These drugs can be tried in sequence, with each given for a one-month trial to assess for efficacy. An NSAID found to be effective can be continued at the same or a lower dose for longer periods. NSAIDs should be used in the lowest dose needed for the shortest time necessary.

There are no data or reported experience to support the use of duloxetine, gabapentinoids, or opioids in patients with DISH. Patients in whom the level of pain becomes substantial, leading to consideration of more potent analgesics such as opioids, should be evaluated for a diagnosis other than or in addition to DISH, such as fracture or neural impingement due to spinal stenosis, because the pain in patients with DISH is generally of low intensity, and stiffness is the more commonly reported complaint.

•Etidronate has been suggested as an experimental therapy for DISH [3,64]. We do not use bisphosphonate therapy given the limited and preliminary nature of the available data.

•Local glucocorticoid injections may provide benefit at sites of painful enthesopathy, although these are only rarely needed. We prefer to perform these injections with imaging guidance, either under x-ray fluoroscopy or using ultrasonography. Methylprednisolone 20 to 40 mg can be injected, depending upon the affected region. A repeat injection, if needed, can be performed after four months if the first is effective in relieving symptoms. (See "Subacute and chronic low back pain: Nonsurgical interventional treatment" and "Intraarticular and soft tissue injections: What agent(s) to inject and how frequently?".)

•A retrospective review compared 12 patients with DISH who were treated with tumor necrosis factor inhibitor drugs after failing to improve with NSAIDs and exercise with 7 patients who were treated with the standard of care. Eight patients had a two-point or greater improvement in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) compared with one patient in the control group [65].

Monitoring and precautions

●Indications for follow-up evaluation – We instruct patients to follow up if they develop new onset of localized spine pain or loss of spinal mobility. Patients with cervical spine involvement should be advised of the need to promptly seek care if they develop any symptoms suggesting myelopathy, such as sharp, shooting neck pain; the sudden loss of cervical spine motion; an unsteady gait; or the development of new sensory symptoms in the extremities. (See 'Symptoms' above.)

●Evaluation for other possible causes of pain – Patients with DISH who report substantial pain should also be evaluated for other possible causes, such as nerve impingement; spinal stenosis, which can be related or unrelated to DISH in a given patient; and other causes of severe back pain. (See "Evaluation of low back pain in adults".)

●Evaluation before endotracheal intubation – In patients with cervical spine involvement who will require endotracheal intubation, imaging studies should be obtained prior to the procedure to provide information about the location of sizeable osteophytes or the presence of ossification of the posterior longitudinal ligament (OPLL).

●Evaluation after trauma – Patients with DISH should be monitored closely after trauma for possible spinal cord complications. In a retrospective review of 70 patients with DISH who underwent urgent or emergency CT or MRI of the spine after trauma, many patients developed spinal epidural hematomas (49 percent), spinal cord impingement (67 percent), and spinal cord injuries (61 percent) [66]. Such lesions can progress to spinal cord injury if not treated by decompression.

●Patients without symptoms or physical findings – Patients without symptoms (eg, stiffness or pain) or findings of restricted spinal motion do not require scheduled follow-up or monitoring.

Indications for surgical consultation — Patients with the following conditions should be referred for surgical evaluation to determine if such intervention is appropriate:

●Dysphagia due to cervical spurs – Surgery is occasionally required to remedy dysphagia caused by large cervical spurs [34]. Patients with difficulty swallowing who have cervical spine osteophytes should be evaluated to determine whether the symptoms are likely due to the cervical spur to determine if surgical intervention is indicated. (See "Oropharyngeal dysphagia: Etiology and pathogenesis" and "Oropharyngeal dysphagia: Clinical features, diagnosis, and management".)

●Ossification of the posterior longitudinal ligament – OPLL of the cervical spine can result in progressive myelopathy, which requires surgery [38]. Patients with OPLL of the cervical spine and symptoms and findings of possible myelopathy (see 'Symptoms' above) should be referred for further evaluation and to determine if surgery is required. The evaluation and treatment of cervical myelopathy are described in detail separately. (See "Cervical spondylotic myelopathy".)

●Nerve root compression and thoracic outlet syndrome – Nerve root compression and thoracic outlet syndrome may also require surgical intervention. (See "Treatment and prognosis of cervical radiculopathy" and "Acute lumbosacral radiculopathy: Treatment and prognosis" and "Subacute and chronic low back pain: Surgical treatment" and "Overview of thoracic outlet syndromes".)

PROGNOSIS — The long-term prognosis for patients with diffuse idiopathic skeletal hyperostosis (DISH) is generally favorable, although some impairment in physical functioning is more commonly reported among patients with DISH than other similarly aged older males and females without the diagnosis [33]. In many patients, DISH remains an asymptomatic finding noted on radiographs. In a small percentage of patients, there may be complications including the development of spinal fractures through ankylosed bone that may constitute a neurosurgical emergency. Patients with DISH undergoing upper gastrointestinal or airway procedures may be at higher risk for the development of complications.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Diffuse idiopathic skeletal hyperostosis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory disease, with the principal manifestation being calcification and ossification of spinal ligaments and of peripheral entheses. Radiographic changes characteristic of DISH may occur in the absence of any musculoskeletal symptoms. (See 'Clinical features' above.)

●The etiology and pathogenesis of DISH remain obscure. Possible roles for mechanical factors, dietary components, metabolic disorders, medications, and a genetic predisposition have been suggested. (See 'Etiology and pathogenesis' above.)

●The prevalence of DISH varies with the population studied. It is particularly high among the Pima people of the United States, is more common in males than females, and is less common in Black than White individuals. The prevalence increases with age. (See 'Epidemiology' above.)

●Pain in the region of the thoracic spine is a common complaint, present in 40 to 80 percent of patients. Morning stiffness, often considered a symptom of inflammatory back pain, may also be present. Dysphagia sometimes results from impingement of cervical osteophytes upon the pharynx. Ossification of the posterior spinal ligament in the cervical spine may cause spinal cord compression, leading to cervical myelopathy. There are no diagnostic physical findings, but limited motion of the thoracic spine is the most commonly reported abnormality. (See 'Symptoms' above and 'Physical findings' above.)

●The distinctive radiographic finding is flowing linear calcification and ossification along the anterolateral aspects of the vertebral bodies, which continue across the disc space of the thoracic spine. Anatomically, these involve the paravertebral ligaments. Calcification or ossification of the posterior longitudinal ligament (OPLL) arises almost solely in the cervical spine and is better visualized with CT scanning than with plain film radiographs. (See 'Radiographic findings' above.)

●Similar calcification and ossification may be seen at peripheral entheseal sites, including the shoulder, iliac crest, ischial tuberosity, trochanters of the hip (whiskering), tibial tuberosities, patellae, and bones of the hands and/or feet. (See 'Extraspinal involvement' above.)

●The clinical diagnosis of DISH is made on the basis of compatible radiographic findings, which are most readily identified in the thoracic spine. The differential diagnosis includes spondylosis deformans (cervical or lumbar spondylosis) and ankylosing spondylitis, and these are distinguished by the absence of longitudinal spinal ligamentous calcification in the former and by the presence of slender, nearly vertical syndesmophytes in the latter. Unlike DISH, patients with degenerative disc disease can exhibit reduced intervertebral disc heights and those with ankylosing spondylitis can show structural changes in the sacroiliac joints and may have ankyloses of the apophyseal joints. (See 'Diagnosis' above and 'Differential diagnosis' above.)

●Treatment of DISH is symptomatic. In patients with symptomatic complaints, such as stiffness or pain, and those with restricted spinal motion, we suggest physical therapy evaluation and management, with the use of therapeutic modalities (eg, heat, ultrasound, exercises, and, if needed, modification of activities of daily living) and orthotics (Grade 2C). We encourage all patients to remain active. (See 'Treatment overview' above and 'Symptomatic management' above.)

●In patients with pain and stiffness that do not respond adequately to physical measures, we suggest using a similar approach to pharmacotherapy as in subacute and chronic low back pain (Grade 2C). Typically this may involve occasional use of acetaminophen for mild pain and of nonsteroidal antiinflammatory drugs (NSAIDs) for moderate pain and for peripheral joint symptoms of pain and/or stiffness. (See 'Symptomatic management' above.)

●Painful enthesopathy that is not adequately controlled by oral agents may respond to local injections of glucocorticoids. Surgery is occasionally required for dysphagia due to cervical spurs, for cervical myelopathy due to ossification of the posterior longitudinal ligament, and for other rare neurologic manifestations. (See 'Indications for surgical consultation' above.)