Section
19 OTHER ARTHROPATHIES AND
MISCELLANEOUS DISORDERS
Diffuse idiopathic skeletal hyperostosis
Key Points
n This chronic, age-related condition is characterized by new bone growth, especially at
entheses.
n Radiologic findings are characteristic but may be confused with those of spondyloarthritis.
n Few symptoms are related to diagnostic changes in the thoracic spine.
n There is increased risk of important cervical and lumbar arthropathy, enthesopathy,
and neural impingement.
n An association exists with obesity, type 2 diabetes, gout, dyslipidemia, hypertension,
hyperinsulinemia, and other features of metabolic syndrome.
n Growth factors, particularly insulin, are implicated in the disorder.
HISTORY
Diffuse idiopathic skeletal hyperostosis (DISH), also known as ankylosing
hyperostosis or Forestier disease, is a ubiquitous skeletal condition, affecting
many species and most human populations studied. Forestier and Rotes-
Querol1 presented comprehensive anatomic, radiologic, and clinical data on
the disorder, which was then termed ankylosing hyperostosis. The condition
is seen as a well-defined syndrome with both axial and peripheral mani-
festations. The diffuse nature of the condition later led to the term diffuse
idiopathic skeletal hyperostosis.2
EPIDEMIOLOGY
There is a 2 : 1 reported male predominance in DISH with the prevalence in
both sexes rising with age and weight3,4; although DISH has been uncom-
monly reported before the age of 45 years, anecdotal observations indicate a
recent trend to a younger age at diagnosis.5
Although used criteria vary, population surveys indicate that this is a
common condition. In Scandinavia, the incidence is estimated to be 7
per 1000 in men and 4 per 1000 in women beyond the age of 30 years.6
Prevalence rates vary in different populations but are broadly consistent
with these findings.7 Approximately 10% to 15% of men and 5% to 10% of
women older than the age of 65 years have DISH, although some popula-
tions (e.g., Pima Indians) have an increased predisposition for the disorder
(Table 206.1).8,9 Some Asian populations may have lower prevalence rates.10
It is likely that the prevalence is increasing in some of these populations.11
The related spinal phenotype of ossification of the posterior longitudinal
ligament (OPLL) occurs in up to 4% of Japanese people, some 80 times the
rate in Europeans. In patients with OPLL, 25% also have DISH.12
CRITERIA AND CHARACTERISTIC DESCRIPTION
CRITERIA
A number of classification criteria have been used in studies of DISH.13 The
Resnick criteria that require the new bone formation to bridge four con-
tiguous vertebral bodies in the absence of degenerative disk disease and
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Geoffrey O. Littlejohn 206
the absence of inflammatory sacroiliac or facet joint changes are the most
used14 (Fig. 206.1). These criteria therefore define DISH unassociated with
another spinal disorder. In routine clinical practice, it is more common to
see significant age-related disk or facet joint degenerative change occurring
in conjunction with changes of DISH. Thus study populations of “pure”
criteria-defined DISH may differ in clinical characteristics from DISH when
it occurs with other common degenerative spinal conditions15 or with an
inflammatory spondyloarthritis. Classification studies to define earlier
stages of DISH are evolving.16
Characteristic bone changes
The condition is characterized by widespread new bone formation, with an
increase in the amount of both normal bone and heterotopic bone forma-
tion, and specifically, the presence of new bone growth into the entheseal
regions (Fig. 206.2). The enthesis is the region where the tendon, ligament,
joint capsule, or annulus fibrosus fibers insert into bone.17 Although it was
the prominent new bone growth in the anterolateral entheseal regions along
the thoracic spine that first brought attention to this condition, it may affect
any skeletal structure to differing degrees.
Diffuse idiopathic skeletal hyperostosis changes are most characteristic
in the thoracic spine, where uninterrupted new bone may “flow” from one
vertebra to another (Fig. 206.3). It is more prominent on the right side of
the thoracic vertebra. This is thought to be a consequence of the pressure
effect of the left-sided aorta (Fig. 206.4).19 The presence of the anterior
longitudinal ligament over the anterior two-thirds of the vertebral bodies
dictates the distribution of the new bone formation. There is often a gap
in the new bone adjacent to the intervertebral disk or between the new
bone and the intact original cortex. When disk changes are absent, the new
bone formation may be applied closely to the vertebral bodies and can, at
times, mimic axial spondyloarthritis. However, in DISH, the original cortex
remains under the ossified ligament; in axial spondyloarthritis, erosion of
the cortex is characteristic, particularly at the vertebral corners, with under-
lying sclerosis being present when inflammation is active. Based on chance
alone, DISH may coexist with axial spondyloarthritis or any other condition.
In particular, because the condition is more prominent with increased age,
it particularly commonly coexists with intervertebral disk change, and in
such situations the bulging of the disk material anteriorly may give rise to
spectacular anterior spinal hyperostotic change. In the more mobile cervical
and lumbar spine regions, hyperostotic changes are more characteristic than
simple bridging, and spinal stenosis may result.
Spectrum of bone changes
There is a spectrum of spinal new bone formation with increasing amounts
laid down with increasing duration.4 The well-defined condition occurs over
several years (Fig. 206.5).20 Regression of new bone growth over a short time
period has been noted in the context of the pressure effect from an enlarging
aortic aneurysm.21 The spinal new bone formation appears to be a dynamic
process, with deposition and remodeling likely to be similar to that that
occurs in other skeletal areas. Peripheral new bone formation is also more
prominent in the entheseal areas, particularly around the heels, knees, and
1811
1812 SECTION 19 Other Arthopathies and Miscellaneous Disorders
elbows, among other regions. Such changes also occur on a spectrum ranging spinal structures may also increase regional symptoms, including tenderness
from minor to quite marked hyperostosis.22 Pronounced peripheral hyperos- through the process of referred pain.31
tosis may precede spinal changes characteristic of DISH. All of these changes In peripheral joints, a restrictive arthropathy caused by thickening and
appear to be part of the one condition; however, the diagnosis of DISH cur- shortening of ligaments has been described long before the characteristic
rently rests on characteristic findings in the spine and not in the periphery. spinal changes and has been associated with hyperinsulinemia.29 Clinically,
there may be painless reduction of internal rotation of shoulders and hips
and reduced flexion of fingers and knees.
GENERAL FINDINGS Pain may be present in some patients who have peripheral enthesopathy
The “diffuse hyperostosis” of DISH includes increased bone formation as (e.g., from a calcaneal spur), the latter being most likely because of abnor-
demonstrated by phalangeal tufting, increased cortical thickness of tubular mal biomechanical stress causing injury to the enthesis. However, although
bones of the hand, and increased size of the sesamoid bones.18 Increased the majority of such extraspinal, entheseal changes are asymptomatic, ade-
bone mineral density using dual x-ray absorptiometry (DXA) has been noted quate controlled studies are lacking.
in the spine possibly caused by the effects of increased entheseal ossifica-
tion,23 but peripheral bone density using quantitative computed tomography
(CT) techniques has shown no differences in bone density or geometry.24
Heterotopic new bone formation after surgical procedures, such as total hip d
replacement, may occur in DISH.25
Diffuse idiopathic skeletal hyperostosis may coexist with inflammatory
joint diseases such as rheumatoid arthritis, psoriatic arthritis, spondyloar-
b
thritis, or gout. It has been shown to modify the radiologic reaction to rheu- c
matoid arthritis, with less destructive bone disease and a tendency to heal
erosions more quickly (RADISH).26 There is an increased prevalence of DISH
in patients with gout and Paget disease,8,27 resulting in exuberant new bone
formation.

CLINICAL FEATURES a
e
The process of new bone deposition in DISH is asymptomatic. However, 28 f
the consequences of new bone growth in the areas described earlier may
cause increased stiffness in neck, back, or peripheral joints.29,30 Tight

Table 206.1
Prevalence of Diffuse Idiopathic Skeletal Hyperostosisa
Population Prevalence
White populations (various studies)6,10 Men: 10%
Women: 8%
Pima Indians Men: 54% FIG. 206.2 Hand of patient with diffuse idiopathic skeletal hyperostosis demonstrates
Women: 14% the full spectrum of bone and entheseal changes in this disorder. Note exostoses ([a]
Men with gout10 58% second and fifth metacarpophalangeal heads), capsule bone ([b] fourth proximal
phalangeal joint), prominent phalangeal enthesopathy ([c] second and third proximal
a
The table gives the prevalence of diffuse idiopathic skeletal hyperostosis at age 65 years or older (selected phalanx), “arrowheading” ([d] tufts of terminal digits), cortical thickening ([e] tubular
studies). Studies in some Asian populations, such as Koreans, suggest a lower prevalence.11 Diagnostic
bones), and enlargement of sesamoid bones (f). The soft tissues and joint spaces
criteria vary slightly; for instance, the number of bony bridges may vary between 2 and 3.13
are normal.18

“Flowing” bone
anterior longitudinal
ligament
R > L thoracic spine

a b

FIG. 206.1 Typical radiographic findings in the thoracic spine on routine chest x-rays (posteroanterior [a] and lateral [b]), with “flowing” new bone formation linking four con-
tiguous vertebrae, predominantly right sided, in absence of intervertebral disk change.

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 CHAPTER 206 Diffuse idiopathic skeletal hyperostosis 1813

FIG. 206.3 Radiographs of the cer-

vical, thoracic, and lumbar spine in
(a) to (c) show characteristic flowing
new bone in the anterior longitudi-
nal ligament in patients with diffuse
idiopathic skeletal hyperostosis.
(d) to (f) show typical peripheral
enthesopathic new bone growth a b c
(highlighted by arrows) in patients
with diffuse idiopathic skeletal
hyperostosis.

d e f

Important clinical features arise when new bone growth obstructs or

impinges on other tissues. In the cervical spine, DISH may give rise to dys-
phagia32 or cervical myelopathy33 (Fig. 206.6). Association with ossification
of the posterior longitudinal ligament34 can result in myelopathy and even
quadriplegia. In the lumbar spine, spinal stenosis may occur secondary to
posterior osteophytic ridges and facet arthropathy with marked hyperostosis.
Uncommonly, traumatic fractures through bony bridges may occur; if so,
they may be difficult to diagnose and treat.35 Bone density increases in the
early years of the condition in patients with DISH but may decrease later if
mobility is impaired by the condition. Anterior spinal ligament ossification
can falsely elevate bone density scores.36
Diffuse idiopathic skeletal hyperostosis is associated with a particular type
of degenerative hip disease37 and increased prevalence of Heberden nodes.38
The elongated tibial spines common in obesity-related knee osteoarthritis
(OA) are ossifications of the entheseal attachments of the cruciate ligaments.22
There is a strong association with lumbar spondylosis and knee OA.39
a b

FIG. 206.4 Computed tomography reconstruction of thoracic spine (a) of patient with
diffuse idiopathic skeletal hyperostosis. There is typical prominent new bone deposi-
tion on the right anterolateral thoracic spine (a and b).
INVESTIGATIONS
Diffuse idiopathic skeletal hyperostosis cannot be diagnosed without
radiologic evaluation. Although it is often first identified on a routine pos-
teroanterior (PA) chest x-ray (see Fig. 206.1), the appropriate view is a

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1814 SECTION 19 Other Arthopathies and Miscellaneous Disorders

a b c

Pre-DISH 8-10 years Criteria DISH

FIG. 206.5 Progressive spinal entheseal changes in diffuse idiopathic skeletal hyperostosis (DISH). (a) The earliest change is seen, with ossification at the site of attachment of
the anterior longitudinal ligament to the middle of the vertebral body, well away from the annulus. Note the separation of the ossification from the intact cortex, except at the
site of attachment. (b) Moderately advanced changes, with ossification bridging the disk space but still firmly attached to cortex at the middle of the vertebral body. (c) Advanced
changes, typical of established DISH, with smooth attachment of the new bone to the original cortex. The ossified ligament is much thickened and interrupted at the lower level.

Table 206.2
Selected Differences Between Diffuse Idiopathic Skeletal Hyperostosis and Axial Spondyloarthritis
Disorder Diffuse Idiopathic Skeletal Hyperostosis Axial Spondyloarthritis
Age at presentation Usually older than 50 years Usually younger than 40 years
Associated metabolic Usually present Not necessarily present
disorder
HLA B27 No association Strong association
Spinal new bone Usually exuberant, with preservation of bony cortex; there may be a Usually narrow, vertically aligned new bone that is confluent with
gap between new bone in anterior longitudinal ligament and vertebra the underlying vertebra
Sacroiliac joints Plain x-rays may show anterior osteophytosis, causing “bland fusion” Plain x-rays show variable joint irregularity caused by erosions,
without erosion, or sclerosis. CT scan may show sacroiliac anterior bridging new bone, and joint line sclerosis. CT scan shows
joint-line fusion, without erosion or sclerosis. Bone scan is normal and variable sacroiliac joint irregularity, erosion, fusion, or sclerosis.
MRI normal with occasional nonspecific subchondral edema. In active inflammatory regions, bone scan shows increased
uptake, and MRI shows bone marrow edema.
Entheseal regions Usually large, well-corticated enthesophyte; sometimes radiologic gap Entheseal new bone usually smaller with less well-defined margins
at the entheseal attachment and irregular fluffy new bone at distal entheseal area

CT, Computed tomography; HLA, human leukocyte antigen; MRI, magnetic resonance imaging.

posteroanterior and lateral x-ray of the thoracic or dorsal spine (see Fig.
206.3).40 CT provides more spectacular images (see Fig. 206.4) but is not
necessary unless the presence of conditions such as spinal stenosis is being
sought. CT, for example of the pelvis, also shows increased enthesopathic
changes in nonspinal regions of patients with DISH.41 Magnetic resonance
imaging (MRI) shows the ligamentous thickening that precedes ossification
and may be useful in distinguishing between the changes seen in DISH and
those seen in axial spondyloarthritis. Some changes, however, such as upper
anterior vertebral body corner fat infiltration, may occur in both disorders.42
Plain films of peripheral areas will show variable degrees of peripheral enthe-
sopathy (see Figs. 206.2 and 206.3). SPECT CT may show changes of active
new bone formation in areas of vertebral hyperostosis and also help identify
an associated process such as OA, spinal fracture, or mechanically induced
inflammatory entheseal changes. Ultrasound is being explored to help better
define and understand the evolution of DISH peripheral enthesopathy.43
Routine biochemical studies and erythrocyte sedimentation rate are nor-
mal. There are often abnormalities associated with hyperinsulinemia, matu-
rity-onset diabetes, dyslipidemia, gout, and the metabolic syndrome.13,44–46
a b

FIG. 206.6 Magnetic resonance imaging of the lateral cervical spine shows osteo-
phytic bone growth in the anterior midcervical spine causing dysphagia in one
patient (a) and new bone growth in the posterior longitudinal ligament, causing cer-
vical cord compression in a second patient (b). Both patients had diffuse idiopathic
skeletal hyperostosis.
DIFFERENTIAL DIAGNOSIS
One of the most important differentials is that of radiographic axial spondy-
loarthritis or related conditions (Table 206.2). The new bone formation in
DISH may be smooth and tightly fused to the underlying cortex, thus mim-
icking radiographic axial spondyloarthritis. Usually, however, exuberant

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FIG. 206.7 Plain x-rays of the pelvis of a 60-year-old man with diffuse idiopathic
skeletal hyperostosis. There is apparent bland “fusion” of both sacroiliac joints.
Computed tomography showed anterior osteophytes bridging the anterior joint line
with preservation of the joint space and no sclerosis or other features of inflammatory
sacroiliitis. Note prominent new bone growth in entheseal attachments to the pelvis.
and bumpy bony changes within the anterior longitudinal ligament, with
preservation of the original cortex, are characteristic of DISH. This presenta-
tion is occasionally compounded by anterior osteophytosis of the sacroiliac
joints, which may lead to a change falsely interpreted on plain PA films as
postinflammatory “fusion” of the joints (Fig. 206.7). In this situation, CT of
sacroiliac joints shows the anterior fusion with no effects of inflammatory
change in the joint itself, and MRI confirms lack of any extensive inflam-
matory-related bone edema, although an overlap of some MRI features can
occur between DISH and spondyloarthritis.42 Peripheral enthesopathy of
DISH shows well-defined and often prominent new bone growth, usually,
but not always, connected to the subjacent bony mass. It lacks the erosions
or periosteal proliferation seen in the B27-related axial spondyloarthritis.
A number of other disorders may need to be distinguished:
1. Degenerative disk disease characteristically gives disk space narrowing
with horizontal osteophytes, prominent anteriorly. Facet joint hyper-
trophic changes are commonly seen and may narrow the intervertebral
neural foramina, as well as the spinal canal.
2. The hyperostotic peripheral joint changes of DISH resemble primary
OA in distribution but are distinguished by early stiffening and relative
preservation of joint space in the early stages.18,29
3. It is distinct from the linear calcifications that may be seen in calcium
pyrophosphate crystal deposition disease.
4. Acromegaly is also characterized by new bone formation, but in addi-
tion, subcutaneous soft tissue and cartilage thickening are prominent.
In early acromegaly, there is hypermobility in striking contrast to the
stiffening characteristic of DISH. The bony spurs and hyperostosis of
DISH may at times be identical to those seen in acromegaly, and both
conditions associate with hyperostosis frontalis interna.47 However, there
is no increase in joint space or in soft tissue thickness in DISH.18
5. Repetitive trauma, fluorosis, hypervitaminosis A, and retinoid therapy
may all produce enthesopathy, which may require differentiation from
DISH.
ETIOLOGY AND PATHOGENESIS
PATHOLOGY
The principal changes in DISH occur at the enthesis. Key cells responsible
for new bone formation include fibrocartilage and mesenchymal cells and
chondrocytes.48 These cells, lying in the entheseal region bordering the bony
interface, are activated and cause changes to the surrounding matrix that
favors subsequent ossification (Fig. 206.8). Later, vascular invasion occurs
from the adjacent cortical haversian canals and preferential ossification
occurs at or close to the enthesis (Fig. 206.9).4,49 The resultant entheseal
bone deposition is further modified by local mechanical factors.50
METABOLIC FACTORS
Diabetes and obesity
The propensity to deposit new bone has an underlying metabolic cause.
Since the early reports of Forestier, an association between obesity and DISH
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CHAPTER 206 Diffuse idiopathic skeletal hyperostosis 1815
PATHOGENESIS OF NEW BONE FORMATION IN DISH
Metabolic syndrome Growth factors
Abdominal obesity • Adipokines
• Insulin
Tenocytes
Collagen fibers
Fibrocartilage cells
Unmineralized fibrocartilage
Mesenchymal cells
Tidemark
Mineralized matrix
Bone
FIG. 206.8 Diagram of the enthesis showing cellular components that respond to
growth factor stimulation to result in the new bone formation that characterizes dif-
fuse idiopathic skeletal hyperostosis (DISH).
has been noted.51 Subsequently a link was observed with impaired glucose
tolerance and related adult-onset type 2 diabetes.13,52 The prevalence of these
abnormalities in patients with DISH reportedly ranges from 17% to 60%;
this is much higher than in the general population. Conversely, the preva-
lence of DISH in patients with adult-onset type 2 diabetes ranges from 13%
to 50%. These findings are greatly in excess of nondiabetic control partici-
pants. Glucose intolerance and obesity seem to act as independent factors in
their association with DISH, although there is no relationship between the
degree of hyperglycemia and the severity of the bony change. No patients
with juvenile-onset type 1 or insulin-deficient diabetes have been found to
have DISH. Abdominal obesity is a consistent finding in various studies into
the metabolic associates of DISH.13,53
Bone growth factors
Candidate bone growth factors such as growth hormone and somatome-
din (insulin-like growth factor) are not consistently abnormal in DISH. In
contrast, insulin, which also has growth factor activity, has been found to
be significantly higher in patients with DISH.13,54 Hyperinsulinemia is seen
in Pima Indians, who have a high prevalence of DISH,9 and it is also asso-
ciated with hyperostosis frontalis interna and ossification of the posterior
ligament (OPPL) (see Fig. 206.8).55 Insulin promotes endochondral ossifica-
tion by entheseal chondrocytes.56 The hyperinsulinemia likely relates to the
documented association among DISH, central obesity, hypertension, lipid
abnormalities, and increased risk of vascular disease,57 all of which are com-
ponents of the metabolic syndrome.45
Adipokines are fat-derived cytokine-like hormones that may have signif-
icant effects on bone metabolism.13,58 Elevation of leptin and visfatin levels
has been shown in DISH.59 Serum adiponectin levels have correlated with
extent of bony bridges in patients with DISH.60
Dickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and low lev-
els link to new bone formation. DKK-1 levels have been found to be low
in DISH and total serum levels associated with severity of hyperostosis,61
although another study did not confirm this observation.62,63
Other metabolic factors
Chronic vitamin A toxicity in animals and humans produces DISH-like
changes. Studies of vitamin A and metabolites in stimulated states indicate
an increased level of these retinoids in patients with DISH,63 but the signif-
icance of this remains speculative. Familial clustering64,65 and association
with the COL6A1 gene in some populations66 suggest that genetic factors
are also likely to be involved in DISH. Certain dog breeds, such as Boxers,
have high rates of DISH, and they may be useful animal models for further
1816 SECTION 19 Other Arthopathies and Miscellaneous Disorders

FIG. 206.9 Histopathologic (a) and

radiologic (b) changes of the inter-
vertebral disk in patient with diffuse
idiopathic skeletal hyperostosis.

a b

study, but no associated metabolic cause has been identified in this breed or Table 206.3
others.67 Management Issues in Diffuse Idiopathic Skeletal Hyperostosis
In summary, it seems likely that a systemic metabolic factor, possibly
hyperinsulinemia or elevated adipokine levels, causes the new bone growth Issue Management
through action on entheseal growth plates. Entheseal cells targeted by
Spinal and peripheral enthesopathy
these growth factors include fibrocartilage cells and mesenchymal cells.
Mechanical forces acting at entheseal regions influence the clinical expres- Asymptomatic (usual) Encourage exercise and ideal body weight;
sion. The resultant changes occurring over several years eventually lead to assess cardiovascular risk factors
the well-characterized syndrome.68 Symptomatic As above plus physical therapy, local
corticosteroid injection therapy, and
analgesic and antiinflammatory agents
MANAGEMENT
Complications
PRIMARY PREVENTION Facet arthritis Physical therapy, corticosteroid injection
Although there have been no clinical trials, it seems sensible that avoid- Spinal stenosis Exercise, corticosteroid injection, surgery
ance of developing the various associated metabolic disorders, particularly Dysphagia Conservative (e.g., smaller meal servings), surgery
abdominal obesity, would prevent DISH. Osteoarthritis Standard approaches
A high risk of DISH may be anticipated in large-boned, large-muscled Associated metabolic syndrome
subjects with abdominal obesity and the metabolic syndrome. Patients with
Hypertension, diabetes, Treat vigorously
gout, noninflammatory peripheral enthesopathies, and stiffness of the hips
dyslipidemia, gout, obesity
and shoulders or large, stiff fingers may have this disorder. Abnormal lipids
characteristic of the metabolic syndrome and abnormal glucose metabolism
including hyperinsulinemia may be found.69 The best therapy at this stage is
weight reduction, ideally with a fitness program (Table 206.3).
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