JDR Review 2008 E Tanaka
-
Upload
anadelrosario -
Category
Documents
-
view
214 -
download
0
Transcript of JDR Review 2008 E Tanaka
INTRODUCTION
In humans, the temporomandibular joint (TMJ) is now generally
considered to be load-bearing during masticatory function. Until
1980, however, this concept was controversial. Wilson (1920)
reported that the fibrocartilage of the TMJ condyle was softer than
hyaline cartilage, and therefore could not be load-bearing. Hylander
and Bays (1979) indirectly measured TMJ condylar loading in the
macaque with rosette strain gauges placed on the condylar neck,
and found that the condylar bone surface was indeed loaded during
function. Brehnan et al. (1981) and Boyd et al. (1990) directly
measured the condylar loading in the macaque by means of a
piezoelectric foil force transducer, and confirmed that the TMJ was
indeed a load-bearing articulation. Other experimental and
analytical studies (Smith et al., 1986; Koolstra et al., 1988; Korioth
et al., 1992; Beek et al., 2000) have also demonstrated that the
human TMJ was load-bearing under function. Although these
studies are all simulations, partially performed on data from
cadavers, they have shown that the fibrocartilaginous tissues,
including the disc and articular cartilage, have important functions
in stress distribution.
TMJ disorders are characterized by intra-articular positional
and/or structural abnormalities. Review studies published in the
1980s showed prevalence rates ranging from 16% to 59% for
symptoms and from 33% to 86% for clinical signs (Carlsson and
LeResche, 1995), although from 3% to 7% of the adult population
has sought care for TMJ pain and dysfunction (Carlsson, 1999). It
has been observed that up to 70% of persons with TMJ disorders
suffer from displacement of the articular disc, coined 'internal
derangement' of the TMJ (Farrar and McCarty, 1979).
Meanwhile, the most common joint pathology affecting the
TMJ is degenerative joint disease, also known as osteoarthrosis or
osteoarthritis. Among individuals with TMJ disorders, 11% had
symptoms of TMJ-osteoarthrosis (TMJ-OA) (Mejersjö and
Hollender, 1984). An epidemiological study, meanwhile, showed
that minimal flattening of the condyle and/or eminence was seen in
35% of TMJs in asymptomatic persons (Brooks et al., 1992). More
advanced osseous changes were not seen; therefore, it was
concluded that minimal flattening was probably of no clinical
significance. However, once the breakdown in the joint starts, TMJ-
OA can be crippling, leading to a variety of morphological and
functional deformities (Zarb and Carlsson, 1999).
This paper is divided into four parts. Part 1 will review the
definition and etiology of TMJ disorders. A basic review of the
TMJ disorders, their etiologies, and the biomechanical and
biochemical factors associated with functional overloading of the
joint will also be discussed. Part 2 will discuss the clinical,
radiographic, and biochemical analytical findings important in the
diagnosis of TMJ-osteoarthrosis. Part 3 will present the non-
invasive and invasive modalities utilized in TMJ-osteoarthrosis
management. Finally, in Part 4, the possibility of tissue-engineering
for treatment of TMJ disorders with degenerative changes will be
discussed.
ABSTRACTTemporomandibular joint (TMJ) disorders have complex
and sometimes controversial etiologies. Also, under
similar circumstances, one person's TMJ may appear to
deteriorate, while another's does not. However, once
degenerative changes start in the TMJ, this pathology can
be crippling, leading to a variety of morphological and
functional deformities. Primarily, TMJ disorders have a
non-inflammatory origin. The pathological process is
characterized by deterioration and abrasion of articular
cartilage and local thickening. These changes are
accompanied by the superimposition of secondary
inflammatory changes. Therefore, appreciating the
pathophysiology of the TMJ degenerative disorders is
important to an understanding of the etiology, diagnosis,
and treatment of internal derangement and osteoarthrosis
of the TMJ. The degenerative changes in the TMJ are
believed to result from dysfunctional remodeling, due to a
decreased host-adaptive capacity of the articulating
surfaces and/or functional overloading of the joint that
exceeds the normal adaptive capacity. This paper reviews
etiologies that involve biomechanical and biochemical
factors associated with functional overloading of the joint
and the clinical, radiographic, and biochemical findings
important in the diagnosis of TMJ-osteoarthrosis. In
addition, non-invasive and invasive modalities utilized in
TMJ-osteoarthrosis management, and the possibility of
tissue engineering, are discussed.
KEY WORDS: temporomandibular joint, degenerative
disease, osteoarthrosis, tissue engineering.
Received April 17, 2007; Last revision January 21, 2008; Accepted
January 23, 2008
Degenerative Disorders of the Temporomandibular Joint:Etiology, Diagnosis, and Treatment
E. Tanaka1*, M.S. Detamore2, and L.G. Mercuri3
1Department of Orthodontics and Dentofacial Orthopedics, TheUniversity of Tokushima Graduate School of Oral Sciences, 3-18-15Kuramoto-cho, Tokushima 770-8504, Japan; 2Department ofChemical and Petroleum Engineering, University of Kansas,Lawrence, KS, USA; and 3Department of Surgery, Division of Oraland Maxillofacial Surgery, Stritch School of Medicine, LoyolaUniversity Medical Center, Maywood, IL, USA; *correspondingauthor, [email protected]
J Dent Res 87(4):296-307, 2008
CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE
296
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 297
DEFINITION ANDETIOLOGY OF TMJDISORDERSClassification of TMJDegenerative DisordersUnlike rheumatoid arthritis, TMJ-
osteoarthrosis has a non-inflam -
matory origin. The pathological
process is characterized by
deterioration and abrasion of
articular cartilage and local
thickening and remodeling of the
underlying bone (Zarb and
Carlsson, 1999). These changes
are frequently accompanied by the
superimposition of secondary
inflammatory changes. Therefore,
mechanically induced osteo -
arthrosis may better reflect TMJ-
osteoarthrosis.
Internal derangement of the
TMJ is defined as an abnormal
positional relationship of the disc
relative to the mandibular condyle
and the articular eminence (Fig.
1). Wilkes (1989) established 5
stages based on clinical and
imaging criteria. In Stage I,
clinical observations include
painless clicking and unrestricted
mandibular motion. When imaged,
the disc is displaced slightly
forward on opening, although it is
reduced at the maximum mouth
opening ('reducing' refers to the
disc sliding back to a "normal"
anatomical position during mouth
opening, producing the audible
clicking sound), and the osseous
contours appear normal (Fig. 1A).
In Stage II, there are complaints of
occasional painful clicking,
intermittent locking, and
headaches. When imaged, the disc
appears slightly deformed and
displaced slightly forward at
maximum opening, but still
reduces at maximum opening (Fig.
1B). The osseous contours appear normal. In Stage III,
clinically, there is frequent joint pain and tenderness,
headaches, locking, and restricted range of mandibular motion,
as well as painful chewing. When imaged, anterior disc
displacement is seen, with moderate thickening (Fig. 1C). This
disc reduces early in Stage III, but progresses to non-reducing
(i.e., locking) on opening in the later stage. The bony contours
remain normal in appearance. At the maximum mouth opening,
the disc is subjected to deformity, because the condyle pushes
the disc forward and downward (Fig. 1C). Recent studies, using
individual oblique-axial magnetic resonance imaging, have
shown that most anteriorly displaced discs were laterally
displaced (YJ Chen et al., 2000, 2002). A series of
experimental studies with surgical induction of anterior disc
displacement in the rabbit showed that disc displacement led to
the degenerative changes in the condylar cartilage (Sharawy etal., 2000, 2003). In contrast, the apparent radiographic
association of articular degeneration with disc displacement has
led to the suggestion that the degenerative process may be a
predisposing factor for disc displacement (Dijkgraaf et al.,1995). However, cadaver (Rohlin et al., 1985), clinical
(Westesson et al., 1989), and magnetic resonance imaging
studies (Kircos et al., 1987) have demonstrated that disc
displacement is a common finding in asymptomatic
Figure 1. Magnetic resonance images of TMJ-internal derangement and -osteoarthrosis. Internalderangement of the TMJ is defined as an abnormal positional relationship of the disc relative to themandibular condyle and the articular eminence, while TMJ-osteoarthrosis is characterized by structuralfailure of articular cartilage in the early stage and by the deterioration of the cartilage and subchondralbone, resulting in shortening of the mandibular ramus and subsequent mandibular retrusion. Both internalderangement and osteoarthrosis of the TMJ are regarded as a frequent cause of pain and/or disturbedmandibular movement. The characteristic radiographic sign of TMJ-osteoarthrosis is dysfunctionalremodeling on the mandibular condyle and articular eminence surfaces with osteophyte formation. (A) Atthe initial stage, the disc reveals a slight anterior disc displacement but not complete displacement at theintercuspal position. At maximum mouth opening, the disc is located between the condylar and temporalbone surfaces, and the condyle and disc move harmoniously. Arrowheads indicate the anterior andposterior ends of the disc. (B) At the intercuspal position, the disc reveals anterior displacement, but notbony remodeling and deformation. On full opening, the disc reduces, usually resulting in 2 noises(reciprocal clicking). Arrowheads indicate the anterior and posterior ends of the disc. (C) Throughmandibular movements, the disc is displaced from its normal position, and on full opening, the discdeformity occurs because the condyles push the disc forward and downward. In this case, bony changeson the condylar surface are not detected. Arrowheads indicate the anterior and posterior ends of the disc.(D) The disc also reveals anterior displacement without reduction, in which the disc is severely deformed onfull opening. Arrowheads indicate the anterior and posterior ends of the disc. Furthermore, the osteophyteof the peripheral cortical bone, indicated by arrows, is clearly detected, indicating TMJ-osteoarthrosis. (E)The condyle shows severe bony deformation with flattening and erosion, indicating severe osteoarthrosis ofthe TMJ. Arrows indicate the deformed surface of the mandibular condyle. The disc also reveals anteriordisplacement without reduction. Arrowheads indicate the anterior and posterior ends of the disc. Theindividual at this stage is likely to have spontaneous joint pain and movement disability.
298 Tanaka et al. J Dent Res 87(4) 2008
individuals. In Stage IV, individuals complain of chronic pain,
headache, and restricted mandibular range of motion. When
imaged, a markedly thickened disc is anteriorly displaced and
does not reduce on opening, and abnormal contours to both the
condyle and articular eminence begin to become evident (Fig.
1D). In Stage V, clinically, individuals experience pain,
crepitus, and pain with mandibular function. When imaged, the
now grossly deformed disc is anteriorly displaced, without
reduction, and degenerative changes are present in the osseous
components of the articulation (Fig. 1E). The disease process is
characterized by deterioration and abrasion of articular
cartilage and disc surfaces, and occurrence of thickening and
remodeling of the underlying bone. Therefore, osteoarthrosis
may be a final common pathway for several joint conditions,
including inflammatory, endocrine, metabolic, developmental,
and biomechanical disorders (Zarb and Carlsson, 1999).
Etiology of TMJ Degenerative DisordersIncreased loading in the TMJ may stimulate remodeling,
involving increased synthesis of extracellular matrices
(Stegenga et al., 1989). Remodeling is an essential biological
response to normal functional demands, ensuring homeostasis
of joint form, and function and occlusal relationships (Smartt etal., 2005). Arnett et al. (1996a,b) proposed an explanation for
the pathophysiology of the degenerative changes as one that
results from dysfunctional articular remodeling due to (1) a
decreased adaptive capacity of the articulating structures of the
joint or (2) excessive or sustained physical stress to the TMJ
articular structures that exceeds the normal adaptive capacity.
The former is the host-adaptive capacity factor, which is
associated with the host's general condition. Advancing age,
systemic illness, and hormonal factors may define the host-
adaptive capacity of the TMJ. This factor may contribute to
dysfunctional remodeling of the TMJ, even when the
biomechanical stresses are within a normal physiologic range.
Age is clearly a predisposing factor, because both frequency
and severity of the disease appear to increase with aging. For
example, the calcium content of the human disc increases
progressively with aging (Takano et al., 1999). This increase in
calcification may be caused by aging as such, or by a changed
mechanical stress (Jibiki et al., 1999). Accordingly, the
material properties of the disc can also be expected to be
related to age (Tanaka et al., 2001). This implies that the disc
becomes more stiff and fragile in nature, reducing its capability
to handle overload. Articular cartilages can also change with
aging. The molecular weight of hyaluronic acid in human
articular cartilage decreases from 2000 to 300 kDa between the
ages of 2.5 and 86 yrs (Holmes et al., 1988). Hyaluronic acid in
articular cartilage is essential for it to maintain its viscosity, and
any decrease in molecular weight can lead to reduction of its
biorheological property in cartilage.
Systemic illness may also influence fibrocartilage
metabolism and could affect the adaptive capacity of the TMJ.
These illnesses may include autoimmune disorders, endocrine
disorders, nutritional disorders, metabolic diseases, and
infectious disease. Hormonal factors may also have a marked
influence on remodeling of the mandibular condyle. In these
cases, the TMJ degenerative disorders may be the result of
systemic disease.
Mechanical factors can also cause changes in the TMJ
structure. Despite host-adaptive capacity, excessive or
unbalanced mechanical loading in the TMJ can cause overload
of articular tissues, resulting in the onset and progression of
TMJ-osteoarthrosis. Furthermore, internal derangement of the
TMJ may be induced by excessive or unbalanced stress in the
TMJ. From a review of etiological mechanical events of TMJ-
internal derangement and -osteoarthrosis, trauma,
parafunction, unstable occlusion, functional overloading,
and increased joint friction play a role (Stegenga et al., 1989;
Arnett et al., 1996a,b; Nitzan, 2001). These factors may occur
alone or may be interrelated, interdependent, and/or co-
existent.
Macrotrauma in the condylar area can cause degeneration
of the articular cartilage and production of inflammatory and
pain mediators. Trauma has been reported to alter the
mechanical properties of the disc (Nickel et al., 2001) and to
cause mechanical fatigue of the disc (Beatty et al., 2001, 2003).
Furthermore, it may cause cartilage degradation and production
of inflammatory and pain mediators. TMJ alterations occurred
over time after the macrotrauma, leading to progressive
condylar resorption and deformation (Arnett et al., 1996b).
However, only about one-third of the individuals with TMJ
degenerative changes reportedly suffered previous trauma to
the head and neck (Laskin, 1994). The mechanism of delayed
condylar resorption and deformation in secondary macrotrauma
is not understood, but the clinician should recognize the
etiologic importance of the macrotrauma and long-term
evaluation of the TMJ form and function after macrotrauma.
Parafunction may produce abnormal compression and
shear forces capable of initiating disc displacement and
condylar and articular eminence degenerative changes (Gallo etal., 2006). Parafunctional hyperactivity of the lateral pterygoid
muscle has been considered to lead to masticatory muscle pain
(Hiraba et al., 2000; Murray et al., 2001). Since the superior
head of the lateral pterygoid muscle attaches partly to the
articular capsule of the TMJ and directly or indirectly to its
articular disc (Murray et al., 2001), it has been hypothesized
that dysfunction of this muscle can lead to TMJ-internal
derangement and -osteoarthrosis (Hiraba et al., 2000).
Functional overloading and increased joint friction may
act together as etiological events for TMJ-internal derangement
and -osteoarthrosis. Growing evidence suggests that functional
overload with subsequent microtrauma is a crucial event for
TMJ-internal derangement and -osteoarthrosis. Milam et al.(1998) proposed the direct mechanical injury and
hypoxia/reperfusion injury model, suggesting that the oxidative
stress results in the accumulation of free radicals that damage
the articular tissues of the TMJ. Several studies have
demonstrated the presence of reactive oxidative radical species
in synovial fluid from diseased TMJs (Kawai et al., 2000;
Takahashi et al., 2003).
Mechanism of Functional Overloading for TMJ Degenerative Disorders (Fig. 2)In chondrocytes of articular cartilage, cyclic tensile loading up-
regulated the expression of matrix metalloproteinase (MMP)-
13 and vascular endothelial growth factor (VEGF) and down-
regulated the expression of tissue inhibitor of matrix
metalloproteinases (TIMP)-1, while cyclic hydrostatic pressure
induced opposite effects (Wong et al., 2003). VEGF expression
in osteoarthritic cartilage appeared to increase progressively
with the applied mechanical overload. Furthermore, VEGF
induction in chondrocytes by mechanical overload has been
linked to activation of hypoxia-induced transcription factor-1
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 299
(Forsythe et al., 1996). Recently,
Tanaka et al. (2005a) showed that
mandibular condylar cartilage in
mechanically induced TMJ-
osteoarthrosis expressed abundant
VEGF. VEGF regulates the production
of MMPs and TIMPs, which are
among the effectors of extracellular
matrix remodeling (Pufe et al., 2004).
Reduction of TIMPs and induction of
MMPs result in an imbalance in the
turnover of extracellular matrix
components, collagens, and
proteoglycans, which are degraded
more rapidly than they are formed.
The loss of balance toward increased
extracellular matrix degradation
results in the destruction of cartilage
(Pufe et al., 2004).
The expression of VEGF is also
up-regulated in the synovial tissues
(Sato et al., 2003) and the TMJ disc
(Leonardi et al., 2003) in TMJ-internal
derangement. This suggests that
VEGF expression is involved in the
development of inflammatory changes
in the TMJ as a reaction to the
cytokine. The increased expression of
VEGF in the joint tissues might lead to
an increase of VEGF in the synovial
fluid of persons with symptomatic
TMJ-internal derangement (Sato et al.,2005). Consequently, mechanical
overload induces hypoxia-induced
transcription factor-1, and the
subsequently generated VEGF
activates the chondrocytes in an
autocrine manner to produce MMPs and reduces TIMPs (Pufe
et al., 2004). This implies that VEGF is probably induced in
chondrocytes by mechanical overload, facilitating hypoxia and
mediating the destructive processes associated with
osteoarthrosis as an autocrine factor.
Furthermore, in the condylar cartilage with TMJ-
osteoarthrosis, the number of blood vessels and osteoclasts is
markedly increased in the area subjacent to the hypertrophic
cell layer, where several VEGF-expressing chondrocytes are
detected (Tanaka et al., 2005a). Since VEGF plays an
important role not only in endothelial cell recruitment, but also
in osteoclast recruitment (Niida et al., 1999), VEGF has
overlapping function in the support of osteoclastic bone
resorption. Then, the increase in osteoclasts stimulated by
VEGF may induce destruction of cartilage, making vascular
invasion into the condylar cartilage easier.
Overloading also causes collapse of joint lubrication, as the
result of hyaluronan degradation by free radicals (Nitzan,
2001). With overloading, the increase in intra-articular
pressure, when it exceeds the capillary perfusion pressure, will
cause temporary hypoxia, which is corrected by re-oxygenation
on cessation of degradation by the overloading. Such a
hypoxia-reperfusion cycle has been reported to release reactive
oxidative radical species non-enzymatically (Grootveld et al.,
1991). Among other effects of reactive oxidative radical
species in synovial joints are inhibition of the biosynthesis and
degradation of hyaluronic acid, both causing marked reduction
in viscosity of synovial fluid (Grootveld et al., 1991).
In the healthy TMJ, the co-efficient of friction between the
cartilage surfaces can be assumed to be almost zero by the
presence of synovial fluid (Tanaka et al., 2004; Nickel et al.,2001, 2006). However, after an experimental abrasion of the
articular cartilage comparable with TMJ-osteoarthrosis, the co-
efficient of friction was 3.5 times greater than that in the intact
joint (Tanaka et al., 2005b). As the coefficient of friction
increases, the shear stresses between the articular surfaces,
within the disc, and articular cartilage become greater. Shear
stress can result in fatigue and damage and irreversibly deform
the TMJ tissues, initiating TMJ-internal derangement and -
osteoarthrosis (Beatty et al., 2003; Tanaka et al., 2003).
Hyaluronan degradation is likely to occur in pathologic
joints because of free-radical de-polymerization of the
hyaluronic acid chain (McNeil et al., 1985) or the abnormal
biosynthesis of hyaluronic acid by type B synovial cells
(Vuorio et al., 1982). Free radicals rapidly depolymerize
hyaluronic acid in vitro, which may implicate them in the
degradation of hyaluronic acid in vivo. Furthermore, the
degradation of hyaluronic acid may lead to cartilage destruction
Figure 2. The concept of the process of cartilage breakdown in the TMJ. A decreased adaptivecapacity of the articulating structures and/or excessive physical stress to the TMJ that exceeds thenormal adaptive capacity can induce dysfunctional remodeling. Functional overloading andincreased joint friction may act together as etiological events for TMJ degenerative changes.Functional overloading can facilitate hypoxia in the TMJ and mediate the destructive processesassociated with osteoarthrosis as an autocrine factor. Vascular endothelial growth factor (VEGF)induction in osteoarthritic cartilage by functional overloading is linked to activation of the hypoxia-induced transcription factor-1, leading to hypoxia in the joint tissue. Furthermore, VEGF regulatesthe production of matrix metalloproteinases and tissue-inhibitors of matrix metalloproteinases, whichare among the effectors of extracellular matrix remodeling. Overloading also causes collapse of jointlubrication as the result of the hyaluronic acid degradation by free radicals. The regulation ofhyaluronic acid production is controlled by various pro-inflammatory cytokines. Of these cytokines,tumor necrosis factor-� and interleukin-1 and -6 play crucial roles in the pathogenesis ofosteoarthrosis with respect to the acceleration and progression of cartilage degradation, becausethey promote bone resorption through the differentiation and activation of osteoclasts.
300 Tanaka et al. J Dent Res 87(4) 2008
in terms of the enhanced expression of MMPs (Ohno-Nakahara
et al., 2004). Since neither healthy nor inflammatory synovial
fluids contain hyaluronidase activity, reactive oxidative radical
species are assumed to cause hyaluronic acid depolymerization
(McNeil et al., 1985). Considering the presence of reactive
oxidative radical species in synovial fluid from diseased TMJs
(Kawai et al., 2000), it is strongly suggested that reactive
oxidative radical species generated in diseased TMJs cause the
depolymerization of hyaluronic acid in synovial fluid.
The process of regulation of hyaluronic acid production is
also controlled by various cytokines, including interleukin-1�,
tumor necrosis factor-�, interferon-�, and transforming growth
factor-�. Tanimoto et al. (2004), using rabbit TMJ synovial
lining cells, demonstrated that TGF�1 enhances the expression
of hyaluronic acid synthase-2 mRNA in the TMJ synovial
membrane fibroblasts and may contribute to the production of
high-molecular-weight hyaluronic acid in the joint fluid.
Several pro-inflammatory cytokines have been detected in the
synovial fluid obtained from persons with TMJ-internal
derangement and -osteoarthrosis (Kubota et al., 1998; Hamada
et al., 2006).
Of these cytokines, tumor necrosis factor-� and interleukin-
1 and -6, produced primarily by stimulated macrophages, play
crucial roles in the pathogenesis of rheumatoid arthritis and
osteoarthrosis, with respect to the acceleration and progression
of cartilage degradation, because they promote bone resorption
through the differentiation and activation of osteoclasts (Boyle
et al., 2003). A significantly high concentration of interleukin-6
was associated with severe synovitis, although interleukin-1�and interleukin-6 were detected even in asymptomatic TMJs
(Kubota et al., 1998). Interleukin-10 has also been suggested to
prevent and reverse cartilage degradation in rheumatoid
arthritis (van Roon et al., 1996). Recently, interleukin-10 was
detected even in synovial fluid obtained from persons with
TMJ-internal derangement (Hamada et al., 2006). These
findings suggested that cytokines in the synovial fluid might be
responsible for the progression and regulation of the
degenerative changes in the TMJ.
DIAGNOSIS OF THE TMJ DEGENERATIVE DISORDERSTMJ arthritic conditions can be classified as low-inflammatory
or high-inflammatory types. Here, the term
"osteoarthritis" classically has been defined as a
low-inflammatory arthritic condition without pain,
either primary or secondary to trauma or other
acute and/or chronic overload situations,
characterized by erosion of articular cartilage,
which becomes soft, frayed, and thinned, resulting
in eburnation of subchondral bone and outgrowth
of marginal osteophytes. Meanwhile, the term
"osteoarthrosis", a synonym for "osteoarthritis" in
the medical orthopedic literature, has recently
come to be identified in the dental TMJ literature
with any non-inflammatory arthritic condition that
results in degenerative changes similar to those in
"osteoarthritis". However, in the dental TMJ
literature, "osteoarthrosis" has come to be
identified with the unsuccessful adaptation of the
TMJ to the mechanical forces placed on it with
disc derangement or disc interference disorders
(Stegenga et al., 1989). Since the basic etiology, pathology, and
management involved are the same, the terms "osteoarthritis"
and "osteoarthrosis" will be used synonymously.
Low-inflammatory arthritic conditions begin in the matrix
of the articular surface of the joint, with the subcondylar bone
and capsule secondarily involved (Table 1). The classic types
of low-inflammatory arthritis are (1) degenerative joint disease,
or primary osteoarthritis, produced by intrinsic degeneration of
articular cartilage, typically the result of age-related functional
loading, and (2) post-traumatic arthritis. Despite the fact that
these low-inflammatory arthritic conditions often involve the
TMJ, these conditions seldom require invasive surgical
intervention if they are managed appropriately in their early
stages. Individuals with the low-inflammatory type have low
leukocyte counts in the synovial fluid and laboratory findings
consistent with low-level inflammatory activity, and the
affected joint shows focal degeneration on imaging.
High-inflammatory arthritic conditions primarily involve
the synovial cells and joint bone (Table 1). The classic type of
high-inflammatory arthritis is rheumatoid arthritis. Other types
of high-inflammatory arthritic conditions include the metabolic
arthritic conditions, such as gout, arthritis of psoriasis, lupus
erythematosus, ankylosing spondylitis, infectious arthritis,
Reiter's Syndrome, and the arthritis associated with ulcerative
colitis. Although these disorders may be histologically and
chemically different, clinical findings and management are
often similar. In all instances, the TMJ can be involved, and
surgical intervention may be required to alleviate symptoms
and correct associated functional and esthetic problems.
Individuals with high-inflammatory-type arthritis have high
leukocyte counts in the synovial fluid and laboratory findings
consistent with high-inflammatory activity, and show a more
diffuse degeneration of the involved joints on imaging.
Signs and Symptoms of Arthritic Changes in the TMJThe most common symptom of any arthritic TMJ condition is
painful joints. The pain arises from the soft tissues around the
affected joint and the masticatory muscles that are in protective
reflex spasm in accordance with Hilton's law. This orthopedic
principle states that the nerves that innervate a joint also
innervate the muscles that move that joint and the overlying
skin. This self-preservation physiologic reflex provides for the
protection of an injured or pathologically affected joint by
Table 1. Classification of Arthritic Conditions Affecting the Joint.
Low-inflammatory Arthritic Disorders Degenerative joint disease (Osteoarthritis) Post-traumatic arthritis
High-inflammatory Arthritic Disorders Infectious arthritis Rheumatoid arthritic conditions- adult and juvenile
Metabolic arthritic conditions- gouty arthritis- psoriatic arthritis- lupus erythematosus- ankylosing spondylitis- Reiter’s Syndrome- arthritis associated with ulcerative colitis
From Mercuri, 2006.
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 301
causing the surrounding
musculature to contract
reflexively in response to
intra-articular injury or
pathology, thus protecting it
from further damage. Pain
may also arise from the
subchondral bone that is
undergoing destruction as
the result of the arthritic
process.
Other common and
significant signs and symp -
toms of TMJ arthritis are
loss of joint function or late-
stage ankylosis, joint
instability, and facial de -
formity due to loss of
posterior mandibular verti -
cal dimension, as pathologic
osteolysis decreases the
height of the condyle and
condyloid process, resulting in apertognathia (Mercuri, 2006).
DiagnosisThe diagnosis in late-stage arthritic TMJ disease is usually
obvious, especially in the late-stage high-inflammatory arthritic
diseases, when the disease process is manifest in other joints.
The problem in diagnosis comes with the uncommon
individual whose arthritic disease first manifests itself as TMJ
pain and mandibular dysfunction. A history of joint overload
due to habits (e.g., excessive gum chewing, unilateral chewing)
or parafunction (e.g., bruxism, clenching) and clinical
examination is important, but lacking any correlation between
the signs and symptoms, as well as the history and physical
findings, the best approach to diagnosis may come in turning to
imaging and laboratory examination.
MANAGEMENT OF THE TMJDEGENERATIVE DISORDERSPrinciples for Management of TMJ-OsteoarthrosisManagement of TMJ-osteoarthrosis may be divided into non-
invasive, minimally invasive, and invasive or surgical
modalities. Finally, in end-stage disease, salvage modalities
must be considered. The decision for surgical management of
TMJ-osteoarthrosis must be based on evaluation of the person's
response to non-invasive management, the person's mandibular
form and function, and the effect the condition has on the
person's quality of life (Mercuri, 2006). The management goals
in TMJ-osteoarthrosis should be: (1) decreasing joint pain,
swelling, and reflex masticatory muscle spasm/pain; (2)
increasing joint function; (3) preventing further joint damage;
and (4) preventing disability and disease-related mor bidity.
Using a classification scheme based on clinical signs and
symptoms and imaging, modified from that developed by
Steinbrocker et al. (1949) and Kent et al. (1986), we will
present an evidence-based discussion for the management of
TMJ-osteoarthrosis (Table 2).
Non-invasive Management ModalitiesThe non-invasive modalities of management include occlusal
splint, medications, orthotics, and physical therapy. In the
clinic, the most common treatment of pain from the TMJ is by
occlusal splints. Occlusal splints are an effective device to
protect the TMJ from involuntary overloading, and to reduce
the muscle hyperactivity and articular strain due to bruxism. In
a controlled study on the effects of occlusal splint therapy in
individuals with severe TMJ-osteoarthrosis, a reduction of
clinical signs was seen (Kuttila et al., 2002). However, critical
evaluation of splint therapy has not yet been conducted, due to
the lack of evidence, and their clinical effectiveness in relieving
pain seems modest when compared with that of pain treatment
methods in general (Forssell and Kalso, 2004). None of the
occlusal adjustment studies provided evidence supporting the
use of this treatment method.
In terms of medications, non-steroidal anti-inflammatory
agents, such as ibuprofen, should be used on a time-
contingent basis to take advantage of their pharmacokinetics.
Muscle relaxants may be helpful in controlling the reflex
masticatory muscle spasm/pain (Dionne, 2006). Oral
orthotics, while assisting in the control of parafunctional
habits in many persons, also can provide relief from
masticatory muscle spasm/pain and, along with a soft diet,
will decrease the loads delivered across the TMJ articulation
under function. Reconstruction of the occlusion to provide
bilateral occlusal stability, temporarily during the early stages
of management, also will decrease the potential for unilateral
joint overload (Clark, 1984). Physical therapeutic modalities
act as counter-irritants to reduce inflammation and pain.
Superficial warm and moist heat or localized cold may relieve
pain sufficiently to permit exercise. Therapeutic exercises are
designed to increase muscle strength, reduce joint
contractures, and maintain a functional range of motion.
Ultrasound, electrogalvanic stimulation, and massage
techniques are also helpful in reducing inflammation and pain
(De Laat et al., 2003).
Active and passive jaw movements, manual therapy
techniques, and relaxation techniques were used in the
management of 20 consecutive persons with TMJ-
osteoarthrosis. After treatment (mean, 46 days), pain at rest was
Table 2. Classification of Osteoarthrosis Based on Symptoms, Signs, and Imaging with Management Options.
Stage Symptoms Signs Imaging Management Options
I Joint/muscle pain Little or no Mild to moderate Non-InvasiveEarly Disease Limited function occlusal or facial erosive changes of or Minimally invasive
Crepitus esthetic changes condyle/fossa/eminence
II Little or no joint pain Class II malocclusion Flattened Bone and JointArrested Disease Muscle pain Apertognathia condyle/eminence Invasive or Salvage
Some joint dysfunctionCrepitus
III Joint/muscle pain High-angle Class II Gross erosive changes SalvageAdvanced Disease Loss of function malocclusion Loss of condyle and
+/-Crepitus Apertognathia eminence heightProgressive Developing Ankylosis retrognathia fibrosis/ankylosis Hypertrophy of coronoid
Modified from Steinbrocker et al., 1949, and Kent et al., 1986.
302 Tanaka et al. J Dent Res 87(4) 2008
reduced in the 20 persons by 80%, and there was no functional
impairment in 37% of the 20 persons (seven persons)
(Nicolakis et al., 2001).
Minimally Invasive Modalities
Injections
Hyaluronic acid as an injectable, large, linear glycosamino -
glycan has been studied in other body joints. In double-blind
studies in other joints after 2 mos, hyaluronic acid has been
shown to provide significantly better results than saline. These
results were sustained for 1 yr. However, no significant
differences were noted in radiographic progression of the
disease (Lohmander et al., 1996).
An in vivo rabbit study reported that the hyaluronic-acid-
injected joints demonstrated limited cartilage change, less
fibrillation, and the presence of clusters of chondrocytes in the
deficit area, while the prednisolone-treated joint exhibited
worsening of the cartilage destruction (Shi et al., 2002). However,
to date, hyaluronic acid has not been approved by the United
States Food and Drug Administration as a safe and effective
medication in the management of arthritic disease in the TMJ.
Intra-articular injections of corticosteroids are of limited
use in other joints of the body (Gray and Gottlieb, 1983). The
main limitations of repeated intra-articular steroid injections are
the risks of infection and the destruction of articular cartilage.
Repeated intra-articular corticosteroid injections have been
implicated in the "chemical condylectomy" phenomenon in the
TMJ (Toller, 1977). Intra-articular injections of steroids should
be considered only in persons with evidence of acute high
inflammation of the joint. Multiple injections of steroids should
not be used. In all cases after intra-capsular injection of
steroids, decreased activities within pain-free limits should be
recommended, to prevent acceleration of the degenerative
process from over-activity and joint overload.
Arthrocentesis and Arthroscopy
Nitzan and Price (2001) presented a 20-month follow-up study
of 36 persons with 38 dysfunctional joints that had not
responded to non-surgical management, to determine the
efficacy of arthrocentesis in restoring functional capacity to the
osteoarthrosis joints. They concluded that arthrocentesis is a
rapid and safe procedure that may result in the TMJ-
osteoarthrosis returning to a functional state. Failure of
arthrocentesis (32%) suggested that painful limitation of TMJ
function might be the result of fibrous adhesions or osteophytes
that require arthrotomy for management.
The value of TMJ arthroscopy may be in the early
diagnosis and management of arthritic processes affecting the
TMJ, especially early-stage arthritic disease, to avoid the
complications of open bite and ankylosis (Holmlund et al.,1986). Holmlund et al. (1986) described the arthroscopic
picture as varying widely, depending on when in the stages of
the arthritic process the procedure is performed and whether
disease-modifying therapeutic agents have been given. Late-
stage marked fibrosis or ankylosis makes arthroscopy
impossible and contraindicates its usefulness.
While the majority of persons with TMJ-osteoarthrosis can
be successfully managed with non-invasive/minimally invasive
procedures, there is a small percentage of persons with
osteoarthrosis (< 20%) who have such severe pathology, pain,
and dysfunction that invasive surgical management must be
considered (Mercuri, 2006). Since the later cases present such a
challenge for management and reconstruction, the authors
believe that, to complete the review of the topic, the invasive
surgical modalities must be discussed in some detail.
Invasive Surgical Modalities (Bone and Joint Procedures)
Arthroplasty
Reshaping the articular surfaces to eliminate osteophytes,
erosions, and irregularities found in osteoarthritis refractory to
other modalities of treatment was described by Dingman and
Grabb (1966). While this technique reportedly provided pain
relief, concerns about the resultant mandibular dysfunctions,
dental malocclusions, facial asymmetries, and the potential for
development of further bony articular degeneration, disc disorders
or loss, and ankylosis led to the development of techniques for
interposing autogenous tissues and alloplastic materials.
The need for replacement of the articular disc in such cases
remains controversial (Merrill, 1986). According to Moriconi etal. (1986), TMJ replacement grafts should fulfill the following
criteria: biological compatibility, adequate strength, restoration
of biomechanical function, and resistance to the adverse affects
of the biological environment.
Autogenous Hemi-arthroplasty
Several different autogenous tissues have been advocated as a
replacement for the TMJ disc (Merrill, 1986); however, the
literature on the use of the vascularized local temporalis muscle
flap appears to present the most applicable data for the
management of the arthritic TMJ (Feinberg and Larsen, 1989).
Osteotomy
Individuals with active TMJ-osteoarthrosis and either
concomitant or resultant maxillofacial skeletal discrepancies,
and treated only with orthognathic surgery, often have poor
outcomes and significant relapse (Wolford et al., 1994, 2003).
Pre-existing TMJ pathology, with or without symptoms that can
lead to unfavorable orthognathic surgery outcomes, includes:
internal derangement, progressive condylar resorption,
osteoarthritis, condylar hyperplasia, osteochondroma, congenital
deformities, and non-salvageable joints (Wolford et al., 1994).
Since the TMJs are the foundation of orthognathic surgery,
the resultant pathology offers a poor base upon which to build
any maxillofacial functional skeletal reconstruction in conditions
where there are gross erosive changes in the articulating
components of both the fossa and condyle, resulting in loss of
vertical height. Further, the degenerative and osteolytic changes
the joint components are undergoing in these conditions make
these components of the TMJ highly susceptible to failure under
the new functional loading resulting from orthognathic surgical
repositioning of the maxillofacial skeleton.
Osseodistraction
Van Strijen et al. (2001) advised that, since osteoclastic activity
in the TMJ has been reported after gradual distraction of the
mandible, distraction osteogenesis may make its own
contribution to TMJ-osteoarthrosis and idiopathic condylar
resorption. They suggested that, in the future, persons being
considered for surgical management of mandibular hypoplasia
be critically evaluated for any traumatic, functional, or
metabolic risk factors for TMJ-osteoarthrosis and idiopathic
condylar resorption.
Salvage Procedures—Total Joint ReplacementThe costochondral graft has been the autogenous bone most
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 303
frequently recommended for the reconstruction of the TMJ, due
to its ease of adaptation to the recipient site, its gross anatomical
similarity to the mandibular condyle, its low morbidity, its
reported low morbidity rate at the donor site, and its
demonstrated growth potential in juveniles (MacIntosh, 2000).
However, orthopedists recommend alloplastic reconstruction
when total joint replacement is required for the management of
a non-growing person affected by either low-inflammatory or
high-inflammatory arthritic disease (Chapman, 2001).
In the TMJ, alloplastic reconstruction has been discussed at
length (McBride, 1994; Mercuri, 1998, 1999, 2000). All of
these authors agree that when the mandibular condyle is
extensively damaged, degenerated, or lost, as in arthritic
conditions, replacement with either autogenous graft or
alloplastic implant is an acceptable approach to achieve optimal
symptomatic and functional improvement. Long-term follow-
up studies include individuals with diagnoses consistent with
low- and high-inflammatory arthritic TMJs in their total
alloplastic reconstruction datasets (Mercuri et al., 2002;
Mercuri and Giobbe-Hurder, 2004; Mercuri, 2006, 2007).
In light of these findings, previously published experience
in both orthopedic and oral and maxillofacial surgery, and the
literature comparing autogenous with alloplastic total TMJ
replacement in arthritic conditions, it appears that total
alloplastic TMJ reconstruction should be considered
appropriate management for advanced-stage TMJ osteoarthritic
disease and idiopathic condylar resorption (Table 2).
LOOKING TO THE FUTURE: TISSUE ENGINEERINGThe next generation of TMJ implants will be biological
constructs fabricated with tissue-engineering technology.
Currently, the TMJ disc and the mandibular condyle have been
the focus of tissue-engineering efforts, pursued by only a
limited number of groups in the world. In the long term,
regenerative therapies may need to combine both of these
structures into a single implant, and to expand the focus to
include surrounding structures, such as the retrodiscal tissue
and the fossa-eminence of the temporal bone (Detamore et al.,2007). However, the disc and condyle are the highest priority
for clinical application.
TMJ Disc Tissue EngineeringTo date, tissue-engineering investigations of the disc and the
condyle have been conducted independent of one another. Both
the condyle and disc tissue-engineering communities have
made significant advances in recent years, although the disc
investigations began much earlier. Four TMJ disc tissue-
engineering studies were published from 1991 to 2001
(Detamore and Athanasiou, 2003), and while important issues
were addressed, such as cell source, biomaterials, and shape-
specific scaffolds, the common theme among these pioneering
studies was an unfamiliarity with the available characterization
data for the TMJ disc in terms of cell content and matrix
composition. In 2001, strategies for TMJ tissue engineering,
including cell sources, scaffolding materials, and signaling,
were reviewed (Glowacki, 2001), and a photopolymerization
method for developing a shape-specific TMJ disc scaffold was
developed (Poshusta and Anseth, 2001). However, it took 3
years before the next wave of TMJ disc tissue-engineering
studies was published, all of which utilized cells derived from
the TMJ disc. Most of these studies were from Athanasiou's
group, which collectively supported the use of polyglycolic
acid over agarose (Almarza and Athanasiou, 2004), promoted
the spinner flask as the preferred seeding method with
polyglycolic acid scaffolds (Almarza and Athanasiou, 2004),
demonstrated the importance of using growth factors such as
insulin-like growth factor-I (Almarza and Athanasiou, 2006b;
Detamore and Athanasiou, 2005a), revealed the detrimental
effects of passaging and pellet culture (Allen and Athanasiou,
2006b), recommended 25 �g/mL as a preferred ascorbic acid
concentration (Bean et al., 2006), and investigated the effects
of hydrostatic pressure (Almarza and Athanasiou, 2006a) and
rotating wall bioreactors (Detamore and Athanasiou, 2005b).
Recently, another study has suggested the use of platelet-
derived growth factor-BB in TMJ disc tissue engineering
(Hanaoka et al., 2006).
Overall, the TMJ disc tissue-engineering studies to date
have utilized various cell sources and biomaterials, evaluating
the effects of different bioactive signals and bioreactors. The
next major investigations into TMJ disc tissue engineering will
be the incorporation of stem cell sources and the evaluation of
in vivo performance of engineered TMJ discs.
Mandibular Condyle/Ramus Tissue EngineeringUnlike the TMJ disc, mandibular condyle/ramus tissue-
engineering studies did not appear in the literature until this
decade. The largest contributions, thus far, have come from the
groups of Hollister and Mao. Beginning in 2000, Hollister and
colleagues developed a strategy for producing person-specific
condyle-shaped scaffolds based on computed tomography
and/or magnetic resonance images. By using solid free-form
fabrication, they have been able to control not only the overall
shape, but also the internal architecture, providing for precise
control over pore size, porosity, permeability, and mechanical
integrity. Solid free-form fabrication methods such as
stereolithography and selective layer sintering work by creating
scaffolds layer by layer. In this manner, Hollister and
colleagues have engineered cylindrical osteochondral
constructs (Schek et al., 2004, 2005) and condyle/ramus-
shaped bone constructs (Williams et al., 2005), using materials
such as hydroxyapatite, polylactic acid, and polycaprolactone
and mature cell sources (fibroblasts with bone morphogenic
protein-7 gene inserted and/or chondrocytes). In vivo studies
collectively demonstrated substantial bone ingrowth and
glycosaminoglycan formation (Schek et al., 2004, 2005;
Hollister et al., 2005; Williams et al., 2005). Mao's group
(Alhadlaq and Mao, 2003, 2005; Alhadlaq et al., 2004) has
taken a different approach, encapsulating marrow-derived
mesenchymal stem cells in a polyethylene glycol diacrylate
hydrogel to create stratified bone and cartilage layers in the
shape of a human condyle. After 12 weeks in vivo, it was
shown that osteopontin, osteonectin, and collagen I were
localized in the osteogenic layer, and collagen II and
glycosaminoglycans were localized in the chondrogenic layer
(Alhadlaq and Mao, 2005).
Beyond these two primary groups, various different
approaches have been used, most of which were in vivo studies
using only histology and/or imaging to validate engineered
constructs. A pair of studies molded coral into the shape of a
human condyle and seeded it with mesenchymal stem cells,
then implanted it either with bone morphogenic protein-2 in
mice, to demonstrate osteogenesis (YJ Chen et al., 2002), or
304 Tanaka et al. J Dent Res 87(4) 2008
under blood vessels in rabbits, to demonstrate construct
vascularization (Chen et al., 2004). Another pair of studies
implanted acellular poly(lactic-co-glycolic acid)-based
constructs with growth factors in rat mandibular defects,
demonstrating either the efficacy of transforming growth
factor-�1 and insulin-like growth factor-I (Srouji et al., 2005)
or the lack of efficacy of bone morphogenic protein-2 (Ueki etal., 2003) under the prescribed conditions. In another case,
osteoblasts were seeded into condyle-shaped polyglycolic
acid/polylactic acid scaffolds, and chondrocytes were painted
on the surface prior to implantation in mice, after which
positive histological results were observed (Weng et al., 2001).
In a related study, porcine mesenchymal stem cells seeded in
condyle-shaped poly(lactic-co-glycolic acid) scaffolds were
cultured under osteogenic conditions in a custom-built rotating
bioreactor, which also yielded positive histological results
(Abukawa et al., 2003). Finally, a recent study compared
human umbilical cord matrix mesenchymal stem cells with
porcine condylar cartilage cells for condylar cartilage tissue
engineering, showing that the umbilical cord matrix stem cells
outperformed the cartilage cells, especially with regard to
proliferation and to chondroitin sulfate and overall
glycosaminoglycan synthesis (Bailey et al., 2007).
The next major step for mandibular condyle/ramus tissue
engineering will be demonstrating long-term in vivo efficacy
with osteochondral condyle/ramus replacements in larger
animals (e.g., pig), which will require an understanding of the
growth and mechanics of the native tissue (Herring and
Ochareon, 2005).
Future Directions in TMJ Tissue EngineeringDespite its short history and the relatively few published
reports, significant advances have already been made in TMJ
tissue engineering. At this stage, we are still several years away
from bringing tissue-engineering technology to the clinic for
individuals with TMJ. Although it would be premature to
speculate as to how and when these models can be applied to
humans, there are nonetheless areas of pressing clinical interest
that have been identified for the near future. In particular,
primary issues to be addressed in the coming years include
attachment, integration, metaplasia, angiogenesis, the person's
age, marketing, and creating a condyle-disc composite scaffold
(Detamore et al., 2007). Biomechanical models of the TMJ are
becoming highly sophisticated, especially with recent additions
to the literature characterizing tissue properties, which will be
invaluable in predicting mechanical design requirements for
engineered constructs.
CONCLUSIONSThe importance of developing an evidence-based approach to
clinical management and treatment must be emphasized. Often,
in the past, treatment of clinical disorders has been based
purely upon experience and knowledge gained through clinical
training. This often resulted in various management modalities
for the same condition, as well as in ineffective, expensive,
unvalidated, and sometimes potentially harmful interventions.
The goal of evidence-based medicine is to move beyond
anecdotal clinical experience by bridging the gap between
research and clinical practice.
With respect to the degenerative pathology of the TMJ, the
treatment goals for affected individuals include restored
function and pain reduction. The management modalities used
to achieve these goals can range from non-invasive therapy, to
minimally invasive and invasive surgery. Most people can be
managed non-invasively, and one must acknowledge the
importance of disease prevention and conservative
management in the overall treatment of persons with TMJ. The
decision to manage TMJ-osteoarthrosis surgically must be
based on evaluation of the person's response to non-invasive
management, his/her mandibular form and function, and the
effect of the condition on his/her quality of life.
To date, although systemic illness, aging processes,
hormonal factors, and behavioral factors have been implicated
in the etiology of TMJ-osteoarthrosis, growing evidence
suggests that mechanical overload may be assumed to be an
initiating factor for a series of degenerative changes in the
TMJ, resulting in condylar resorption and deformity. Therefore,
an evaluation of the biomechanical environment in the TMJ
would lead to a better understanding of the inducing
mechanism of TMJ pain and disability, which result in proper
diagnosis and available treatment planning for TMJ
degenerative disorders.
A proper understanding of the biomechanical behavior of
the joint components and biomechanical environment within
the TMJ also provides better focus in the search for and
selection of mechanically compatible synthetic or regenerative
biomaterials for TMJ reconstruction. While tissue engineering
may revolutionize the future of TMJ treatment, it will be
absolutely necessary to remember the lessons learned from
decades of successes and failures with TMJ implants.
Moreover, tissue-engineered joint structures may be doomed to
failure unless the etiology of the underlying degenerative
processes is identified and managed. Therefore, an
understanding of the pathobiology of TMJ degenerative
disorders and current clinical treatment, as described in this
article, will be essential to the successful integration of tissue
engineering into the future surgical management of TMJ
pathology.
REFERENCESAbukawa H, Terai H, Hannouche D, Vacanti JP, Kaban LB, Troulis MJ
(2003). Formation of a mandibular condyle in vitro by tissue
engineering. J Oral Maxillofac Surg 61:94-100.
Alhadlaq A, Mao JJ (2003). Tissue-engineered neogenesis of human-shaped
mandibular condyle from rat mesenchymal stem cells. J Dent Res82:951-956.
Alhadlaq A, Mao JJ (2005). Tissue-engineered osteochondral constructs in
the shape of an articular condyle. J Bone Joint Surg Am 87:936-944.
Alhadlaq A, Elisseeff JH, Hong L, Williams CG, Caplan AI, Sharma B, etal. (2004). Adult stem cell driven genesis of human-shaped articular
condyle. Ann Biomed Eng 32:911-923.
Allen KD, Athanasiou KA (2006). Growth factor effects on passaged TMJ
disk cells in monolayer and pellet cultures. Orthod Craniofac Res9:143-152.
Almarza AJ, Athanasiou KA (2004). Seeding techniques and scaffolding
choice for tissue engineering of the temporomandibular joint disk.
Tissue Eng 10:1787-1795.
Almarza AJ, Athanasiou KA (2006a). Effects of hydrostatic pressure on
TMJ disc cells. Tissue Eng 12:1285-1294.
Almarza AJ, Athanasiou KA (2006b). Evaluation of three growth factors in
combinations of two for temporomandibular joint disc tissue
engineering. Arch Oral Biol 51:215-221.
Arnett GW, Milam SB, Gottesman L (1996a). Progressive mandibular
retrusion—idiopathic condylar resorption. Part I. Am J OrthodDentofacial Orthop 110:8-15.
Arnett GW, Milam SB, Gottesman L (1996b). Progressive mandibular
retrusion—idiopathic condylar resorption. Part II. Am J Orthod
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 305
Dentofacial Orthop 110:117-127.
Bailey MM, Wang L, Bode CJ, Mitchell KE, Detamore MS (2007). A
comparison of human umbilical cord matrix stem cells and TMJ
condylar chondrocytes for tissue engineering TMJ condylar cartilage.
Tissue Eng 13:2003-2010.
Bean AC, Almarza AJ, Athanasiou KA (2006). Effects of ascorbic acid
concentration on the tissue engineering of the temporomandibular joint
disc. Proc Inst Mech Eng [H] 220:439-447.
Beatty MW, Bruno MJ, Iwasaki LR, Nickel JC (2001). Strain rate
dependent orthotropic properties of pristine and impulsively loaded
porcine temporomandibular joint disk. J Biomed Mater Res 57:25-34.
Beatty MW, Nickel JC, Iwasaki LR, Leiker M (2003). Mechanical response
of the porcine temporomandibular joint disc to an impact event and
repeated tensile loading. J Orofac Pain 17:160-166.
Beek M, Koolstra JH, van Ruijven LJ, van Eijden TMGJ (2000). Three-
dimensional finite element analysis of the human temporomandibular
joint disc. J Biomech 33:307-316.
Boyd RL, Gibbs CH, Mahan PE, Richmond AF, Laskin JL (1990).
Temporomandibular joint forces measured at the condyle of Macacaarctoides. Am J Orthod Dentofac Orthop 97:472-479.
Boyle WJ, Simonet WS, Lacey DL (2003). Osteoclast differentiation and
activation. Nature 423:337-342.
Brehnan K, Boyd RL, Laskin J, Gibbs CH, Mahan P (1981). Direct
measurement of loads at the temporomandibular joint in Macacaarctoides. J Dent Res 60:1820-1824.
Brooks SL, Westesson PL, Eriksson L, Hansson LG, Barsotti JB (1992).
Prevalence of osseous changes in the temporomandibular joint of
asymptomatic persons without internal derangement. Oral Surg OralMed Oral Pathol 73:118-122.
Carlsson GE (1999). Epidemiology and treatment need for
temporomandibular disorders. J Orofac Pain 13:232-237.
Carlsson GE, LeResche L (1995). Epidemiology of temporomandibular
disorders. In: Temporomandibular disorders and related pain
conditions. Sessle BJ, Bryant PS, Dionne RA, editors. Seattle: IASP
Press.
Chapman MW (2001). Chapman's orthopaedic surgery. Philadelphia:
Lippincott, Williams & Wilkins.
Chen F, Mao T, Tao K, Chen S, Ding G, Gu X (2002). Bone graft in the
shape of human mandibular condyle reconstruction via seeding
marrow-derived osteoblasts into porous coral in a nude mice model. JOral Maxillofac Surg 60:1155-1159.
Chen F, Chen S, Tao K, Feng X, Liu Y, Lei D, et al. (2004). Marrow-
derived osteoblasts seeded into porous natural coral to prefabricate a
vascularised bone graft in the shape of a human mandibular ramus:
experimental study in rabbits. Br J Oral Maxillofac Surg 42:532-537.
Chen YJ, Gallo LM, Meier D, Palla S (2000). Individualized oblique-axial
magnetic resonance imaging for improved visualization of mediolateral
TMJ disc displacement. J Orofac Pain 14:128-139.
Chen YJ, Gallo LM, Palla S (2002). The mediolateral temporomandibular
joint disc position: an in vivo quantitative study. J Orofac Pain 16:29-
38.
Clark GT (1984). A critical evaluation of orthopedic interocclusal appliance
therapy: design, therapy, and overall effectiveness. J Am Dent Assoc108:359-364.
De Laat A, Stappaerts K, Papy S (2003). Counseling and physical therapy as
treatment for myofascial pain of the masticatory system. J Orofac Pain17:42-49.
Detamore MS, Athanasiou KA (2003). Motivation, characterization, and
strategy for tissue engineering the temporomandibular joint disc. TissueEng 9:1065-1087.
Detamore MS, Athanasiou KA (2005a). Evaluation of three growth factors
for TMJ disc tissue engineering. Ann Biomed Eng 33:383-390.
Detamore MS, Athanasiou KA (2005b). Use of a rotating bioreactor toward
tissue engineering the temporomandibular joint disc. Tissue Eng11:1188-1197.
Detamore MS, Mao JJ, Athanasiou KA (2007). A call to action for
bioengineers and dental professionals: directives for the future of TMJ
bioengineering. Ann Biomed Eng 35:1301-1311.
Dijkgraaf LC, De Bont LGM, Boering G, Liem RSB (1995). The structure,
biochemistry and metabolism of osteoarthritic cartilage: a review of the
literature. J Oral Maxillofac Surg 53:1182-1192.
Dingman RO, Grabb WC (1966). Intracapsular temporomandibular joint
arthroplasty. Plast Reconstr Surg 38:179-185.
Dionne RA (2006). Pharmacologic approaches. In: TMDs, an evidence-
based approach to diagnosis and treatment. Laskin DM, Greene CS,
Hylander WL, editors. Chicago: Quintessence, pp. 347-357.
Farrar WB, McCarty WL Jr (1979). The TMJ dilemma. J AL Dent Assoc63:19-26.
Feinberg SE, Larsen PE (1989). The use of a pedicled temporalis muscle-
pericranial flap for the replacement of the TMJ disc. J Oral MaxillofacSurg 47:142-146.
Forssell H, Kalso E (2004). Application of principles of evidence-based
medicine to occlusal treatment for temporomandibular disorders: are
there lessons to be learned? J Orofac Pain 18:9-22.
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, et al.(1996). Activation of vascular endothelial growth factor gene
transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604-
4613.
Gallo LM, Chiaravalloti G, Iwasaki LR, Nickel JC, Palla S (2006).
Mechanical work during stress-field translation in the human TMJ. JDent Res 85:1006-1010.
Glowacki J (2001). Engineered cartilage, bone, joints, and menisci. Potential
for temporomandibular joint reconstruction. Cells Tissues Organs169:302-308.
Gray RG, Gottlieb NL (1983). Intra-articular corticosteroids. An updated
assessment. Clin Orthop Relat Res 177:235-263.
Grootveld M, Henderson EB, Farrell A, Blake DR, Parkes HG, Haycock P
(1991). Oxidative damage to hyaluronate and glucose in synovial fluid
during exercise of the inflamed rheumatoid joint. Detection of
abnormal low-molecular-mass metabolites by proton-n.m.r.
spectroscopy. Biochem J 273:459-467.
Hamada Y, Kondoh T, Holmlund AB, Yamamoto M, Horie A, Saito T, etal. (2006). Inflammatory cytokines correlated with clinical outcome of
temporomandibular joint irrigation in patients with chronic closed lock.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:596-601.
Hanaoka K, Tanaka E, Takata T, Miyauchi M, Aoyama J, Kawai N, et al.(2006). Platelet-derived growth factor enhances proliferation and
matrix synthesis of temporomandibular joint disc-derived cells. AngleOrthod 76:486-492.
Herring SW, Ochareon P (2005). Bone—special problems of the
craniofacial region. Orthod Craniofac Res 8:174-182.
Hiraba K, Hibino K, Hiranuma K, Negoro T (2000). EMG activities of two
heads of the human lateral pterygoid muscle in relation to mandibular
condylar movement and biting force. J Neurophysiol 83:2120-2137.
Hollister SJ, Levy RA, Chu TM, Halloran JW, Feinberg SE (2000). An
image-based approach for designing and manufacturing craniofacial
scaffolds. Int J Oral Maxillofac Surg 29:67-71.
Hollister SJ, Lin CY, Saito E, Lin CY, Schek RD, Taboas JM, et al. (2005).
Engineering craniofacial scaffolds. Orthod Craniofac Res 8:162-173.
Holmes MW, Bayliss MT, Muir H (1988). Hyaluronic acid in human
articular cartilage. Age-related changes in content and size. Biochem J250:435-441.
Holmlund A, Hellsing G, Wredmark T (1986). Arthroscopy of the
temporomandibular joint: a clinical study. Int J Oral Maxillofac Surg15:715-721.
Hylander WL, Bays R (1979). An in vivo strain-gauge analysis of
squamosal-dentary joint reaction force during mastication and incision
in Macaca mulata and Macaca fascicularis. Arch Oral Biol 24:689-
697.
Jibiki M, Shimoda S, Nakagawa Y, Kawasaki K, Asada K, Ishibashi K
(1999). Calcifications of the disc of the temporomandibular joint. JOral Pathol Med 28:413-419.
Kawai Y, Kubota E, Okabe E (2000). Reactive oxygen species participation
in experimentally induced arthritis of the temporomandibular joint in
rats. J Dent Res 79:1489-1495.
Kent JN, Block MS, Homsy CA, Prewitt JM 3rd, Reid R (1986). Experience
with polymer glenoid fossa prosthesis for partial or total
temporomandibular joint reconstruction. J Oral Maxillofac Surg44:520-533.
Kircos LT, Ortendahl DA, Mark AS, Arakava M (1987). Magnetic
resonance imaging of the TMJ disc in asymptomatic volunteers. J OralMaxillofac Surg 45:852-854.
306 Tanaka et al. J Dent Res 87(4) 2008
Koolstra JH, van Eijden TMGJ, Weijs WA, Naeije M (1988). A three-
dimensional mathematical model of the human masticatory system
predicting maximum possible bite forces. J Biomech 21:563-576.
Korioth TW, Romilly DP, Hannam AG (1992). Three-dimensional finite
element analysis of the dentate human mandible. Am J Phys Anthropol88:69-96.
Kubota E, Kubota T, Matsumoto J, Shibata T, Murakami K-I (1998).
Synovial fluid cytokines and proteinases as markers of
temporomandibular joint disease. J Oral Maxillofac Surg 56:192-198.
Kuttila M, Le Bell Y, Savolainen-Niemi E, Kuttila S, Alanen P (2002).
Efficiency of occlusal appliance therapy in secondary otalgia and
temporomandibular disorders. Acta Odontol Scand 60:248-254.
Laskin DM (1994). Etiology and pathogenesis of internal derangement of
the temporomandibular joint (current controversies in surgery for
internal derangements of the temporomandibular joint). OralMaxillofac Surg Clin NA 6:217-222.
Leonardi R, Lo Muzio L, Bernasconi G, Caltabiano C, Piacentini C,
Caltabiano M (2003). Expression of vascular endothelial growth factor
in human dysfunctional temporomandibular joint disc. Arch Oral Biol48:185-192.
Lohmander LS, Dalén N, Englund G, Hamalainen M, Jensen EM, Karlsson
K, et al. (1996). Intra-articular hyaluronan injections in the treatment of
osteoarthritis on the knee: a randomized, double blind, placebo
controlled trial. Hyaluronan Multicentre Trial Group. Ann Rheum Dis55:424-431.
MacIntosh RB (2000). The use of autogenous tissue in temporomandibular
joint reconstruction. J Oral Maxillofac Surg 58:63-69.
McBride KL (1994). Total temporomandibular joint reconstruction. In:
Controversies in oral and maxillofacial surgery. Worthington P, Evans
JR, editors. Philadelphia: W.B. Saunders Co., pp. 381-396.
McNeil JD, Wiebkin OW, Betts WH, Cleland LG (1985). Depolymerisation
products of hyaluronic acid after exposure to oxygen-derived free
radicals. Ann Rheum Dis 44:780-789.
Mejersjö C, Hollender L (1984). Radiography of the temporomandibular
joint in female patients with TMJ pain or dysfunction. Acta RadiolDiagn 25:169-176.
Mercuri LG (1998). Alloplastic temporomandibular reconstruction. OralSurg Oral Med Oral Pathol Oral Radiol Endod 85:631-637.
Mercuri LG (1999). Subjective and objective outcomes in patients with a
custom-fitted alloplastic temporomandibular joint prosthesis. J OralMaxillofac Surg 57:1427-1430.
Mercuri LG (2000). The TMJ Concepts patient fitted total temporo -
mandibular joint reconstruction prosthesis. Oral Maxillofac Surg ClinNorth Am 12:73-91.
Mercuri LG (2006). Surgical management of TMJ arthritis. In: TMDs, an
evidence-based approach to diagnosis and treatment. Laskin DM,
Greene CS, Hylander WL, editors. Chicago: Quintessence, pp. 455-468.
Mercuri LG (2007). A rationale for total alloplastic temporomandibular joint
reconstruction in the management of idiopathic/progressive condylar
resorption. J Oral Maxillofac Surg 65:1600-1609; erratum in J OralMaxillofac Surg 66:208, 2008.
Mercuri LG, Giobbe-Hurder A (2004). Long-term outcomes after total
alloplastic temporomandibular joint reconstruction following exposure
to failed materials. J Oral Maxillofac Surg 62:1088-1096.
Mercuri LG, Wolford LM, Sanders B, White RD, Giobbie-Hurder A (2002).
Long-term follow-up of the CAD/CAM patient fitted total
temporomandibular joint reconstruction system. J Oral Maxillofac Surg60:1440-1448.
Merrill RG (1986). Historical perspectives and comparisons of TMJ surgery
for internal disk derangements and arthropathy. Cranio 4:74-85.
Milam SB, Zardeneta G, Schmitz JP (1998). Oxidative stress and
degenerative temporomandibular joint disease: a proposed hypothesis. JOral Maxillofac Surg 56:214-223.
Moriconi ES, Popowich LD, Guernsey LH (1986). Alloplastic
reconstruction of the temporomandibular joint. Dent Clin North Am30:307-325.
Murray GM, Phanachet I, Uchida S, Whittle T (2001). The role of the
human lateral pterygoid muscle in the control of horizontal jaw
movements. J Orofac Pain 15:279-305.
Nickel JC, Iwasaki LR, Feely DE, Stormberg KD, Beatty MW (2001). The
effect of disc thickness and trauma on disc surface friction in the
porcine temporomandibular joint. Arch Oral Biol 46:155-162.
Nickel JC, Iwasaki LR, Beatty MW, Moss MA, Marx DB (2006). Static and
dynamic loading effects on temporomandibular joint disc tractional
forces. J Dent Res 85:809-813.
Nicolakis P, Burak EC, Kollmitzer J, Kopf A, Piehslinger E, Wiesinger GF,
et al. (2001). An investigation of the effectiveness of exercise and
manual therapy in treating symptoms of TMJ osteoarthritis. Cranio19:26-32.
Niida S, Kaku M, Amano H, Yoshida H, Kataoka H, Nishikawa S, et al.(1999). Vascular endothelial growth factor can substitute for
macrophage colony-stimulating factor in the support of osteoclastic
bone resorption. J Exp Med 190:293-298.
Nitzan DW (2001). The process of lubrication impairment and its
involvement in temporomandibular joint disc displacement: a
theoretical concept. J Oral Maxillofac Surg 59:36-45.
Nitzan DW, Price A (2001). The use of arthrocentesis for the treatment of
osteoarthritic temporomandibular joints. J Oral Maxillofac Surg59:1154-1159.
Ohno-Nakahara M, Honda K, Tanimoto K, Tanaka N, Doi T, Suzuki A, etal. (2004). Induction of CD44 and MMP expression by hyaluronidase
treatment of articular chondrocytes. J Biochem 135:567-575.
Poshusta AK, Anseth KS (2001). Photopolymerized biomaterials for
application in the temporomandibular joint. Cells Tissues Organs169:272-278.
Pufe T, Harde V, Peterson W, Goldring MB, Tillmann B, Mentlein R
(2004). Vascular endothelial growth factor (VEGF) induces matrix
metalloproteinase expression in immortalized chondrocytes. J Pathol202:367-374.
Rohlin M, Westesson PL, Eriksson L (1985). The correlation of
temporomandibular joint sounds with joint morphology in fifty-five
autopsy specimens. J Oral Maxillofac Surg 43:194-200.
Sato J, Segami N, Yoshitake Y, Nishikawa K (2003). Correlations of the
expression of fibroblast growth factor-2, vascular endothelial growth
factor, and their receptors with angiogenesis in synovial tissues from
patients with internal derangement of the temporomandibular joint. JDent Res 82:272-277.
Sato J, Segami N, Kaneyama K, Mashiyama Y, Fujimura K, Yoshitake Y
(2005). Vascular endothelial growth factor concentrations in synovial
fluids of patients with symptomatic internal derangement of the
temporomandibular joint. J Oral Pathol Med 34:170-177.
Schek RM, Taboas JM, Segvich SJ, Hollister SJ, Krebsbach PH (2004).
Engineered osteochondral grafts using biphasic composite solid free-
form fabricated scaffolds. Tissue Eng 10:1376-1385.
Schek RM, Taboas JM, Hollister SJ, Krebsbach PH (2005). Tissue
engineering osteochondral implants for temporomandibular joint repair.
Orthod Craniofac Res 8:313-319.
Sharawy M, Ali AM, Choi WS, Larke V (2000). Ultrastructural
characterization of the rabbit mandibular condyle following
experimental induction of anterior disk displacement. Cells TissuesOrgans 167:38-48.
Sharawy M, Ali AM, Choi WS (2003). Experimental induction of anterior
disk displacement of the rabbit craniomandibular joint: an immuno-
electron microscopic study of collagen and proteoglycan occurrence in
the condylar cartilage. J Oral Pathol Med 32:176-184.
Shi ZD, Yang F, He ZX, Shi B, Yang MZ (2002). Comparative study on
effects of sodium hyaluronate and prednisolone injections on
experimental temporomandibular joint osteoarthritis of rabbits. ChineseJ Repair Reconstr Surg 16:5-10.
Smartt JM Jr, Low DW, Bartlett SP (2005). The pediatric mandible: I. A
primer on growth and development. Plast Reconstr Surg 116:14e-23e.
Smith DM, McLachlan KR, McCall WD (1986). A numerical model of
temporomandibular joint loading. J Dent Res 65:1046-1052.
Srouji S, Rachmiel A, Blumenfeld I, Livne E (2005). Mandibular defect
repair by TGF-beta and IGF-1 released from a biodegradable
osteoconductive hydrogel. J Craniomaxillofac Surg 33:79-84.
Stegenga B, DeBont LGM, Boering G (1989). Osteoarthrosis as the cause of
craniomandibular pain and dysfunction: a unifying concept. J OralMaxillofac Surg 47:249-256.
Steinbrocker O, Traeger CH, Batterman RC (1949). Therapeutic criteria in
rheumatoid arthritis. J Am Med Assoc 140:659-662.
Takahashi T, Homma H, Nagai H, Seki H, Kondoh T, Yamazaki Y, et al.
J Dent Res 87(4) 2008 Degenerative Disorders of the TMJ 307
(2003). Specific expression of inducible nitric oxide synthase in the
synovium of the diseased temporomandibular joint. Oral Surg OralMed Oral Pathol Oral Radiol Endod 95:174-181.
Takano Y, Moriwake Y, Tohno Y, Minami T, Tohno S, Utsumi M, et al.(1999). Age-related changes of elements in the human articular disk of
the temporomandibular joint. Biol Trace Elem Res 67:269-276.
Tanaka E, Sasaki A, Tahmina K, Yamaguchi K, Mori Y, Tanne K (2001).
Mechan ical properties of human articular disk and its influence on
TMJ loading studied with the finite element method. J Oral Rehabil28:273-279.
Tanaka E, Hanaoka K, van Eijden T, Tanaka M, Watanabe M, Nishi M, etal. (2003). Dynamic shear properties of the temporomandibular joint
disc. J Dent Res 82:228-231.
Tanaka E, Kawai N, Tanaka M, Todoh M, van Eijden T, Hanaoka K, et al.(2004). The frictional coefficient of the temporomandibular joint and its
dependency on the magnitude and duration of joint loading. J Dent Res83:404-407.
Tanaka E, Aoyama J, Miyauchi M, Takata T, Hanaoka K, Iwabe T, et al.(2005a). Vascular endothelial growth factor plays an important
autocrine/paracrine role in the progression of osteoarthritis. HistochemCell Biol 123:275-281.
Tanaka E, Iwabe T, Dalla-Bona DA, Kawai N, van Eijden T, Tanaka M, etal. (2005b). The effect of experimental cartilage damage and
impairment and restoration of synovial lubrication on friction in the
temporomandibular joint. J Orofac Pain 19:331-336.
Tanimoto K, Suzuki A, Ohno S, Honda K, Tanaka N, Doi T, et al. (2004).
Effects of TGF-beta on hyaluronan anabolism in fibroblasts derived
from the synovial membrane of the rabbit temporomandibular joint. JDent Res 83:40-44.
Toller P (1977). Use and misuse of intra-articular corticosteroids in the
treatment of TMJ pain. Proc R Soc Med 70:461-463.
Ueki K, Takazakura D, Marukawa K, Shimada M, Nakagawa K, Takatsuka
S, et al. (2003). The use of polylactic acid/polyglycolic acid copolymer
and gelatin sponge complex containing human recombinant bone
morphogenetic protein-2 following condylectomy in rabbits. JCraniomaxillofac Surg 31:107-114.
van Roon JAG, van Roy JLAM, Gmelig-Meyling FHJ, Lafeber FPJG,
Bijlsma JWJ (1996). Prevention and reversal of cartilage degradation in
rheumatoid arthritis by interleukin-10 and interleukin-4. ArthritisRheum 39:829-835.
Van Strijen PJ, Breuning KH, Becking AG, Tuinzing DB (2001). Condylar
resorption following distraction osteogenesis: a case report. J OralMaxillofac Surg 59:1104-1107.
Vuorio E, Einola S, Hakkarainen S, Penttinen R (1982). Synthesis of
underpolymerised hyaluronic acid by fibroblasts cultured from
rheumatoid and non-rheumatoid synovitis. Rheumatol Int 2:97-102.
Weng Y, Cao Y, Silva CA, Vacanti MP, Vacanti CA (2001). Tissue-
engineered composites of bone and cartilage for mandible condylar
reconstruction. J Oral Maxillofac Surg 59:185-190.
Westesson PL, Eriksson L, Kurita K (1989). Reliability of a negative
clinical temporomandibular joint examination: prevalence of disk
displacement in asymptomatic temporomandibular joints. Oral SurgOral Med Oral Pathol 68:551-554.
Wilkes CH (1989). Internal derangements of the temporomandibular joint.
Path ological variations. Arch Otolaryngol Head Neck Surg 115:469-477.
Williams JM, Adewunmi A, Schek RM, Flanagan CL, Krebsbach PH,
Feinberg SE, et al. (2005). Bone tissue engineering using
polycaprolactone scaffolds fabricated via selective laser sintering.
Biomaterials 26:4817-4827.
Wilson GH (1920). The anatomy and physics of the temporomandibular
joint. J Nat Dent Assoc 7:414-420.
Wolford LM, Cottrell DA, Henry CH (1994). Temporomandibular joint
reconstruction of the complex patient with the Techmedica custom-
made total joint prosthesis. J Oral Maxillofac Surg 52:2-10.
Wolford LM, Reich-Fischel O, Mehra P (2003). Changes in
temporomandibular joint dysfunction after orthognathic surgery. J OralMaxillofac Surg 61:655-660.
Wong M, Siegrist M, Goodwin K (2003). Cyclic tensile strain and cyclic
hydrostatic pressure differentially regulate expression of hypertrophic
markers in primary chondrocytes. Bone 33:685-693.
Zarb GA, Carlsson GE (1999). Temporomandibular disorders: osteoarthritis.
J Orofac Pain 13:295-306.