Journal of Dental Research

http://jdr.sagepub.com/

Remodeling the Dentofacial Skeleton: The Biological Basis of Orthodontics and Dentofacial
Orthopedics
M.C. Meikle
J DENT RES 2007 86: 12
DOI: 10.1177/154405910708600103

The online version of this article can be found at:

http://jdr.sagepub.com/content/86/1/12

Published by:

http://www.sagepublications.com

On behalf of:
International and American Associations for Dental Research

Additional services and information for Journal of Dental Research can be found at:

Email Alerts: http://jdr.sagepub.com/cgi/alerts

Subscriptions: http://jdr.sagepub.com/subscriptions

Reprints: http://www.sagepub.com/journalsReprints.nav

Permissions: http://www.sagepub.com/journalsPermissions.nav

>> Version of Record - Jan 1, 2007

What is This?

Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.

International and American Associations for Dental Research

 CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE
Remodeling the Dentofacial Skeleton: The Biological Basis
of Orthodontics and Dentofacial Orthopedics
M.C. Meikle
Department of Oral Sciences, Faculty of Dentistry, University of
Otago, PO Box 647, Dunedin, New Zealand;
murray.meikle@dent.otago.ac.nz
J Dent Res 86(1):12-24, 2007
ABSTRACT
Orthodontic tooth movement is dependent upon the
remodeling of the periodontal ligament and alveolar bone
by mechanical means. Facial sutures are also fibrous
articulations, and by remodeling these joints, one can alter
the positional relationships of the bones of the facial
skeleton. As might be expected from the structure and
mobility of the temporomandibular joint (TMJ), this
articulation is more resistant to mechanical deformation,
and whether functional mandibular displacement can alter
the growth of the condyle remains controversial. Clinical
investigations of the effects of the Andresen activator and
its variants on dentofacial growth suggest that the changes
are essentially dento-alveolar. However, with the
popularity of active functional appliances, such as the
Herbst and twin-block based on 'jumping the bite',
attention has focused on how they achieve dentofacial
change. Animal experimentation enables informed
decisions to be made regarding the effects of orthodontic
treatment on the facial skeleton at the tissue, cellular, and
molecular levels. Both rat and monkey models have been
widely used, and the following conclusions can be drawn
from such experimentation: (1) Facial sutures readily
respond to changes in their mechanical environment; (2)
anterior mandibular displacement in rat models does not
increase the mitotic activity of cells within the condyle to
be of clinical significance, and (3) mandibular
displacement in non-human primates initiates remodeling
activity within the TMJ and can alter condylar growth
direction. This last conclusion may have clinical utility,
particularly in an actively growing child.
KEY WORDS: facial sutures, temporomandibular joint,
condylar cartilage, articular remodeling, functional
appliances.
Received January 30, 2006; Accepted April 19, 2006
12 Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
INTRODUCTION
Twhich
he bones and articulations of the craniofacial skeleton grow and
function in an environment of mechanical forces. These forces—
include muscle activity, mastication, the expansile growth of
the brain, gravity, and man-made orthodontic appliances—influence
the shape and relative position of each bone in the complex, through
the process of biological adaptation termed 'remodeling' (Moffett,
1971, 1973). With the exception of the cranial base synchondroses
and the temporomandibular joints (TMJ), all the articulations
between the bones of the skull (and teeth) are fibrous joints. Such
articulations are responsive to alterations in mechanical loading;
indeed, orthodontic treatment is dependent upon the ease with
which the periodontal ligament (PDL) and supporting alveolar bone
can be remodeled by mechanical means. (For a recent review of the
tissue, cellular, and molecular mechanisms regulating orthodontic
tooth movement, see Meikle, 2006.)
Numerous well-documented animal studies have also showed
that craniofacial sutures, as well as the TMJs, can be remodeled by
externally applied mechanical force. The aim of this review is to
discuss the significance of these findings and the extent to which they
can be utilized clinically in the correction of skeletal malocclusion.
An understanding of the cellular and molecular mechanisms that
enable bones and other connective tissues of the dentofacial skeleton
to adapt to changes in their mechanical environment is fundamental
to the practice of orthodontics and dentofacial orthopedics, based on
sound biological and bioengineering principles.
FACIAL SUTURES
Sutures are found only in the skull and have two main functions: (1)
as a site of active bone growth; and (2) to provide a firm union
between adjacent bones, while at the same time permitting slight
movement in response to mechanical stress. The fibrous and cellular
organization of sutures is not uniform and will vary, depending on
site and age, and within the same suture over time (Persson, 1973).
As a generalization, however, each is formed by a continuation of the
fibrous and cellular periosteum around the margins of adjacent bones,
united by a central intermediate layer of fibrous tissue and blood
vessels (Pritchard et al., 1956). The cellular layer provides the cells
required for osteogenesis at the sutural margins; the intermediate
layer allows for continued growth of the sutural connective tissue and
permits small adjustments of the bones relative to each other.
Morphology of Facial Sutures
Suture morphology is determined by the site and mechanical stresses
to which they are exposed. In general, midline sutures are described
as butt-end, while others are of the overlapping beveled type
(Kokich, 1976). During the growth period, sutures have a
predominantly linear configuration, but with age, more complex
beveled and interdigitating sutures develop through functional
modification. Where strong bonds are required, interdigitating
sutures develop to enhance surface contact and resist separation. All
sutures eventually undergo various degrees of fusion by osseous
union or synostosis. Sutural synostosis begins at different ages in the
J Dent Res 86(1) 2007 Remodeling the Dentofacial Skeleton 13

Table 1. Time of Closure of Some Craniofacial Sutures in Humans

Closure Closure
Begins Begins
Cranial Suture (yrs) Facial Suture (yrs)

Interfrontal (metopic) 2 Intermaxillary (palatal) 20-25

Interparietal (sagittal) 22 Frontomaxillary 68-71
Frontoparietal (coronal) 24 Frontonasal 68
Occipitoparietal (lambdoid) 26 Nasomaxillary 68
Frontozygomatic 72
Temporoparietal (squamosal) 35-39 Zygomaticomaxillary 70-72

Data derived from Todd and Lyon (1924, 1925); Kokich (1976, 1986);
Persson and Thilander (1977).

various sutures of the skull and proceeds at the endocranial

slightly earlier than at the ectocranial surface (Todd and Lyon,
1924, 1925). In contrast to cranial sutures, facial sutures can
remain patent quite late into adult life (Table 1).
Patency of Facial Sutures
There are two plausible explanations why cranial and facial
sutures differ in their time of closure, one biochemical, the
other mechanical. Much of what is known about suture biology
at the molecular level comes from human studies of premature
fusion. Despite their widely differing phenotypes, accelerated
suture closure in several autosomal-dominant cranio-
synostoses—such as Crouzon, Apert, Jackson-Weiss, and
Pfeiffer syndromes—has been shown to be due to gain-of-
function mutations in the FGFR-2 (fibroblast growth factor
receptor-2) gene. The extent to which facial sutures are affected
is less clear, although many of these syndromes are
characterized by maxillary hypoplasia. In addition to causing Figure 1. Dorsal view of a miniature pig skull (Sus scrofa) showing
achondroplasia, mutations of the FGFR-3 gene are also average peak strains during mastication. Solid arrows directed toward
sutures indicate compressive strains; open arrows indicate tensile
responsible for Crouzon syndrome with acanthosis nigricans strains. The sutures of the braincase are predominantly tensed, while
and Muenke-type craniosynostosis. (For further discussion and those of the snout are compressed. 500 ␮␧ = 500 microstrains.
references, see Meikle, 2002.) (Redrawn from Rafferty and Herring, 1999)
The evidence from animal models suggests specific roles
for growth factors as well as the BMP (bone morphogenetic
protein), Shh (sonic hedgehog), and FGF signaling pathways.
Nevertheless, where each of these factors and their target genes snout (internasal and nasofrontal), mainly compressive (Fig. 1).
fits into a complex morphogenetic cascade remains poorly Nevertheless, sutural strain is a very dynamic parameter, and
understood. Insulin-like growth factors (IGFs; Bradley et al., many sutures show temporal and regional variations in strain
1999), transforming growth factor-␤ (TGF-␤) isoforms polarity; some sutures even show a small compressive strain
(Opperman et al., 1997, 1998; Roth et al., 1997)), and FGF-2, before or after the tensile peak (Herring and Mucci, 1991).
FGFR-1, and FGFR-2 (Mehrara et al., 1998) have all been Variations in the strains to which facial sutures are exposed
localized in the cells and matrix of the dura mater, osteoblasts, (tensile, compressive, shear) by masticatory muscle function
and sutures in rats. Their expression is increased during will be reflected in their morphology.
synostosis, suggesting a paracrine signaling role for these Sutures that are exposed to a predominantly compressive
factors; since facial sutures differ from cranial sutures in the strain will continue to grow, however, and it seems likely that,
absence of dura, this may partly explain why facial sutures in sutures with complex interdigitations, the oblique
remain patent longer. arrangement of the fibers of the sutural ligament may convert
The other reason is related to the intermittent mechanical what was initially a compressive load into a tensile strain
loading of the circum-maxillary suture system that occurs (Herring and Rafferty, 2000). For this reason, trying to
during mastication (Behrents et al., 1978; Wagemans et al., establish the loading pattern of a suture from the histological
1988; Jaslow, 1990; Herring and Mucci, 1991). Animal models appearance in animal models can be difficult and prone to
indicate that the various craniofacial sutures are under distinct subjective interpretation.
and dissimilar strain regimes (Rafferty and Herring, 1999).
Experiments conducted on the miniature pig have showed that, REMODELING THE MAXILLA
for the sutures of the calvaria (interparietal, interfrontal, IN NON-HUMAN PRIMATES
coronal), peak strains are mainly tensile, and for those of the The first evidence that changes in maxillary position could be
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.

International and American Associations for Dental Research

14
Figure 2. Structure of facial sutures. (A) Photomicrograph of the
zygomatico-frontal suture of an adult Macaca mulatta monkey.
Hematoxylin and eosin stain, original magnification 75x. Numerous
reversal lines (arrowheads) are indicative of past remodeling activity.
The absence of cellular activity within the sutural ligament is indicative of
a quiescent suture. (B) Section through the frontomaxillary suture of an
adolescent Macaca mulatta monkey after application of a posteriorly
directed force to the maxillary teeth. Mallory stain. Original
magnification, 120x. This active suture shows a complex pattern of
remodelling activity, with highly cellular new bone (blue) deposited on
old bone (red). Sutures consist of type I collagen and non-collagenous
glycoproteins uniting adjacent bone surfaces; also visible (arrowheads)
is a central zone of fibroblastic cells. Scale bars not available.
achieved by the application of load came from cephalometric
studies of individuals who had worn extra-oral traction or
headgear (HG) during orthodontic treatment (Moore, 1959;
Ricketts, 1960). These landmark investigations provided the
impetus for research into the effects of externally induced
mechanical forces on the craniofacial skeleton of the macaque
monkey at the University of Washington (Moffett, 1971), and
other centers with primate facilities.
In experiments with both adolescent and adult monkeys,
forces have been applied to the dentomaxillary skeleton by a
wide variety of mechanical devices. Most of the early studies
involved the use of HG to apply a posterior force, and a
combination of metallic implants, radiography, in vivo bone
markers, and histology to analyze the outcome (Sproule, 1968;
Fredrick, 1969; Cutler et al., 1972; Droschl, 1973; Elder and
Tuenge, 1974; Meldrum, 1975; Triftshauser and Walters, 1976).
All showed that, by using mechanical forces to create controlled
remodeling of facial sutures (Fig. 2), it is possible to alter the
positional relationships of the bones of the facial skeleton. In
growing animals, however, this effect is transitory; after the
termination of HG treatment, the maxilla resumes its normal
forward growth pattern (Tuenge and Elder, 1974). In some cases,
the remodeling response may even extend to the lower jaw. An
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
Meikle J Dent Res 86(1) 2007
unexpected finding in a study of cervical traction in adult
monkeys was the presence of resorption craters on the articular
surface of the condylar head, suggesting distal displacement of
the mandible by occlusal forces (Brandt et al., 1979).
The maxilla can also be distracted anteriorly by extra-oral
forward traction applied to the dentition (Dellinger, 1973;
Kambara, 1977; Nanda, 1978; Jackson et al., 1979). However,
the drawback of trying to remodel facial sutures by applying
forces directly to the teeth is their tendency to move, thereby
reducing the orthopedic effect. Skeletal anchorage has therefore
been used to exert force directly to the bone via endosseous
implants (Turley et al., 1980; Smalley et al., 1988). Smalley et
al. applied forward traction to osseointegrated titanium
implants inserted into the maxillae of 4 pigtail monkeys.
Cephalometric and dry skull analyses showed that the amount
of skeletal protraction was significantly greater when compared
with that generated by conventional tooth-borne appliances.
Given the importance of these findings, it is surprising that
skeletal anchorage has only recently entered mainstream
clinical orthodontic practice.
CLINICAL REMODELING OF THE MAXILLA
While numerous primate studies have shown that mechanical
forces of appropriate strength and duration can remodel facial
sutures, the extent to which these changes can be utilized
clinically continues to be the subject of debate.
Remodeling the Maxilla with Headgear
Several investigations have shown that HG treatment can alter
the positional relationship of the maxilla to the cranial base
(Moore, 1959; Ricketts, 1960; Poulton, 1967; Watson, 1972;
Weislander, 1974, 1975), but others have been unable to detect
significant orthopedic change, the main effect being tooth
movement (Badell, 1976; Bernstein et al., 1977; Baumrind et
al., 1979). The reasons for this have been discussed previously
(Meikle, 1980), but the evidence suggests that optimal
conditions for achieving orthopedic change in the maxilla are
fulfilled when (1) the force is of sufficient magnitude (1000 gm
per side) to be transmitted beyond the periodontal joints, and
(2) as many teeth as possible have been incorporated into the
appliance. The direction in which the force is applied (cervical
vs. occipital) will also influence the outcome, depending upon
whether the sutures are exposed to a predominantly tensile or
compressive mechanical strain.
Prospective Studies of Headgear Treatment
The only published prospective randomized clinical trial (RCT)
of HG treatment, prior to the three RCTs of Class II treatment
funded by the National Institute of Dental Research in 1988,
was by Jakobsson (1967), a man clearly ahead of his time. In
Jakobsson's study, 60 children aged 8-9 yrs with a Class II
division 1 malocclusion were randomly assigned to either an
Andresen activator, HG, or control group. Both HG and
activator treatments were found to have had a distalizing effect
on the maxilla.
In the RCT undertaken at the University of North Carolina
(Tulloch et al., 1997a,b, 1998), 166 persons having mixed
dentitions with an overjet greater than 7 mm were randomly
assigned to early treatment with either a headgear or bionator,
or to control. There was considerable variation in the pattern of
change in all three groups, with the HG group showing
restricted forward movement of the maxilla averaging about 1
J Dent Res 86(1) 2007 Remodeling the Dentofacial Skeleton
mm. The University of Florida RCT involved 249 participants
aged 9-10 years who were randomly assigned to control,
bionator, or HG/biteplate treatments (Keeling et al., 1998).
Neither the HG/biteplate nor the bionator had a significant
effect on maxillary growth, although both appliances were
reported to enhance the growth of the mandible. In a study of
63 participants conducted at the University of Pennsylvania,
early treatment outcome with either a HG or Fränkel functional
regulator were compared (Ghafari et al., 1998). Both treatments
were found to be effective at reducing overjets, but the study
did not include a control group.
Rapid Maxillary Expansion
The most dramatic example of sutural remodeling is the result of
rapid maxillary expansion (RME), when a diastema is opened
between the central incisor teeth. Angell (1860), who introduced
the technique using a screw mechanism, claimed that the
apparatus produced a separation of the two halves of the maxilla.
In commenting on the article, the Editor of the Dental Cosmos,
while being unwilling to assert that such a thing was not utterly
impossible, found this exceedingly doubtful (the italics are the
Editor's). For the next 100 years, RME had a somewhat
checkered history, until Haas (1961, 1965) popularized the fixed
palatal expander in the 1960s, and showed that RME in
adolescents had a predictable outcome. For RME to be effective
as an orthopedic appliance, the magnitude of the applied force
must be of sufficient magnitude to be transmitted beyond the
periodontal joints; otherwise, the stresses will be absorbed within
the alveolar bone, resulting in tooth movement alone. Although
not usually recognized by orthodontists as such, rapid maxillary
expansion is an example of distraction osteogenesis.
It is a common belief that the mid-palatal suture fuses at
around the age of 15 yrs. However, there is some anatomical and
clinical evidence that this is not necessarily true. In a histological
study of 60 human autopsy specimens aged 0-18 yrs, Melsen
(1975) found that growth of the mid-palatal suture continued up
to the ages of 16 in girls and 18 in boys. Furthermore, Persson
and Thilander (1977) reported, in an older age group (15-35 yrs),
that although palatal sutures may show evidence of obliteration
during the juvenile period, a marked degree of closure was rarely
found until the third decade, i.e., 20-30 yrs of age.
The key issue is not whether osseous union has begun, but
the overall percentage of the suture that has actually fused.
Persson and Thilander speculated that if osseous bridging of 5%
represented the upper limit for splitting the mid-palatal suture,
this would not be reached in most people before the age of 25
years. In a combined radiographic-histological investigation,
Wehrbein and Yildizhan (2001) concluded that if this were true,
RME would have been successful in nine of the 10 individuals
(aged 18-38 yrs) in their study sample. They also showed that a
radiologically invisible suture does not necessarily mean that the
suture is fused histologically. In any event, undue focus on the
palate rather obscures the fact that the greatest resistance to RME
comes not from the mid-palatal suture, but from the circum-
maxillary suture network (Isaacson and Ingram, 1964; Wertz,
1970) that attaches the maxilla to the rest of the skull (Fig. 3).
Clinical studies of RME undertaken in adults (Alpern and
Yurosko, 1987; Capelozza et al., 1996; Handelman et al., 2000)
further support the histological evidence that palatal expansion
without surgery is possible in young adults well into their
twenties. Nevertheless, the technique remains controversial and
unacceptable to many clinicians. It may not always have the
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
15
Figure 3. Undue emphasis on the midpalatal suture (11) rather obscures
the fact that, for rapid maxillary expansion to be successful, several
facial sutures, particularly the zygomatico-maxillary (9) and the
zygomatico-frontal (4,5), will need to be extensively remodeled and then
retained to eliminate any residual strain. (From McMinn et al. (1981), A
Colour Atlas of Head and Neck Anatomy, Wolfe Medical Publishers Ltd.
Reproduced with the kind permission of Mr. Ralph Hutchings.)
desired outcome, but, in many cases, whether for financial
reasons or fear of surgery, it may be the only alternative.
Maxillary Protraction
Maxillary protraction in the treatment of Class III malocclusion
has increased in popularity in recent years, due to the work of
Delaire with the orthopedic face mask (Delaire, 1971; Delaire
et al., 1972), and the animal experimentation discussed earlier
showing that the maxilla can be distracted (Dellinger, 1973;
Kambara, 1977; Nanda, 1978; Jackson et al., 1979).
Nevertheless, the degree to which maxillary skeletal change
can be achieved clinically is age- and technique-dependent.
Several studies have reported the skeletal and dental effects
of maxillary protraction in the correction of skeletal Class III
malocclusion, both with RME (Ngan et al., 1996, 1998; Kapust
et al., 1998; Franchi et al., 2004) and without RME (Wisth et
al., 1987; Takada et al., 1993). Together with the findings of a
meta-analysis (Jäger et al., 2001), these studies showed that
maxillary protraction is more effective if (1) undertaken in the
late deciduous or early mixed dentition, and (2) combined with
RME. Given that the aim of RME is to loosen the articulations
of the maxillary complex from the rest of the skull, this is not
surprising. The next logical step in the evolution of maxillary
distraction techniques is to combine RME with the use of
osseous mini-screws to provide forward distraction directly to
the bones. Not only will this avoid unwanted tooth movement,
but it will also enable the method to be effective in a much
older age group than at present.
EXPERIMENTAL REMODELING OF THE TMJ
The major aim of dentofacial orthopedic treatment in Class II
individuals with mandibular retrognathia (approximately 70%)
is to enhance or optimize the growth of the condyle by
16
Figure 4. Autoradiograph of a coronal section through the squamo-
mandibular joint of a rat, 24 hrs after an intraperitional injection of 3H-
thymidine to label cells synthesizing DNA. Most of the labeled cells are
located within the proliferative zone. It is the mesenchymal stem cells of
the PZ that differentiate into the chondroblasts of the cartilage layer
under the influence of function. Counting both labeled and unlabeled
cells in a 'representative' field to obtain a labeling index is a laborious
procedure, and, in young animals, it is also sometimes difficult to
distinguish the boundaries between different cellular layers. SJS,
superior joint space; D, interarticular disc; AZ, articular zone; PZ,
proliferative zone; CC condylar cartilage. Hematoxylin stain. Original
magnification, 350x. Scale bar not available.
functional anterior displacement of the mandible. The extent to
which this can be achieved, however, and whether it has any
clinical significance are topics of long-standing controversy.
Both rat and monkey models have been used to study TMJ
adaptation to protrusive function, and although the use of non-
human primates has declined, rat models continue to be widely
used.
As might be deduced from its structure and function, the
TMJ is morphologically adapted to resist the effects of
mechanical loading, and therefore is more difficult to remodel
than fibrous joints. This is due to the physical properties of the
cartilaginous matrix, the function of which is to protect the
subchondral bone from resorptive remodeling.
Functional Mandibular Protrusion in Rats
Experiments conducted by Petrovic and his co-workers at the
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
Meikle J Dent Res 86(1) 2007
University of Strasbourg have suggested that anterior
displacement of the mandible in growing rats can bring about
additional growth of condylar cartilage (Fig. 4), and hence the
growth of the mandible, by stimulating the cells of the
proliferative zone (PZ) to undergo mitosis (Charlier et al., 1969;
Petrovic et al., 1975; Petrovic and Stutzmann, 1977). Attempts
to reproduce these results, however, using biochemical,
histomorphometric, and autoradiographic methods, have been
unsuccessful (Tonge et al., 1982; Degroote, 1984; Ghafari and
Degroote, 1986; Tewson et al., 1988).
The reasons would seem to be a question of experimental
design and methodology. Histomorphometry is not an exact
science, and it helps to have experience with the technique to
fully understand the problems involved. These include the
following:
(1) Since it is impracticable to carry out a quantitative
analysis of the hundreds of sections cut from each condyle, it is
customary to select 4-5 fields in sections considered to be
'representative' for measurement purposes. This introduces an
element of subjective bias in the choice of experimental and
control sections.
(2) Another source of subjective bias is not counting the
number of 3H-thymidine-labeled cells (Fig. 4) in histological
sections 'blind', which makes any attempt at quantitation
potentially unsafe.
(3) The data are not always normalized. In other words, no
attempt has been made to relate the number of labeled cells to
the total number in a representative field, to establish a labeling
index. This is a fundamental principle of quantitation to
compensate for the variation inherent in all biological systems,
regardless of whether one is using biochemical or histological
techniques. Not all condyles, even in the rat, are the same size.
It has also been suggested that the discrepancies reported in
the literature could be due to differences in appliance
construction and such factors as the degree of opening,
continuous vs. intermittent displacement, and the extent to
which a definite forward shift of the mandible might be
achieved (Degroote, 1984; Ghafari and Degroote, 1986;
Tsolakis and Spyropoulos, 1997; Tsolakis et al., 1997). To
address this problem, Tsolakis et al. (1997) designed a new
device to produce a controlled, stable, and reproducible anterior
advancement of the mandible in rats by rubber elastics rather
than by functional displacement. Following the application of a
force of 25 gm for 12 hrs/day for 30 days, they found that
growth of the lower jaw was affected to some extent. Although
linear measurements indicated that mandibles in the
experimental group were longer than in the controls, they were
unable to conclude if this was due to an increase in the growth
of condylar cartilage.
Alterations in Gene Expression following
Protrusive Function in Rats
Whether functional appliance therapy can accelerate or enhance
the growth of the condyle is a question that has been revived
recently by Rabie and colleagues, at the University of Hong
Kong, who have applied molecular methods to the problem
(Rabie and Hägg, 2002; Rabie et al., 2003, 2004; Tang et al.,
2004). They have showed, in a rat model, that the transcription
factor Sox-9 and its target gene type II collagen are up-
regulated in the glenoid fossa following forward mandibular
positioning. Over an experimental period of 17 days, this
reached a maximum on day 3 but declined thereafter (Rabie et
J Dent Res 86(1) 2007 Remodeling the Dentofacial Skeleton
al., 2003). Mandibular advancement also triggered an increase
in the expression of the cell-cell signaling molecule Indian
hedgehog (Ihh) in the cells of the PZ and adjacent
chondroblasts (Tang et al., 2004). This coincided with an
increase in cell proliferation within the PZ. Both these
increases proved to be transient, however, reaching a peak after
7 days and returning to control levels by day 14.
Rabie et al. have interpreted these findings as proof that
functional appliances enhance condylar growth by stimulating
the differentiation of PZ cells into chondroblasts. Elegant
though these experiments may be, the temporary nature of the
reported changes does present a problem. The responses of
cells and tissues to mechanically induced strain are well-
established (for reviews, see Sandy et al., 1993; Meikle, 2006),
so it is not surprising to find that mechanically deformed cells
in the craniomandibular joint of the rat respond in a similar
manner, in terms of both changes in metabolic activity and
proliferation.
If one bears in mind the stimulatory effect of mechanical
stress on cell proliferation and DNA synthesis in other model
systems (Roberts and Jee, 1974; Meikle et al., 1979), the
transient burst in mitotic activity reported by Rabie et al. is
likely to result from the release of G2-blocked cells, allowing
them to undergo mitosis, as well as enabling G1-blocked cells
to enter the S phase. Ihh has also been shown to be an essential
component of mechanical force transduction in chondrocyte
proliferation (Wu et al., 2001), and to up-regulate the
expression of cyclin D1, a kinase required for the transition of
cells from G1 to the S phase of the cell cycle (Long et al.,
2001).
TMJ Remodeling in Non-human Primates
While the evidence from rat experimentation has been
controversial and subject to various interpretations, anterior
displacement of the mandible in the rhesus (Macaca mulatta)
monkey has been shown consistently to produce significant
morphological changes in the TMJ (Breitner, 1940, 1941;
Baume and Derichsweiler, 1961; Meikle, 1970; Stockli and
Willert, 1971; Adams et al., 1972).
Prior to Carl Breitner, investigations into the effects of
orthodontic treatment at the histological level in animal models
had been confined to changes in the PDL and alveolar bone.
Breitner was the first to look beyond the teeth and study the
tissue changes induced in the TMJ and other sites in the
mandible. His findings were first published in the German
literature during the 1930s and later in English in two classic
papers entitled "Bone changes resulting from experimental
orthodontic treatment" and "Further investigations of bone
changes..." (Breitner, 1940, 1941). These provided convincing
histological evidence that the influence of orthodontic
treatment in experimental animals was not limited to the teeth,
but extended to other parts of the mandible, causing remodeling
of the glenoid fossa and condyle. Breitner's papers have been
criticized for containing only one animal in each experimental
group, and little, if any, evidence of control material.
Nevertheless, despite the introduction of vital staining,
improved histological techniques, metallic bone implants, and
cephalometric radiography, subsequent investigations have
added comparatively little new information to Breitner's
original findings (Baume and Derichsweiler, 1961; Meikle,
1970; Stockli and Willert, 1971; Elgoyhen et al., 1972;
McNamara and Carlson, 1979; Woodside et al., 1987). A
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
17
Figure 5. Summary of remodeling changes in the surface contours of the
TMJ in the rhesus monkey following experimental anterior mandibular
displacement. Condylar growth appears to be directed more posteriorly,
and the shape of the condyle becomes less rounded; bone is also
deposited along the anterior surface of the post-glenoid tubercle.
Compensatory resorption occurs along the posterior surface of the post-
glenoid tubercle, and the insertion of the lateral pterygoid muscle into
the neck of the condyle.
summary of the adaptive changes in the TMJ of the rhesus
monkey following anterior mandibular displacement based on
the above studies is shown in Fig. 5.
Breitner believed that forward displacement of the
mandible could enhance condylar growth. This conclusion has
received support from McNamara and Bryan (1987), in a
cephalometric study of 23 juvenile Macaca mulatta monkeys.
After 144 weeks, the mandibles of treated animals (measured
by the linear distance infradentale-condylion) were 5-6 mm
longer than those of controls. Changes between the ramus and
body of the mandible were measured by the condylar-ramus-
occlusal (CRO) angle. In the control group, a closure in the
CRO angle (indicative of a forward growth rotation), averaging
8.8 degrees, occurred, while in the experimental group, the
CRO angle opened an average of 2.8 degrees.
As in humans (Björk, 1963; Björk and Skieller, 1972), the
condyle of monkeys undergoes an age-dependent change in
growth direction (McNamara and Graber, 1975; Luder, 1987).
One interpretation of the above findings is that anterior
displacement of the mandible remodeled the condylar head in a
more posterior direction, thereby neutralizing the forward
growth rotation observed in the control animals. This would
account for the increased length of the mandible in the
experimental group, and provides a valuable indicator as to
what might be happening clinically in growing children treated
with 'bite jumping' appliances.
IS CONDYLAR CARTILAGE UNIQUE?
Condylar cartilage is different in many ways from the articular
cartilage of long bones and has always held a certain 'mystique'
for the dental profession. However, a recent claim (Shen and
Darendeliler, 2005) that "...The most marked uniqueness of
condylar cartilage lies in its capability of adaptive remodeling
in response to external stimuli during or after natural growth" is
not one of them. Nor is the implication that the articular
surfaces of long bones are unchanging inert structures that do
not undergo endochondral ossification.
Remodeling Articular Cartilage
It has been known, at least since Alexander Ogston (Ogston,
18
1875, 1878), that articular cartilage has the ability to adapt to
alterations in the mechanical equilibrium of the skeleton, even
in the adult. Ogston believed that articular cartilage was
continually renewing itself from a central focus of growth. He
observed that growth occurred outward to compensate for wear
and tear at the surface, as well as inward, where it added to the
subchondral bone by endochondral osteogenesis.
This was confirmed experimentally 90 years later by the
autoradiographic studies of Mankin (1962), in which the
injection of 3 H-thymidine into the knee joint of rabbits
demonstrated the presence of a central zone of proliferative
cells in the femoral articular cartilage. Also, in a study of
articular remodeling in human synovial joints, Johnson (1959)
calculated that progressive remodeling added 3 mm of new
bone to the femoral head between the ages of 30 and 60 yrs.
The remodeling of articular cartilage is a process of biological
adaptation to changing environmental circumstances; there is a
large body of literature on the subject. (For a review of TMJ
remodeling, see Meikle, 1992, 2002.)
Condylar Cartilage is Derived from the Periosteum
Central to an understanding of condylar growth is the
question of why cartilage is present in a membrane bone in
the first place. Of the many examples of connective tissues
adapting to changing mechanical circumstances, the one
most relevant to the condyle is from the work of Murray
(1963), who described the development of adventitious
(secondary) cartilage in several articulations in the skull of
the embryonic chick. He found that secondary cartilage
always developed in membrane bones, but only at
articulations that were mobile, or where the musculature set
up conditions of strain. In subsequent experiments with
grafted and paralyzed embryos (Murray and Smiles, 1965),
cartilage did not form, and cells that normally formed
cartilage produced bone instead.
Studies in which mandibular condyles have been
transplanted into a non-functional environment have also
showed that the progenitor cells of the PZ differentiate into
osteoblasts, and not chondroblasts as in situ (Duterloo, 1967;
Meikle, 1973a,b). The cells are therefore multipotential and can
form either cartilage or bone, depending upon the
environmental circumstances. Simple microscopic observation
makes it obvious that the articular and proliferative zones of the
condyle are no more than a continuation of the fibrous and
cellular layers of the periosteum. The change from osteogenesis
to chondrogenesis has resulted from the evolutionary
development of an articular condylar process in the mandible
(dentary) of mammals and, as a consequence, the altered
functional demands of the periosteum covering the articular
joint surfaces (Meikle, 1973a,b).
Only by recognizing that condylar cartilage is a product of
the periosteum can the differences in cellular kinetics,
structure, and growth that exist between condylar and
epiphyseal cartilage be understood. These include failure of the
chondrocytes to divide (growth is appositional as in bone), and,
as a result, the cells are not organized into parallel columns. It
is also worth being aware that functional activity also plays a
role in the growth of epiphyseal cartilage. In the absence of
function, the growth plates of rat metacarpals fail to maintain a
satisfactory increase in transverse diameter, and the cells of the
perichondrium at the perimeter differentiate into osteoblasts,
not chondrocytes (Meikle, 1975).
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
Meikle J Dent Res 86(1) 2007
Genetic Control Mechanisms
Both condylar and epiphyseal cartilages share some of the
genetic control mechanisms regulating chondrogenesis. These
include expression of the transcription factor Sox-9, essential
for chondrocyte differentiation from mesenchymal stem cells,
and the negative feedback loop involving PTH-rP (parathyroid
hormone-related protein) and Ihh that controls the rate of
differentiation of chondrocytes in the growth plate (Lanske et
al., 1996; Vortkamp et al., 1996); PTH-rP is produced mainly
in the perichondrium, while the PTH/PTH-rP receptor is
expressed by pre-hypertrophic chondrocytes.
Also common is the degradation of the mineralized matrix
that occurs during endochondral ossification by a combination
of osteoclastic action and MMP (matrix metalloproteinases)
expression. All three major classes of MMPs and their inhibitor
TIMPs (tissue inhibitors of metalloproteinases) have been
identified in the chondrocytes and matrix of long bones (Brown
et al., 1989) and condylar cartilage (Breckon et al., 1994).
However, condylar cartilage is not affected by gain-of-function
mutations in the FGFR-3 gene (a negative regulator of
chondrocyte differentiation in bones of the primary
cartilaginous skeleton) that cause achondroplasia (Rousseau et
al., 1994; Shiang et al., 1994), as well as other skeletal
dysplasias, such as hypochondroplasia and thanatophoric
dysplasia in humans.
CLINICAL REMODELING OF THE TMJ
Prior to the introduction of cephalometric radiography, most
clinicians believed the teaching of the Angle school. With a
few notable exceptions (Case, 1911), inheritance was dismissed
as an etiological factor, and the occurrence of malocclusion in
parents and siblings was believed to occur because each had
experienced exactly the same environment (Dewey, 1914).
Malocclusion was considered to be the consequence of
inadequate bone growth and could be stimulated by alignment
of the teeth—a rather liberal interpretation of Wolff's law. In
other words, the stimulating effects of orthodontic tooth
movement and the establishment of normal occlusion, if started
young enough, would cause the jaws to grow. Malocclusion
could be treated without extracting teeth by growing bone.
The first cephalometric investigation of treatment outcome
(Brodie et al., 1938) effectively destroyed the myth that
orthodontic appliances could stimulate the growth of bone. This
was followed by the first longitudinal cephalometric
investigation of the early growth of the head (Brodie, 1941),
which suggested that the growth pattern of the individual was
established at an early age, and that, once attained, it did not
change. At the time, these publications had a profound impact
on orthodontic thought, giving rise to the linked concepts of (1)
the immutability of the facial or morphogenetic pattern of the
individual, and (2) the inability of the clinician to alter it in any
way. As a result, the old dogma was replaced by a new one.
Orthodontic treatment was limited to tooth movement alone.
Some clinicians still believe this.
Age-related Changes in the Human Condyle
Before we discuss the clinical evidence, it is worth considering
the age-related changes in the morphology of the human TMJ
and condyle that have been reported during the time that
growth modification is normally undertaken (Fig. 6). It also
helps put the findings of rat and primate experimentation into
J Dent Res 86(1) 2007 Remodeling the Dentofacial Skeleton 19

perspective. The material is of necessity limited and is likely to

remain so.
In a series of 51 human TMJs (24 male, 27 female)
collected at autopsy, Wright and Moffett (1974) observed the
following histological changes from birth to 21 yrs:
Throughout this period, the articular tissue (AZ) consists of
fibrous connective tissue with fibrocytes interspersed among
the collagen fibers, but no cartilage cells were observed at any
time. The proliferative layer (PZ) was approximately 6-10 cells
in width and continuous with the osteogenic layer of the
periosteum; however, no mitoses were observed. The cartilage
layer was 1.25-1.5 mm in thickness at birth and became
progressively thinner with growth, showing no recognizable
increase in thickness at adolescence that might be correlated
with increased pubertal growth.
During the mixed-dentition stage (6-12 yrs), while the Figure 6. Photomicrograph of a sagittal section through the head of the
condyle gradually increased all its dimensions, the cartilage mandibular condyle ( human, aged 10-12 yrs, the age when functional
remained uniformly thin (at 0.3-0.5 mm) and became limited to appliance treatment is usually started). There is some evidence of
the anterosuperior aspect of the condylar head, opposite the endochondral ossification, but chondrogenesis itself does not appear to
be particularly active. IJS, inferior joint space; AZ, articular zone; PZ,
posterior slope of the articular eminence. This is consistent proliferative zone; CC, condylar cartilage. Hematoxylin and eosin stain.
with the role of the cartilage in the protection of the Original magnification, 20x. Scale bar not available.
subchondral bone. At 16-17 yrs, the cartilage becomes thinner,
and a closing plate of bone coalesces below it. Human condylar
cartilage is a rather less impressive structure than it is in the
adolescent monkey or the 6-week-old rat. It is also worth poor research design; it also encourages post hoc deductions. In
bearing in mind that condylar cartilage is not the only site in the new era of evidence-based medicine, the prospective RCT
the condyle where osteogenesis is taking place during growth. is seen by many to be the 'gold standard' for analyzing
treatment outcome, and the only valid source of clinical data.
The Evidence of Retrospective Investigations
Europe has a tradition of dentofacial orthopedics, and most of The Evidence of Prospective Randomized Clinical Trials
the various appliance systems currently used in the treatment The effects of functional appliances of various designs on
method referred to as 'functional jaw orthopedics' originated in mandibular growth in each of the relevant RCTs published to
Europe. The skeletal and dental effects of several functional date are summarized in Table 2. These suggest that (1) small
appliances based on the
Norwegian system (Andresen Table 2. Randomized Clinical Trials of Class II Treatment: Effects on Mandibular Growth
and Häupl, 1942; Korkhaus,
1960; Fränkel, 1966; Marschner Study and Analysis Appliance Number Treated/Control Age Change (mm)a
and Harris, 1966; Demisch,
1972; McNamara et al., 1985), Jakobsson (1967) Andresen activator 17/19 8.5 (mean) NS
as well as more active devices Change in Pog
such as the Herbst and twin-
block (Pancherz, 1979; Nelson et al. (1993) Fränkel FFR 13/17 11.6 (mean) NS
Weislander, 1984; Hägg and Co-Pog Harvold activator 12/17
Pancherz, 1988; DeVincenzo,
1991; Mills and McCulloch, Tulloch et al. (1997a) Bionator 53/61 1 year pre-PHV 1.33b
1998; Baccetti et al, 2000), have Co-Pog
been reported in numerous
investigations. Nearly all have Keeling et al. (1998) Bionator 78/78 9.6 ± 0.8 0.8b
reported successful treatment, Johnston analysis
but whether the appliance in
question altered facial growth, Pancherz (1982) Herbst 22/20 12.1 ± 0.11 2.2
particularly mandibular growth, Pancherz analysis
sufficiently to attain clinical
significance remains Lund and Sandler (1998) Twin-block 36/27 12.4 (mean) 2.4
controversial. Ar-Pog
The scientific value of the
retrospective study has been O'Brien et al. (2003) Twin-block 73/74 8-10 (range) 1.55
criticized for several valid Pancherz analysis 9.7 (mean)
reasons, including selection bias,
inadequate sample size, lack of a Mean difference between experimental and control groups. NS, not significant; all other differences
contemporaneous controls, and are small but statistically significant.
b Mean annualized change (mm/yr). In the Pancherz (1982) study, the treatment time was 6 months.

Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.

International and American Associations for Dental Research

20
Figure 7. Growth velocity curves for the mandibular condyle based on
the movement of the condylion on serial mandibular tracings
superimposed on natural reference structures (Björk's structures).
Percentiles were used to describe individual variation and growth curves
drawn by growth rates plotted at each age, with the lines between
smoothed. (Redrawn from Buschang et al., 1999)
but statistically significant differences in mandibular length
were produced in the majority of these studies, and (2)
functional appliances such as the Herbst and twin-block, based
on the principle of 'jumping the bite', are more effective at
modifying mandibular growth than are passive appliances such
as the Andresen activator and its variants.
However, unlike a laboratory experiment, in which it is
possible to limit the differences between experimental and
control groups to the single factor being investigated, in clinical
investigations, an orthodontic appliance is just one of several
variables affecting the outcome. Clinical studies also deal with
population data with an emphasis on averages, not on
individuals. Clinicians treat individuals, and population data are
of little use in predicting the likely outcome for specific
individuals, characterized as they are by endless anatomical and
physiological variations. Apart from questions of individual
compliance and the operator effect, outcome measurements and
hence conclusions will therefore be influenced by the
following:
• The inaccuracy of the cephalometric method
The measurement error may be greater than the growth changes
one is hoping to identify. Condylion, a key landmark, is
notoriously difficult to identify accurately on conventional
cephalometric radiographs. Until imaging techniques improve,
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
Meikle J Dent Res 86(1) 2007
and cone beam computed tomography is showing promise
(Hilgers et al., 2005), the TMJ will continue to be something of
a 'black box'.
• Validity of the measurements
The cephalometric measurements themselves used to quantitate
change are of questionable validity. Linear dimensions such as
condylion-pogonion (Co-Pog), or its surrogate, articulare-
gnathion (Ar-Gn), to quantify changes in mandibular growth
are not valid measurements. They do not take into account
condylar growth rotation (Björk, 1963) and underestimate
condylar growth on average by 3-4 mm (Hägg and Attström,
1992). The Pancherz analysis (Pancherz, 1982) used in some
RCTs (Table 2) will similarly underestimate mandibular
growth, since it is a linear measurement that does not take into
account variations in condylar growth rotation (Meikle, 2005).
To be valid, measurements should be made between pre- and
post-treatment condylions; not only will this give a more
accurate estimate of the amount of condylar growth, but it will
also provide information regarding condylar growth direction.
• The pubertal growth spurt
Variabilities in the timing, magnitude, and duration of the
pubertal growth spurt are difficult to predict accurately. There
are also differences in the timing of peak height velocity (PHV)
and pubertal spurts in facial growth. Velocity curves for a
French-Canadian population (Buschang et al., 1999) showed
that, for males, the average annual growth velocity for the
condyle ranges from 2.1-3.1 mm, with a peak at 14.3 yrs (Fig.
7). There was, however, substantial variation. For a male
individual in the 90th percentile, for example, condylar growth
will average 5 mm/year, while for another in the 25th
percentile, the annual increment will be as little as 1-2 mm.
This will have a significant effect on treatment outcome.
It is generally recognized that optimal conditions for
achieving growth modification occur when treatment coincides
with the pubertal growth spurt and, in particular, peak height
velocity (PHV). Hägg and Pancherz (1988), for example,
showed that the skeletal contribution to changes in dental arch
relationship from Class II to Class I will be greater in persons
treated at PHV or during the succeeding year. The ages of the
population samples in Table 2 suggest that many of the
participants were some distance from achieving PHV. In only
one, the UNC investigation discussed earlier (Tulloch et al.,
1997a), was treatment timed to start within 1 yr of PHV, which
might explain the differences in their results compared with
those of Keeling et al. (1998), despite both groups using the
bionator. It seems likely that, given the above, all the RCTs
published to date significantly underestimate mandibular
change.
Can the TMJ be Remodeled Clinically?
It is clear that functional displacement of the mandible in
primate models alters the surface contours of the condyle,
glenoid fossa, and post-glenoid tubercle. In that respect, it is no
different from any other joint. There is also evidence to suggest
that condylar growth can be directed in a more posterior
direction. Remodeling the TMJ in monkeys is one thing.
Remodeling it clinically is quite another. Nevertheless, there is
evidence, from those treated with the Herbst appliance,
suggesting that it might be possible.
In a systematic review of the literature regarding the effects
J Dent Res 86(1) 2007 Remodeling the Dentofacial Skeleton
of Herbst treatment on TMJ morphology, Popowich et al.
(2003) identified 80 studies related to the topic. Publications
that used transpharyngeal radiographs to document
morphological change were excluded, leaving five publications
meeting their criteria. In one of these (Ruf and Pancherz, 1998),
magnetic resonance imaging (MRI) was used to analyze TMJ
growth adaptation in 15 consecutive Class II patients treated for
a period of 7 months. After 6-12 wks, signs of condylar
remodeling were seen at the postero-superior border in 29 of
the 30 condyles, while glenoid fossa remodeling was noted in
22 joints.
Of interest is the major study (Paulsen, 1997) of 100
consecutive patients treated with the Herbst appliance. This
was not included in the Popowich et al. review, since
orthopantomographic and transpharyngeal radiography were
used to obtain the condylar images. Paulsen reported that, in
most cases, a visible change in the morphology of the condyle
occurred—a double contour of the postero-superior part of the
condyle, and sometimes at the distal surface of the ramus. In
children/youth at the peak of puberty, the double contour was
distinct only for a short time, while in late puberty it persisted
for several months. Paulsen concluded that the observed
changes were due to bone remodeling.
These findings suggest that condylar growth occurred in a
more posterior direction, which is consistent with the evidence
from functional mandibular displacement in monkeys. They
further suggest that remodeling of the TMJ with the Herbst
appliance (and probably the twin-block) can be regarded as a
definite clinical possibility, particularly in an actively growing
child.
Growth Stimulation vs. Growth Remodeling
Mechanical stimuli arising from the functional activity of the
TMJ are essential for the differentiation and maintenance of
condylar cartilage. Put simply, no function, no cartilage.
However, is one then justified in concluding that so-called
functional appliances increase chondrogenesis and bone
formation, or do the transient changes in cell proliferation and
metabolism reported by some groups simply represent localized
adjustments to alterated mechanical strain?
Given the ambiguity of the experimental and anatomical
evidence, the hypothesis that functional mandibular
displacement stimulates the mitosis of PZ cells, and hence the
growth of the condyle in humans, should remain firmly in the
category labeled 'unproven'. It would seem to be a weak basis
on which to make statements such as, '...this indicates that
functional appliance therapy can truly enhance condylar
growth' (Rabie et al., 2003). It would be nice to think so, but
clinical experience suggests otherwise. The point may be
regarded as largely one of semantics, but from the clinical point
of view, the term growth remodeling seems preferable to
growth stimulation for describing the morphological changes in
the TMJ that result from the use of dentofacial orthopedic
appliances.
REFERENCES
Adams CD, Meikle MC, Norwick KW, Turpin DL (1972). Dentofacial
remodelling produced by intermaxillary forces in Macaca mulatta.
Arch Oral Biol 17:1519-1535.
Alpern MC, Yurosko JJ (1987). Rapid palatal expansion in adults with and
without surgery. Angle Orthod 57:245-263.
Andresen J, Häupl K (1942). Funktionkieferorthopädie. Die Grundlage des
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
21
Norwegischen Systeme. Leipzig, Germany: Verlag von JA Barthe.
Angell EH (1860). Treatment of irregularity of the permanent or adult teeth.
Dental Cosmos 1:540-544; 599-600.
Baccetti T, Franchi L, Toth LR, McNamara JA Jr (2000). Treatment timing
for Twin-block therapy. Am J Orthod Dentofacial Orthop 118:159-170.
Badell MC (1976). An evaluation of extraoral combined high-pull traction
and cervical traction to the maxilla. Am J Orthod 69:431-446.
Baume L, Derichsweiler J (1961). Is the condylar growth centre responsive
to orthodontic therapy? An experimental study in Macaca mulatta.
Oral Surg Oral Med Oral Pathol 14:347-362.
Baumrind S, Molthen R, West EE, Miller DM (1979). Distal displacement
of the maxilla and the upper first molar. Am J Orthod 75:630-640.
Behrents RG, Carlson DS, Abdelnour T (1978). In vivo analysis of bone
strain about the sagittal suture in Macaca mulatta during masticatory
movements. J Dent Res 57:904-908.
Bernstein L, Ulbrich RW, Gianelly AA (1977). Orthopedics versus
orthodontics in class II treatment: an implant study. Am J Orthod
72:549-559.
Björk A (1963). Variations in the growth pattern of the human mandible:
longitudinal radiographic study by the implant method. J Dent Res
42(Pt 2):400-411.
Björk A, Skieller V (1972). Facial development and tooth eruption. An
implant study at the age of puberty. Am J Orthod 62:339-383.
Bradley JP, Han VR, Roth DA, Levine JP, McCarthy JG, Longaker MT
(1999). Increased IGF-I and IGF-II mRNA and IGF-I peptide in fusing
rat cranial sutures suggest evidence for a paracrine role of insulin-like
growth factors in suture fusion. Plastic Reconstr Surg 104:129-138.
Brandt HC, Shapiro PA, Kokich VG (1979). Experimental and
postexperimental effects of posteriorly directed extraoral traction in
adult Macaca fascicularis. Am J Orthod 75:301-317.
Breckon JJ, Hembry RM, Reynolds JJ, Meikle MC (1994). Regional and
temporal changes in the synthesis of matrix metalloproteinases and
TIMP-1 during development of the rabbit mandibular condyle. J Anat
184:99-110.
Breitner C (1940). Bone changes resulting from experimental orthodontic
treatment. Am J Orthod 26:521-547.
Breitner C (1941). Further investigations of bone changes resulting from
experimental orthodontic treatment. Am J Orthod 27:605-632.
Brodie AG (1941). On the growth pattern of the human head from the third
month to the eighth year of life. Am J Anat 68:209-262.
Brodie AG, Downs WB, Goldstein A, Myer E (1938). Cephalometric
appraisal of orthodontic results: a preliminary report. Angle Orthod
8:261-265.
Brown CC, Hembry RM, Reynolds JJ (1989). Immunolocalization of
metalloproteinases and their inhibitor in the rabbit growth plate. J Bone
Joint Surg Am 71:580-593.
Buschang PH, Santos-Pinto A, Demirjian A (1999). Incremental growth
charts for condylar growth between 6 and 16 years of age. Eur J Orthod
21:167-173.
Capelozza Filho L, Cardoso Neto J, da Silva Filho OG, Ursi WJ (1996).
Non-surgically assisted rapid maxillary expansion in adults. Int J Adult
Orthodon Orthognath Surg 11:57-66; discussion 67-70.
Case CS (1911). The question of extraction in orthodontia. Trans Nat Dent
Assoc. Reprinted (1964) as part of the series "Extraction debate of 1911
by Case, Dewey and Cryer", Am J Orthodont 50:656-691, 751-768,
843-851, 900-911.
Charlier JP, Petrovic A, Herrmann-Stutzmann J (1969). Effects of
mandibular hyperpropulsion on the prechondroblastic zone of the
young rat condyle. Am J Orthod 55:71-74.
Cutler BS, Hassig FH, Turpin DL (1972). Dentofacial changes produced
during and after use of a modified Milwaukee brace on Macaca
mulatta. Am J Orthod 61:115-137.
Degroote CW (1984). Alterability of mandibular condylar growth in the
young rat and its implications [doctoral thesis]. Leuven, Belgium:
Catholic University of Louvain.
Delaire J (1971). La croissance maxillaire: déductions thérapeutiquue
[Maxillary growth: therapeutic conclusions]. Trans Eur Orthod Soc 81-
102 [article in French].
Delaire J, Verdon P, Lumineau JP, Cherga-Negrea A, Talmant J, Boisson M
(1972). Quelques rèsultats des tractions extra-orales a appui fronto-
mentonnier dans le traitment orthopèdique des malformations maxillo-
22
mandibulaires de classe III et des sèquelles osseuses des fentes labio-
maxillaires [Some results of extra-oral tractions with front-chin rest in
the orthodontic treatment of class 3 maxillomandibular malformations
and of bony sequelae of cleft lip and palate]. Rev Stomatol Chir
Maxillofac 73:633-642 [article in French].
Dellinger EL (1973). A preliminary study of anterior maxillary
displacement. Am J Orthod 63:509-516.
Demisch A (1972). Effects of activator therapy on the craniofacial skeleton
in class II, division 1 malocclusion. Trans Eur Orthod Soc 295-310.
DeVincenzo JP (1991). Changes in mandibular length before, during, and
after successful orthopedic correction of Class II malocclusions, using a
functional appliance. Am J Orthod Dentofacial Orthop 99:241-257.
Dewey M (1914). Practical orthodontia. St. Louis, MO: C.V. Mosby
Company, pp. 87-90.
Droschl H (1973). The effect of heavy orthopedic forces on the maxilla in
the growing Saimiri sciureus (squirrel monkey). Am J Orthod 63:449-
461.
Duterloo HS (1967). In vivo implantation of the mandibular condyle of the
rat. An experimental investigation of the growth of the lower jaw
[thesis]. The Netherlands: University of Nijmegen.
Elder JR, Tuenge RH (1974). Cephalometric and histologic changes
produced by extraoral high-pull traction to the maxilla in Macaca
mulatta. Am J Orthod 66:599-617.
Elgoyhen JC, Moyers RM, McNamara JA Jr, Riolo ML (1972). Craniofacial
adaptation of protrusive function in young rhesus monkeys. Am J
Orthod 62:469-480.
Franchi L, Baccetti T, McNamara JA (2004). Postpubertal assessment of
treatment timing for maxillary expansion and protraction therapy
followed by fixed appliances. Am J Orthod Dentofacial Orthop
126:555-568.
Fränkel R (1966). The theoretical concept underlying treatment with
function correctors. Rep Congr Eur Orthod Soc 42:233-254.
Fredrick DL (1969). Dentofacial changes produced by extraoral high-pull
traction to the maxilla of Macaca mulatta; a histologic and serial
cephalometric study [MSD thesis]. Seattle: University of Washington.
Ghafari J, Degroote C (1986). Condylar cartilage response to continuous
mandibular displacement in the rat. Angle Orthod 56:49-57.
Ghafari J, Shofer FS, Jacobsson-Hunt U, Markowitz DL, Laster LL (1998).
Headgear versus function regulator in the early treatment of Class II
division 1 malocclusion: a randomized clinical trial. Am J Orthod
Dentofacial Orthop 113:51-61.
Haas AJ (1961). Rapid expansion of the maxillary dental arch and nasal
cavity by opening the midpalatal suture. Angle Orthod 31:73-90.
Haas AJ (1965). The treatment of maxillary deficiency by opening the
midpalatal suture. Angle Orthod 35:200-217.
Hägg U, Attström K (1992). Mandibular growth estimated by four
cephalometric measurements. Am J Orthod Dentofacial Orthop
102:146-152.
Hägg U, Pancherz H (1988). Dentofacial orthopaedics in relation to
chronological age, growth period and skeletal development. An
analysis of 72 male patients with Class II division 1 malocclusion
treated with the Herbst appliance. Eur J Orthod 10:169-176.
Handelman CS, Wang L, BeGole EA, Haas AJ (2000). Nonsurgical rapid
maxillary expansion in adults: report on 47 cases using the Haas
expander. Angle Orthod 70:129-144.
Herring SW, Mucci RJ (1991). In vivo strain in cranial sutures: the
zygomatic arch. J Morphol 207:225-239.
Herring SW, Rafferty KL (2000). Cranial and facial sutures: functional
loading in relation to growth and morphology. In: Biological
mechanisms of tooth eruption, resorption and replacement by implants.
Davidovitch Z, Mah J, editors. Boston, MA: Harvard Society for the
Advancement of Orthodontics, pp. 269-276.
Hilgers ML, Scarfe WC, Scheetz JP, Farman AG (2005). Accuracy of linear
temporomandibular joint measurements with cone beam computed
tomography and digital cephalometric radiography. Am J Orthod
Dentofacial Orthop 128:803-811.
Isaacson RJ, Ingram AH (1964). Forces produced by rapid maxillary
expansion. II. Forces present during treatment. Angle Orthod 34:261-
270.
Jackson GW, Kokich VG, Shapiro PA (1979). Experimental and
postexperimental response to anteriorly directed extraoral force in
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
Meikle J Dent Res 86(1) 2007
young Macaca nemestrina. Am J Orthod 75:319-333.
Jäger A, Braumann B, Kim C, Wahner S (2001). Skeletal and dental effects
of maxillary protraction in patients with angle class III malocclusion. A
meta-analysis. J Orofac Orthop 62:275-284 [article in English/German].
Jakobsson SO (1967). Cephalometric evaluation of treatment effect on Class
II, Division I malocclusions. Am J Orthod 53:446-457.
Jaslow CR (1990). Mechanical properties of cranial sutures. J Biomech
23:313-321.
Johnson LC (1959). Kinetics of osteoarthritis. Lab Invest 8:1223-1241.
Kambara T (1977). Dentofacial changes produced by extraoral forward
force in Macaca irus. Am J Orthod 71:249-277.
Kapust AJ, Sinclair PM, Turley PK (1998). Cephalometric effects of face
mask/expansion therapy in Class III children: a comparison of three age
groups. Am J Orthod Dentofacial Orthop 113:204-212.
Keeling SD, Wheeler TT, King GJ, Garvan CW, Cohen DA, Cabassa S, et
al. (1998). Anteroposterior skeletal and dental changes after early Class
II treatment with bionators and headgear. Am J Orthod Dentofacial
Orthop 113:40-50.
Kokich VG (1976). Age changes in the human frontozygomatic suture. Am
J Orthod 69:411-430.
Kokich VG (1986). Biology of sutures. In: Craniosynostosis: diagnosis,
evaluation and management. Cohen MM Jr, editor. New York: Raven
Press, pp. 81-103.
Korkhaus G (1960). Present orthodontic thought in Germany. Am J Orthod
46:187-206.
Lanske B, Karaplis AC, Lee K, Luz A, Vortkamp A, Pirro A, et al. (1996).
PTH/PTHrP receptor in early development and Indian hedgehog-
regulated bone growth. Science 273:663-666.
Long F, Zhang XM, Karp S, Yang Y, McMahon AP (2001). Genetic
manipulation of hedgehog signalling in the endochondral skeleton
reveals a direct role in the regulation of chondrocyte proliferation.
Development 128:5099-5108.
Luder HU (1987). Growth direction in the mandibular condyle of pre-
pubertal and pubertal monkeys (Macaca fascicularis) studied by
morphometry and radioautography. Arch Oral Biol 32:239-247.
Lund DI, Sandler PJ (1998). The effects of twin blocks: a prospective
controlled study. Am J Orthod Dentofacial Orthop 113:104-110.
Mankin HJ (1962). Localization of tritiated thymidine in articular cartilage of
rabbits. I. Growth in immature cartilage. J Bone Joint Surg 44:682-688.
Marschner JF, Harris JE (1966). Mandibular growth and class II treatment.
Angle Orthod 36:89-93.
McMinn RMH, Hutchings RT, Logan BM (1981). A colour atlas of head
and neck anatomy. London: Wolfe Medical Publishers, Ltd.
McNamara JA Jr, Bryan FA (1987). Long-term mandibular adaptations to
protrusive function: an experimental study in Macaca mulatta. Am J
Orthod Dentofacial Orthop 92:98-108.
McNamara JA Jr, Carlson DS (1979). Quantitative analysis of
temporomandibular adaptations to protrusive function. Am J Orthod
76:593-611.
McNamara JA Jr, Graber LW (1975). Mandibular growth in the rhesus
monkey (Macaca mulatta). Am J Phys Anthropol 42:15-24.
McNamara JA Jr, Bookstein FL, Shaughnessy TG (1985). Skeletal and
dental changes following functional regulator therapy on class II
patients. Am J Orthod 88:91-110.
Mehrara BJ, Mackool RJ, McCarthy JG, Gittes GK, Longaker MT (1998).
Immunolocalization of basic fibroblast growth factor and fibroblast
growth factor receptor-1 and receptor-2 in rat cranial sutures. Plast
Reconstr Surg 102:1805-1817; discussion 1818-1820.
Meikle MC (1970). The effect of a class II intermaxillary force on the
dentofacial complex in the adult Macaca mulatta monkey. Am J Orthod
58:323-340.
Meikle MC (1973a). In vivo transplantation of the mandibular joint of the
rat: an autoradiographic investigation into cellular changes at the
condyle. Arch Oral Biol 18:1011-1020.
Meikle MC (1973b). The role of the condyle in the postnatal growth of the
mandible. Am J Orthod 64:50-62.
Meikle MC (1975). The influence of function on chondrogenesis at the
epiphyseal cartilage of a growing long bone. Anat Rec 182:387-399.
Meikle MC (1980). The dentomaxillary complex and overjet correction in
Class II division 1 malocclusion: objectives of skeletal and alveolar
remodelling. Am J Orthod 77:184-197.
J Dent Res 86(1) 2007 Remodeling the Dentofacial Skeleton
Meikle MC (1992). Remodelling. In: The temporomandibular joint—a
biological basis for clinical practice. 4th ed. Sarnat BG, Laskin DM,
editors. Orlando, FL: W.B. Saunders & Company, pp. 93-107.
Meikle MC (2002). Craniofacial development, growth and evolution.
Bressingham, Norfolk, England: Bateson Publishing.
Meikle MC (2005). What do prospective randomized clinical trials tell us
about the treatment of class II malocclusions? A personal viewpoint
[guest editorial]. Eur J Orthod 27:105-114.
Meikle MC (2006). The tissue, cellular and molecular regulation of
orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J
Orthod 28:221-240.
Meikle MC, Reynolds JJ, Sellers A, Dingle JT (1979). Rabbit cranial
sutures in vitro: a new experimental model for studying the response of
fibrous joints to mechanical stress. Calcif Tissue Int 28:137-144.
Meldrum RJ (1975). Alterations in the upper facial growth of Macaca
mulatta resulting from high-pull headgear. Am J Orthod 67:393-411.
Melsen B (1975). Palatal growth studied on human autopsy material. A
histologic microradiographic study. Am J Orthod 68:42-54.
Mills CM, McCulloch KJ (1998). Treatment effects of the twin block
appliance: a cephalometric study. Am J Orthod Dentofacial Orthop
114:15-24.
Moffett B (1971). Remodelling of the craniofacial articulations by various
orthodontic appliances in rhesus monkeys. Trans Eur Orthod Soc, 207-
216.
Moffett BC (1973). Remodelling of the craniofacial skeleton produced by
orthodontic forces. In: Symposia of the Fourth International Congress
of Primatology. Vol. 3. Basel: S. Karger, pp. 180-190.
Moore AW (1959). Observations on facial growth and its clinical
significance. Am J Orthod 45:397-423.
Murray PDF (1963). Adventitious (secondary) cartilage in the chick, and the
development of certain bones and articulation in the chick skull. Aust J
Zool 11:368-430.
Murray PDF, Smiles M (1965). Factors in the evocation of adventitious
(secondary) cartilage in the chick embryo. Aust J Zool 13:351-382.
Nanda R (1978). Protraction of maxilla in rhesus monkeys by controlled
extraoral forces. Am J Orthod 74:121-141.
Nelson C, Harkness M, Herbison P (1993). Mandibular changes during
functional appliance treatment. Am J Orthod Dentofacial Orthop
104:153-161.
Ngan P, Hägg U, Yiu C, Merwin D, Wei SH (1996). Soft tissue and
dentoskeletal profile changes associated with maxillary expansion and
protraction headgear treatment. Am J Orthod Dentofacial Orthop
109:38-49.
Ngan P, Yiu C, Hu A, Hägg U, Wei SH, Gunel E (1998). Cephalometric and
occlusal changes following maxillary expansion and protraction. Eur J
Orthod 20:237-254.
O'Brien K, Wright J, Conboy F, Sanjie Y, Mandall N, Chadwick S, et al.
(2003). Effectiveness of early orthodontic treatment with the Twin-
block appliance: a multicenter, randomized, controlled trial. Part 1:
Dental and skeletal effects. Am J Orthod Dentofacial Orthop 124:234-
243.
Ogston A (1875). On articular cartilage. J Anat Physiol 10:48-74.
Ogston A (1878). The growth and maintenance of the articular ends of adult
bones. J Anat 12:503-517.
Opperman LA, Nolen AA, Ogle RC (1997). TGF-beta1, TGF-beta2 and
TGF-beta3 exhibit distinct patterns of expression during cranial suture
formation and obliteration in vivo and in vitro. J Bone Min Res 12:301-
310.
Opperman LA, Chhabra A, Nolen AA, Bao Y, Ogle RC (1998). Dura mater
maintains rat cranial sutures in vitro by regulating suture cell
proliferation and collagen production. J Craniofac Genet Dev Biol
18:150-158.
Pancherz H (1979). Treatment of class II malocclusions by jumping the bite
with the Herbst appliance. A cephalometric investigation. Am J Orthod
76:423-442.
Pancherz H (1982). The mechanism of Class II correction in Herbst
appliance treatment. A cephalometric investigation. Am J Orthod
82:104-113.
Paulsen HU (1997). Morphological changes in the TMJ condyles of 100
patients treated with the Herbst appliance in the period of puberty to
adulthood: a long-term radiographic study. Eur J Orthod 19:657-668.
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
23
Persson M (1973). Structure and growth of facial sutures. Odont Revy
24(Suppl 26):1-146.
Persson M, Thilander B (1977). Palatal suture closure in man from 15 to 35
years of age. Am J Orthod 72:42-52.
Petrovic AG, Stutzmann JJ (1977). Further investigations into the
functioning of the peripheral comparator of the servosystem in the
control of the condylar cartilage growth rate and the lengthening of the
jaw. In: The biology of occlusal development. McNamara JA, editor.
Monograph 7. Ann Arbor, MI: Center for Human Growth and
Development, University of Michigan, pp. 255-291.
Petrovic AG, Stutzmann JJ, Oudet C (1975). Control processes in the
postnatal growth of the condylar cartilage of the mandible. In:
Determinants of mandibular form and growth. McNamara JA, editor.
Monograph 4. Ann Arbor, MI: Center for Human Growth and
Development, University of Michigan, pp. 101-153.
Popowich K, Nebbe B, Major PW (2003). Effect of Herbst treatment on
temporomandibular joint morphology: a systematic literature review.
Am J Orthod Dentofacial Orthop 123:388-394.
Poulton DR (1967). The influence of extraoral traction. Am J Orthod 53:8-
18.
Pritchard JJ, Scott JH, Girgis FG (1956). The structure and development of
cranial and facial sutures. J Anat 90:73-86.
Rabie AB, Hägg U (2002). Factors regulating mandibular condylar growth.
Am J Orthod Dentofacial Orthop 122:401-409.
Rabie AB, She TT, Harley VR (2003). Forward mandibular positioning up-
regulates SOX9 and type II collagen expression in the glenoid fossa. J
Dent Res 82:725-730.
Rabie AB, Tang GH, Hägg U (2004). Cbfa1 couples chondrocytes
maturation and endochondral ossification in rat mandibular condylar
cartilage. Arch Oral Biol 49:109-118.
Rafferty KL, Herring SW (1999). Craniofacial sutures: morphology, growth
and in vivo masticatory strains. J Morphol 242:167-179.
Ricketts RM (1960). The influence of orthodontic treatment on facial
growth and development. Angle Orthod 30:103-133.
Roberts WE, Jee WS (1974). Cell kinetics of orthodontically-stimulated and
non-stimulated periodontal ligament in the rat. Arch Oral Biol 19:17-
21.
Roth DA, Longaker MT, McCarthy JG, Rosen DM, McMullen HF, Levine,
JP, et al. (1997). Studies in cranial suture biology: Part I. Increased
immunoreactivity for TGF-beta isoforms (beta1, beta2, and beta3)
during rat cranial suture fusion. J Bone Min Res 12:311-321.
Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux
P, et al. (1994). Mutations in the gene encoding fibroblast growth factor
receptor-3 in achondroplasia. Nature 371:252-254.
Ruf S, Pancherz H (1998). Temporomandibular joint growth adaptation in
Herbst treatment: a prospective magnetic resonance imaging and
cephalometric Roentgenographic study. Eur J Orthod 20:375-388.
Sandy JR, Farndale RW, Meikle MC (1993). Recent advances in
understanding mechanically induced bone remodeling and their
relevance to orthodontic theory and practice. Am J Orthod Dentofacial
Orthop 103:212-222.
Shen G, Darendeliler MA (2005). The adaptive remodeling of condylar
cartilage—a transition from chondrogenesis to osteogenesis. J Dent Res
84:691-699.
Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, et
al. (1994). Mutations in the transmembrane domain of FGFR3 cause
the most common genetic form of dwarfism, achondroplasia. Cell
78:335-342.
Smalley WM, Shapiro PA, Hohl TH, Kokich VG, Brånemark PI (1988).
Osseointegrated titanium implants for maxillofacial protraction in
monkeys. Am J Orthod Dentofacial Orthop 94:285-295.
Sproule WR (1968). Dentofacial changes produced by extraoral cervical
traction to the maxilla of Macaca mulatta; a histologic and serial
cephalometric study [MSD thesis]. Seattle: University of Washington.
Stockli PW, Willert HG (1971). Tissue reactions in the temporomandibular
joint resulting from anterior displacement of the mandible in the
monkey. Am J Orthod 60:142-155.
Takada K, Petdachai S, Sakuda M (1993). Changes in dentofacial
morphology in skeletal Class III children treated by a modified
maxillary protraction headgear and a chin cup: a longitudinal
cephalometric appraisal. Eur J Orthod 15:211-221.
24
Tang GH, Rabie AB, Hägg U (2004). Indian hedgehog: a mechano-
transduction mediator in condylar cartilage. J Dent Res 83:434-438.
Tewson DH, Heath JK, Meikle MC (1988). Biochemical and
autoradiographic evidence that anterior mandibular displacement in the
young growing rat does not stimulate cell proliferation or matrix
formation at the mandibular condyle. Arch Oral Biol 33:99-107.
Todd TW, Lyon DW (1924). Endocranial suture closure, its progress and
age relationship. I. Adult males of white stock. Am J Phys Anthrop
7:325-384.
Todd TM, Lyon DW (1925). Cranial suture closure. Its progress and age
relationship. Part II. Ectocranial closure in adult males of white stock.
Am J Phys Anthrop 8:23-45.
Tonge EA, Heath JK, Meikle MC (1982). Anterior mandibular displacement
and condylar growth. An experimental study in the rat. Am J Orthod
82:277-287.
Triftshauser R, Walters RD (1976). Cervical traction of the maxillae in the
Macaca mulatta monkey using heavy orthopedic force. Angle Orthod
46:37-46.
Tsolakis AI, Spyropoulos MN (1997). An appliance designed for
experimental mandibular hyperpropulsion in rats. Eur J Orthod 19:1-7.
Tsolakis AI, Spyropoulos MN, Katsavrias E, Alexandridis K (1997). Effects
of altered mandibular function on mandibular growth after
condylectomy. Eur J Orthod 19:9-19.
Tuenge RH, Elder JR (1974). Posttreatment changes following extraoral
high-pull traction to the maxilla of Macaca mulatta. Am J Orthod
66:618-644.
Tulloch JF, Phillips C, Koch G, Proffit WR (1997a). The effect of early
intervention on skeletal pattern in Class II malocclusion: a randomized
clinical trial. Am J Orthod Dentofacial Orthop 111:391-400.
Tulloch JF, Proffit WR, Phillips C (1997b). Influences on the outcome of
early treatment for Class II malocclusion. Am J Orthod Dentofacial
Orthop 111:533-542.
Tulloch JF, Phillips C, Proffit WR (1998). Benefit of early Class II
treatment: progress report of a two-phase randomized clinical trial. Am
Downloaded from jdr.sagepub.com at PONTIFICIA UNIVERSIDAD CATOLICA DE CHILE on September 22, 2014 For personal use only. No other uses without permission.
International and American Associations for Dental Research
Meikle J Dent Res 86(1) 2007
J Orthod Dentofacial Orthop 113:62-72.
Turley P, Shapiro PA, Moffett BC (1980). The loading of bioglass-coated
aluminium oxide implants to produce sutural expansion of the
maxillary complex in the pigtail monkey (Macaca nemestrina). Arch
Oral Biol 25:459-469.
Vortkamp A, Lee K, Lanske B, Segre GV, Kronenberg HM, Tabin CJ
(1996). Regulation of rate of cartilage differentiation by Indian
hedgehog and PTH-related protein. Science 273:613-621.
Wagemans PA, van de Velde JP, Kuijpers-Jagtman AM (1988). Sutures and
forces: a review. Am J Orthod Dentofacial Orthop 94:129-141.
Watson WG (1972). A computerized appraisal of the high-pull face-bow.
Am J Orthod 62:561-579.
Wehrbein H, Yildizhan F (2001). The mid-palatal suture in young adults. A
radiological-histological investigation. Eur J Orthod 23:105-114.
Weislander L (1974). The effect of force on craniofacial development. Am J
Orthod 65:531-538.
Weislander L (1975). Early or late cervical traction therapy of Class II
malocclusion in the mixed dentition. Am J Orthod 67:432-439.
Weislander L (1984). Intensive treatment of severe Class II malocclusions
with a headgear-Herbst appliance in the early mixed dentition. Am J
Orthod 86:1-13.
Wertz RA (1970). Skeletal and dental changes accompanying rapid
midpalatal suture opening. Am J Orthod 58:41-66.
Wisth PJ, Tritrapunt A, Rygh P, Boe OE, Norderval K (1987). The effect of
maxillary protraction on front occlusion and facial morphology. Acta
Odontol Scand 45:227-237.
Woodside DG, Metaxas A, Altuna G (1987). The influence of functional
appliance therapy on glenoid fossa remodeling. Am J Orthod
Dentofacial Orthop 92:181-198.
Wright DM, Moffett BC (1974). The postnatal development of the human
temporomandibular joint. Am J Anat 141:235-249.
Wu Q, Zhang Y, Chen Q (2001). Indian hedgehog is an essential component
of mechanotransduction complex to stimulate chondrocyte
proliferation. J Biol Chem 276:35290-35296.