The effects of altered maxillary growth on patternsof mandibular rotation in a pig model

Nathan E. Holton a,b,*, Christina L. Nicholas b,c, Steve D. Marshall a,Robert G. Franciscus b, Thomas E. Southard a

aDepartment of Orthodontics, The University of Iowa, Iowa City, IA 52242, USAbDepartment of Anthropology, The University of Iowa, Iowa City, IA 52242, USAcDows Research Institute, The University of Iowa, Iowa City, IA 52242, USA

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0

a r t i c l e i n f o

Article history:

Accepted 21 February 2015

Keywords:

Mandibular rotation

Integration

Sus scrofa

a b s t r a c t

Objectives: A thorough understanding of influence of maxillary growth on patterns of man-

dibular rotation during development is important with regard to the treatment of skeletal

discrepancies. In the present study, we examined whether experimentally altered maxillary

position has a significant influence on patterns of mandibular rotation in a pig model.

Design: Maxillary growth was altered in a sample of n = 10 domestic pigs via surgical fixation of

the circummaxillary sutures. We compared the experimental group to control and surgical

sham samples and assessed the effects of altered maxillary growth on mandibular form using

geometric morphometric techniques. We tested for significant differences in mandibular

shape between our samples and examined axes of morphological variation. Additionally, we

examined whether altered mandibular shape resulting from altered maxillary position was

predictably associated with morphological changes to the condylar region.

Results: There was a statistically significant difference in mandibular shape between the

experimental and control/sham groups. As a result of vertical displacement of the snout,

mandibles in the experimental sample resulted in greater anterior rotation when compared

to the control/sham pigs. Variation in rotation was correlated with morphological changes

in the condyle including the shape of the articular surface and condylar orientation

indicative of greater anterior mandibular rotation.

Conclusions: Vertical displacement of the maxilla had a significant effect on mandibular shape

by encouraging anterior mandibular rotation. This result has important implications for

understanding the effects of altered mandibular posture on condylar remodeling the treat-

ment of skeletal discrepancies such as the correction of hyperdivegent mandibular growth.

# 2015 Elsevier Ltd. All rights reserved.

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1. Introduction

A significant proportion of variation in human cranioman-

dibular form is arrayed along the vertical dimensions of the

facial skeleton.1–3 As an important contributing factor, the

* Corresponding author at: Department of Orthodontics, The UniversiE-mail address: nathan-holton@uiowa.edu (N.E. Holton).

http://dx.doi.org/10.1016/j.archoralbio.2015.02.0190003–9969/# 2015 Elsevier Ltd. All rights reserved.

height of the lower facial skeleton is markedly influenced by

patterns of mandibular rotation during ontogeny. The mor-

phogenetic influences on mandibular rotation are complex

and multifactorial as evidenced by the various rotational

patterns documented in classic implant studies.4 In more

general terms however, mandibular rotation can be divided

ty of Iowa, Iowa City, IA 52242, USA. Tel.: +1 319 384 4786.

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0934

into two categories, i.e., forward rotation and backward

rotation, which are tied to a larger integrated suite of

morphological features of the mandible.2–4

Variation in mandibular rotation is influenced by the

amount and direction of mandibular condylar growth during

development.5,6 Increased anterior growth at the condyles

produces greater forward mandibular rotation whereas

greater posterior condylar growth results in a greater degree

of backward mandibular rotation.4

While numerous factors likely affect the direction of

condylar growth, variation in mandibular posture has a

significant influence.7 Changes in mandibular posture and

thus condylar position alter the biomechanical environment

of the temporomandibular joint thereby affecting the growth

of the condylar cartilage.8 While the precise influence of

altered mandibular posture on condylar growth is incom-

pletely understood, experimental studies have demonstrated

the effects of postural variation on the condylar growth and

resulting gross phenotypic changes in mandibular form.9,10

For example, posterior relocation of the glenoid fossa relative

to the mandibular condyle in a rabbit model results in

significant morphological changes in the shape of the condylar

surface and an increase in mandibular length.11,12 Sugiyama

et al.13 found that altering the vertical relationship between

the maxilla and mandible using a plate bonded to the

maxillary molars in a rat model resulted in altered condylar

growth associated with greater posterior mandibular rotation.

In a similar fashion, Ferrari and Herring14 examined the effects

of bite blocks on craniomandibular growth using a sample of

miniature pigs. In addition to a number of morphological

changes in the maxillary region, the mandible exhibited a

pattern that suggests increased posterior rotation including a

larger gonial angle (see,14 Fig. 2) as well as significant changes

to the condylar surface.

Whereas many experimental studies have examined the

influence of functional appliances that encourage posterior

condylar growth and thus backward mandibular rotation, less

is understood about the morphological effects of develop-

mental modifications that encourage anterior rotation of the

mandible. This is particularly important from an orthodontic

perspective given that treatment of hyperdivergent patients

with retrognathic mandibles via functional appliances

achieves dental correction but is unable to correct associated

vertical and sagittal skeletal discrepancies.15 Moreover,

maxillary impaction surgery producing autorotation of the

mandible in growing patients does not appear to inhibit

mandibular growth or affect the long-term rotational pattern

of the mandible.16 A limited number of studies, however, have

documented that anterior mandibular rotation induced by

molar intrusion results in favorable skeletal changes in

hypodivergent patients such as increased chin projection,

reduced facial height and a decreased gonial angle.15,17,18

In the present study, we examined whether experimentally

altered maxillary position has a significant influence on

patterns of mandibular rotation in a pig model. This is a

continuation of our research examining the influence of rigid

plate fixation of the circummaxillary sutures on facial growth

and development.17–19 Previously we found that sutural

fixation affects maxillary morphology such that pigs with

restricted sutural growth exhibited shorter and more dorsally

rotated (i.e., superiorly displaced) snouts. Using geometric

morphometric techniques, we report how altered vertical

maxillary position affects the growth of the mandible by

addressing the following research questions. First, to what

degree does variation in vertical maxillary position affect the

pattern of mandibular rotation in our experimentally modified

pigs when compared to normal, non-experimentally modified

sample of control pigs? Second, if the pattern of rotation is

altered as a result of the vertical displacement of the maxilla,

how is this pattern reflected in the morphology of the condylar

region?

2. Materials and methods

Ten female Sus scrofa sibship cohorts, each consisting of three

individuals, were allocated to one of three trial groups (i.e.,

experimental, sham and control). Surgical procedures are

described in detail in Holton et al.18 Briefly, in the experimental

group (n = 10), rigid miniplates were bilaterally affixed across

the zygomaxillary, frontonasal and nasomaxillary sutures at

two months of age. The sham group (n = 10) underwent an

identical surgical procedure but received only microscrew

implantation. The control group (n = 10) underwent no surgical

procedure. All animals were euthanized following four months

of post-surgical growth (i.e., six months of age). One control pig

did not survive to age 6 months, and one sham pig was

damaged during post-mortem processing resulting in a total of

n = 28 pigs available for analysis (i.e., n = 10 control, n = 9 sham

and n = 9 control). Since there were no significant differences

between our control and sham pigs, these were combined into

a single control group for all analyses. The University of Iowa

Institutional Animal Care and Use Committee approved all

procedures. For comparison, CT images illustrating the gross

morphological differences between an experimental pig and a

control pig are found in Fig. 1.

To assess variation in mandibular form, we collected a

series of k = 25 two-dimensional traditional and semiland-

marks from CT images that were imported into tpsDIG 2.12

software.20 We selected landmarks that adequately repre-

sented the mandibular corpus, mandibular ramus and

condylar process including the articular surface of the condyle

(Fig. 2). All landmarks were superimposed and scaled using

generalized Procrustes analysis (GPA). This method translates

objects to a common centroid origin, scales for size, and

rotates objects using a least-squares criterion. In the case of

our semilandmarks, a sliding semilandmark analysis was also

conducted (as a component of the GPA). Sliding semilandmark

analysis superimposes the semilandmarks by sliding them

along the curve to a consensus position that minimizes the

summed squared deviations for each given landmark across

the sample. This renders the semilandmarks homologous,

allowing semilandmarks henceforth to be treated the same as

standard landmarks in further analyses.21

With regard to our first research question, (i.e., effect of

maxillary variation on mandibular rotation), we first tested for

significant differences in overall mandibular shape between

our experimental and control trial groups using Procrustes

ANOVA. Next, we used principal components analysis (PCA) of

Procrustes scaled shape variables to examine axes of variation

Fig. 1 – Comparison of control (a) and experimental (b) pigs.

Fig. 2 – Landmarks used to examine variation in mandibular form between our trial groups. White numbered landmarks are

described in Table 1. Gray un-numbered landmarks represent semilandmarks used to assess the shape of the condyloid

process and articular surface of the condyle.

Table 1 – Standard landmark descriptions/definitions.

Landmark Description/definition

1 Infradentale

2 Menton

3 Antegonial notch

4 Inferior border of the gonial region

5 Gonion

6 Alveolus on the distal aspect of the molars

7 Anterior surface of the coronoid process located

at the level of the deepest point of the

mandibular notch

8 Coronion

9 Deepest point of the mandibular notch

10 Anterior border of the condylar articular surface

11 Apex of curvature of the condylar articular surface

(i.e., highest point determined by the intersection

between the articular surface and a line

perpendicular to chord between landmarks 10 and 12.

12 Posterior border of the condylar articular surface

13 Posterior surface of the ramus on the superior border

of the gonial region

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0 935

across our sample and to determine whether there are

meaningful differences in mandibular shape associated with

rotational variation between our trial groups.

To assess our second goal (i.e., is rotational variation

reflected in condylar shape), we examined the pattern and

strength of morphological integration between the condylar

region and non-condylar mandibular morphology. Specifical-

ly, we examined whether the shape of the condylar neck and

surface topography of the condylar articular surface were

predictably associated with variation in mandibular rotation

resulting from the experimental protocol. We examined the

pattern of integration using partialleast squares analysis (PLS),

which is a statistical method used to investigate the covaria-

tion between two of more ‘‘blocks’’ of data.21 To assess

covariation between the condylar and non-condylar regions,

we divided the mandible into two blocks (Fig. 2), the first

consisting of landmarks 9–13 and all semilandmarks (condylar

block) and the second consisting of landmarks 1–8 (non-

condylar) (Table 1).

When applied to geometric morphometric data, PLS allows

for the examination of patterns of covariation between

anatomical structures (i.e., blocks), which are defined a priori.

PLS analysis produces linear combinations of variables called

Fig. 3 – Scatter plot of individual principal component

scores for the first two principal components. White

circles = experimental pigs; gray circles = control pigs.

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0936

singular axes, which maximize covariation between the

blocks of data. The strength of the covariation between the

singular axes is measured as the correlation (r) of individual

singular warp scores along the singular axes. We additionally

assessed the strength of the relationship between the two

blocks using the RV coefficient,22,23 which is a multivariate

analogue of the coefficient of determination (r2). Statistical

significance for both the PLS analysis and RV coefficient were

assessed using permutation tests (n = 999) to determine

whether the strength of the relationship between the two

blocks using both measures is greater than would be expected

to occur by chance.21,24 All analyses were conducted using the

Geomorph package in R.25

Fig. 5 – Superimpositions of mean experimental (black) and me

superimposed along condylar landmarks. (b) Mean shapes sup

Fig. 4 – Thin-plate splines illustrating morphological variation a

the positive end of PC1 is shown in (a) while shape variation a

3. Results

There was a statistically significant difference in mandibular

shape between the experimental and control groups as

indicated by the result of the Procrustes ANOVA (ss = 0.0078;

df = 1; P = 0.01). Mandibular shape differences between trial

groups were also reflected in the results of the PCA. The

experimental and control groups were largely separated along

PC1 (26.9%) although there was some overlap especially with

regard to one control pig that fell at the extreme end of the

experimental trial group’s morphospace (Fig. 3). PC1 primarily

described variation in the angular relationship between the

mandibular ramus and corpus. As a result of the surgically

induced dorsal orientation of the snout, mandibular shape in

the experimental group tended to exhibit a pattern consistent

with greater anterior mandibular rotation. As evidenced by the

thin-plate spline in Fig. 4a, the experimental pigs were

characterized by anterior displacement of mandibular ramus

landmarks (including the coronoid and condyloid processes)

and superior displacement of the anterior corpus landmarks.

This resulted in a more acute gonial angle and a relative

reduction in the overall anterior–posterior dimensions of the

mandible. The control pigs (Fig. 4b), in contrast, exhibited a

mandibular shape consistent with relatively less anterior

mandibular rotation. In particular, the control pigs were

characterized by a more posteriorly oriented ramus and an

inferior displacement of the anterior corpus resulting in a

larger gonial angle and relatively longer anterior–posterior

mandibular dimensions.

Morphological variation between the experimental and

control groups is further illustrated in Fig. 5 in which trial

group mean shapes have been superimposed at the mandibu-

lar condyle (Fig. 5a) and mandibular plane (Fig. 5b). We note

an control (gray) mandibular shapes. (a) Mean shapes

erimposed along the mandibular plane.

long the first principal component. Mandibular shape along

long the negative end of PC1 is shown in (b).

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0 937

that unlike the Procrustes superimposition used for the

statistical analyses, these superimpositions are used for

illustrative purposes only (i.e., they were not used for

quantitative analysis). When superimposed at the mandibular

condyle, the mean experimental mandibular shape clearly

exhibits a dorsal rotation of the corpus following the dorsal

reorientation of the experimental trial group pigs. In addition,

there is an inferior displacement of the gonial region relative

to superior ramus. When superimposed along the mandibular

plane, the mandibular ramus of the mean experimental shape

is anteriorly displaced and the condylar region is more

vertically oriented when compared to the oblique orientation

of the mean control shape.

The results of our PLS analysis (Fig. 6a and b) reveal that

there is a strong significant correlation between the morphol-

ogy of the condylar and non-condylar regions across our

experimental and control trial groups (r = 0.90; P < 0.001). The

strength of the pattern of covariation between the two blocks

is further evident from the RV coefficient (RV = 0.53; P < 0.001)

which falls to the far right of the distribution of RV coefficients

calculated from randomly permuted landmark combinations,

indicating that the two blocks are integrated.

Correlated patterns of morphological variation along the

first singular axes are illustrated in Fig. 6c and d. These results

are similar to the morphological variation arrayed along PC1.

As the mandibular ramus becomes more vertically oriented

relative to the mandibular corpus, resulting in a smaller gonial

Fig. 6 – Results of the PLS analysis. (a) Scatter plot of PLS scores

(block 2). White circles = experimental pigs; gray circles = contro

correlations. The arrow indicates the correlation of the condyla

illustrating patterns of morphological covariation between the c

(black landmarks).

angle, there is a tendency for the condylar process to become

more anteriorly displaced. Moreover, the condylar articular

surface is rounded indicating greater vertical positioning of

the superior aspect of the condyle. In contrast, a more oblique

ramus relative to corpus is associated with a more posteriorly

displaced condylar process with a flattened articular surface

that is similarly posteriorly displaced.

4. Discussion and conclusions

The effects of altered mandibular posture via protrusive

functional appliances are well documented in both human

subjects,6,26 and experimental animal models.9,10,13,14 These

studies have shown that mandibular protrusion results in

altered mandibular condylar development and greater posteri-

or rotation of the mandible. However, despite the large number

of studies that have focused on the effects of protrusion, far

fewer studies have examined growth modifications that

encourage anterior rotation of the mandible. In the present

study, we examined the influence of experimentally altered

mandibular posture on mandibular form via superior reposi-

tioning of the maxilla in a pig model. Pigs are well regarded as

the best non-primate model for the human temporomandibular

joint,26–28 and as such, the results from our analysis are

particularly relevant to understanding mandibular growth

dynamics in humans. Ultimately, the results of our analysis

for the corpus/ramus (block 1) and the condyloid process

l pigs. (b) Distribution of randomly permuted PLS

r and non-condylar blocks. (c and d) Thin-plate splines

ondylar block (gray landmarks) and non-condylar block

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0938

are important for a more thorough understanding of the

influence of mandibular posture on patterns of rotation, the

potential utility of applied anterior mandibular rotation for the

correction of hyperdivergent mandibular growth, and a broader

understanding of the integrative effects of maxillary form on

the growth of the mandible.

The most apparent changes in mandibular form associated

with superior displacement of the maxilla were found in the

gonial region. The morphological differences between our

experimental and control trial groups were largely consistent

with the suite of mandibular features commonly associated

with anterior and posterior mandibular rotation in human

subjects.2,3,29 As a result of maxillary growth modification,

there was a considerable reduction in the gonial angle in the

experimental trial group. This resulted from the dorsal

reorientation of the mandibular corpus relative to the ramus

and mirrored the reorientation of the snout documented in

our previous analysis.18 Coupled with the reorientation of the

snout and reduced gonial angle, there was a relative increase

in mandibular ramus height. This is evident in the patterns of

thin-plate spline deformation in the inferior gonial region, and

in the inferior displacement of the lower border of the gonial

region relative to the condyles when superimposing the mean

experimental and control trial group shapes at the condyles.

This result is consisted with Sugiyama et al.13 who found that

protrusive appliances resulted in a reduction in mandibular

ramus height in their rat model.

Increased anterior rotation of the mandible in our

experimental trial group was significantly correlated with

morphological changes in the condylar region. The results of

our partial least squares analysis indicate that anterior

mandibular rotation is associated with a more vertically

oriented condyloid process. This is evident both in the position

of the condyloid process relative to the mandibular ramus and

the shape of the condylar articular surface. This suggests that

altered mandibular posture associated with superior displace-

ment of the maxilla may have resulted in greater vertical

condylar growth in contrast to the control sample to produce

the altered mandibular morphology. In general, this result

follows previous experimental animal studies that have

documented significant adaptive chances in condylar growth

and remodeling via altered mandibular posture using protru-

sive appliances.9,10,13,30

The effects of altered maxillary position on the morphology

of the mandibular condyle suggest that the experimentally

induced change in mandibular posture had a significant effect

on the mechanical environment of the temporomandibular

joint8 resulting in a change in condylar shape. Indeed, an

alteration in the mechanical environment of the condylar

region resulting from distraction osteogenesis also results in

an alteration in the shape of articular surface of the

condyle.31,32 Rafferty et al.32 documented in a pig model that

the distraction side condyle exhibited a decrease and

reorientation in mechanical strain. This was associated with

greater convexity of the condyle resulting from an increase in

mineralization in the central region of the articular surface.

Previous studies have documented that variation in man-

dibular posture has a significant influence on the anterior–

posterior dimensions of the mandible. This is evidenced

by increased mandibular length resulting from the use of

protrusive appliances in both experimental animal mod-

els14,33,34 and human samples.35 In a similar fashion our

experimental sample, with increase anterior rotation exhibited

a relative reduction in mandibular length as evidenced by thin-

plate spine deformation in our principal components and

partial least squares analyses. The effects of altered posture on

mandibular length have lead researchers to suggest that

variation in condylar position has a significant influence on

the rates of growth the condylar cartilages.33,34 Araujo et al.6

have argued, however, that mandibular length variation is more

likely the result of the direction of condylar growth rather than

changes in the overall magnitude. Given the nature of the

sample used in the present study (i.e., static vs. longitudinal

comparisons) we are unable to directly assess whether reduced

mandibular length is the result of a reduction in growth at the

condyle. Nevertheless, the reduction in mandibular length in

our experimental sample is at least partly a function of shape

differences associated with the reorientation of the corpus and

reduced gonial angle. As such, this result is consistent with the

conclusions drawn by Araujo et al.6

The changes in mandibular morphology in our experimen-

tal trial group suggest that orthodontic treatments designed to

encourage anterior rotation of the mandible may be useful for

skeletal correction of hyperdivergent patients. The use of

protrusive appliances and headgear normally used to treat

hyperdivergent patients often produces changes in dental

arch relationships but does not correct increased posterior

mandibular rotation associated with hyperdivergent mor-

phology.15,36 Treatments that encourage anterior mandibular

rotation, on the other hand, are expected to increase vertical

condylar growth thereby resulting in skeletal correction of

hyperdivergent mandibular growth. Buschang et al.15 for

example, have shown that molar intrusion using miniscrew

implants in Class II hyperdivergent patients can produce

favorable skeletal changes in the mandible during treatment.

This includes increased vertical condylar growth, a reduction

in the gonial angle and a flatter mandibular plane. The results

of our analysis provide important experimentally derived

evidence that further underscores the influence of altered

mandibular posture on encouraging anterior rotation of the

mandible.

The results of our analysis indicate that experimentally

altered growth in the maxillary region via ridged plate fixation

of the circummaxillary sutures has a significant influence on

the growth of both the anterior and posterior aspects of the

mandible. While our understanding of the patterns of

integration between the cranium and mandible are incom-

plete, generally speaking, previous researchers have docu-

mented a relative modularity of the anterior and posterior

mandibular regions both animal models37,38 and in humans39.

Following Enlow’s Counterpart Principle,2 the mandibular

corpus forms the inferior component of the anterior facial

column and as such, its form is influenced by the integrated

growth of the ethmomaxillary complex. Variation in the

mandibular ramus, on the other hand, is influenced to a

greater degree by the development of the posterior facial

column. Indeed, recent studies have underscored the close

morphological relationship between the mandibular ramus

and middle cranial fossa suggesting that these structures form

an integrated ‘‘petroso-mandibular unit.’’40 In spite of the

a r c h i v e s o f o r a l b i o l o g y 6 0 ( 2 0 1 5 ) 9 3 3 – 9 4 0 939

relative modularity of the anterior and posterior regions of the

mandible, our results underscore that morphological variation

in the maxillary region results in significant morphological

changes across the anterior and posterior components of the

mandible. As such, while the there is a level of modularity

between the corpus and ramus, morphological changes that

affect the posture of the mandible have a more global effect on

mandibular form.

Ultimately, a more thorough understanding of the devel-

opmental relationship between the cranium and mandible are

integral for understanding the precise influence of larger

cranial growth dynamics on mandibular form. This is

particularly important given that recent work by Alcaron

et al.29 found that the strength and pattern of cranial–

mandibular integration varies with facial type (i.e., dolicho-

facial vs. brachyfacial). Moreover, their results indicate that

morphological integration between the cranium and mandible

has a strong influence on the manifestation of skeletal

malocclusion. Nevertheless, a significant amount of variation

in skeletal malocclusion is independent of cranial–mandibular

integration. This has significant implications for the success-

ful treatment of skeletal discrepancies using orthopedic

appliances given that the response to treatment may be

affected by the relative level of cranial and mandibular

integration. As such, a greater understanding of the influence

of maxillary growth on mandibular form is important with

regard to the etiology of skeletal discrepancies, especially

given that skeletal discrepancies are predictably associated

with patterns of mandibular rotation.

Funding

This research was funded by an internal University of Iowa

OVPR BSFP Developmental Biology Grant #50255004.

Competing interest

None declare.

Ethical approval

Approval was given by The University of Iowa Institutional

Animal Care and Use Committee.

Acknowledgements

We would like to thank the editor and reviewer for their

helpful comments regarding this manuscript. This research

was funded by a University of Iowa OVPR BSFP Developmental

Biology Grant.

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