University of Iowa

Iowa Research Online

Theses and Dissertations

Spring 2013

The relationship between the absence of third

molars and the development and eruption of the
adjacent second molar
Mina Eileen Abdolahi
University of Iowa

Copyright 2013 Mina Eileen Abdolahi

This thesis is available at Iowa Research Online: http://ir.uiowa.edu/etd/2429

Recommended Citation
Abdolahi, Mina Eileen. "The relationship between the absence of third molars and the development and eruption of the adjacent
second molar." MS (Master of Science) thesis, University of Iowa, 2013.
http://ir.uiowa.edu/etd/2429.

Follow this and additional works at: http://ir.uiowa.edu/etd

Part of the Orthodontics and Orthodontology Commons

THE RELATIONSHIP BETWEEN THE ABSENCE OF THIRD MOLARS AND THE
DEVELOPMENT AND ERUPTION OF THE ADJACENT SECOND MOLAR

by
Mina Eileen Abdolahi

A thesis submitted in partial fulfillment

of the requirements for the Master of
Science degree in Orthodontics
in the Graduate College of
The University of Iowa

May 2013

Thesis Supervisor: Professor Thomas E. Southard

 Graduate College
The University of Iowa
Iowa City, Iowa

CERTIFICATE OF APPROVAL
_______________________

MASTER'S THESIS
_______________

This is to certify that the Master's thesis of

Mina Eileen Abdolahi

has been approved by the Examining Committee

for the thesis requirement for the Master of Science
degree in Orthodontics at the May 2013 graduation.

Thesis Committee: __________________________________

Thomas E. Southard, Thesis Supervisor

__________________________________
Robert Franciscus

__________________________________
Steven D. Marshall

__________________________________
Clayton T. Parks
To my husband, Ali

ii
 ACKNOWLEDGMENTS

I would like to thank the members of my committee, Dr. Thomas Southard, Dr.
Robert Franciscus, Dr. Steven Marshall, and Dr. Clayton Parks for their generous
guidance in completing this thesis. I would like to thank Dr. Nathan Holton for
performing the statistical analyses on the data collected and for reviewing this thesis.
Additionally, I would like to thank Chris Hartman for his help in collecting the data.
Finally, I would like to thank my co-residents Laura Bonner, Jordan Poss, Alison Ray,
and Brendon Swenson, and my husband, Ali, for their unconditional support with this
thesis and throughout residency.

iii
 TABLE OF CONTENTS

LIST OF TABLES .............................................................................................................. v

LIST OF FIGURES .......................................................................................................... vii
INTRODUCTION .............................................................................................................. 1
LITERATURE REVIEW ................................................................................................... 2
Dental Development ........................................................................................ 2
Dental Eruption ................................................................................................ 5
Dental Agenesis ............................................................................................... 9
Third Molar Agenesis .................................................................................... 10
Hypotheses ..................................................................................................... 11
MATERIALS AND METHODS ...................................................................................... 12
Statistical Analysis......................................................................................... 14
RESULTS ....................................................................................................................... 15
Descriptive Statistics ..................................................................................... 15
Hypothesis 1 .................................................................................................. 27
Hypothesis 2 .................................................................................................. 35
DISCUSSION ................................................................................................................... 43
Limitiations and Future Research .................................................................. 45
CONCLUSIONS............................................................................................................... 47
REFERENCES ................................................................................................................. 48

iv
 LIST OF TABLES

Table
1. Mean ages of tooth emergence divided by gender and race ...................................... 6
2. Cumulative frequency of third molar absence ......................................................... 15
3. Frequency of each third molar’s absence ................................................................ 16
4. Mann-Whitney U-values and p-values for each third molar, comparing the
ages of those with and without third molars ............................................................ 16
5. Frequency of developmental stages of maxillary right second molars,
separated by presence and absence of adjacent third molar .................................... 18
6. Frequency of developmental stages of maxillary left second molars, separated
by presence and absence of adjacent third molar .................................................... 19
7. Frequency of developmental stages of mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 20
8. Frequency of developmental stages of mandibular right second molars,
separated by presence and absence of adjacent third molar .................................... 21
9. Frequency of eruption stages of maxillary right second molars, separated by
presence and absence of adjacent third molar ......................................................... 23
10. Frequency of eruption stages of maxillary left second molars, separated by
presence and absence of adjacent third molar ......................................................... 24
11. Frequency of eruption stages of mandibular left second molars, separated by
presence and absence of adjacent third molar ......................................................... 25
12. Frequency of eruption stages of mandibular right second molars, separated by
presence and absence of adjacent third molar ......................................................... 26
13. Frequency of fully-developed and developing maxillary right second molars,
separated by presence and absence of adjacent third molar .................................... 27
14. Frequency of fully-developed and developing maxillary left second molars,
separated by presence and absence of adjacent third molar .................................... 29
15. Frequency of fully-developed and developing mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 31
16. Frequency of fully-developed and developing mandibular right second
molars, separated by presence and absence of adjacent third molar ....................... 33
17. Frequency of fully-erupted and erupting maxillary right second molars,
separated by presence and absence of adjacent third molar .................................... 35

v
18. Frequency of fully-erupted and erupting maxillary left second molars,
separated by presence and absence of adjacent third molar .................................... 37
19. Frequency of fully-erupted and erupting mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 39
20. Frequency of fully-erupted and erupting mandibular right second molars,
separated by presence and absence of adjacent third molar .................................... 41

vi
 LIST OF FIGURES

Figure
1. Stages of tooth development ...................................................................................... 3
2. Epithelial-mesenchymal signaling regulating tooth devleopment ............................. 4
3. A diagnostic algorithm for delayed tooth eruption .................................................... 8
4. Assessment of tooth germ formative condition, as defined by Demirjian............... 13
5. Age span of patients with maxillary left third molar absent compared to those
with maxillary left third molar present .................................................................... 17
6. Frequency of developmental stages of maxillary right second molars,
separated by absence and presence of adjacent third molar .................................... 19
7. Frequency of developmental stages of maxillary left second molars, separated
by presence and absence of adjacent third molar .................................................... 20
8. Frequency of developmental stages of mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 21
9. Frequency of developmental stages of mandibular right second molars,
separated by presence and absence of adjacent third molar .................................... 22
10. Frequency of eruption stages of maxillary right second molars, separated by
presence and absence of adjacent third molar ......................................................... 23
11. Frequency of eruption stages of maxillary left second molars, separated by
presence and absence of adjacent third molar ......................................................... 24
12. Frequency of eruption stages of mandibular left second molars, separated by
presence and absence of adjacent third molar ......................................................... 25
13. Frequency of eruption stages of mandibular right second molars, separated by
presence and absence of adjacent third molar ......................................................... 26
14. Frequency of fully-developed and developing maxillary right second molars,
separated by presence and absence of adjacent third molar .................................... 28
15. Percentage of fully-developed and developing maxillary right second molars,
separated by presence and absence of adjacent third molar .................................... 28
16. Frequency of fully-developed and developing maxillary left second molars,
separated by presence and absence of adjacent third molar .................................... 30
17. Percentage of fully-developed and developing maxillary left second molars,
separated by presence and absence of adjacent third molar .................................... 30

vii
18. Frequency of fully-developed and developing mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 32
19. Percentage of fully-developed and developing mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 32
20. Frequency of fully-developed and developing mandibular right second
molars, separated by presence and absence of adjacent third molar ....................... 34
21. Percentage of fully-developed and developing mandibular right second
molars, separated by presence and absence of adjacent third molar ....................... 34
22. Frequency of fully-erupted and erupting maxillary right second molars,
separated by presence and absence of adjacent third molar .................................... 36
23. Percentage of fully-erupted and erupting mandibular right second molars,
separated by presence and absence of adjacent third molar .................................... 36
24. Frequency of fully-erupted and erupting maxillary left second molars,
separated by presence and absence of adjacent third molar .................................... 38
25. Percentage of fully-erupted and erupting maxillary left second molars,
separated by presence and absence of adjacent third molar .................................... 38
26. Frequency of fully-erupted and erupting mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 40
27. Percentage of fully-erupted and erupting mandibular left second molars,
separated by presence and absence of adjacent third molar .................................... 40
28. Frequency of fully-erupted and erupting mandibular right second molars,
separated by presence and absence of adjacent third molar .................................... 42
29. Percentage of fully-erupted and erupting mandibular right second molars,
separated by presence and absence of adjacent third molar .................................... 42

viii
 1

INTRODUCTION

The timing of the eruption of permanent teeth is critical in dictating a patient’s

orthodontic treatment. The timing of dental eruption can be extremely variable. Research
has shown that many factors can affect the timing of dental eruption, including race,
gender, and environmental factors (Garn et al. 1973, Adler 1963, Clements et al. 1957,
Eveleth 1966). Additionally, dental eruption can be disrupted due to mechanical
obstructions, syndromes, and nutritional deficiencies (Suri et al. 2004). Research also
shows that dental agenesis, or missing teeth, has been associated with delayed dental
development and eruption (Harris et al. 2011, Tunç et al. 2011, Uslenghi et al. 2006,
Bailit et al. 1968, Ruiz-Mealin et al. 2012). The third molar is the most common tooth to
be missing in humans (Celikoglu & Kamak 2012, Baba-Kawano et al. 2002, Garn et al.
1963). A few studies have suggested a relationship between third molar agenesis and
delayed dental eruption of the remaining teeth. Garn et al. (1963) showed a relationship
between third molar agenesis and delay in cusp calcification and alveolar eruption of the
remaining mandibular posterior teeth. Baba-Kawano et al. (2002) also concluded delayed
dental development occurs more often in patients missing mandibular third molars.
The purpose of the present study is to determine whether patients exhibiting third
molar agenesis also exhibit delayed formation and eruption of the adjacent second
molar(s). Knowing whether the second molars will erupt at a normal age or later can help
an orthodontist in planning a patient’s treatment. This study will allow orthodontists to
better predict the timing of second molar eruption in preparation for their patients’
treatment.
 2

LITERATURE REVIEW

Dental Development
Teeth develop from stomodeal or pharyngeal epithelium and from neural crest-
derived mesenchyme, and it is a sequence of reciprocal interactions between the
epithelium and mesenchyme that dictates the process of tooth morphogenesis (Thesleff &
Sharpe 1997). Sharpe (1995) proposed that tooth shape and position are determined by
the actions of different homeobox genes expressed in facial mesenchyme that is derived
from the neural crest. Therefore, the pattern of the teeth in the oral cavity is believed to
be determined by different populations of neural crest cells. Qiu et al. (1997)
demonstrated that several homeobox genes, Dlx-1 and Dlx-2 for molars, for example, are
expressed in spatially-restricted areas of oral mesenchyme before the initiation of tooth
development.
During tooth development, the oral epithelium first thickens and buds into the
underlying mesenchyme. The remainder of tooth morphogenesis is instructed by the
dental mesenchyme. The mesenchyme condenses around the bud (see Figure 1), and the
epithelium folds, forming the shape of the tooth crown. This is called the cap stage. The
peripheral cells of the condensed mesenchyme extend around the epithelial portion,
which forms the dental follicle. The follicle contains cementoblasts that lay dental
cementum during root formation. At the junction of the epithelial and mesenchymal
tissues, the odontoblasts and ameloblasts develop to form the dentin and enamel,
respectively. This occurs during the bell stage of tooth development (Thesleff & Sharpe
1997).
 3

Figure 1 Stages of tooth development

Source: Thesleff, I. and P. Sharpe. 1997. “Signalling networks regulating dental

development.” Mechanisms of Development 67(2):111-23.

There are several signaling pathways that occur between the epithelium and mesenchyme
that allow tooth development to occur, including the BMP (bone morphogenetic protein)
signaling pathway, FGF (fibroblast growth factor) signaling pathway, Hedgehog
signaling pathway, and the Wnt (wingless protein) signaling pathway. BMPs and FGFs
have been shown to stimulate the expression of muscle segment homeobox-1 (Msx-1),
which has a critical role in regulating epithelial-mesenchymal interactions during tooth
development (Shimizu & Maeda 2009). Mutations in the Msx-1 gene have been shown to
arrest tooth development at the bud stage. FGFs also stimulate cell proliferation in the
dental epithelium and mesenchyme during tooth development. Sonic hedgehog (Shh) is
expressed in the dental epithelium at different stages and is believed to be involved in
tooth bud initiation. In the Wnt signaling pathway, lymphoid enhancer-binding factor
(Lef)-1 is activated, and Lef-1 knockout mice showed tooth development arrested at the
 4

bud stage. Figure 2 is a diagram showing the epithelial-mesenchymal signaling regulating

tooth development. (Thesleff & Sharpe 1997)

Figure 2 Epithelial-mesenchymal signaling regulating tooth development

Source: Source: Thesleff, I. and P. Sharpe. 1997. “Signalling networks regulating dental
development.” Mechanisms of Development 67(2):111-23.
 5

Dental Eruption
The eruption of teeth into the oral cavity occurs after the crown of the tooth has
developed and while the roots are developing (Thesleff & Sharpe 1997). The crown of
the tooth moves away from the area of root development. There are two necessities for
tooth eruption to occur: there must be a force generated to move the tooth along its
eruption path, and bone and primary roots in the eruption path must be resorbed. It is still
unclear what the mechanism is to force a tooth along its eruption path, as teeth have still
been shown to erupt without a periodontal ligament (PDL) and with the root apex cut off
(Proffit & Frazier-Bowers 2009); however, a study by Oikawa et al. (2011) suggests that
active eruption occurs predominantly by alveolar bone formation associated with
formation of alveolar crest fibers and rearrangement of periodontal fibers in the PDL, and
it is believed that transforming growth factor (TGF)-!1 is involved in this. Proffit &
Frazier-Bowers (2009) also suggest that the eruption path is not cleared due to the tooth
erupting, but rather it is cleared prior to eruption. The osteoclasts that resorb the bone
come from the dental follicle (Frazier-Bowers et al. 2010). There are four stages of
eruption once the tooth emerges into the oral cavity. The first is the pre-functional spurt,
which occurs as the tooth erupts to the occlusal plane. The next three stages occur with
the growth of the face. Juvenile equilibrium occurs as the jaw is slowly growing, the teeth
slowly erupt. The adolescent eruptive spurt occurs as facial growth accelerates, and the
teeth continue to erupt to stay in occlusion. The adult equilibrium is the final stage, where
teeth continue to erupt even after growth is complete. This is exhibited when a tooth
erupts after its antagonist is lost in late adult life. (Proffit & Frazier-Bowers 2009)
The timing of eruption of the permanent teeth has been shown to be affected by
different factors, including race and gender (Garn et al. 1973). Table 1 shows the average

age at which each permanent tooth erupts for Caucasoid and Negro boys and girls (Garn
et al. 1973).
 6

Table 1 Mean ages of tooth emergence divided by gender and race

Source: Garn, S.M.; Sandusky, S.T.; Nagy, J.M.; and F.L Trowbridge. 1973. “Negro-
Caucasoid differences in permanent tooth emergence at a constant income level.”
Archives of Oral Biology 18(5):609-15.

Additionally, environmental factors such as caries in the deciduous dentition can affect
the timing of permanent tooth eruption (Adler 1963). Clements et al. (1957) showed that
a socioeconomic factor could be involved in the timing of tooth eruption. They concluded
that the permanent teeth of children attending urban elementary schools erupt later than
the teeth of children attending independent and rural elementary schools (Clements et al.
1957). Climate may also have a role in the timing of tooth eruption, as suggested by
Eveleth (1966), who showed earlier dental eruption in American children living in the
tropics than those living in the United States.
The rate of tooth eruption can also be affected by different local factors. Proffit
and Frazier-Bowers (2009) found that intermittent light force against an erupting tooth
does not affect the rate of eruption. However, they suggest that a surge in growth
hormone level can increase tooth eruption rate during the pre-functional eruptive spurt.
 7

Additionally, they showed that an increase in blood flow to a tooth also increases its rate
of eruption.
Disruption in tooth eruption ranges from delayed eruption to a complete failure of
eruption and may or may not be associated with syndromes. Johnsen (1977) reported a
four percent incidence of disrupted dental eruption, with the most commonly affected
teeth being third molars, maxillary canines, and mandibular second premolars (Grover &
Lorton 1985). Problems in the appositional/resorptive mechanism in alveolar bone can
cause ankylosis, primary failure of eruption, and failure of eruption due to insufficient
arch length. There can be mechanical obstruction of the teeth to erupt, for example, by
lateral tongue pressure, or there can be genetic causes. Defects in the parathyroid
hormone receptor 1 (PTH1R) gene have been found in families exhibiting primary failure
of eruption. Frazier-Bowers et al. (2010) found that PTH1R acts with genes associated
with bone remodeling and eruption. Sano et al. (2010) showed that in a Japanese
population with delayed eruption of maxillary first molars, the development of these teeth
was delayed on average by 2.5 years as compared to the Japanese average. Suri et al.
(2004) developed an algorithm to diagnose different conditions that delayed dental
eruption has been shown to occur under (see Figure 3). The conditions range from pre-
term birth and nutritional deficiency to physical obstruction from scarring and cysts to
Down and Gardner syndromes (Suri et al. 2004).
 8

Figure 3 A diagnostic algorithm for delayed tooth eruption

Source: Suri, L.; Gagari, E.; and H. Vastardis. 2004. “Delayed tooth eruption:
pathogenesis, diagnosis, and treatment. A literature review.” American Journal of
Orthodontics and Dentofacial Orthopedics 126(4):432-45.
 9

Dental Agenesis
Dental agenesis is defined as the failure of a tooth to develop. Many studies have
reported a prevalence of 3 to 11% in European and Asian populations. Tooth agenesis
occurs more commonly in females than males and is more often associated with non-
syndromic causes than syndromic ones (Shimizu & Maeda 2009). In patients with more
than one tooth missing, agenesis is found to occur more often unilaterally than bilaterally
(Harris et al. 2011). Causes of agenesis include genetic defects, radiotherapy,
chemotherapy, and over 60 syndromes including Down syndrome, cleft lip and/or palate,
and ectodermal dysplasia (Nieminen 2009, Shimizu & Maeda 2009). A family presenting
with agenesis of second premolars and third molars was found to have a defect in the
Msx-1 gene (Shimizu & Maeda 2009, Vastardis 2000, Mostowska et al. 2012). This
defect prevents the mesenchyme from inducing the epithelial signaling center, the enamel
knot, ceasing tooth developing at the bud stage. Mutations in paired box 9 (Pax-9),
necessary for condensation of the dental mesenchyme around the tooth bud epithelium,
and axis inhibition protein 2 (AXIN2), which inactivates the Wnt-signaling pathway,
have also been shown to play a role in tooth agenesis (Boeira Junior & Echeverrigaray
2012, Galluccio et al. 2012, Shimizu & Maeda 2009).
Dental agenesis has been found to be associated with other dental anomalies.
Harris et al. (2011) showed that children with simple hypodontia (missing one to four
permanent teeth, omitting third molars) exhibit more asymmetric timing in tooth
formation from one side of the mouth to the other, as compared to children without dental
agenesis. Patients with dental agenesis also tend to display overall delayed tooth
formation, with the amount of dental delay increasing with the magnitude of agenesis
(Ruiz-Mealin et al. 2012, Uslenghi et al. 2006). Tunç et al. (2011) found dental

development is delayed by 0.3 years in patients with hypodontia, while Uslenghi et al.
(2006) found a delay of 1.51 years. Bailit et al. (1968) reported that patients with
 10

hypodontia (omitting third molars) exhibit generalized delayed dental eruption, but not
significantly different from those without hypodontia (Bailit et al. 1968).

Third Molar Agenesis

The third molar is the most common tooth to be missing in humans, followed by
second premolars and maxillary lateral incisors, with an agenesis prevalence reported to
range from 1.0-51.1% among groups of different races (Celikoglu & Kamak 2012, Baba-
Kawano et al. 2002, Garn et al. 1963). Out of a group of 476 American whites, Garn et al.
(1963) reported a third molar agenesis prevalence of 16%. Third molar formation
typically begins around 9 to 10 years of age, but onset has been shown to occur anywhere
from age 5.86 to 14.66 years (Bolaños et al. 2003). Complete calcification is typically
complete by 14 years of age, and root formation is typically completed around 18 years
of age (Bolaños et al. 2003). The most common form of third molar agenesis is missing
all four third molars (Celikoglu et al. 2011, Bolaños et al. 2003). Third molar agenesis
most frequently occurs in the mandible and is more common in females (Garn et al.
1963). As mentioned above, the Wnt signaling pathway is critical in tooth development,
specifically in molar dentin formation. This pathway can be blocked by excess levels of
Dickkopf-related protein 1 (DKK1) secreted from pulpal cells, which inhibits further
development of the third molar and also results in molars of reduced size and with shorter
root length (Han et al. 2011).
Studies have reported that patients missing at least one third molar have an 11.2-
13% increased likelihood of missing other teeth and show a generalized delay in dental
development and eruption (Celikoglu et al. 2011, Garn et al. 1963, Baba-Kawano et al.
2002). Those missing more third molars showed a general tendency to be missing more
of their remaining teeth (Garn et al. 1963). Garn et al. (1963) showed an association

between third molar agenesis and delay in cusp calcification and alveolar eruption of
mandibular posterior teeth, most notably the second molar. Garn et al. (1963) suggest the
 11

agenesis of the third molar may be the extreme expression of the factor affecting the
timing of tooth formation, causing a delay in development of the remaining teeth as well.
When examining the unaffected (no third molar agenesis) siblings of the third molar
agenesis group, they also noted a significant delay in cusp calcification and eruption of
the same posterior teeth, suggesting a possible genetic relationship.

Hypotheses
For the present study, we hypothesize that patients missing a third molar will
exhibit delayed development of the adjacent second molar. Therefore, the null hypothesis
states that third molar agenesis will have no effect on the development of the adjacent
second molar. We predict that those without third molars present will have a statistically
significant delay in adjacent second molar development as compared to those with third
molars present.
In addition, we hypothesize that patients missing a third molar will also exhibit
delayed eruption of the adjacent second molar. The null hypothesis is that third molar
agenesis will have no effect on the eruption of the adjacent second molar. We predict that
those without third molars present will have a statistically significant delay in adjacent
second molar eruption as compared to those with third molars present.
 12

MATERIALS AND METHODS

For the present study, a search was performed of the patients of the University of
Iowa Department of Orthodontics using Dolphin Imaging software. The search criteria
put into Dolphin Imaging included patients at least 13 years of age with a panoramic
radiograph taken at their initial visit. This search yielded 2,667 patients. The next step
was to eliminate the patients that were younger than 13 years of age and at least 18 years
of age at their initial visit by using their birthdays and initial visit dates to calculate their
age at their initial visit. The age range of 13-17 years was chosen in order to find patients
both with delayed second molar eruption and their third molars still present. Next,
patients not of Caucasian race were eliminated using their photographs in Dolphin
Imaging. Patients with no photographs available to confirm their race were excluded.
This resulted in a sample size of 832. The panoramic radiographs of these 832 patients
were examined and the following were recorded: the presence or absence of each third
molar, the developmental stage of each second molar (1-8) according to Demirjian’s
eight-stage tooth development classification system (see Figure 4), and the eruption stage
of each second molar. The eruption stage of each second molar was classified as a 0 if the
second molar was unerupted, a 2 if it was erupting, and a 3 if it was fully erupted. A 1
was assigned if the second molar was erupting slower than the other erupting second
molars. Patients at least 17 years of age that were missing all four third molars were
excluded due to the possibility of the third molars having been extracted. Patients age 13
through 15 years without any third molars were excluded due to the possibility of later
development of their third molars, unless a future panoramic radiograph was available to
confirm the development of their third molars. Additionally, any patients with visible
syndromes or disorders in their photographs were excluded. These criteria resulted in a

final sample size of 739 patients.

 13

Figure 4 Assessment of tooth germ formative condition, as defined by Demirjian

Source: Baba-Kawano, S.; Toyoshima, Y.; Regalado, L.; Sa’do, B.; and A. Nakasima.
2002. “Relationship between congenitally missing lower third molars and late
formation of tooth germs.” Angle Orthodontist 72(2):112-7.
 14

Statistical Analysis
First, in order to determine if there was a significant difference in age between
those with and without third molars (p-value less than 0.05), a Mann-Whitney U test was
performed for each third molar. Because dental development and eruption differ with age,
this test was done to ensure that difference in age is not a confounding factor. Therefore,
age would not be the sole factor affecting the timing of dental development and eruption,
and samples of all ages could be studied together.
The hypotheses of this study are that patients with third molar agenesis will
exhibit delayed development and delayed eruption of the adjacent second molar. Due to
small sample sizes of second molar developmental stages 0-7 (see Results), these stages
were combined into a “developing” category, thereby establishing a two-stage system
based on whether the second molar was fully-developed or less than fully-developed.
Additionally, due to small sample sizes of second molar eruption stages 0-2, these stages
were combined into an “erupting” category, creating a two-stage system based on
whether the second molar was fully-erupted or less than fully-erupted. The two categories
were then divided into those with an adjacent third molar and those without. Pearson chi-
squared tests were then performed to determine whether there was a significant difference
in development and eruption of the second molar with the adjacent third molar absent
versus with the adjacent third molar present (p-value less than 0.05 for significance).
 15

RESULTS

Descriptive Statistics
In this sample of 739 patients, 597 (80.8%) had all four third molars present,
meaning the remaining 142 patients (19.2%) presented with at least one missing third
molar. Sixty-four patients (8.7%) presented missing one third molar, 49 patients (6.6%)
were missing two third molars, 11 patients (1.5%) were missing three third molars, and
18 patients (2.4%) were missing all four third molars, as seen in Table 2.

Table 2 Cumulative frequency of third molar absence

Number of 3rd molars Frequency Percent

missing

0 597 80.8

1 64 8.7

2 49 6.6

3 11 1.5

4 18 2.4

Total 739 100.0

Looking at each individual third molar, the maxillary right third molar was absent
in 67 patients (9.1%), the maxillary left third molar was absent in 60 patients (8.1%), the
mandibular left third molar was absent in 72 patients (9.7%), and the mandibular right
third molar was absent in 68 patients (9.2%), as seen in Table 3.
 16

Table 3 Frequency of each third molar’s absence

Third molar Absent Present

Maxillary right 67 (9.1%) 672 (90.9%)

Maxillary left 60 (8.1%) 679 (91.9%)

Mandibular left 72 (9.7%) 667 (90.3%)
Mandibular right 68 (9.2%) 671 (90.8%)

Table 4 shows the Mann-Whitney U-values and p-values for each third molar,
comparing the ages of those with and without third molars. The only third molar with a
significant age difference between the absent and present groups is the maxillary left
third molar (p < 0.05).

Table 4 Mann-Whitney U-values and p-values for each third molar, comparing the ages
of those with and without third molars

Third Molar U-value p-value

Maxillary right 22462.5 0.975

Maxillary left 16246.5 0.007
Mandibular left 22801.0 0.463
Mandibular right 21769.5 0.516
 17

Figure 5 shows the difference in ages between those with their maxillary left third
molar absent and present, exhibiting that those patients with their maxillary left third
molar missing are significantly older than those with their maxillary left third molar
present.

Figure 5 Age span of patients with maxillary left third molar absent compared to those
with maxillary left third molar present
 18

Tables 5 through 8 and Figures 6 through 9 show the frequency of developmental

stages for each second molar, as defined by Demirjian, divided into those with an
adjacent third molar absent and those with an adjacent third molar present. A
developmental stage of 8 means the tooth is fully-developed, while those below 8 are still
developing. A stage of 0 indicates the second molar has not begun developing. Again,
due to the small sample sizes in developmental stages 0-7, they were collapsed into a
single category of “developing.”

Table 5 Frequency of developmental stages of maxillary right second molars, separated

by presence and absence of adjacent third molar

Developmental Maxillary right 3rd Maxillary right 3rd Total

Stage molar absent molar present
4 1 (0.1%) 0 (0.0%) 1 (0.1%)

5 2 (0.3%) 0 (0.0%) 2 (0.3%)

6 0 (0.0%) 5 (0.7%) 5 (0.7%)

7 8 (1.1%) 14 (1.9%) 22 (3.0%)

8 56 (7.6%) 653 (88.3%) 709 (95.9%)

Total 67 (9.1%) 672 (90.9%) 739 (100.0%)

 19

Figure 6 Frequency of developmental stages of maxillary right second molars, separated

by absence and presence of adjacent third molar

Table 6 Frequency of developmental stages of maxillary left second molars, separated by

presence and absence of adjacent third molar

Developmental Maxillary left 3rd Maxillary left 3rd Total

Stage molar absent molar present
0 0 (0.0%) 1 (0.1%) 1 (0.1%)

6 0 (0.0%) 4 (0.5%) 4 (0.5%)

7 6 (0.8%) 14 (1.9%) 20 (2.7%)

8 54 (7.3%) 660 (89.3%) 714 (96.6%)

Total 60 (8.1%) 679 (91.9%) 739 (100.0%)

 20

Figure 7 Frequency of developmental stages of maxillary left second molars, separated

by absence and presence of adjacent third molar

Table 7 Frequency of developmental stages of mandibular left second molars, separated

by presence and absence of adjacent third molar

Developmental Mandibular left Mandibular left Total

Stage 3rd molar absent 3rd molar present
0 1 (0.1%) 0 (0.0%) 1 (0.1%)

5 2 (0.3%) 0 (0.0%) 2 (0.3%)

6 6 (0.8%) 3 (0.4%) 9 (1.2%)

7 20 (2.7%) 240 (32.5%) 260 (35.2%)

8 43 (5.8%) 424 (57.4%) 467 (63.2%)

Total 72 (9.7%) 667 (90.3%) 739 (100.0%)

 21

Figure 8 Frequency of developmental stages of mandibular left second molars,

separated by absence and presence of adjacent third molar

Table 8 Frequency of developmental stages of mandibular right second molars, separated

by presence and absence of adjacent third molar

Developmental Mandibular right Mandibular right Total

Stage 3rd molar absent 3rd molar present
0 4 (0.5%) 0 (0.0%) 4 (0.5%)

6 5 (0.7%) 3 (0.4%) 8 (1.1%)

7 20 (2.7%) 238 (32.2%) 258 (34.9%)

8 39 (5.3%) 430 (58.2%) 469 (63.5%)

Total 68 (9.2%) 671 (90.8%) 739 (100.0%)

 22

Figure 9 Frequency of developmental stages of mandibular right second molars,

separated by absence and presence of adjacent third molar

Tables 9 through 12 and Figures 10 through 13 show the frequency of eruption

stages for each second molar, divided into those with an adjacent third molar absent and
those with an adjacent third molar present. Eruption stage 0 indicates the second molar
has not begun erupting. Stages 1 and 2 mean the second molar is in the process of
erupting, and 3 indicates a fully-erupted second molar. Again, due to the small sample
sizes in eruption stages 0-2, they were collapsed into a single category of “erupting.”
 23

Table 9 Frequency of eruption stages of maxillary right second molars, separated by

presence and absence of adjacent third molar

Eruption Stage Maxillary right 3rd Maxillary right 3rd Total

molar absent molar present
0 12 (1.6%) 36 (4.9%) 48 (6.5%)

1 3 (0.4%) 3 (0.4%) 6 (0.8%)

2 8 (1.1%) 52 (7.0%) 60 (8.1%)

3 44 (6.0%) 581 (78.6%) 625 (84.6%)

Total 67 (9.1%) 672 (90.9%) 739 (100.0%)

Figure 10 Frequency of eruption stages of maxillary right second molars, separated

by presence and absence of adjacent third molar
 24

Table 10 Frequency of eruption stages of maxillary left second molars, separated by

presence and absence of adjacent third molar

Eruption Stage Maxillary left 3rd Maxillary left 3rd Total

molar absent molar present

0 10 (1.4%) 37 (5.0%) 47 (6.4%)

1 3 (0.4%) 2 (0.3%) 5 (0.7%)

2 3 (0.4%) 59 (8.0%) 62 (8.4%)

3 44 (5.9%) 581 (78.6%) 625 (84.5%)

Total 60 (8.1%) 679 (91.9%) 739 (100.0%)

Figure 11 Frequency of eruption stages of maxillary left second molars, separated

by presence and absence of adjacent third molar
 25

Table 11 Frequency of eruption stages of mandibular left second molars, separated by

presence and absence of adjacent third molar

Eruption Stage Mandibular left Mandibular left Total

3rd molar absent 3rd molar present
0 8 (1.1%) 15 (2.1%) 23 (3.2%)

1 1 (0.1%) 1 (0.1%) 2 (0.2%)

2 7 (0.9%) 34 (4.6%) 41 (5.5%)

3 56 (7.6%) 617 (83.5%) 673 (91.1%)

Total 72 (9.7%) 667 (90.3%) 739 (100.0%)

Figure 12 Frequency of eruption stages of mandibular left second molars, separated by

presence and absence of adjacent third molar
 26

Table 12 Frequency of eruption stages of mandibular right second molars, separated by

presence and absence of adjacent third molar

Eruption Stage Mandibular right Mandibular right Total

3rd molar absent 3rd molar present
0 9 (1.2%) 14 (1.9%) 23 (3.1%)

1 0 (0.0%) 1 (0.1%) 1 (0.1%)

2 5 (0.7%) 40 (5.4%) 45 (6.1%)

3 54 (7.3%) 616 (83.4%) 670 (90.7%)

Total 68 (9.2%) 671 (90.8%) 739 (100.0%)

Figure 13 Frequency of eruption stages of mandibular right second molars, separated by

presence and absence of adjacent third molar
 27

Hypothesis 1
Tables 13 through 16 and Figures 14 through 21 show the frequencies, chi-square
values, and p-values for each second molar grouped into those fully-developed and those
developing with and without an adjacent third molar present.
Table 13 and Figure 15 show that there is a significant difference in maxillary
right second molar development between those with an adjacent third molar present and
those with the adjacent third molar absent (p < 0.05). There are significantly more fully-
developed maxillary right second molars in patients with their adjacent third molar
present. In patients missing their maxillary right third molar, there are significantly more
developing adjacent second molars.

Table 13 Frequency of fully-developed and developing maxillary right second molars,

separated by presence and absence of adjacent third molar

2nd molar Maxillary Maxillary Chi-square p-value

developmental right 3rd right 3rd
status molar present molar absent
Fully- 653 (97.2%) 56 (83.6%) 28.893 0.000
developed
Developing 19 (2.8%) 11 (16.4%)
 28

Figure 14 Frequency of fully-developed and developing maxillary right second molars,

separated by presence and absence of adjacent third molar

Figure 15 Percentage of fully-developed and developing maxillary right second molars,

separated by presence and absence of adjacent third molar
 29

Table 14 and Figure 17 show that there is a significant difference in maxillary left
second molar development between those with an adjacent third molar present and those
with the adjacent third molar absent (p < 0.05). In patients with their maxillary left third
molar present, there are significantly more fully-developed adjacent second molars. In
patients their maxillary left third molar absent, there are significantly more developing
adjacent second molars.

Table 14 Frequency of fully-developed and developing maxillary left second molars,

separated by presence and absence of adjacent third molar

2nd molar Maxillary left Maxillary left Chi-square p-value

developmental 3rd molar 3rd molar
status present absent
Fully- 660 (97.2%) 54 (90.0%) 8.748 0.003
developed
Developing 19 (2.8%) 6 (10.0%)
 30

Figure 16 Frequency of fully-developed and developing maxillary left second molars,

separated by presence and absence of adjacent third molar

Figure 17 Percentage of fully-developed and developing maxillary left second molars,

separated by presence and absence of adjacent third molar
 31

Table 15 and Figure 19 show that there is not a significant difference in

mandibular left second molar development between those with an adjacent third molar
present and those with the adjacent third molar absent (p > 0.05), however the data does
suggest a tendency towards later development of the mandibular left second molar when
the adjacent third molar is absent.

Table 15 Frequency of fully-developed and developing mandibular left second molars,

separated by presence and absence of adjacent third molar

2nd molar Mandibular Mandibular Chi-square p-value

developmental left 3rd molar left 3rd molar
status present absent
Fully- 424 (63.6%) 43 (59.7%) 0.413 0.520
developed
Developing 243 (36.4%) 29 (40.3%)
 32

Figure 18 Frequency of fully-developed and developing mandibular left second molars,

separated by presence and absence of adjacent third molar

Figure 19 Percentage of fully-developed and developing mandibular left second molars,

separated by presence and absence of adjacent third molar
 33

Table 16 and Figure 21 show that there is not a significant difference in

mandibular right second molar development between those with an adjacent third molar
present and those with the adjacent third molar absent (p > 0.05), however the data does
suggest a tendency towards later development of the mandibular right second molar when
the adjacent third molar is absent.

Table 16 Frequency of fully-developed and developing mandibular right second molars,

separated by presence and absence of adjacent third molar

2nd molar Mandibular Mandibular Chi-square p-value

developmental right 3rd right 3rd
status molar present molar absent
Fully- 430 (64.1%) 39 (57.4%) 1.206 0.272
developed
Developing 241 (35.9%) 29 (42.6%)
 34

Figure 20 Frequency of fully-developed and developing mandibular right second molars,

separated by presence and absence of adjacent third molar

Figure 21 Percentage of fully-developed and developing mandibular right second molars,

separated by presence and absence of adjacent third molar
 35

Hypothesis 2
Tables 17 through 20 and Figures 22 through 29 show the frequencies, chi-square
values, and p-values for each second molar grouped into those fully-erupted and those
erupting with and without an adjacent third molar present. The percentages were
calculated out of the total of the specific third molar.
Table 17 and Figure 23 show that there is a significant difference in maxillary
right second molar eruption between those with an adjacent third molar present and those
with the adjacent third molar absent (p < 0.05). In patients with their maxillary right third
molar present, there are significantly more fully-erupted adjacent second molars. In
patients with their maxillary right third molar absent, there are significantly more
erupting adjacent second molars.

Table 17 Frequency of fully-erupted and erupting maxillary right second molars,

separated by presence and absence of adjacent third molar

2nd molar Maxillary right 3rd Maxillary right Chi-square p-value

eruption molar present 3rd molar absent
status
Fully- 581 (86.5%) 44 (65.7%) 20.178 0.000
erupted
Erupting 91 (13.5%) 23 (34.3%)
 36

Figure 22 Frequency of fully-erupted and erupting maxillary right second molars,

separated by presence and absence of adjacent third molar

Figure 23 Percentage of fully-erupted and erupting maxillary right second molars,

separated by presence and absence of adjacent third molar
 37

Table 18 and Figure 25 show that there is a significant difference in maxillary left
second molar eruption between those with an adjacent third molar present and those with
the adjacent third molar absent (p < 0.05). In patients with their maxillary left third molar
present, there are significantly more fully-erupted adjacent second molars. In patients
with their maxillary left third molar absent, there are significantly more erupting adjacent
second molars.

Table 18 Frequency of fully-erupted and erupting maxillary left second molars, separated
by presence and absence of adjacent third molar

2nd molar Maxillary left Maxillary left Chi-square p-value

eruption 3rd molar 3rd molar
status present absent
Fully-erupted 581 (85.6%) 44 (73.3%) 6.324 0.012
Erupting 98 (14.4%) 16 (26.7%)
 38

Figure 24 Frequency of fully-erupted and erupting maxillary left second molars,

separated by presence and absence of adjacent third molar

Figure 25 Percentage of fully-erupted and erupting maxillary left second molars,

separated by presence and absence of adjacent third molar
 39

Table 19 and Figure 27 show that there is a significant difference in mandibular

left second molar eruption between those with an adjacent third molar present and those
with the adjacent third molar absent (p < 0.05). In patients with their mandibular left third
molar present, there are significantly more fully-erupted adjacent second molars. In
patients with their mandibular left third molar absent, there are significantly more
erupting adjacent second molars.

Table 19 Frequency of fully-erupted and erupting mandibular left second molars,

separated by presence and absence of adjacent third molar

2nd molar Mandibular Mandibular Chi-square p-value

eruption left 3rd molar left 3rd molar
status present absent
Fully-erupted 617 (92.5%) 56 (77.8%) 17.327 0.000
Erupting 50 (7.5%) 16 (22.2%)
 40

Figure 26 Frequency of fully-erupted and erupting mandibular left second molars,

separated by presence and absence of adjacent third molar

Figure 27 Percentage of fully-erupted and erupting mandibular left second molars,

separated by presence and absence of adjacent third molar
 41

Table 20 and Figure 29 show that there is a significant difference in mandibular

right second molar eruption between those with an adjacent third molar present and those
with the adjacent third molar absent (p < 0.05). In patients with their mandibular right
third molar present, there are significantly more fully-erupted adjacent second molars. In
patients with their mandibular right third molar absent, there are significantly more
erupting adjacent second molars.

Table 20 Frequency of fully-erupted and erupting mandibular right second molars,

separated by presence and absence of adjacent third molar

2nd molar Mandibular Mandibular Chi-square p-value

eruption right 3rd right 3rd
status molar present molar absent
Fully-erupted 616 (91.8%) 54 (79.4%) 11.200 0.001
Erupting 55 (8.2%) 14 (20.6%)
 42

Figure 28 Frequency of fully-erupted and erupting mandibular right second molars,

separated by presence and absence of adjacent third molar

Figure 29 Percentage of fully-erupted and erupting mandibular right second molars,

separated by presence and absence of adjacent third molar
 43

DISCUSSION

Studies have reported a large range (1.0-51.1%) of third molar agenesis in

different races (Celikoglu & Kamak 2012, Baba-Kawano et al. 2002, Garn et al. 1963).
The present study shows that 19.2% of patients exhibit a form of third molar agenesis,
similar to the finding by Garn et al. (1963) of 16% third molar agenesis in Caucasians.
Contrary to Celikoglu et al. (2011) and Bolaños et al. (2003), who reported missing all
four third molars as the most common form of third molar agenesis, the present study
found the most common form of third molar agenesis to be missing one third molar
(8.7%). This may be due to genetic and environmental differences between different
populations, as Turkish patients were studied by Celikoglu et al. (2011), and Spanish
patients were studied by Bolaños et al. (2003). When looking at each third molar
individually, they each had about the same chance of being absent, with agenesis
prevalence rates around 9%.
As seen in Table 4, there is no significant difference, except for the maxillary left
third molar, between the ages of those with and without third molars present, therefore all
ages were able to be combined and studied together. Figure 5 shows that although there is
a difference in age between those with their maxillary left third molar present and those
with it absent, the subjects with that third molar absent are older. This supports our
results that although the subjects missing their maxillary left third molar are older, their
adjacent second molars are delayed in development and eruption as compared to those
with their maxillary left third molar present.
In the present analysis, a majority of the second molars were found to be fully-
developed (stage 8), with very few second molars in each of the lower stages of
development. This makes sense with the age group examined in this study (13-17 years)

and the fact that second molars typically erupt around age 12 in Caucasians and teeth
complete development 2-3 years after eruption (Garn et al. 1973). It is notable that
 44

mandibular second molars exhibited a larger percentage in developmental stage 7 than

maxillary second molars. This suggests that mandibular second molars begin developing
after maxillary second molars.
A majority of the second molars were found to also be fully-erupted (stage 3),
with few second molars either unerupted or erupting. Again, this makes sense because of
the patients in this study being older than 12 years of age, when second molars typically
erupt. It is also notable here that there are more fully-erupted mandibular second molars
(approximately 91%) than maxillary second molars (approximately 85%). Therefore,
although maxillary second molars tend to complete development before mandibular
second molars, mandibular second molars complete eruption before maxillary second
molars. This is supported by Garn et al. (1973) and can be seen in Table 1. However, no
studies to date have shown this disconnect between developmental timing and eruptive
timing of second molars. This may have resulted from more anatomic noise around the
apices of maxillary second molars, making their classification of developmental stage
more difficult.
Due to the small individual sample sizes of the lower developmental and eruption
stages (0-7 and 0-2, respectively) as seen in Figures 6 through 13, these stages were
combined and compared to those fully-developed and fully-erupted (stages 8 and 3,
respectively) for analysis.
The present study found that there is a significant difference in both maxillary
right and maxillary left second molar development between those adjacent to a third
molar and those missing an adjacent third molar. This means that second molars without
an adjacent third molar are delayed in development as compared to those with an adjacent
third molar present. Although the difference between mandibular second molar

development is not significant between those adjacent to a third molar and those missing
an adjacent third molar, the findings do suggest the same trend as found with the
maxillary second molars. This may be due to the fact that mandibular second molars
 45

typically begin development later in age than the maxillary second molars, so there is less
of a difference between developmental timing of mandibular molars with and without an
adjacent third molar present.
The present study shows a significant difference in regards to eruption of all
second molars between those with and without an adjacent third molar present. This
means that second molars without an adjacent third molar are erupting later than those
with an adjacent third molar present. This delay in development and eruption of the
second molar when the third molar is missing reflects the findings of Celikoglu et al.
(2011), Garn et al. (1963), and Baba-Kawano et al. (2002). Garn et al. (1963) suggest that
the same factor may be related to both delayed dental development and dental agenesis,
with agenesis being the extreme expression of the factor.
The findings of the present study can help orthodontists more accurately diagnose
and treatment plan cases. Much orthodontic treatment involves waiting for teeth to erupt,
especially the second molars, which are one of the last teeth to erupt into the oral cavity.
If a patient is missing one or more of their third molars, orthodontic treatment could be
extended due to delayed development and eruption of second molars. Better knowing
when teeth will erupt can allow the orthodontist to begin treatment at the proper stage and
decrease the amount of time a patient is in orthodontic treatment.

Limitations and Future Research

A limitation of the present study is that it was cross-sectional. Panoramic
radiographs from the patients’ initial orthodontic visit were examined. This meant that a
limited age range had to be examined in order to be able to study both second molar
development/eruption and to confirm third molar absence/presence. The age range of 13-
17 years contained a majority of second molars in the fully-developed and fully-erupted

stages, with very few in the lower stages. In the future, a longitudinal study should be
conducted over a larger age range, where one can track the development of the second
 46

molar from a younger age and still be able to confirm whether or not the third molars will
be present. Another interesting approach in the future may be to determine if there is a
significant difference in second molar development and eruption within a patient with
some third molars present and others absent. This again would require a longitudinal
study in order to determine the exact chronological age at which second molar
development and eruption occurs.
 47

CONCLUSIONS

The timing of dental development and eruption vary greatly and can be affected
by many different factors. It is important to be able to predict the timing of eruption in
order to accurately diagnose and treatment plan patients for orthodontic treatment. It was
found that in our population of 739 Caucasians, third molar agenesis occurred in 19.2%
of the patients. Each individual third molar had an equal chance to be missing,
approximately 9%. Patients missing their maxillary third molars exhibited delayed
development of the adjacent maxillary second molars. Patients missing their mandibular
third molars showed a trend toward delayed development of the adjacent second molars,
however not significantly different than those with their mandibular third molars present.
Patients missing any of the four third molars exhibited delayed eruption of the adjacent
second molars. The data also suggests that although maxillary second molars exhibit
earlier development than mandibular second molars, mandibular second molars tend to
erupt earlier than maxillary second molars.
 48

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