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Detrimental effects of dental encroachment on secondary alveolar bone graft outcomes in the treatment of patients with cleft lip and palate: a cone-beam computed tomography study

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Detrimental effects of dental encroachment on secondary alveolar bone graft outcomes in the treatment of patients with cleft lip and palate: a cone-beam computed tomography study

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Detrimental Effects of Dental Encroachment on
Secondary Alveolar Bone Graft Outcomes in the
Treatment of Patients with Cleft Lip and Palate:
A Cone-Beam Computed Tomography Study

By

ANDREW PALERMO, D.D.S.
May, 2019

A Thesis Presented to the Faculty of the USC Graduate School
University of Southern California in Partial Fulfillment of the Requirements for the
Degrees Master of Science (Craniofacial Biology)

Copyright 2019 Andrew Palermo
2
Acknowledgements:
I would like to thank Dr. Stephen Yen for your guidance, wisdom and experience,
which has helped to usher me through this difficult process.

Special thanks to Dr. Waleed Soliman and Dr. Xuanyu Lu for assisting me in my data
collection.

I would also like to thank Dr. Glenn Sameshima and Dr. Kaifeng Yin for their help
with my statistical analysis.

Finally, I would like to thank Dr. Toshihiko Yasumura for his words of wisdom and
moral support along the way.

3
Table of Contents
I. Table of Contents 3
II. Abstract 4
III. Literature Review 6
1. Embryology and Development 6
2. Classification Systems 7
3. Genetic and Environmental Factors 10
4. Management and Care 20
5. Alveolar Bone Grafting 27
IV. Introduction 32
V. Materials and Methods 40
VI. Results 50
VII. Discussion 58
VIII. Conclusion 62
IX. References 64

4
Abstract
Introduction:
Cleft lip and palate (CLP) is the most common facial birth defect, with an incidence
of 1 in 700 live births in the United States. A critical step in treating CLP is
performing an alveolar bone graft (ABG) to stabilize the maxillary arch.
Traditionally, 2-dimentional radiographs were used to determine ABG success. With
the advent of cone-beam computer tomography (CBCT), 3-dimensional images can
safely and easily be taken to aid in accurate diagnosis and treatment planning prior
to performing the ABG and evaluate graft success. The purpose of this study was to
determine whether tooth related factors can negatively affect secondary alveolar
bone grafting (SABG) results in patients with craniofacial clefts with alveolar
involvement using CBCT images.

Materials and Methods:
This retrospective study had 52 patients with full unilateral or bilateral CLP, ages 7-
12 years old, who received CBCT using a Carestream CS 9300 6-months following a
SABG. The 3-D rendering of each CBCT was evaluated using the Carestream
software and each cleft was placed into 1 of 4 graft outcome groups: type I
(complete fill), type II (coronal/cervical bridging), type III (apical bridging) or type
IV (complete failure). Carestream’s proprietary software for 3-D imaging was then
used to evaluate succedaneous canine position and existence of impacted teeth,
while Osirix MD DICOM viewer was used to measure bone-loss around teeth for
each CBCT. Patients were also evaluated for age, left versus right sidedness of cleft,
5
bilateral versus unilateral cleft and graft material used (Iliac crest derived
cancellous bone vs. rhBMP-2 with a demineralized bone matrix).

Results:
The most common graft outcome was type III followed by type IV, type II and type I
was the least common. There was a statistically significant correlation between the
position of canine exposure into the cleft site and existence of voids in the graft
(p=0.0404). The degree of periodontal bone loss was also significantly related to the
graft outcome (p=5.34x10
-5
), as was the existence of bilateral versus unilateral bone
loss (p=9.577x10
-6
). Other significant findings included male versus female
(p=4.29x10
-5
) and unilateral versus bilateral clefts (p=0.0055). There was no
statistically significant correlation between graft outcome and impacted teeth
(0.7730), right versus left sided clefts (p=0.5271) or graft material (p=0.7028).

Discussion:
Graft outcomes with bony voids were associated with the lack of bone around the
cleft margins in the form of periodontal bone loss or canine exposure into the cleft-
site. The fact that there were no significant findings associated with impacted teeth
suggests that it is the disruption of bone along the cleft margin and not the existence
of tooth structure close to it that negatively affects graft outcome. This study
suggests that CBCTs should be used to evaluate the margins of alveolar clefts prior
to SABG so that any issues can be addressed before the graft is performed.

6
Literature Review
Embryology and Development:
With an incidence of 1 in 700 live births, cleft lip and palate (CLP) is the most
common facial birth defect among Americans (Parker et al. 2010). These clefts of the
nose and palate arise from disturbances in the normal embryologic development of
the lip and palate, a highly complex series of interactions during gestation.

At approximately 26 days in utero, the developing face consists of five prominences:
the frontonasal process, a pair of maxillary processes and a pair of mandibular
processes (Jiang et al. 2006). By 32 days, nostrils begin to form on the enlarged
frontonasal process, splitting it into lateral and medial nasal processes (Jiang et al.
2006). Further growth over the next three days forces the maxillary and medial
nasal processes into close approximation, facilitating their fusion into the lip by the
6
th
week of development (Jiang et al. 2006).

This initial fusion of the medial nasal
and maxillary processes also gives rise to the primary palate (Tarr et al. 2018).

Following development of the primary palate, palatogenesis of the secondary palate
begins (Tarr et al. 2018). Outgrowths of maxillary prominences grow inferiorly,
flanking the tongue (Bush and Jiang, 2012). Between the 7
th
-8
th
week of
development, the primitive tongue drops to take its mature shape, while the palatal
shelves begin to rise (Tarr et al. 2018). The newly formed palatal shelves continue to
grow towards the midline until they meet and fuse during the 12
th
week of
7
development (Bush and Jiang, 2012). Several situations may arise during this
process, which will result in clefting of the lip and/or palate.

Chai and Maxson describe five categories of palatal shelf failure, which would result
in CLP. The first, and most severe, is failure of palatal shelf development (Chai and
Maxson, 2006). This rare occurrence results in full clefting of the palate. The second
is aberrant fusion of the palatal shelf with the tongue or mandible, preventing
elevation of the affected palatal shelves (Chai and Maxson, 2006). Third is failure of
palatal shelf elevation, without fusion to the tongue or mandible (Chai and Maxson,
2006). The fourth category, failure of palatal shelves to meet following elevation, is
the most common cause of cleft palate (Chai and Maxson, 2006). Finally, the fifth
category is clefting due to persistence of medial edge epithelium following fusion of
the palatal processes (Chai and Maxson, 2006). These failures of the palatal process
and failure of fusion of the lip may present as a number of different types and
degrees of clefts.

Classification Systems:
Classification of facial clefts has proven a difficult and complex matter, leading to
many different classification systems, with no consensus on a universal system
(Allori et al. 2017). In his textbook, Berkowitz provided the following figure
(Berkowitz, 2013):
8

Figure #1: (a) and (b) show the degrees of clefting in the primary palate. Primary
palate clefts can range from a small defect isolated to the lip to a full defect of the lip
and primary palate. These clefts can also present as unilateral or bilateral. (c) shows
the secondary palate clefts, ranging from soft-tissue clefts of the uvula to full clefting of
the hard and soft tissue through to the boarder of the primary palate. (d) and (e)
represent various presentations of combined primary and secondary palate clefts both
unilaterally and bilaterally, respectively (Berkowitz, 2013).
9
Though a valuable resource for understanding the basic presentations of cleft lip
and palate, this figure fails to capture the full complexity of CLP. Clefts of the lip and
palate can present along a continuum from minor soft tissue defects to full bony and
soft tissue clefts in three dimensions.

It is understandable that such a complex presentation of CLPs is difficult to
categorize. Various multi-categorical systems have arisen to try and fully describe
any individual cleft (Elisherbiny and Mazeed, 2017; Davis and Ritchie, 1922;
Kernahan and Stark, 1958; Harkins et al. 1962; Spina, 1973). In 2017, The Cleft
Palate-Craniofacial Journal published an article suggesting the following should be
considered while classifying a cleft: laterality and severity of the labial defect,
acknowledgement of an alveolar defect and a morphological characterization of the
palatal defect (Allori et al. 2017). They, further, provided the following example to
explain their proposition:

Figure #2: An example of how to describe a CLP, as presented by Allori et al, 2017.
10

Current debates argue between which characteristics are necessary in describing a
cleft and those that are superfluous.

Genetic and Environmental Factors:
The underlying causes of CLP are equally as complex as their development and
classification. Clefts are often multifactorial in nature and due to a combination of
environmental and genetic factors (Worley et al. 2018). These patients carry genetic
risk variants for CLP, the variable expression and combination of which results in
orofacial clefting. Clefts of the lip and/or palate are highly heritable, with a 3%
chance to be passed from one parent to their offspring (Goudy and Buckmiller,
2014). If a single sibling has already inherited a cleft from their parent, the risk
increases to 5% in subsequent children and again to 14% if two siblings are affected
(Goudy and Buckmiller, 2014).

A number of these genetic risk variants have been identified and result in
“subphenotypes” of CLP in individuals without clefts (Miller et al. 2014; Weinberg et
al. 2008). Subphenotypes can be classified as either postcranial or craniofacial in
nature (Miller et al. 2014). The craniofacial subphenotypes code for facial
morphology and craniofacial dimensions (Weinber et al. 2006). Two examples of the
postcranial subphenotypes include directional asymmetry and non-right-
handedness (Weinber et al. 2006). The following tables show a list of several known
risk variants and their roles in normal development:
11

Table #1: Descriptions of orofacial cleft risk variant genes (Miller et al. 2014).
12

13

14

Table #2: Description of L/R patterning genetic risk variants for orofacial clefts
(Miller et al. 2014).

Studies have shown a significant increase in these genes and subphenotypes among
relatives of patients with orofacial clefts when compared to control populations,
strengthening their candidacy as risk factors for CLP (Weinberg et al. 2008;
Weinberg et al. 2009). The majority (61.6%) of orofacial clefts exhibit this
multifactorial etiology, resulting in isolated clefts (Tolarova and Cervenka, 1998;
Leslie and Marazita, 2013).

15
In addition to isolated, non-syndromic, clefts, roughly 38.4% of orofacial clefts are
syndromic in nature (Tolarova and Cervenka, 1998; Leslie and Marazita, 2013).
These clefts are one minor malformation in a group of malformation that are
consistently found to make up the over-all syndromes. Syndromic clefts are more
commonly associated with isolated palatal clefts than with cleft lips with or without
palatal involvement (Watkins et al. 2014). They can be classified as monogenic
(Mendelian) syndromes, chromosomal syndromes and teratogenic syndromes
(Leslie and Marazita, 2013; Watkins et al. 2014; Venkatesh, 2009).

Chromosomal syndromes involve additions or deletions of large portions of, or even
entire, chromosomes. Monogenic syndromes result from a single mutation and are
inherited in typical Mendelian fashion (Cohen, 1978). Roughly 2% of orofacial clefts
are due to the Mendelian inherited Van der Woude syndrome (Bennun et al. 2018).
Mutations in the IRF6 and GRHL3 genes result in autosomal dominantly inherited
Van der Woude syndrome in 75% of Van der Woude cases (Kondo et al. 2002;
Peyrard-Janvid et al. 2014; Kumar et al. 2017). While Van der Woude’s is the most
common, hundreds of monogenic cleft syndromes have been identified, resulting
from single-point mutations that cause autosomal or X-linked, dominant or
recessive inheritance of the syndrome (Leslie and Marazita, 2013). The following
table shows a number of identified syndromes and their candidate genes:
16

17

18

19

Table #3: List of 56 known orofacial cleft-associated syndromes with genes, loci and
articles of publication (Seto-Salvia and Stanier, 2014).

Environmental factors are also known to play a large role in the development of
both isolated and syndromic orofacial clefts (Leslie and Marazita, 2013; Rahimov et
al. 2012; Kawalec et al. 2015). One well-established environmental factor is
maternal tobacco use during pregnancy, which definitively increases the risk of CLP
(Kawalec et al. 2015; Zeiger et al. 2005; Little et al. 2004; Lie et al. 2008). There is
also strong evidence that folic acid supplementation during early pregnancy can
decrease the risk of isolated orofacial clefts (Wilcox et al. 2007; Badovinca et al.
2007).

This suggests that maternal nutrition can also play a role in the development
of CLP. Maternal alcohol consumption has long been believed to play a large role in
cleft development; however, recent studies suggest that this may only be true if the
mother or developing child possesses the slow-metabolizing ADH1C genetic variant
(Kawalec et al. 2015; Boyles et al. 2010). In addition to these well-established
factors, retinoic acid, valproic acid, phenytoin, maternal illness, maternal
20
hyperthermia and maternal diabetes and obesity are suspected environmental risk
factors relating to orofacial clefts (Leslie and Marazita, 2013; Rahimov et al. 2012;
Kawalec et al. 2015; Kutbi et al. 2017).
Management and Care:
Management of orofacial clefts is an ongoing process from the prenatal period until
early adulthood, and is best provided by an interdisciplinary team of specialists
(The Cleft Palate-Craniofacial Journal, 2018). Clefts can be detected by 28 weeks in
utero via routine 2D and 3D ultrasounds (Rotten and Levaillant, 2004; Maarse et al.
2011; Micot et al. 2018). Once a cleft is identified, a craniofacial team can be
assigned to the family to begin counseling.

Prior to birth, it is important for the parents to meet with a genetic counselor
(Worley et al. 2018). As discussed, orofacial clefts can be isolated or exist as part of a
syndrome. Many of the other signs and symptoms of these syndromes do not
manifest until later in life (The Cleft Palate-Craniofacial Journal, 2018). Genetic
screening can be performed for early detection of syndromes and aid in long-term
management.

It is also important for the family to meet with a speech language pathologist prior
to birth, in order to prepare them for the difficulties of feeding (Worley et al. 2018).
Due to the open communication between the oral and nasal passages, patients with
cleft palates are often unable to produce sufficient negative oral pressure to
facilitate adequate feeding (Reid et al. 2007). Similarly, infants with cleft lips may be
21
unable to form a proper seal for feeding (Worley et al. 2018). Without timely
counseling and intervention, infants with orofacial clefts can become chronically
dehydrated and malnourished (Marin and Greatrex-White, 2013; Livingstone et al.
2000). The use of lip taping as a pre-surgical intervention for feeding issues is
widely used prior to the initial cleft lip repair at 3-months of age (Worley et al. 2018;
Pool and Farnworth, 1994).

In addition to aiding in feeding, early approximation of the lip, nose and maxillary
tissues with lip taping can result in positive orthopedic changes in the cleft patient
(Pool and Farnworth, 1994). Lip taping has been shown to reduce the need for early
orthodontic intervention by narrowing, remodeling and approximating the alveolar
arches (Pool and Farnworth, 1994). This usually occurs from birth to 5 months of
age, or until the initial cleft lip repair is performed.

Nasoalveolar molding (NAM) is another effective technique for achieving positive
orthopedic and soft tissue changes in infants prior to initial cleft lip and palate
repair (Worley et al. 2018). Studies show that NAM can be used to increase nasal
symmetry, reduce cleft size and increase alveolar arch length and perimeter when
performed properly (Van der Heijden et al. 2013; Sabarinath et al. 2010). NAM is
achieved by fabricating an acrylic appliance to mold the alveolus during infancy. The
appliance has an attachment that fits up against the ala of the nose, allowing for
molding of the nasal soft-tissue from within the nostril as well. The patient must
wear the appliance 24 hours a day and modification to the appliance must be
22
performed every 1-2 weeks by a prosthodontist, orthodontist or other dental
specialist. Full NAM treatment takes up to 6 months, and may result in delayed
initial lip repair and palatoplasty (Worley et al. 2018). Use of NAM is somewhat
controversial, as its technique varies from center to center and it requires a large
commitment from the parents (Worley et al. 2018). Parents must be properly
screened for compliance prior to deciding to perform NAM, otherwise the procedure
will be costly and ineffective.

If lip taping and NAM are unsuccessful, surgical labial adhesion can be performed
between ages 1 week to 3 months (Thierens et al. 2017). Labial adhesion effectively
turns a full cleft lip into a partial cleft and encourages similar soft tissue and
orthopedic advantages as lip taping and NAM (Thierens et al. 2017). At 3 months of
age, definitive surgical cleft lip repair is typically performed (Worley et al. 2018).
Cleft lip repair may be delayed by active lip taping and NAM. Roughly 10-40% of
patients require a lip revision surgery due to esthetic and psychological concerns
from scaring after the initial lip repair (Ranganathan et al. 2016). This lip revision
will occur between 4-6 years of age (Worley et al. 2018).

Hearing and inner ear issues are very common in patients with orofacial clefts,
particularly patients with palatal clefts (Chen et al. 2008). An estimated 95% of
patients with cleft palate exhibit Eustachian tube dysfunction (ETD) (Worley et al.
2018). Between birth and 5 months of age, patients with CLP are monitored for ETD
and hearing loss, starting with the Newborn Hearing Screening (NBHS) (Worley et
23
al. 2018). If necessary, tympanostomy tubes are surgically placed between 0 to 12
months of age (Worley et al. 2018). Significant improvement in both hearing and
ETD usually occurs by age 6 in CP patients (Smith et al. 1994).

Typically, a palatoplasty is performed around 9-12 months of age to correct the cleft
palate (Dorf and Curtin, 1982). It has been shown that patients who have their cleft
palate repair prior to the onset of speech production have significantly better
speech than those who undergo their palatoplasty at 12-27 months of age (Dorf and
Curtin, 1982). However, there is controversy over whether the palatoplasty should
be performed in one stage or two stages (Chepla and Gosain, 2013).

With a two-stage palate repair, there is an initial surgery at 12 months to repair the
soft palate, while the hard palate is repaired at 18 months (Chepla and Gosain,
2013).

Inconsistent evidence suggests that patients undergoing single-stage palate
repair have a higher incidence of maxillary retrusion than patients with two-stage
repair (Chepla and Gosain, 2013). Given this inconsistent data and the known
speech benefits of single-stage repair, single-stage cleft palate repair remains the
most popular (Chepla and Gosain, 2013).

Around the same time as the palatoplasty, patients should begin seeing a pediatric
dentist for basic information on dental care and evaluation of the developing
dentition. Dental anomalies are very common in patients with craniofacial clefts
(Jiroutova and Mullerova, 1994; Suzuki and Takahama, 1992; Tsai et al. 1998).
24
Studies found that 40% of patients with craniofacial clefts exhibit a missing
permanent lateral incisor on the cleft side, while 30% have supernumerary teeth in
the incisor region (Rullo et al. 2015). Furthermore, shape anomalies, lateral incisor
microdontia and enamel hypoplasia were seen in 25.6%, 5.6% and 18.9% of cleft
patients, respectively Rullo et al. 2015).

Between 1 and 4 years of age, these patients should be monitored for proper
language development (Worley et al. 2018). If patients exhibit speech issues that
cannot be corrected with non-surgical therapy, corrective speech surgery may be
considered between 4-6 years old (Worley et al. 2018). Patients should also be
monitored and treated for velopharyngeal dysfunction (VPD) from 18 months to 6
years of age (Worley et al. 2018). VPD and speech pathology are often observed
together and treatment with a speech pathologist may help to correct both issues
(Worley et al. 2018). If speech therapy is not enough to correct VPD, the patients
may require surgery or the use of an obturator to facilitate proper closure of the
velopharynx (Worley et al. 2018). Lip revisions and minor esthetic nasal surgeries
may also be performed during these years (Worley et al. 2018).

When the permanent canine roots are one-half to two thirds completed (8 to 12
years of age), the alveolar bone graft are traditionally performed in order to provide
bone for the canine to erupt into, to provide bony continuity between cleft segments
and to support the nose (Lidral and Vig, 2002). Due to collapse of the maxillary
alveolar arch into the cleft site, patients typically require orthodontic intervention
25
prior to secondary alveolar bone grafting (Lidral and Vig, 2002). Any
supernumerary or impacted teeth should be removed either prior to or during the
secondary alveolar bone graft. Once expansion is completed and the graft is placed,
orthodontic appliances should be used to maintain the transverse dimension of the
maxilla and facilitate phase I alignment of the teeth (Lidral and Vig, 2002).

Scaring from multiple surgeries in the maxilla inhibits normal forward and
downward growth of the upper jaw in patients with craniofacial clefts, resulting in a
skeletal class III appearance (Baik, 2009). As a result, patients with craniofacial
clefts often require orthognathic surgery to advance the maxilla. If surgery is
indicated, phase II orthodontic treatment should be delayed until the patient has
completed growth (between 18-21 years of age) so that it can be coordinate with
the orthognathic surgery (Lidral and Vig, 2002).

Post-orthodontic retention is particularly important in these patients, as scarring
from multiple surgeries increases the relapse rate following orthognathic surgery
(Baik, 2009). Prosthodontic treatment should be performed as soon as possible, to
help maintain the proper dental occlusion (Baik, 2009). In addition, the definitive
rhinoplasty should be performed after orthognathic surgery, as maxillary
advancement will change the appearance of the nose (Worley et al. 2018). This is
the final step in treatment for patients with cleft lip and palate from prenatal period
to early adulthood. The following images list the members of a craniofacial team and
summarize the timeline for CLP treatment.
26

Figure #3: Pinwheel diagram showing the various specialties and members involved
in the craniofacial team (Vig and Mercado, 2015).
27

Figure #4: Summary and order of treatment for patients with cleft lip with or without
cleft palate (Worley et al. 2018).
Alveolar Bone Grafting:

A crucial step in the treatment of craniofacial clefts with alveolar involvement is
alveolar bone grafting. Attempts at alveolar bone grafts (ABG) for cleft lip and palate
28
treatment can be dated back to the fourth century BC (Meara et al. 2011). Successful
breakthroughs in alveolar bone grafting did not occur until the early 1900’s
(Eiselsberg, 1901). The first successful ABG occurred in 1914 using autogenous
tibial bone with periosteum (Coots, 2012).

ABG did not become popular until the 1950’s (Coots, 2012). From the 50’s through
the 70’s, primary alveolar bone grafting with autogenous tibial or rib fragments was
the procedure of choice for cleft lip and palate treatment (Coots, 2012). Primary
alveolar bone grafting was originally performed during the first few months of life
with the belief that early repair of the maxillary arch would stabilize the cleft-site
with the maxillary growth center and facilitate normal maxillary growth (Brauer et
al. 1962). However, long-term follow-up studies of primary ABG found that the
opposite was true, resulting in more severe maxillary retrusion (Coots, 2012).

In the late 1960’s, secondary alveolar bone grafting began to grow in popularity
(Coots, 2012). Secondary ABG is defined as ABG that has been delayed to at least 2
years of age (Alonso et al. 2018). There are 3 subcategories of secondary ABG: early
secondary (between 2-5 years of age); transitional secondary or just secondary (6-
12 years of age); and late secondary or tertiary (after 12 years of age) (Alonso et al.
2018). ABG is now typically performed when patients are between 6-12 years of
age, prior to eruption of the permanent canine.

Performing the ABG at this age
allows the maxilla to growth to a more normal antero-posterior position prior to
29
grafting, while providing stabilization of the maxillary arch and bone for the
permanent canine to erupt into (Coots, 2012).

Over the years, many different materials have been used for ABG ranging from
autogenously harvested bone materials to sterilized calcified matrixes of xenograft
(typically bovine or porcine) (Kumar et al. 2013). Xenografts are used as a
scaffolding and often mixed with growth factors, such as recombinant human bone
morphogenetic protein-2 (rhBMP-2), to initiate recruitment of recipient osteoblasts
to infiltrate the matrix and begin the process of bone formation and
osseointegration (Kumar et al. 2013; Kang, 2017). Allografts, donated by a human
other than the recipient, come in three forms: fresh or fresh-frozen bone, freeze-
dried bone allograft (FDBA) and demineralized freeze-dried bone allograft (DFDBA)
(Kumar et al. 2013). Again, allografts are sterilized, demineralized and used with
rhBMP-2 to work as a scaffold for recipient cells to infiltrate and deposit new bone.
Synthetic variants such as flexible hydrogel-hydroyapatite (HA), calcium
phosphates, bioglass and calcium sulphate are also commonly used in conjunction
with rhBMP-2 for alveolar bone grafting (Kumar et al. 2013).

Providing a scaffold for new bone formation is termed osteoconduction, while the
recruitment of cells from the recipient into the graft to form new bone is
osteoinduction (Kumar et al. 2013). Both of these mechanisms are found in
xenografts/allografts with rhBMP-2. Osteogenesis is the recruitment of osteoblasts
from within the graft itself to contribute to new bone formation and is only found in
30
autografts (Kumar et al. 2013). Autografts are harvested from the recipient host site
and can be from a cortical or cancellous source (Kang, 2017). In the cleft site,
cancellous bone is more successful and has become the preferred type of autograft
(Coots, 2012; Rawashdeh and Telfah, 2008).

There are many sites throughout the body to harvest an autologous graft. Some of
the earliest autografts were harvested from the tibia and the rib (Coots, 2012). The
rib has shown to be a poor graft material, as it inhibits eruption of the permanent
canine (Coots, 2012). Although the tibia is a viable source of cancellous bone for
ABG, there is often insufficient amounts of bone to harvest, causing the surgeons to
have to harvest from both legs for a single graft (Kang, 2017). The mandibular
symphysis is another viable site for harvesting; however, there is often too little
bone for the ABG (Kang, 2017). In addition, there is significant risk of canine, incisor
root and mental nerve damage associated with harvesting from the mandibular
symphysis (Rahpeyman and Khajehahmadi, 2014).

The most abundant sources of cancellous bone to harvest for ABG are the cranium
and the iliac crest. Benefits of harvesting from the cranium include high graft
survival rate, less postoperative pain than from the iliac crest and a concealed scar
(Hudak et al. 2014). Unfortunately, cranial harvesting is a much longer procedure
than that of the iliac crest and runs the risk of very serious complications, including:
hematoma, seroma, dural tear, dural exposure and cerebrospinal fluid leakage
(Kang, 2017). The gold standard for autologous donor site is the iliac crest (Coots,
31
2012; Kang, 2017). Despite resulting in significant post-operative pain and running
the risk of significant scarring and cutaneous nerve damage, the iliac crest is a safe
and easy site to harvest large amounts of cancellous bone for ABG (Coots, 2012;
Kang, 2017).

Autologous alveolar bone grafting with iliac crest derived cancellous bone is the
autograft and is the current gold standard for treating a cleft alveolar ridge (Alonso
et al. 2018). It has a history of predictable and stable results with a success rate over
80% (Alonso et al. 2018). However, recent studies have shown that osteoconductive
matrices combined with rhBMP-2 have similar success to iliac crest derived
autologous grafts and are viable alternatives (Alonso et al. 2018; Fallucco and
Carstens, 2009; Francis et al. 2013).

Despite shortening surgery time and
significantly decreasing post-operative morbidity while appreciating similar success
to autologous grafts, the high cost of this alternative has restricted its use (Alonso et
al. 2018).

32
Introduction:

Since its description by Boyne and Sands (1972), secondary alveolar bone grafting
(SABG) has become a critical step in the treatment of craniofacial clefts involving the
alveolus (Boyne and Sands, 1972). Benefits and goals of SABG treatment include:
repair of the bony defect of the alveolar ridge, floor of nose and alar base; closure of
residual oronasal fistulae; provision of a stable alveolus for the eruption of the
lateral incisors and canines; stabilization of the alveolar arch; increased bony
support for implant placement (Table #4) (Fahradyan et al. 2018).

Table #4: Summary of the objectives for SABG with reference articles (Witherow et al.
2002).

Traditionally, SABG is classified as an alveolar bone graft performed later than 2
years of age (Kyung and Kang, 2015); however, this is a very broad range,
encompassing many different stages of development. This has given rise to further
classifications of secondary alveolar bone grafting in recent years. Currently, SABG
33
has been separated into 3 categories: early secondary (2-5 years), secondary (6-12
years) and late secondary (>12 years) (Grisius et al. 2006).

The 3 subcategories of SABG correlate with the patients’ dental age, early secondary
occurring during the primary dentition, secondary during mixed dentition and late
during the permanent dentition. A number of studies have been performed, which
suggest that SABG performed between 6-12 years of age have significant advantages
over the other age groups (Fahradyan et al. 2018). As a result, SABG at 6-12 years
has become the current standard of care in most craniofacial teams (Fahradyan et
al. 2018).

Historically, 2-dimensional radiographic images were used to perform post-
operative evaluations for SABG success. For years, Bergland’s evaluation of post-
operative alveolar bone grafts was the gold standard for radiographic evaluation.
Bergland used periapical radiographs of the graft-site to categorize graft success
into one of 4 categories based on the type of inter-alveolar septum observed. In type
I outcomes, the inter-alveolar septum height is approximately the same as if there
was no cleft (normal height). Type II had at least ¾ the normal height, while type III
had less than ¾ the normal height. Type IV outcomes had no continuous bony
bridge and were thus full graft failures (Bergland et al. 1986).

The Bergland scale is an evaluation of the inter-alveolar septum height between a
fully erupted canine and the tooth directly mesial to it. This timepoint for
34
evaluation presents a significant limitation for the Bergland scale, as the ideal time
for SABG is prior to the canine eruption (Witherow et al. 2002). Using the Bergland
scale, the graft outcome cannot be evaluated until after the permanent canine has
fully erupted; at which time, the failure rate of any subsequent grafts is significantly
higher (Witherow et al. 2002). Furthermore, the Bergland scale only takes the
septum height into account, without evaluating for apical voids in the graft.

In 1998, the Clinical Standards Advisory Group Cleft lip and Palate audit of cleft
services in the United Kingdom found that 42% of alveolar bone grafts performed in
the United Kingdom were inadequate, according to a modified Bergland scale
(Sandy et al. 1998). In response to this, Witherow (2002) created the Chelsea
alveolar bone graft scale, which took subcervical voids into account and was not
dependent on an erupted permanent canine (Witherow et al. 2002).

The Chelsea scale uses the closest fully erupted tooth on the mesial and distal
aspects of the cleft as references, allowing the graft success to be evaluated prior to
full eruption of the permanent canine (Witherow et al. 2002). Witherow made a
map that separated the roots of each of these teeth into 4 quadrants, from cervical
to apical, and extended to the midline (Fig. #3).
35

Figure #3: Map used by Witherow to evaluate SABG success. The root of each tooth on
either side of the cleft-site is divided into 4 quadrants from the apex to the
cementoenamel junction (CEJ). Each of these sections is extended to a midline between
the two teeth and the bone is evaluated. A score of 1 is given to each section where
there is complete extension of the alveolar bone from the root to the midline. A score of
0.5 is given if there is bone present on the root, but it does not extend to the midline. A
score of 0 is given if there is no bone present in the section. A total of 8 points can be
designated for a complete fill of the cleft-site (Witherow et al. 2002).

Using the map in Fig. #3, each graft is assigned anywhere from 0-8 points. The graft
success can then be placed into one of 6 categories (Witherow et al. 2002):

A. Full bone graft spanning at the CEJ, with at least 75% of the root
surface covered with spanning bone.
B. Full bone graft spanning at the CEJ, with at least 25% of the root
surface covered with spanning bone.
36
C. Only 25% of the coronal root is deficient of bone.
D. 50% of the coronal root is deficient of bone.
E. Does not have bridging at either the apical or CEJ levels, but does
have bridging between both intermediate levels.
F. 75% or greater of the coronal root is deficient in bone.

This 2-D analysis uses an upper anterior occlusal radiograph taken through the cleft
line, 70% to the horizontal for evaluation (Witherow et al. 2002).

The inherent limitations of 2-dimensional radiographs hinder the accuracy and
reliability of these traditional evaluations for SABG success. Enlargement and
distortion, superimposition of adjacent structures, limited number of identifiable
landmarks and difficulty in reproducible positioning all affect the outcomes of these
2-dimensional evaluations (Reddy et al. 2015). Studies have shown that cone beam
computerized tomography (CBCT) scans are particularly useful in the diagnosis and
treatment of patients with craniofacial clefts (De Grauwe et al. 2018). These 3-
dimensional evaluations overcome the diagnostic limitations of their 2-dimensional
predecessors. Furthermore, at 8-10 times lower effective dose, they are much safer
for patients than medical CT scans (De Grauwe et al. 2018).

Recent attempts have been made to incorporate the use of CBCT evaluation into a
universal imaging protocol for treatment of patients with cleft lip and palate (Table
#5) (De Mulder et al. 2018). Studies have validated the use of CBCTs as reliable tools
37
for determining SABG success and produced several suggested protocols (Oberoi et
al. 2009; Janssen et al. 2017; Suomalainen et al. 2014). In addition, it has been
shown that root exposures, crown position, tooth morphology and borders of the
cleft margin can be accurately evaluated on CBCTs (Wriedt et al. 2017).

38

39

Table #5: Recently proposed universal imaging protocol for the treatment of patients
with craniofacial clefts including the: type of scan, age when scan is to be performed,
site and size of field of view and justification of each scan (De Mulder et al. 2018).

Beyond their use in determining the outcome of a SABG, CBCTs can be valuable
research tools for identifying what, if any, intrinsic factors affect the success of
SABGs. Previous studies using 2-dimensional evaluations have suggested that the
relative absence of bone around the cleft site (in the form of partial versus complete
alveolar clefts) and active eruption of the permanent canine during SABG result in
significantly poorer graft results (Leal et al. 2018; Ruppel et al. 2016). The purpose
of this 3-dimensional, retrospective study is to design a protocol for determining
secondary alveolar bone graft success and use it to determine whether tooth-related
factors around the cleft-site affect the SABG outcome.

40
Materials and Methods

This retrospective study was performed between May 2018 and December 2018 at
the department of dentistry and orthodontics of Children’s Hospital Los Angeles
(CHLA) using a protocol that was approved by the internal review board at CHLA
(reference ID: CHLA-16-00540). The patient inclusion criteria were as follows: 1.)
Patients diagnosed with cleft lip and palate; 2.) Presence of unilateral or bilateral
cleft of the alveolar process; 3.) Patients who had an alveolar graft for cleft
treatment between the ages of 7 and 12 years old; 4.) Patients who received an
alveolar bone graft for treatment of an alveolar cleft between the years of 2016-
2017; 5.) Patients who had post-operative 5cm x 5cm CBCT images taken 6 months
after alveolar graft surgery. Patient exclusion criteria included: 1.) Patients whose
post-operative CBCT visual quality was too poor to accurately interpret; 2.) Patients
missing all teeth on one or both sides of cleft site; 3.) Patients lacking a premaxilla.

All post-operative CBCT images were taken on a Carestream CS 9300 machine.
Each individual cleft was evaluated, so that if a patient presented with bilateral
alveolar clefts, the two clefts were evaluated independently of each other. 3-
Dimensional volumetric renderings were created using proprietary software from
Carestream for grading each cleft according to surgical outcome. Four groups were
established:

Type I Complete fill of bone (Fig. #4)
41
Type II Coronal bridging with subsurface void (Fig. #5)
Type III Apical bridging (Fig. #6)
Type IV Complete graft failure (Fig. #7)

Carestream CBCT images were also used to evaluate the clefts for:

1. Permanent canine position to the cleft site
a. Apical perforation across cleft margin (Fig. #8)
b. Cervical perforation across cleft margin (Fig. #9)
c. Spanning perforation across cleft margin (Fig. #10)
d. No perforation
2. Existence of impacted crowns around the cleft site (Fig. #11)

In addition, OsiriX MD DICOM viewer for macOS (version 10.0.1) was used to
evaluate the post-operative CBCT’s for mesial and distal bone loss on teeth adjacent
to the cleft-site. Using the 3-D MPR tool, CBCT’s were re-sectioned down the long
axis of the teeth directly mesial or distal to the cleft-site for each cleft (Fig. #12-14).
The measurement tool was then used to determine the amount of bone loss on these
teeth by measuring the distance from the CEJ to the alveolar crest. If the alveolar
crest was not visually clear, but the visual quality of the overall image was
acceptable for the other evaluations, the cleft was excluded from the bone-loss
analysis, but not from the other evaluations.

42
Three categories of periodontal bone loss along the cleft adjacent teeth were
established: <2mm, >2-5mm and >5mm. For further analysis, teeth that had >2mm
of bone loss were said to have clinically significant bone loss, while those that had
<2mm were said to have no bone loss. The mesial and distal bone loss was not
interpreted independently; instead, the side of the cleft that exhibited the greatest
degree of bone loss was used to assign the bone loss for each cleft. The clefts were
also evaluated for the existence of bone loss on one side of the cleft, both sides of the
cleft or on neither side of the cleft.

An examiner (A.P.) was trained on the use of Carestream and OsiriX imaging to
collect the previously described data. Each cleft was evaluated twice for graft-
outcome, at least 24 hours apart, with no time limit on the evaluation. If the two
outcomes differed, the cleft was evaluated a third time by the same examiner and
the agreeing graft-outcome was selected. Intra-rater reliability was calculated using
the Cronbach’s alpha test.

The patients were then randomly assigned numbers and the evaluator was blinded
to the identities of the patients. Each cleft for the randomized patients was
evaluated for canine position, existence of impacted crowns and bone loss. Again,
evaluations and measurements were performed twice, at least 24 hours apart, with
no time limit on the evaluation. If the two outcomes differed, the cleft was evaluated
a third time by the same examiner and the agreeing result was selected.

43
The data was organized into separate extended contingency tables comparing the
graft type outcome to one of multiple possible findings for canine position,
presence/absence of impacted crowns or bone loss. The data was also organized
into tables comparing:

1. Male vs. Female
2. Left vs. Right sided
3. Unilateral vs. Bilateral clefts
4. Graft Material: Iliac crest derived cancellous bone vs. rhBMP-2
with a demineralized bone matrix (BMP-2 with DBM)

Extended Chi-square tests were performed on Microsoft Excel 2011 for mac to
determine whether any significant findings existed (p< .05). The Chi-square tests
were run again in SAS STATS to verify values and Fisher’s exact test was performed
for any set of data that SAS STATS recommended. Bar graphs were then created to
interpret the trends that existed for each set of data.
44

Figure #4: Type I Outcome – Complete Fill

Figure #5: Type II Outcome – Coronal Bridging

45

Figure #6: Type III Outcome – Apical Bridging

Figure #7: Type IV Outcome – Graft Failure
46

Figure #8: 3-D rendering of CBCT showing perforation of the canine crown (right side
of image) into the apical half of the cleft-site.

Figure #9: 3-D rendering of CBCT showing perforation of the canine crown (left side
of image) into the cervical half of the cleft-site.
47

Figure #10: 3-D rendering of CBCT showing perforation of the canine crown (right
side of image) across the cervical and apical area of the cleft-site.

Figure #11: 3-D rendering of CBCT showing impacted crowns (right side of image)
adjacent to the cleft-site.
48

Figure #12: 3-D MPR re-sectioning of CBCT (via OsiriX MD) down the long access of
the tooth adjacent to the cleft site exhibiting <2mm of bone loss.

Figure #13: 3-D MPR re-sectioning of CBCT (via OsiriX MD) down the long access of
the tooth adjacent to the cleft site exhibiting 2-5mm of bone loss.
49

Figure #14: 3-D MPR re-sectioning of CBCT (via OsiriX MD) down the long access of
the tooth adjacent to the cleft site exhibiting >5mm of bone loss.

50
Results

Of the 52 patients, 6 patients did not meet the inclusion criteria for a final count of
46 patients with N=62 clefts. An additional 4 clefts were excluded from the
periodontal bone loss analyses due to poor visibility of the alveolar crest on at least
one side of the cleft-site, resulting in a total N=58 clefts for these analyses. There
were 37 clefts grafted with iliac crest derived cancellous bone and 23 clefts grafted
with a combination of rhBMP-2 with a demineralized bone matrix (BMP-2 with
DBM). One patient with bilateral clefts received an initial BMP-2 with DBM graft,
followed by an iliac crest graft. These two clefts were excluded from the graft
material analysis. The results of Cronbach’s alpha test for intra-rater reliability
found an alpha score of 0.996 with a p-value <0.0001, indicating very high
constancy in data collection.

This study population consisted of 28 males and 18 females, contributing 40 and 22
clefts, respectively. Of the total 62 clefts, there were: 27 right-sided, 35 left-sided, 29
unilateral and 33 bilateral. The most common graft outcome was type III (n=24),
followed by type IV (n=16), then type II (n=13) and finally, the least common graft
outcome was type I (n=9) (Table #6).
Graft Outcome: I II III IV Total
Total: 9 13 24 16 62
Male: 2 6 19 13 40
Female: 7 7 5 3 22
Right Side: 4 5 13 5 27
Left Side: 5 8 11 11 35
Unilateral: 3 8 10 8 29
Bilateral: 6 5 15 7 33
51
Iliac Crest
Derived: 6 8 15 8 37
BMP-2 with
DBM: 3 5 7 8 23
Total Number of Patients: 46
Number of Male Patients: 28
Number of Female Patients: 18
Table #6: Summary of study demographics.

Fisher’s exact test for the distribution of graft outcomes in males versus females
yielded a significant result (p=4.29x10
-5
). Nearly four times as many type III and
type IV graft outcomes were found in males versus females, while males only
exhibited less than one third of the type I outcomes that the females had (Fig. #15).
Fisher’s exact test was also used to evaluate unilateral versus bilateral clefts and,
again, found a significant result with p=0.0055. Bilateral clefts resulted in
significantly more type I and III grafts, while unilateral clefts resulted in more type II
grafts (Fig. #16). The Chi-square test was used to evaluate right versus left sided
clefts and iliac crest derived versus BMP-2 with DBM graft material. Neither finding
was significant, with p=0.5271 and p=0.7028, respectively.
52

Figure #15: Distribution of graft outcomes for males versus females, where N=the
number of graft outcomes found in either males or females.

Figure #16: Distribution of graft outcomes for unilateral versus bilateral clefts, where
N=the number of graft outcomes found in individuals with either unilateral or
bilateral clefts.
0
2
4
6
8
10
12
14
16
18
20
I II III IV
N=
Graft Outcome
Male
Female
0
2
4
6
8
10
12
14
16
I II III IV
N=
Graft Outcome
Unilateral Cleft:
Bilateral Cleft:
53

Fischer’s exact tests found the results for canine perforation into the cleft-site to be
insignificant, with a p=0.0524. A graph of the results shows that canine perforation
into the cervical portion of the cleft resulted in a type III outcome at least twice as
often as any other outcome and three times as often as a type I outcome. A canine
that spanned the cleft was most often associated with a type IV outcome, which was
over twice as common as a type II and six times as common as type I, though only
slightly more common than type III. Type IV graft outcomes were only seen when
the canine perforation was cervical or spanning. Canine perforation into the apical
portion of the cleft most often resulted in a type III outcome; however, the
proportion of apical perforation to the other canine perforation groups was highest
for the type II graft outcome. The most common outcome associated with no canine
perforation into the cleft site was type I. Type I outcomes were also the least likely
graft outcome to be found if any exposure of the canine existed in the cleft-site (Fig.
#17).
54

Figure #17: Graft outcomes associated with canine perforation into the cleft-site,
where N= the number of graft outcomes found for each canine presentation. The
presentation of canine perforation was either spanning across the whole cleft-site, into
the cervical portion (near the alveolar crest), into the apical portion (by the apex of
the fully erupted permanent teeth) or not at all.

The results for impactions versus no impactions around the cleft site were
statistically insignificant, with a Chi-square p-value of 0.7730. Of the 13 clefts that
resulted in a type II graft outcome, 69% had no impactions adjacent to the cleft site.
Impacted crowns adjacent to the cleft site were less prevalent with type I, II and III
graft outcomes. There was a 1:1 ratio of impactions versus no impactions for the
type IV graft outcome group (Fig. #18).
0
2
4
6
8
10
12
14
I II III IV
N=
Graft Outcome
Canine crown
emergence into cleft on
apical
Canine crown
emergence into cleft on
crestal
Spanning
No Canine Emerging
into cleft
55

Figure #18: Comparison of the percent of each group of graft outcomes that
exhibited impactions adjacent to the cleft site versus no impactions adjacent to the
cleft site.

Results for greatest periodontal bone loss adjacent to the cleft-site was statistically
significant, with a Fisher’s exact test p=5.34x10
-5
. Moderate bone loss (>2-5mm)
was most commonly associated with a type III graft outcome. Type III and IV graft
outcomes were significantly more common when there was severe bone loss
(>5mm) (Fig. #19). The percent of type IV graft outcomes associated with severe
bone loss was higher than that for type III graft outcomes. Type I graft outcomes
were significantly less likely if any alveolar bone loss was present around the cleft-
site (Fig. #20).

The existence of periodontal bone loss on both sides of the cleft site resulted in
significantly more type III graft outcomes than any other graft outcome. There were
0%
10%
20%
30%
40%
50%
60%
70%
80%
I II III IV
Percent of Graft Outcome
Graft Outcome
Impactions in Cleft
Site
No Impactions in
Cleft Site
56
no type I graft outcomes if periodontal bone loss was found on both sides of the
cleft-site (Fig. #21). These results were statistically significant with a Fisher’s exact
p value of 9.577x10
-6
.

Figure #19: Graft outcomes associated with periodontal bone loss adjacent to the
cleft-site, where N= the number of graft outcomes found for each degree of bone loss.
The degree of periodontal bone loss was defined as: no bone loss (<2mm), moderate
bone loss (>2-5mm) or severe bone loss (>5mm).

0
2
4
6
8
10
12
I II III IV
N=
Graft Outcome
No Bone Loss
Moderate Bone
Loss
Severe Bone Loss
0
2
4
6
8
10
12
14
16
18
20
I II III IV
N=
Graft Outcome
No Periodontal
Bone Loss
Periodontal Bone
Loss
57
Figure #20: Graft outcomes associated with periodontal bone loss adjacent to the
cleft-site, where N= the number of graft outcomes found for each degree of bone loss.
Periodontal bone loss was defined as >2mm measured from the CEJ to the alveolar
crest of teeth adjacent to the cleft-site. <2mm was defined as no periodontal bone loss.

Figure #21: Graft outcomes associated with laterality of periodontal bone loss
adjacent to the cleft-site, where N= the number of graft outcomes found for each
category of bone loss laterality. Bilateral bone loss was defined as >2mm measured
from the CEJ to the alveolar crest of the teeth on both sides of the cleft-site. Unilateral
bone loss was defined as >2mm measured from the CEJ to the alveolar crest on only
one side of the cleft-site. If both sides of the cleft-site measured <2mm, there was no
bone loss.

0
2
4
6
8
10
12
I II III IV
N=
Graft Outcome
No Bone Loss
Unilateral Bone
Loss
Bilateral Bone
Loss
58
Discussion

Alveolar cleft repair via alveolar bone grafting is a key step in the treatment of
patients with craniofacial clefts with alveolar involvement (Boyne and Sands, 1972;
Fahradyan et al. 2018; Witherow et al. 2002). The superior diagnostic potential of 3-
dimensional CBCTs over traditional 2-dimensional occlusal radiographs allows
more accurate diagnosis of the cleft condition prior to SABG (De Grauwe et al.
2018). The results of this study suggest that several pre-existing conditions related
to the cleft-site can affect the overall graft outcome.

One finding was that the existence of bone loss on teeth adjacent to the cleft-site
significantly affects alveolar graft quality. Moderate bone loss resulted in
significantly more type III graft outcomes, while severe bone loss resulted in type IV
outcomes. The results also demonstrated far fewer type I graft outcomes if any
degree of bone loss was observed. This shows a trend of worsening graft outcomes
with increased bone loss. Additionally, there were no type I grafts if any bone loss
existed on both the mesial and distal aspects of the cleft. The bone level of the
alveolar bone graft dropped to the position of the alveolar bone covering the dental
roots.

These results agree with the findings of Leal et al. (2018). In this recent study, it was
shown that a reduction in bony support around the cleft-site negatively impacted
the results of SABG (Leal et al. 2018). The Leal et al. study was performed using 2-
dimensional occlusal radiographs and periodontal probings to confirm 2- versus 3-
59
walled defects as a measure of bony support. With the use of CBCTs to visualize the
reduced level of bony support along the root of teeth adjacent to the cleft, we too
were able to show that lack of bony support can be used to predict negative graft
outcomes. Additional investigation that measures alveolar bone level in terms of
distance from the CEJ, a continuous value, would permit a scatter plot to be created
that compares periodontal bone level against drop in bone level. This type of study
would demonstrate a correlation between level of bone graft and periodontal bone
loss of adjacent teeth.

The position of the permanent canine was also an important indicator of graft
outcome. As may be expected, when the canine erupted into the cleft towards the
alveolar crest (cervical perforation across cleft margin) we found significantly more
type III graft outcomes with voids below the canine. If the canine erupted across the
entire cleft-site, significantly more type IV grafts were observed. Due to the
relatively rare occurrence of type II graft outcomes, this study could not provide
statistically significant data on whether canine eruption into the apical site allowed
bony bridges to form at the level of the cervical level; however, a greater percent of
type II graft outcomes were associated with canine exposure into the apical portion
of the cleft-site than any other graft outcome. Finally, there were significantly less
type I outcomes if any canine emergence was found across the cleft margin.

Again, these results agree with Leal et al. and Ruppel et al. who found that active
canine eruption during SABG resulted in poor graft outcomes (Leal et al. 2018;
60
Ruppel et al. 2016); however, our study takes this results even farther. The results
of our study showed a clear correlation between graft failure at the vertical location
of the erupting canine. In other words, if the permanent canine erupted into the
cleft-site prior to SABG, we can expect a void in the graft at the level of the canine
exposure. This is presumably due to the lack of alveolar bone for proper integration
of the graft available in these regions.

Interestingly, there was a significant difference between male vs. female groups.
Female patients had strikingly better graft results than male patients, with less than
one-third of the type III and type IV graft outcomes. One wonders whether there
might be a different in oral hygiene during the post-graft period between males and
females. There was also a significant difference between the bilateral versus
unilateral clefts, with types I and III outcomes more frequent in bilateral clefts and II
and IV more frequent in unilateral clefts. Both of these findings were unexpected
and more research needs to be performed to determine the causes of these
significant differences in treatment outcome.

Statistically insignificant results were found for tooth impactions and graft type. Our
findings on graft type agree with the current literature stating that that rhBMP-2
with a matrix has comparable success rate to an alveolar bone graft when compared
to cancellous bone harvested from the iliac crest (Alonso et al. 2018; Fallucco and
Carstens, 2009; Francis et al. 2013). The tooth impaction comparison looked at teeth
that were impacted around the cleft site, but did not perforate through the bone into
61
the cleft-site itself. There were no statistically significant differences between
impaction and non-impaction groups, suggesting that it is not the existence of teeth
within the bone around cleft-sites that has an impact on graft success, but rather the
actual perforation of tooth-structure through the cleft margin into the cleft-site.

62
Conclusion
Using cone-beam computer tomographic 3-D radiographs, we were able to identify
several dental factors near the cleft-site that was associated with negative outcomes
for secondary alveolar bone grafting in patients with cleft lip and palate. The results
of this study show that a lack of bony support around the cleft-site, whether that be
due to periodontal bone loss or exposure of developing teeth into the cleft-site,
negatively impacts the success of the SABG. One remedy to improve graft outcomes
could be earlier timing of bone grafts, well before the adjacent succedaneous teeth
erupt toward the cleft-site. Teeth that are in the cleft site should be removed prior
to SABG in order to minimize the risk of graft failures. Teeth with periodontal bone
loss should be evaluated for extraction if there is evidence of a one-wall periodontal
defect that faces the cleft-site, even when the tooth is a permanent tooth.

An early imaging protocol involving pre-surgical CBCT’s at the age of six prior to the
eruption of the permanent maxillary incisors should be used to evaluate whether
the permanent teeth will be forced out of bone and into the cleft site due to dental
crowding. Rather than base the timing of the bone graft on the eruption of the
permanent canine, the early conebeam CT could help assess whether to base the
timing on the eruption of the permanent maxillary incisors in order to maintain the
integrity and continuity of the cleft margins to encase the teeth that are erupting
near the cleft site. The direction and position of the erupting permanent teeth can
be estimated by the angulation of the crowns in order to predict whether a canine
will erupt out of bone and span the cleft site. The findings of this study support the
63
use of an early pre-graft radiographs and early timing of bone grafts when there are
signs of dental crowding near the cleft site in order to avoid some of the graft failure
problems that occur after teeth erupt out of bone and place dental cementum and
enamel along the alveolar cleft margins. Bone cannot be directly grafted to
cementum or enamel as there is no follicle or periodontium that normally separates
bone from tooth. An early bone graft would allow these cleft-adjacent teeth to erupt
in bone rather than out of bone into the cleft site and avoid future problems with
late alveolar bone grafts. Further studies are needed to determine whether early
bone grafts at age 6 have overall better outcomes than later bone grafts and
whether the teeth adjacent to the cleft site have better periodontal health and bone
support.

64
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Creator Palermo, Andrew James (author)

Core Title Detrimental effects of dental encroachment on secondary alveolar bone graft outcomes in the treatment of patients with cleft lip and palate: a cone-beam computed tomography study

School School of Dentistry

Degree Master of Science

Degree Program Craniofacial Biology

Publication Date 03/08/2021

Defense Date 02/22/2019

Publisher University of Southern California (original), University of Southern California. Libraries (digital)

Tag alveolar bone graft,cleft lip and palate,cone beam computer tomography,cone-beam computer tomography,craniofacial cleft,OAI-PMH Harvest,secondary alveolar bone graft

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Advisor Sameshima, Glenn (committee chair), Grauer, Dan (committee member), Yen, Stephen (committee member)

Creator Email ajpalerm@usc.edu,palermoa88@gmail.com

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