when should an orthodontist seek the advice of an endocrinologist by almuzian
TRANSCRIPT
When Should an Orthodontist Seek the Advice of an Endocrinologist?
Much is now known about the influence of hormones on orthodontic treatment.
Hormones exert their influences in a variety of ways: endocrine (hormones acting on remote
tissues), paracrine (hormones acting on nearby tissues), and autocrine (hormones acting on the
tissues that secrete them).
Orthodontic tooth movement and bone remodeling are closely linked and depend on both
systemic and local hormone actions.
The modeling and remodeling necessary for orthodontic tooth movements are part of a
continuous process where mature bone is removed (bone resorption) and new bone is formed
(bone formation).
Bone resorption and formation are dependent on hormones including parathyroid hormone (PTH),
1,25 (OH)2 vitamin D, insulin-like growth factor 1 (IGF-1), and thyroid hormones.
Endocrine disorders with dental/oral manifestations
Condition Etiology Dental/oral manifestations
Growth hormone
deficiency
Variable genetic etiology, most
idiopathic
Delayed dentition, small mandible,
midfacial hypoplasia, single central
incisor
Acromegaly/gigantis
m
Most commonly due to a pituitary
adenoma, can be seen in
association with McCune–
Albright syndrome and
neurofibromatosis type 1
Widely spaced teeth, prominent
lower jaw, crossbite, coarse facial
features
Thyroid disease Variable, congenital versus
acquired
Delayed or premature eruption of
teeth, gum disease, large tongue
Hyperparathyroidism-
jaw tumor syndrome HRPT2 gene mutations
Ossifying fibroma of the mandible or
maxilla
Hypophosphatasia ALPL gene mutations Premature loss of primary teeth
Nutritional rickets
Associated with calcium,
phosphate, or vitamin D
deficiency
Enamel hypoplasia
Delayed dentition
Increased susceptibility for caries
Large pulp chambers and short
roots
X-linked
hypophosphatemic
rickets
PHEX gene mutations Defective dentin leading to
recurrent dental abscesses
Fibrous dysplasia GNAS1 gene mutations
Well-defined radiolucent bony
lesions with ground-glass
appearance in maxilla or mandible
Diabetes
Type 1 diabetes is autoimmune
mediated and polygenic, type 2
diabetes is associated with
obesity and is polygenic; most
genetic mechanisms responsible
for both type 1 and type 2
diabetes are unknown
Gingivitis and periodontitis; the
latter can lead to early tooth loss
Primary adrenal
insufficiency
Variable, congenital versus
acquired Hyperpigmented gingivae
Turner syndrome Complete or partial loss of one of
the X chromosomes
High-arched palate, crowding of
teeth, mandibular retrognathia
Growth Hormone Deficiency
Growth hormone deficiency (GHD) can either be isolated or seen in conjunction with other
pituitary hormone abnormalities.
Growth hormone, which is produced by the pituitary gland under regulation by the hypothalamus,
is necessary for normal growth and development in children and for maintaining proper body fat
distribution, muscle and bone health in adults.
Clinical and Biochemical Findings
Delayed eruption of both primary and permanent teeth.
smaller facial heights and widths and smaller head circumferences than their age-matched peers
(Segal et al., 2004).
disparity in size between the mandible and maxilla and often exhibit a retrognathic mandible and
crowding of teeth.
A single central incisor has also been described in isolated GHD and GHD in association with
additional pituitary hormone deficiencies (Artman and Boyden, 1990; Hamilton et al., 1998).
Diagnosis
low insulin-like growth factor 1 (IGF-1 or somatomedin-C) level
low growth hormone levels on pharmacological stimulation testing
Glucose tolerance test
MRI
Management
daily subcutaneous injections
Growth hormone therapy increases facial height, with a lesser effect on facial width, and may
affect jaw alignment (Segal et al., 2004). Overtreatment with growth hormone can cause
mandibular overgrowth.
Pituitary gland abnormalities and Acromegaly
Background
1. Anatomy
The Sella Turcica lies on the intracranial surface of the body of the sphenoid
It consists of a central pituitary fossa bounded anteriorly by the tuberculum sellae and
posteriorly by the dorsum sellae.
Two anterior and two posterior clinoid processes project over the pituitary fossa.
The anterior clinoid processes are formed by the medial and anterior prolongations of the
lesser wing of the sphenoid bone,
The posterior cliniod processes represent terminations of the dorsum sellae.
The Sella Turcica contains the pituitary gland. It is also known as the hypophysis and is
separated into anterior and posterior portions with its main role being the regulation of the
endocrine system.
2. Growth changes
Growth of the Sella Turcica has been documented by both Melsen (1974) and Bjork
(1955).
Using human autopsy samples Melsen reported remodelling of the anterior part of the
interior surface of sella turcica to be complete at an early age (5yrs) with continuing resorption of
the posterior wall continuing up until the late teenage years resulting in a backward and downward
displacement of Sella Turcica.
3. Normal morphology classification
The morphology of Sella Turcica assessed radiographically shows great variation.
Camp (1924) described three basic shapes of sella turcica: oval, round and flat.
Recently, Axelsson et al (2004) in a Norwegian sample identified five distinct
morphological aberrations of sella:
I. Oblique anterior wall,
II. Double contour of the floor,
III. Notching in the posterior part of dorsum sellae
IV. Pyramidal shape of dorsum sellae.
V. Sella Turcica bridging: represents fusion of the anterior and posterior clinoid processes.
Becktor et al (2000) described two variations: 1) ribbon like and 2) bony extension between the
anterior and posterior clinoid processes.
4. Dimensions of Sella Turcica
Various dimensions of Sella Turcica have been reported with the literature.
Camp (1924) reported the normal A-P length to be within the range of 5-16mm and the
depth within the range of 4-12mm.
In contrast, Taveras and Wood (1964) reported the upper limit of the A-P dimension to be
17mm and the limit of the depth to be 13mm.
These differences can be explained by the use of differing landmarks and radiographic
techniques and by the magnification of radiographs which are not reported or compensated for in
the reported results.
5. Abnormalities
The radiographic incidence of bridging has been reported as 16.7% and 18.6%.
Interestingly, the detection of sella Turcica bridging appears to be a radiographic indicator of
severe jaw disharmony. However, the accuracy of detection of true sella bridging from plain
radiographs has to be questioned.
An abnormal morphology of the anterior wall and a reduced size of Sella Turcica have
also been reported to be associated with congenital disorders.
6. The differential diagnosis of an enlarged sella turcica
Most commonly a primary intrasellar pituitary tumour which accounts for 15% of all
intracranial tumours.
Aneurysm
Mucocele
Melsen syndrome
Rathke’s cleft cyst
7. Primary intrasellar pituitary tumour
Pituitary adenomas are benign neoplasms which can present with variable clinical
manifestations ranging in severity.
The clinical features are caused by local expansion of the tumour and excessive or
reduced production of particular hormones.
Generalised features include:
I. headaches,
II. visual disturbance,
III. changes in growth pattern
IV. Galactorrhea: Galactorrhea (also spelled galactorrhoea) (galacto- + -rrhea) or lactorrhea
(lacto- + -rrhea) is the spontaneous flow of milk from the breast, unassociated with childbirth or
nursing.
V. Galactorrhea is reported to occur in 5–32% of women. Much of the difference in reported
incidence can be attributed to different definitions of galactorrhea. Although frequently benign, it
may be caused by serious underlying conditions and should be properly investigated.
Galactorrhea also occurs in males, newborn infants and adolescents of both sexes.
Pitutary adenomas can be classified according to size and functional activity
(hyperfunctioning or non-functioning).
Tumours measuring up to 10mm are termed microadenomas and macroadenomas if
greater than 10mm.
Diagnosis
I. It is generally accepted that magnetic resonance imaging (MRI) scans are the gold
standard for diagnosis of sella enlargement and confirmation of pituitary tumours;
II. however abnormalities of the Sella Turcica can also be detected on plain films. Du Boulay
and Trickey (1967) reported the sensitivity of plain films for the detection of sellar changes in a
range between 67-77%.
Acromegaly
Acromegaly is caused by a benign neoplasm of the anterior pituitary gland resulting in
excessive secretion of growth-hormone (GH).
The incidence of this disorder has been reported at 60 cases per million.
The clinical features can be local or systemic and are principally related to excessive GH
secretion.
Acromegaly can develop insidiously over decades without the presence of clear clinical
markers. Hence, late onset presentation.
Difference between gigantism and acromegaly:
1) Gigantism - excessive GH secretion during growth
2) Acromegaly - excessive GH secretion post- growth
Typical general clinical features include:
1) Headaches
2) Visual disturbances
3) Development of Diabetes mellitus
4) Hypertension and associated heart failure, coronary artery disease.
5) Intolerance to hot and cold temperatures
6) Enlargement of the small bones of the hand and feet (spade like)
7) History of an increase of shoe size
8) Change in size of fingers that required alteration of his wedding ring.
9) Arthralgia
10) Arthritis
11) Soft tissue overgrowth (thick and greasy skin)
Craniofacial features:
1) Radiographically abnormal appearance of Sella
2) Enlargement of the supraorbital ridges
3) Skeleton enlargement of the membranous bones of the cranium occur such as frontal
bossing
4) Overgrowth of soft tissues causes enlargement of lips and nose
5) Patients presenting complaint e.g. difficulty in eating and the development of an anterior
open bite
6) Change in facial appearance e.g. mandibular prognathism
7) Change in occlusion – Development of Class III occlusion, midline diastemas and spacing
8) Macroglossia
9) Dentures not fitting anymore (alteration and enlargement of alveolar ridges)
Diagnosis
Questioning of the patient about the features mentioned above
Refer to a GMP but will require neurosurgeon and endocrinologist for specialist opinion.
Investigations
1) Gold standard for radiographic diagnosis – MRI scan
2) Blood Tests.
A. Glucose tolerance test is diagnostic:
Growth hormone levels and blood glucose levels are also connected. In someone without
acromegaly, a higher blood glucose level usually causes the body to stop producing GH.
Therefore, a doctor will purposely raise your blood glucose level using an OGTT and watch how
your GH level responds.
To begin the test, your doctor will measure your blood glucose level and your GH level.
You'll then drink 75 g of a very sugary drink—a glucose drink. Over the course of the next 2 hours,
the doctor will test your glucose and GH levels 4 more times: 30, 60, 90, and 120 minutes after
you've had the glucose drink.
If your GH level doesn't drop to below 1 ng/mL (ng/mL is the standard measurement used
for GH levels) during the OGTT, you have acromegaly. Your GH level should respond to so much
glucose by dropping, so if it doesn't, that tells the doctor that your body isn't listening to its own
signals: The delicate feedback loop of the endocrine system has been disturbed.
B. Testing Insulin-like Growth Factor-1 (IGF-1):
Insulin-like growth factor-1 (IGF-1) is a hormone that's closely tied to growth hormone. GH
tells the body to make IGF-1, which in turn causes tissues in your body to grow.
In someone without acromegaly, a high IGF-1 level is the body's signal to stop producing
GH which in turn reduce the level of IGF-1.
For a person with acromegaly, though, the body continues producing GH, regardless of
high IGF-1 levels.
IGF-1 levels are much more constant throughout the day than GH levels, so doctors
measure IGF-1 levels using a blood test. An elevated IGF-1 level may indicate acromegaly.
3) Doctors can't simply test for the level of growth hormone (GH) in your body because the
level varies so much in one day—even in someone without acromegaly.
4) Visual field assessment. Usually impaired.
Management
1) Surgery. Can be transfrontal or transsphenoidal and combined with radiotherapy as
resection of tumour is rarely complete.
2) External beam radiotherapy.
3) Pharmacological agents: Aim to reduce tumour size. (Octreotide)
Orthodontic considerations
1) Potentially detect abnormal changes in Sella Turcica appearance on lateral cephalograms
2) A “double” appearance of the Floor of sella maybe due to a pathological lesion.
3) When one dimension (A-P or vertical) or when both values approach their respective
upper limits then the appearance of sella should be viewed with caution.
4) If gross acromegalic features are present, then the pituitary tumour would require active
treatment and stabilisation prior to the commencement of any orthodontic treatment in order to
reduce the effects of adverse growth on the patient’s corrected occlusion.
5) Treatment options camouflage or combined approach will depend on severity of Class III
malocclusion. Primary aetiological factor in class III will be mandibular prognathism.
ISFE Question 4th of March 2009
Photograph of male with coarsening of features and severe class III skeletal. Pt gave a history of
changing bite. Ceph showed enlargement of the sella turcica
Describe what you see. What is your likely diagnosis? What is acromegaly? What else might the
patient complain of? What would you do if this patient
presented on your consultant clinic? What blood parameters would be raised? What is the
treatment? How would you address this patient s main complaint
once his medical condition is stabilised?
Thyroid Disease
The thyroid gland produces two hormones, calcitonin and thyroxine.
Calcitonin is a minor hormone in bone metabolism, which works opposite to PTH and decreases
serum calcium levels.
Calcitonin therapy has been reported to be useful for osteoporosis and giant cell granulomas of
the jaw.
However, its utility is limited due to possible allergic reactions and tachyphylaxis with multiple
doses.
No disease related to calcitonin excess or deficiency in humans has yet been described.
Therefore, the remainder of this discussion will be about thyroid hormones.
Thyroxine (T4) is a prohormone that is converted to its active form triiodothyronine (T3).
This active hormone influences the activity and metabolism of all cells, and it plays an important
role in physical development and growth.
Thyroid disease can be congenital or acquired.
Most common etiology for acquired thyroid disease is autoimmune.
Hashimoto thyroiditis is most commonly associated with hypothyroidism, whereas Graves disease
is the most common cause of hyperthyroidism.
Both hypothyroidism and hyperthyroidism can affect dental health, as can the treatment for thyroid
cancer.
Persons with either hypo- or hyperhyroidism may also have a goiter (enlarged thyroid gland)
palpable on examination which should prompt a referral to an endocrinologist.
Clinical Findings
1. Hypothyroidism
Common symptoms of hypothyroidism are fatigue, increased sleepiness, dry skin and brittle hair,
cold intolerance, mild weight gain, and constipation.
Children with hypothyroidism may have a wide variety of dental problems, including malocclusion,
delayed eruption of primary and permanent teeth, a prominent tongue and swollen gingivae, and
an increased risk of caries and gingival disease.
Adults with hypothyroidism may have an enlarged tongue, delayed postoperative wound healing,
and defects in taste and smell.
2. Hyperthyroidism
Hyperthyroidism is associated with symptoms of weight loss, difficulty in sleeping, and a decline
in school or work performance.
Bulging of the eyes (exophthalmos) is characteristic of Graves disease.
Children with hyperthyroidism may experience premature tooth eruption.
The most common forms of thyroid cancers are treated with high doses of radioactive iodine. This
treatment can cause gingival pain and swelling, and increased salivation.
Diagnosis
The diagnosis of thyroid disease is made based on clinical and laboratory findings.
The presence of a goiter, particularly with palpable nodularity,
Thyroid function testing usually measurement of thyroid-stimulating hormone (TSH) and thyroxine
levels [T4 or free T4])
An elevated TSH level in association with low thyroxine levels is diagnostic of primary
hypothyroidism whereas a low TSH level in association with an elevated thyroxine level usually
indicates primary hyperthyroidism.
Management
Treatment of hypothyroidism is with thyroid hormone replacement.
Treatment of hyperthyroidism depends on the etiology and may include radioactive iodine, anti-
thyroid medications, and/or surgery. High levels of thyroxine (either from primary hyperthyroidism
or from ingestion of too much thyroxine) may result in increases in osteoclastic activity and faster
tooth movement rates (Shirazi et al., 1999).
Close collaboration with an endocrinologist is preferred so that the thyroid hormone levels are
monitored and controlled while orthodontic forces are applied for achieving optimal results.
Hyperparathyroidism-Jaw Tumor Syndrome
Parathyroid hormone is secreted by the parathyroid glands and stimulates bone resorption,
primarily through its effects on vitamin D metabolism.
PTH also reduces renal clearance of calcium and increases intestinal calcium absorption.
In primary hyperparathyroidism, autonomous production of PTH from the parathyroid glands leads
to increased serum calcium levels.
Secondary hyperparathyroidism is seen when PTH secretion is increased because of
hypocalcemia.
Hyperparathyroidism can be associated with ossifying fibromas as part of the
hyperparathyroidism-jaw tumor syndrome.
A painless mass in the mandible or maxilla could represent an ossifying fibroma, A variety of renal
lesions and uterine tumors.
When ossifying fibromas are suspected, a careful family history should be taken, focusing on
history of hypercalcemia and hyperparathyroidism, which is important in making decisions
regarding further investigations and management
Clinical and Biochemical Findings
Symptoms of hypercalcemia are often subtle but include increased thirst and urination, nausea,
vomiting, constipation, weakness, restlessness, confusion, and altered mental status.
In hyperparathyroidism, serum calcium levels are elevated in association with low serum
phosphorus levels.
An ossifying fibroma presents as a bony, hard, non-tender mandibular swelling.
Diagnosis
Diagnosis is based on clinical, biochemical, radiological and histological findings.
Radiographically, the lesions are either completely radiolucent or mixed, depending on the
amount of calcification, or are completely radiopaque and surrounded by a radiolucent rim. In
each type, there is a sclerotic border around the lesion.
Histologically, the tumor consists of cementum-like or bony masses distributed in a highly cellular
fibrous stroma
Treatment
Ossifying fibromas are treated surgically. Large lesions, particularly of the maxilla, are often
aggressive and require radical surgery. Small lesions can be treated with conservative excision.
After curettage, nearly a third of mandibular lesions will recur. To minimize the likelihood of
recurrence, en bloc or partial jaw resections are preferred.
Hypophosphatasia
Hypophosphatasia is a rare metabolic disease, with an estimated incidence of 1:100 000 (Mulivor
et al., 1978).
A history of premature tooth exfoliation should raise concerns for hypophosphatasia, which results
from a mutation in the ALPL (alkaline phosphatase, liver/bone/kidney) gene encoding the tissue-
nonspecific alkaline phosphatase enzyme (TNSALP) (Mornet and Simon-Bouy, 2004).
TNSALP is important for normal bone and tooth mineralization.
Five clinical forms are described: perinatal (lethal), infantile, childhood, adult, and
odontohypophosphatasia.
Children with the perinatal, infantile, and childhood forms can present with severe skeletal
manifestations of under-mineralized bone, including frequent fractures. In
odontohypophosphatasia, clinical manifestations are limited to the teeth.
Clinical, Radiological, and Biochemical Findings
Premature loss of deciduous teeth is a characteristic finding in the various forms of
hypophosphatasia.
The incisors tend to be the most commonly affected (Beumer et al., 1973).
Premature tooth loss may result from quantitative and qualitative defects in cementum formation.
Root resorption and enamel hypoplasia may also occur (Bruckner et al., 1962).
Radiographic studies show enlarged pulp chambers and root canals with reduced cortical bone
thickness of the mandible.
Decreased cementum, varying with severity of the disease, is apparent on histological
examination of the teeth. The deficiency of serum and bone alkaline phosphatase (ALP) activity
leads to rickets and osteomalacia.
Babies with the perinatal form are usually stillborn or die within few days of life.
Patients with the infantile form develop clinical signs of hypophosphatasia during the first 6
months of life, including hypercalcemia with hypercalciuria.
Premature craniosynostosis and respiratory problems due to rib fractures and rachitic deformities
of the chest are common.
Approximately 50% of those with the infantile form of hypophosphatasia will have spontaneous
improvement in bone and dental symptoms with advancing age.
Childhood hypophosphatasia is the form that most commonly presents to the dentist due to
premature loss of deciduous teeth (Chapple, 1993).
Affected children present with skeletal deformities such as a dolichocephalic skull, widely opened
fontanels, and rachitic skeletal changes.
Delayed motor milestones, failure to thrive, and short stature are common.
The adult form is rare and tends to be diagnosed in middle age. This milder form of
hypophosphatasia needs to be distinguished from odontohypophosphatasia, since both can
present with premature loss of teeth and have indistinguishable biochemical findings.
Clinically, patients with the adult form present with recurrent and multiple long bone fractures and
pseudofractures.
Diagnosis
The diagnosis is often made on the basis of clinical suspicion, relying on history, physical
examination, and radiographic findings, in addition to demonstrating low serum ALP activity.
Management
Management of hypophosphatasia relies on supportive measures to minimize disease-related
complications.
There are currently no medical treatments for hypophosphatasia, although bone marrow
transplants have been tried for the infantile forms and enzyme replacement trials are underway
for the severe types.
Dental interventions alone may be all that is needed and limited to the primary teeth.
There has been one case report of a pediatric patient with hypophosphatasia and a posterior
crossbite requiring palatal expansion along with total dentures, demonstrating a role for
orthodontists in the management of anodontia due to hypophosphatasia (Altay et al., 1995).
Rachitic Disorders
Active Vitamin D synthesis (1,25(OH)2 vitamin D) is a multistep process that starts both with the
formation of cholecalciferol (vitamin D3) in the skin from cholesterol, under the stimulus of
ultraviolet B light, and with the absorption of vitamin D2 and vitamin D3 from plant and animal
dietary sources or nutritional supplements.
In the liver, vitamin D2 and D3 undergo 25-hydroxylation, producing 25(OH) vitamin D.
A second hydroxylation occurs in the kidney at position 1 (via 1-α hydroxylase),
Active metabolite 1,25(OH)2 vitamin D, which promotes intestinal absorption of calcium and
phosphorus, increases renal phosphate reabsorption, and acts on bone to release calcium and
phosphate.
Deficiency states produce rickets and osteomalacia in children and adolescents, and
osteomalacia in adults. Rickets and osteomalacia lead to softening and deformity of bones.
Rickets is the failure of osteoid to mineralize during the process of bony modeling when new bone
forms at growth plates.
Osteomalacia is the failure of bone to remineralize during bone remodeling.
A child with rickets may present to the orthodontist with delayed development and emergence of
the dentition, and enamel hypoplasia, particularly in association with poor weight gain or linear
growth, and skeletal findings such as frontal bossing or bowing of the legs.
Clinical, Radiological, and Biochemical Findings
Rickets can be associated with delayed tooth eruption, with deciduous incisors not appearing until
9 months of age and first molars not appearing before 14 months.
The enamel may be hypoplastic, leading to greater susceptibility to caries (Wharton and Bishop,
2003).
Clinical features of rickets include hypotonia, craniotabes (softening and thinning of the infant
skull), frontal bossing, costochondral junction swelling (rachitic rosary), scoliosis, and bowing of
the legs due to weight-bearing.
Often the infant will have darker skin tone, a history of prolonged breastfeeding, and/or little
cutaneous sun exposure.
Characteristic X-ray findings include cupping, flaring, and splaying of the metaphyses
Nutritional rickets due to vitamin D deficiency is associated with low 25(OH) vitamin D levels, and
elevated serum ALP and PTH levels.
Low calcium and phosphate levels are also often seen.
Diagnosis
The diagnosis of nutritional rickets due to vitamin D deficiency relies on clinical and biochemical
findings, as detailed above.
Management
Depending on the form of rickets, medical therapy usually involves administration of vitamin D or
one of its metabolites, which affect tooth development and orthodontic tooth movement.
Kawakami and Takano-Yamamoto (2004) found that local application of 1,25 (OH)2 vitamin D3
to molar roots of rats increased mineral appositional rate on alveolar bone after orthodontic force
application.
Nutritional Rickets
Dietary deficiencies in calcium, phosphate, and/or vitamin D can result in rickets and
osteomalacia.
Treatment of nutritional rickets consists of replacement of the missing dietary components
(Wharton and Bishop, 2003).
Osteopetrosis
The observation of radiodense bone on plain radiographs should raise suspicion of osteopetrosis,
a rare, inherited bone disease with an overall incidence of 1 in 100 000–500 000 (Stark and
Savarirayan, 2009).
Osteopetrosis encompasses a group of heterogeneous conditions, ranging in severity from being
fatal in infancy to asymptomatic.
The more severe forms tend to have an autosomal recessive inheritance, while the milder forms
are inherited in an autosomal dominant manner.
Osteopetrosis results from defects in osteoclast function that leads to a decrease in bone
resorption.
The defect in bone turnover characteristically results in skeletal fragility despite increased bone
mass.
Lack of osteoclastic activity and thereby bone remodeling is of concern in orthodontics.
Children with the infantile forms of osteopetrosis have been reported to have dental issues
including delays in tooth eruption, missing and malformed teeth, enamel hypoplasia, problems
with dentinogenesis, mandibular protrusion, and odontomas (Luzzi et al., 2006).
Tooth removal in either condition should be handled conservatively, as such procedures can
result in bony fractures and osteomyelitis.
Clinical, Radiological, and Biochemical Findings
Oral and facial manifestations of osteopetrosis include facial growth anomalies, altered
mineralization of bone, increased radiodensity of the maxilla and mandible, malformed teeth,
unerupted teeth, delayed development of the dentition, early tooth exfoliation, and ankylosed
teeth.
Recurrent osteomyelitis of the mandible is a serious complication that commonly occurs in
patients with the autosomal recessive form and in approximately 10% of patients with the
autosomal dominant form. It results from an abnormal blood supply to the bones.
Affected infants with recessive osteopetrosis fail to grow and gain weight.
Neuropathies related to cranial nerve entrapment occur due to failure of skull foramina to widen
completely.
These entrapments may result in deafness and visual loss.
Defective bone tissue tends to replace bone marrow, causing bone marrow failure. As a result,
patients develop anemia, thrombocytopenia with resultant easy bruising and bleeding, and
leukopenia with recurrent infections.
Bone pain and fractures are common. Osteomyelitis of the maxilla or mandible typically occurs in
older adults (Waguespack et al., 2007).
Radiographic findings in osteopetrosis include osteosclerosis. Bones may be uniformly sclerotic,
or sclerotic areas may alternate with lucent bands.
Diagnosis
The diagnosis of osteopetrosis is based on clinical, laboratory, and radiographic findings. Family
history is also informative in dominant cases.
Management
Treatment for infantile osteopetrosis is primarily supportive of hypercalcemia and anemia followed
by bone marrow transplantation at an experienced center (Mazzolari et al., 2009).
Treatment of dominant osteopetrosis is generally supportive, and consists of orthopedic
management of fractures, neurosurgical intervention for cranial nerve entrapments, and iron
supplementation and/or transfusions, if needed for anemia.
Large doses of 1,25(OH)2 vitamin D, along with restricted calcium intake, have been reported to
improve osteopetrosis in a few selected cases (Key et al., 1984).
1,25(OH)2 vitamin D may help by stimulating osteoclastic bone resorption. However, clinical
improvement is not sustained after therapy is discontinued.
Fibrous Dysplasia
Fibrous dysplasia is a skeletal developmental anomaly of the bone-forming mesenchyme that
manifests as a defect in osteoblastic differentiation and maturation, resulting in destruction and
replacement of normal bone with fibrous bone tissue (Whyte, 1999).
Gingival swelling and/or facial asymmetry may be representative of craniofacial fibrous dysplasia.
Fibrous dysplasia generally presents in childhood, usually between the ages of 3 and 15 years.
When this diagnosis is made, a referral to the endocrine clinic should be undertaken to evaluate
for possible associated endocrinopathies as part of the McCune–Albright syndrome, which
classically is a triad of polyostotic fibrous dysplasia, hyperpigmented skin patches called café-au-
lait macules, and hyperfunction of one or more endocrine systems.
Clinical, Radiological, and Biochemical Findings
Fibrous lesions in bones often result in pain, fracture, and/or deformity.
Craniofacial fibrous dysplasia of the skull most commonly affects the mandible and maxilla, with
an equal likelihood of disease in either location (Dhiravai-Angkura et al., 1994).
Radiologically, fibrous dysplasia lesions are well defined and are characterized by thin cortices
and a ground-glass appearance resulting from calcification of fibrous tissue and bone formation.
In children, fibrous dysplasia lesions can affect tooth eruption by direct destruction of tooth buds.
ALP activity and markers of bone remodeling may be sometimes elevated (Chapurlat et al., 1997)
although calcium and phosphorus levels tend to be normal.
Precocious puberty is common in girls with McCune–Albright syndrome, resulting from
development of estrogen-secreting ovarian cysts.
The café-au-lait macules associated with McCune–Albright syndrome have a typical appearance
and distribution. Lesions have irregular borders, follow dermatomal distributions and, generally,
do not cross the midline
Diagnosis
When fibrous dysplasia is diagnosed, the treating physician should have a high level of suspicion
for associated McCune–Albright syndrome. Thus, a careful examination of the skin for café-au-
lait macules and endocrine testing is recommended for all patients with fibrous dysplasia since
McCune–Albright syndrome can be overlooked.
The panoramic radiograph will show the asymmetry and heterogenic structure of the bone with
areas of ‘ground glass’.
Management
In patients with mild disease, lesions tend to remain unchanged over time.
In those with severe disease, lesions may progress and new lesions may develop. Patients with
progressive bone lesions tend to develop significant deformities of the long bones and skull and
have recurrent fractures.
Bisphosphonates may decrease bone pain in some patients, but do not affect the natural history
of the bony lesions (DiMeglio, 2007).
A diagnosis of fibrous dysplasia of the skull commands periodic observation. In general,
orthodontic treatments should be postponed until after puberty, since lesions are less likely to
change much during adulthood.
Most patients who undergo orthodontic therapy do not experience satisfactory results, with
frequent relapses requiring subsequent re-treatments (Akintoye et al., 2003
Diabetes
Diabetes is defined by high blood glucose levels due to either insulin deficiency or resistance to
insulin action.
Signs and symptoms of diabetes include polydipsia, polyuria, and weight loss.
The two most common forms are type 1 and type 2 diabetes. Type 1 diabetes, formerly known as
juvenile diabetes results from autoimmune destruction of insulin-producing islet cells of the
pancreas.
The onset of type 1 diabetes is usually in childhood and treatment is with insulin and nutritional
therapy.
Type 2 diabetes is characterized by insulin resistance and relative insulin deficiency, and is the
form of diabetes linked to obesity.
The incidence of both type 1 and type 2 diabetes is increasing, and with the rise in obesity in
children, type 2 diabetes in particular is increasing in prevalence in children and adolescents.
Poor vascular circulation, decreased immunity, and high glucose levels in saliva, all in association
with poorly controlled diabetes, can increase susceptibility to gingival as well as periodontal
infections (Iacopino, 2001).
Clinical Findings
Individuals with uncontrolled diabetes are prone to develop periodontal disease. Gingivitis is an
initial presentation, manifesting as erythematous and swollen gingivae that tend to bleed easily
and separate from the teeth. If left untreated, this can progress to periodontitis and can lead to
tooth loss.
Management
Maintenance of good diabetes control is important to prevent periodontal disease.
Good oral hygiene, avoiding smoking and frequent dental check-ups are essential for preventing
gingival disease.
Type 2 diabetes is generally initially managed with increasing exercise and dietary modification if
the hyperglycemia is mild but as the condition progresses medical intervention in the form of oral
hypoglycemic agents or insulin therapy is generally necessary.
Poorly controlled diabetic patients are poor candidates for orthodontic treatment as the
mechanical force applied might lead to exaggerated tissue response and tooth mobility.
Moreover, periodontal support in these patients is always compromised.
Close collaboration with endocrinologists is warranted in these situations, so that the disease is
under control throughout the course of orthodontic treatment.
Adrenal Disorders
Primary adrenal insufficiency (PAI) results when the adrenal gland is not able to produce cortisol
and aldosterone.
The most common cause is autoimmune adrenal gland destruction (Addison disease) followed
by tuberculosis infection (Ten et al., 2001).
The presence of hyperpigmented oral mucosa in combination with unusual skin
hyperpigmentation should alert the treating dentist to the possibility of PAI.
Clinical and Biochemical Findings
Persons with chronic adrenal insufficiency have a variety of symptoms, including fatigue,
anorexia, weight loss, abdominal pain, nausea, vomiting, and/or weakness.
Patients have increased skin pigmentation, particularly within scars and areas unexposed to the
sun, such as the areolae, palmar creases, and axillae.
Symptoms of hypoglycemia and hypotension may be present.
Characteristic laboratory findings include low serum sodium
high potassium in combination with a low cortisol
elevated adrenocorticotropic hormone (ACTH) levels.
Diagnosis
Diagnosis of PAI is based on clinical and biochemical findings.
Treatment
Treatment of PAI is with oral glucocorticoid and mineralocorticoid replacement.
Of note, special care should be provided to patients with established adrenal insufficiency
requiring orthodontic treatment since in times of stress or illness they must increase their
glucocorticoid replacement dosage to mimic normal physiological responses.
Again, consulting with an endocrinologist prior to surgery is an essential part of management of
these individuals, since surgical procedures (and other stresses) require an increase in
glucocorticoid dosage.
Turner Syndrome
Turner syndrome is the result of complete or partial loss of one of the X chromosomes and should
be suspected in girls and women with high-arched palates and crowding of the teeth
The presence of additional facial features such as epicanthal folds, low-set ears, proptosis, a
webbed neck or a short neck with a low posterior hair line should prompt confirmatory evaluation.
Since nearly all untreated girls and women with Turner syndrome have short stature, assessment
of height and growth patterns is also important in establishing the diagnosis (Sybert and
McCauley, 2004).
Clinical and Radiological Findings
In addition to short stature, girls with Turner syndrome also usually have premature ovarian
failure, leading initially to failure to go through normal puberty and later infertility.
Premature ovarian failure results from rapid oocyte apoptosis and fibrosis of the ovaries.
Short stature is partially due to the loss of one copy of the SHOX (short stature homeobox gene)
gene on the X chromosome.
Girls with Turner syndrome often have a high-arched palate as well as cephalometric features
that differ from those of other family members (mothers and sisters).
These features include: shortened posterior cranial base length; shorter distance between the
sella and the palate, glenoid fossa, and gonion; and shorter mandibular length and the presence
of mandibular retrognathia (Perkiömäki et al., 2005).
Diagnosis
The diagnosis of Turner syndrome is based on clinical findings and chromosomal analysis.
Management
Height is improved with growth hormone therapy.
Most girls require estrogen replacement at the time of puberty to induce or complete pubertal
development.
Orthodontic treatment plans may need to incorporate: antibiotic prophylaxis if the patient has
associated cardiac anomalies; occlusal adjustments for altered dental morphology; changes in
timing of therapies in order to accommodate differences in growth and progress towards puberty;
and consideration of effects of growth hormone therapy (Russell, 2001).
Close collaboration with the treating endocrinologist, cardiologist, and geneticist is warranted to
prevent any untoward effects during the course of treatment.
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