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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