Ch14 Bone Path (Part I)

Question 1

Prevelance of Osteogenesis Imperfecta?

Answer 1

6 to 7 per 100,000

Question 2

What % of cases of Osteogenesis Imperfecta are AD?

Answer 2

90%

Question 3

In 90% of AD cases of OI, which two genes are mutated? What do they code for?

Answer 3

COL1A1 or COL1A2 they code for Type 1 collagen

Question 4

Since THIS TYPE OF COLLAGEN is present in bone, dentin, sclerae, ligaments, and skin, OI can affect all of them

Answer 4

TYPE 1 COLLAGEN

Question 5

Problems in production of Type 1 collagen in OI lead to low ______ strength, therefore making bone _____

Answer 5

LOW TENSILE STRENGTH…brittle

Question 6

What is the most common form of Osteogenesis Imperfecta?

Answer 6

Osteogenesis Imperfecta Type I, its also the mildest

Question 7

What is the MOST SEVERE form of Osteogenesis Imperfecta? What is the typical survival of this pt?

Answer 7

Osteogenesis Imperfecta Type II…likely die in utero or shortly after birth

Question 8

What are the 3 clinical presentations of Osteogenesis Imperfecta?

Answer 8

1. blue sclerae 2. hearing loss 3. joint hyperextensibility / contracture

Question 9

What are the 4 radiographic hallmarks of Osteogenesis Imperfecta?

Answer 9

1.osteopenia 2. bowing of the long bones 3. multiple fractures 4.increased # of Wormian bones in the skull (also seen in CLEIDOCRANIAL DYSPLASIA)

Question 10

The dental alterations (clinically and radiographically) in Osteogenesis Imperfecta are IDENTICAL to what other entity? Which 2 types of OI specifically?

Answer 10

Dentinogenesis Imperfecta.. Types III and IV OI

Question 11

What three colors are associated with the dentition in OI or DI?

Answer 11

blue, brown, yellow translucence

Question 12

Radiographs of OI (and therefore DI) teeth reveal?

Answer 12

premature pulpal obliteration

Question 13

What do the tooth roots in OI / DI look like?

Answer 13

narrow or CORNCOB-shaped

Question 14

Since OI and DI are separate entities, but have similar radiographic features for the teeth, what is the proper term for teeth to describe OI?

Answer 14

Opalescent teeth

Question 15

OI patients have an increased prevalence of which malocclusion?

Answer 15

Class III (maxillary hypoplasia)

Question 16

What is a medication threatment that can possibly reduce fractures, increase mobility in a child with OI?

Answer 16

IV Bisphosphonates

Question 17

OI Types: Mild phenotype, minimal bone deformity, bone fractures, normal or near normal stature, blue sclerae, joint laxity, hearing loss, rarely opalescent teeth

Answer 17

Type I

Question 18

OI Types: Type I mutated gene?

Answer 18

COL1A1 (null allele)

Question 19

OI Types: Perinatal lethal, multiple fractures of ribs and long bones, respiratory distress, limb deformities, dark blue sclerae

Answer 19

Type II

Question 20

OI Types: Type II mutated gene(s)?

Answer 20

COL1A1, COL1A2

Question 21

OI Types: Severely deforming, very short stature, frequent fractures, wheelchair-dependent at an early age, triangular facies, coxa vara, “popcorn calcifications” of femoral head, blue-gray sclerae, often opalescent teeth, most patients die during childhood secondary to complications of kyphoscoliosis

Answer 21

Type III

Question 22

OI Types: Type III mutated gene(s)?

Answer 22

COL1A1, COL1A2

Question 23

OI Types: Mild to moderate bone fragility and deformity, white to gray sclerae, often opalescent teeth

Answer 23

Type IV

Question 24

OI Types: Type IV mutated gene(s)?

Answer 24

COL1A1, COL1A2

Question 25

What are two other names for Osteopetrosis?

Answer 25

Albers-Schonberg Disease, Marble bone disease

Question 26

What is the cell to blame in osteopetrosis?

Answer 26

failure of osteoclast function or differentiation

Question 27

What are the three disease subtypes in osteopetrosis?

Answer 27

1.AR infantile (malignant) type 2.AR intermediate type 3.AD adult (benign) type

Question 28

This severe form usually is diagnosed at birth or in early infancy. Typical findings include a diffusely sclerotic skeleton, bone marrow failure, frequent fractures, cranial nerve compression, and growth impairment.

Answer 28

Autosomal Recessive Infantile Osteopetrosis

Question 29

What disease? The initial signs often are normocytic anemia with hepatosplenomegaly resulting from compensatory extramedullary hematopoiesis.

Answer 29

Autosomal Recessive Infantile Osteopetrosis

Question 30

What disease? Affected children often exhibit a broad face, hypertelorism, snub nose, and frontal bossing. Failure of resorption and remodeling of the skull produces narrow skull foramina and cranial nerve compression, which may result in blindness, deafness, and facial paralysis.

Answer 30

Autosomal Recessive Infantile Osteopetrosis

Question 31

What disease? The bone is dense but prone to pathologic fracture. OSTEOMYELITIS of the jaws is a frequent complication of tooth extraction

Answer 31

Autosomal Recessive Infantile Osteopetrosis

Question 32

What disease? Radiographically, there is a widespread increase in skeletal density with defects in metaphyseal remodeling.

Answer 32

Autosomal Recessive Infantile Osteopetrosis

Question 33

What disease? On dental radiographs, tooth roots often are difficult to visualize because of the density of the surrounding bone. In addition, failure of tooth eruption is common.

Answer 33

Autosomal Recessive Infantile Osteopetrosis

Question 34

What disease? Affected patients often are asymptomatic at birth but exhibit fractures by the end of the first decade. Mild to moderate anemia and extramedullary hematopoiesis are common, but bone marrow failure is rare. Short stature, mandibular prognathism, unerupted teeth, and osteomyelitis also have been reported.

Answer 34

Autosomal Recessive Intermediate Osteopetrosis

Question 35

What disease? This most common type usually is discovered in adolescence or adulthood and exhibits less severe manifestations. Sclerosis mainly affects the axial skeleton, with relative sparing of the long bones.

Answer 35

Autosomal Dominant Adult Osteopetrosis

Question 36

What disease? Occasionally, the diagnosis is discovered initially on review of dental radiographs that reveal diffusely increased radiopacity of the medullary bone.

Answer 36

Autosomal Dominant Adult Osteopetrosis

Question 37

What are the three differentials for AD Adult Osteopetrosis?

Answer 37

1.AD OsteoSclerosis 2.SclerOsteosis 3.van Buchem disease

Question 38

What are the three histopathological features of AD Adult Osteopetrosis?

Answer 38

1. Tortuous lamellar trabeculae replacing the cancellous | portion of the bone 2. Globular amorphous bone deposition in the marrow spaces 3. Osteophytic bone formation

Question 39

Histologically in AD Adult Osteopetrosis what characteristic osteoclast feature is absent?

Answer 39

Howship's Lacunae are not visible

Question 40

What is the gene responsible for Cleidocranial Dysplasia? (2 names) Where is it found?

Answer 40

RUNX2 (CBFA1) on chromosome 6p21

Question 41

RUNX2 plays an important role in _________ via participation in odontoblast differentiation, enamel organ formation, and dental lamina proliferation.

Answer 41

odontogenesis

Question 42

What is the inheritance pattern for cleidocranial dysplasia? What is the proposed % of spontaneous mutations?

Answer 42

AD..40%

Question 43

What % of cleidocranial dysplasia pts have COMPLETELY ABSENT clavicles?

Answer 43

10%

Question 44

What condition?: On skull radiographs, the sutures and fontanels show delayed closure or may remain open throughout life.

Answer 44

cleidocranial dysplasia

Question 45

Oral & Maxillofacial features of Cleidocranial Dysplasia: Patients often have a narrow, high-arched palate, and there is an increased prevalence of ______.

Answer 45

cleft palate

Question 46

Oral & Maxillofacial features of Cleidocranial Dysplasia: Over-retained ________ and delay or complete failure of permanent tooth eruption

Answer 46

deciduous teeth

Question 47

Oral & Maxillofacial features of Cleidocranial Dysplasia: There may be abnormal ________ in the mandibular incisor area because of widening of the alveolar bone.

Answer 47

spacing

Question 48

Oral & Maxillofacial features of Cleidocranial Dysplasia: On dental radiographs, what is the MOST DRAMATIC finding?

Answer 48

numerous unerupted permanent and supernumerary teeth (up to 60), often exhibiting distorted crown and root shapes (+/- dentigerous cysts)

Question 49

Oral & Maxillofacial features of Cleidocranial Dysplasia: Generalized hypoplasia of the paranasal sinuses may predispose the patient to ________.

Answer 49

recurrent sinus infections

Question 50

The __________ is an area of hematopoietic marrow that is sufficient in size to produce a radiolucency.

Answer 50

focal osteoporotic marrow defect

Question 51

Focal osteoporotic marrow defect: gender and location

Answer 51

75% female, 70% posterior mandible most often in edentulous areas

Question 52

When explaining a focal osteoporotic marrow defect to a patient, what will you tell them if they ask how it happens?

Answer 52

3 theories: 1 Aberrant bone regeneration after tooth extraction 2. Persistence of fetal marrow 3. Marrow hyperplasia in response to increased demand for erythrocytes

Question 53

Idiopathic osteosclerosis: gender? race? age? location?

Answer 53

no sex predilection, blacks/asians, 1st-2nd decades ..90% mandible (1st molar area)

Question 54

WHAT SHOULD BE EXCLUDED IF MULTIPLE IDIOPATHIC OSTEOSCLEROSIS LESIONS ARE FOUND?

Answer 54

Gardner Syndrome can present with multiple osteomas

Question 55

Well shit, idiopathic osteosclerosis CAN have associated root ______ and tooth ________

Answer 55

resorption and movement

Question 56

Name that bone pathology: The destroyed bone is replaced by a vascular proliferation and, ultimately, dense fibrous tissue without bone regeneration.

Answer 56

Massive osteolysis

Question 57

What are the 5 goddam names for massive osteolysis?

Answer 57

1. GORHAM DISEASE 2. GORHAM-STOUT SYNDROME 3. VANISHING BONE DISEASE 4.PHANTOM BONE DISEASE 5.IDIOPATHIC OSTEOLYSIS

Question 58

What are the 5 mechanisms proposed for massive osteolysis?

Answer 58

1.Trauma-induced proliferation of vascular granulation tissue 2.Trauma-induced activation of a previously silent hamartoma 3.Increased osteoclastic activity mediated by interleukin-6 (IL-6) 4.Lymphangiogenesis mediated by vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) 5.Agenesis or dysfunction of thyroid C cells

Question 59

massive osteolysis: age, location?

Answer 59

BROAD range, but predominantly children and young adults...all over body, but most gnathic lesions present in the mandible

Question 60

Name that bone pathology: Loss of lamina dura and thinning of cortical plates often precede development of obvious radiolucency...it can also mimic PERIODONTITIS or PERIAPICAL inflammatory disease

Answer 60

Massive osteolysis

Question 61

What stain is typically postive in massive osteolysis?

Answer 61

D2-40 highlighting the lymphatic endothelium

Question 62

What is the most hopeful treatment available for massive osteolysis?

Answer 62

some investigators have reported disease stabilization with administration of bisphosphonates and/ or alpha-2b interferon

Question 63

Autosomal recessive types of osteogenesis imperfecta are caused by defects in what ? (4)

Answer 63

Chaperone defects Mineralization defects 3-hydroxylation defects (collagen cross-linking) C-propetide cleavage

Question 64

Serologies for osteogenesis imperfecta

Answer 64

Serologies all normal usually: calcium, alk phos(can be slightly elevated), vit D, phosphorus

Question 65

Patients diagnosed with osteogenesis imperfecta have an increased risk of _____ (3)

Answer 65

Cardiac malformations Bleeding disorders Hyperthermia

Question 66

Prevalence of osteopetrosis overall

Answer 66

1:100,000-500,000

Question 67

Most common mutations in osteopetrosis

Answer 67

RANK and/or RANKL | 30% the mutation is unknown

Question 68

Defects in the ____ channel are implicated in AR infantile osteopetrosis. Defects in the _____ ____ subunit are also implicated.

Answer 68

chloride ion channel | proton pump subunit

Question 69

Prevalence of cleidocranial dysplasia

Answer 69

1:1,000,000

Question 70

Short lower face height aka ___ _____ ____ is seen in patients with cleidocranial dysplasia

Answer 70

acute gonial angle

Question 71

T/F: There is an association between focal osteoporotic marrow defect and hematologic malignancies or anemias

Answer 71

False- no association

Question 72

Prevalence of idiopathic osteosclerosis

Answer 72

5%