Ch14 Bone Path (Part I) Flashcards
Prevelance of Osteogenesis Imperfecta?
6 to 7 per 100,000
What % of cases of Osteogenesis Imperfecta are AD?
90%
In 90% of AD cases of OI, which two genes are mutated? What do they code for?
COL1A1 or COL1A2 they code for Type 1 collagen
Since THIS TYPE OF COLLAGEN is present in bone, dentin, sclerae, ligaments, and skin, OI can affect all of them
TYPE 1 COLLAGEN
Problems in production of Type 1 collagen in OI lead to low ______ strength, therefore making bone _____
LOW TENSILE STRENGTH…brittle
What is the most common form of Osteogenesis Imperfecta?
Osteogenesis Imperfecta Type I, its also the mildest
What is the MOST SEVERE form of Osteogenesis Imperfecta? What is the typical survival of this pt?
Osteogenesis Imperfecta Type II…likely die in utero or shortly after birth
What are the 3 clinical presentations of Osteogenesis Imperfecta?
- blue sclerae 2. hearing loss 3. joint hyperextensibility / contracture
What are the 4 radiographic hallmarks of Osteogenesis Imperfecta?
1.osteopenia 2. bowing of the long bones 3. multiple fractures 4.increased # of Wormian bones in the skull (also seen in CLEIDOCRANIAL DYSPLASIA)
The dental alterations (clinically and radiographically) in Osteogenesis Imperfecta are IDENTICAL to what other entity? Which 2 types of OI specifically?
Dentinogenesis Imperfecta.. Types III and IV OI
What three colors are associated with the dentition in OI or DI?
blue, brown, yellow translucence
Radiographs of OI (and therefore DI) teeth reveal?
premature pulpal obliteration
What do the tooth roots in OI / DI look like?
narrow or CORNCOB-shaped
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?
Opalescent teeth
OI patients have an increased prevalence of which malocclusion?
Class III (maxillary hypoplasia)
What is a medication threatment that can possibly reduce fractures, increase mobility in a child with OI?
IV Bisphosphonates
OI Types: Mild phenotype, minimal bone deformity, bone fractures, normal or near normal stature, blue sclerae, joint laxity, hearing loss, rarely opalescent teeth
Type I
OI Types: Type I mutated gene?
COL1A1 (null allele)
OI Types: Perinatal lethal, multiple fractures of ribs and long bones, respiratory distress, limb deformities, dark blue sclerae
Type II
OI Types: Type II mutated gene(s)?
COL1A1, COL1A2
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
Type III
OI Types: Type III mutated gene(s)?
COL1A1, COL1A2
OI Types: Mild to moderate bone fragility and deformity, white to gray sclerae, often opalescent teeth
Type IV
OI Types: Type IV mutated gene(s)?
COL1A1, COL1A2
What are two other names for Osteopetrosis?
Albers-Schonberg Disease, Marble bone disease
What is the cell to blame in osteopetrosis?
failure of osteoclast function or differentiation
What are the three disease subtypes in osteopetrosis?
1.AR infantile (malignant) type 2.AR intermediate type 3.AD adult (benign) type
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.
Autosomal Recessive Infantile Osteopetrosis
What disease? The initial signs often are normocytic anemia with hepatosplenomegaly resulting from compensatory extramedullary hematopoiesis.
Autosomal Recessive Infantile Osteopetrosis
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.
Autosomal Recessive Infantile Osteopetrosis
What disease? The bone is dense but prone to pathologic fracture. OSTEOMYELITIS of the jaws is a frequent complication of tooth extraction
Autosomal Recessive Infantile Osteopetrosis
What disease? Radiographically, there is a widespread increase in skeletal density with defects in metaphyseal remodeling.
Autosomal Recessive Infantile Osteopetrosis
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.
Autosomal Recessive Infantile Osteopetrosis
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.
Autosomal Recessive Intermediate Osteopetrosis
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.
Autosomal Dominant Adult Osteopetrosis
What disease? Occasionally, the diagnosis is discovered initially on review of dental radiographs that reveal diffusely increased radiopacity of the medullary bone.
Autosomal Dominant Adult Osteopetrosis
What are the three differentials for AD Adult Osteopetrosis?
1.AD OsteoSclerosis 2.SclerOsteosis 3.van Buchem disease
What are the three histopathological features of AD Adult Osteopetrosis?
- Tortuous lamellar trabeculae replacing the cancellous
portion of the bone 2. Globular amorphous bone deposition in the marrow spaces 3. Osteophytic bone formation
Histologically in AD Adult Osteopetrosis what characteristic osteoclast feature is absent?
Howship’s Lacunae are not visible
What is the gene responsible for Cleidocranial Dysplasia? (2 names) Where is it found?
RUNX2 (CBFA1) on chromosome 6p21
RUNX2 plays an important role in _________ via participation in odontoblast differentiation, enamel organ formation, and dental lamina proliferation.
odontogenesis
What is the inheritance pattern for cleidocranial dysplasia? What is the proposed % of spontaneous mutations?
AD..40%
What % of cleidocranial dysplasia pts have COMPLETELY ABSENT clavicles?
10%
What condition?: On skull radiographs, the sutures and fontanels show delayed closure or may remain open throughout life.
cleidocranial dysplasia
Oral & Maxillofacial features of Cleidocranial Dysplasia: Patients often have a narrow, high-arched palate, and there is an increased prevalence of ______.
cleft palate
Oral & Maxillofacial features of Cleidocranial Dysplasia: Over-retained ________ and delay or complete failure of permanent tooth eruption
deciduous teeth
Oral & Maxillofacial features of Cleidocranial Dysplasia: There may be abnormal ________ in the mandibular incisor area because of widening of the alveolar bone.
spacing
Oral & Maxillofacial features of Cleidocranial Dysplasia: On dental radiographs, what is the MOST DRAMATIC finding?
numerous unerupted permanent and supernumerary teeth (up to 60), often exhibiting distorted crown and root shapes (+/- dentigerous cysts)
Oral & Maxillofacial features of Cleidocranial Dysplasia: Generalized hypoplasia of the paranasal sinuses may
predispose the patient to ________.
recurrent sinus infections
The __________ is an area of hematopoietic marrow that is sufficient in size to produce a radiolucency.
focal osteoporotic marrow defect
Focal osteoporotic marrow defect: gender and location
75% female, 70% posterior mandible most often in edentulous areas
When explaining a focal osteoporotic marrow defect to a patient, what will you tell them if they ask how it happens?
3 theories: 1 Aberrant bone regeneration after tooth extraction 2. Persistence of fetal marrow 3. Marrow hyperplasia in response to increased demand for
erythrocytes
Idiopathic osteosclerosis: gender? race? age? location?
no sex predilection, blacks/asians, 1st-2nd decades ..90% mandible (1st molar area)
WHAT SHOULD BE EXCLUDED IF MULTIPLE IDIOPATHIC OSTEOSCLEROSIS LESIONS ARE FOUND?
Gardner Syndrome can present with multiple osteomas
Well shit, idiopathic osteosclerosis CAN have associated root ______ and tooth ________
resorption and movement
Name that bone pathology: The destroyed bone is replaced by a vascular proliferation and, ultimately, dense fibrous tissue without bone regeneration.
Massive osteolysis
What are the 5 goddam names for massive osteolysis?
- GORHAM DISEASE 2. GORHAM-STOUT SYNDROME 3. VANISHING BONE DISEASE 4.PHANTOM BONE DISEASE 5.IDIOPATHIC OSTEOLYSIS
What are the 5 mechanisms proposed for massive osteolysis?
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
massive osteolysis: age, location?
BROAD range, but predominantly children and young adults…all over body, but most gnathic lesions present in the mandible
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
Massive osteolysis
What stain is typically postive in massive osteolysis?
D2-40 highlighting the lymphatic endothelium
What is the most hopeful treatment available for massive osteolysis?
some investigators have reported disease stabilization with administration of bisphosphonates and/ or alpha-2b interferon
Autosomal recessive types of osteogenesis imperfecta are caused by defects in what ? (4)
Chaperone defects
Mineralization defects
3-hydroxylation defects (collagen cross-linking)
C-propetide cleavage
Serologies for osteogenesis imperfecta
Serologies all normal usually: calcium, alk phos(can be slightly elevated), vit D, phosphorus
Patients diagnosed with osteogenesis imperfecta have an increased risk of _____ (3)
Cardiac malformations
Bleeding disorders
Hyperthermia
Prevalence of osteopetrosis overall
1:100,000-500,000
Most common mutations in osteopetrosis
RANK and/or RANKL
30% the mutation is unknown
Defects in the ____ channel are implicated in AR infantile osteopetrosis. Defects in the _____ ____ subunit are also implicated.
chloride ion channel
proton pump subunit
Prevalence of cleidocranial dysplasia
1:1,000,000
Short lower face height aka ___ _____ ____ is seen in patients with cleidocranial dysplasia
acute gonial angle
T/F: There is an association between focal osteoporotic marrow defect and hematologic malignancies or anemias
False- no association
Prevalence of idiopathic osteosclerosis
5%
