Diseases of Bone

7/28/2019 Diseases of Bone

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DISEASES OF BONE


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Osteogenesis imperfectaOsteopetrosisCleidocranial dysplasia

Fibrous dysplasiaPagets disease CherubismGardners Syndrome


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OSTEOGENESIS IMPERFECTA

Osteogenesis Imperfecta must be considered as adifferential diagnosis in a child having multiplerepeated fractures

Heterogeneous group of heritable disorderscharacterized by impairment of collagen maturation


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Abnormal collagenous maturation results in bonewith a thin cortex, fine trabeculation, and diffuseosteoporosis

Upon fracture, healing will occur but may beassociated with exuberant callus formation


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O THER NAMES

Brittle bonesFragilitas OssiumOsteopsathyrosis

Lobsteins disease


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C LINICAL AND R ADIOGRAPHIC FEATURES

Affects 1 in 8000 individuals, with many beingstillborn or dying shortly after birthBoth AD & AR occur

Bone fragility, blue sclera , altered teeth, hypoacusis(hearing loss), long bone and spine deformities,and joint hyperextensibilityRadiographic hallmarks : osteopenia, bowing,angulation or deformity of the long bones, multiplefractures, and wormian bones ( Also seen incleidocranial dysplasia)


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C LINICAL AND R ADIOGRAPHIC FEATURES

Oral findings:identical to dentinogenesis imperfecta ,both dentitions are involveddemonstrate blue to brown translucenceRadiographs typically reveal premature pulpalobliteration,

Although shell teeth rarely maybe seenSuch dental defects in association with the systemicbone disease should be termed opalescent teeth,reserving the diagnosis of dentinogenesis imperfecta for those patients with alterations isolated to the teethIncreased prevalence of class I II m alocclu s ion that iscaused by m axi llary hy pop las ia , with or withoutmandibular hyperplasia


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Large number of impactionsUnerupted first and second permanent molars


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OSTEOPETROSIS

ALBERS-SCHONBERG DISEASE;MARBLE BONE DISEASE


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Consequently primary spongiosa (calcifiedcartilage deposited during endochondralbone formation) persists and serves ashistopathologic marker for these disorders

RG: Erlenmeyer flask deformity

Alternating dense Ro and RL bands

Rugger jersey vertebrae

Bone in bone: endobone


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L AB FINDINGS :

Hypocalcemia can occur and may be severeenough to cause rachitic changes in growth plates.Secondary hyperparathyroidism

Acid phosphatase (ACP) activity raised in serumBiochemical marker: brain isoenzyme of creatinekinase (BB-CK) in serum

ACP and BB-CK : originate from osteoclasts

Immunoreactive PTH levels in serum are elevated


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Osteopetrosis with neuronal storage disease(accumulation of ceroid lipofuscin) may involve a defectcentered in the lysosomesVirus like inclusions have been found in theosteoclasts of a few sporadic cases of benignosteopetrosisSynthesis of abnormal PTHDefective production of IL-2 or superoxide: factorsnecessary for bone resorption


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Abnormality in circulating monocytes andgranulocytesImpaired bone resorption causes skeletalfragility because fewer collagen fibrils properlyconnect osteons, and there is defectiveremodeling of woven bone to compact bone


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There is reduced Ca/P ratio in both enamel anddentin that may alter OH-App crystal formation andcontribute to increased caries index

SCHEUTHAUER


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SCHEUTHAUER-MARIESAINTON

SYNDROMECLEIDOCRANIAL

DYSPLASIA

Delayed ossification of skull,excessively large fontanelles, delayedclosure of suturesBrachycephalic skull

Saggital suture ~ sunken, flatappearance to skull

Bossing of frontal, parietal & occipitalregions give skull a large globular

shape ~ Arnold Head

Clavicular hypoplasia or agenesis , ~approximation of shoulders in front of chest


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Etiology

Familial, autosomal dominantTranslocation- chrom. 8(8q22) & long arm of chrom. 6Mutations in core binding factoralpha-l ( CBFA1) gene , locatedon chrom 6p21


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Oral manifestations

High, narrow, arched palate,actual cleft palate

Maxilla underdeveloped & smaller than mandible

Prolonged retention of deciduous teeth & subsequentdelay in eruption of

succedaneous teeth

Roots of teeth ~ shorter & thinner than usual, absence of cellular cementum

Supernumerary teeth


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FIBROUS DYSPLASIA

Skeletal developmental anomaly of the bone-forming mesenchyme that manifests

as a defect in osteoblastic differentiationand maturation


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Etiology :

Mutation in GNAS I, a-stimulating activity polypeptide I gene ~ encodes Gs-alpha subunit> cAMP to hormone receptors

GTPase perturbations > prolonged Gs alphaactivation & stimulation of endocrine receptors

Elevated intracellular cAMP in bone marrow

osteoprogenitor cells > cell proliferation withdifferentiation defects


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Mutation Undiff. stem cells~ early embryologic lifeOsteoblasts, melanocytes, & endocrine cells ~ carry mutation

C/Fs ~ multiple bone lesions, cut. pigmentation & endcrn. disturbances

Skeletal progenitor cells ~ later stages

skeleton resulting in multiple bone lesions of FD

Mutation ~ post natal life,

Confined to one site, resulting in FD affecting single bone


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C LINICAL AND R ADIOGRAPHIC F EATURES :

Monostotic FD of jaws :

Disease limited to single bone80% to 85% of all cases,

Jaws ~ most commonLate 1 st & early 2 nd decades

No gender/racial predilectionSlow growing painless osseousexpansion with facial asymmetry

Maxilla > mandibleTeeth involved ~ firm but may bedisplaced by bony mass


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R/F ~ vary

Early onset ~ R/L & later calcify >

ground glass or mottled mixedR/L / R/O pattern

Critical to diagnosis ~ fails tomanifest any discrete margins

Mandibular involv. ~ expansion of lingual & buccal plates, bulging of lower border

Narrowing ~ Pdl space , ill-defined lamina dura Maxilla: lesion displaces sinus

floor superiorly, obliterates sinus


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Craniofacial FD

2 or more bones, few to 75 % of entire skeleton 20-30 % of cases Pain, hockey stick deformity, pathologic fracture With cafe au lait pigmentation ~ Jaffe-Lichtenstein syndrome With cafe au lait pigmentation & multiple endocrinopathies ~

McCune-Albright syndrome

Cafe au lait: well-defined, unilateral tan macules,

trunk & thighs

Oral mucosal macules ~ marginsirregular, resembling a map of coastline of Maine

(neurofibromatosis has smooth borders like coast of California )

Polyostotic fibrous dysplasia
http://en.wikipedia.org/wiki/File:Caff%C3%A8llatte_as_being_served_at_Kaffebrenneriet_Torshov,_Oslo,_Norway_2_600x600_100KB.jpg


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H ISTOPATHOLOGIC F EATURES

Irregularly shaped trabeculae

of immature (woven) bone incellular, loosely arrangedfibrous stroma

Trabeculae ~ not connected,curvilinear shapes ~

Chinese script writing, considered to arise bymetaplasia & not surrounded

by plump appositionedosteoblasts

No capsule or line of demarcation


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LABORATORY F INDINGS

No consistent significant changes in serum calcium or phosphorus

Alkaline serum phosphatase level is sometimes elevated

Premature secretion of pituitary follicle stimulating hormone reported

Moderately elevated basal metabolic rate

TREATMENT AND P ROGNOSIS

Surgical resection in their entirety

25% & 50% pt.s ~ regrowth after surgical shave downOsteosarcoma ~ rarely associated with FD

Radiation therapy for FD is contraindicated because itcarries risk for development of post irradiation bonesarcoma


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OSTEITIS DEFORMANS/P AGET DISEASE OF BONE

Disease characterised by excessive and abnormal remodelling of bone ,

is a common disorder in middle aged & elderly

Etiology: .

Defective function of the osteoprotegerin/ TNFRSF11A orB/RANKL/RANK pathway , a molecular regulator of osteoclastogenesisMutations in SQSTM1 (p62), sequestosome gene that encodes a scaffold

protein

NFKappaB signaling pathway mutations

o Phases

Lytic

Mixed lytic and blastic

Sclerotic or burned out


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C LINICAL AND R ADIOGRAPHIC F EATURES :

Late adult onset

M ~ F

Most ~ British Isles & New Zealand , > 1% of the population,

less common in Italy, other European countries & US

Rapid turnover of bone ~ osseous expansion, skeletal deformities

Tubular bones ~ bowing, spinal curvature ~ vertebral collapse in later stages

All bones of craniofacial complex ~ affected to varying degrees

Cranial nerve neuropathies because of foramina narrowing ~ deafness


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O RAL MANIFESTATIONS

Maxilla > Mandible, 2.3:1,alv. Ridge ~ widened,Palate ~ flattened

Teeth ~ loose, migrate, spacingProminent dental finding ~ hypercementosis , on PM &M teethMouth remains open

Edentulous pt.s ~ appliances remade


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In early stages of disease,radiolucent coin shapedlesions appear in flat bones of skull ~ osteitis circumscripta

With progression, sclerosis isseen radiographically yielding

the so-called cotton wool appearance


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Bone scintigraphy : bone scan may demonstratemarked uptake throughout the entire mandible fromcondyle to condyle, a feature that has been termedLincoln's sign


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H ISTOPATHOLOGIC F EATURES

Initial osteolytic phase ~disordered areas of resorption, osteoclasticresorptive lacunae

Osteoblastic phase ~haphazard woven bone

Resting & reversal lines

Mosaic patternJigsaw puzzle

Marrow spaces ~ loosevascularised tissue


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LABORATORY F INDINGS

Serum calcium and phosphorus levels ~ within normal limits

Serum alkaline phosphatase level ~ elevatedValues 250 Bodansky units ~ osteoblastic phase, polyostotic

Upto 50 Bodansky units ~ monostoticSerum acid phosphatase levels not increasedUrinary hydroxyproline levels ~ elevated,

N- telopeptide, alpha C telopeptide

TREATMENT AND P ROGNOSIS

No specific treatment

Calcitonin, parathormone antagonist which suppresses bone resorptionComplications ~ pathological fractures,

dvlpmnt of osteosarcoma


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CHERUBISM

rare hereditary non-neoplastic bone diseasecharacterized by clinically evidentbilateral, painless enlargements of the jaws thatare said to give the patient a cherubicappearance.

fullness of the cheeks and retraction of the lower eyelids giving an upward turned appearance of the eyes comparable to a cherub angel

Also called : "familial fibrous dysplasia"


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ORAL MANIFESTATIONS

Absence of teeth,impacted or displaced teeth andRoot resorption.

These anomalies are caused by the substitution of bone into a fibrous tissue


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RADIOGRAPHIC FEATURES

multilocular, expansile RL


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H ISTOPATHOLOGIC F EATURES :

Similar to giant cell granulomasVascular fibrous tissue containing variable numbersof multinucleated giant cellsStroma: more loosely arranged than that seen ingiant cell granulomasSome cases reveals eosinophilic, cuff likedeposits surrounding small blood vesselsthroughout the lesion.

In older, resolving lesions of cherubism, the tissuebecomes more fibrous, the number of giant cellsdecreases, and new bone formation is seen.


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TREATMENT

self-limiting lesion and spontaneously regresseswith age.

Some authors point medical therapy in the form of calcitonin


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G ARDNER S YNDROME

Rare autosomal dominant disease characterized by

GI po lyps ,

Mult iple os teom as, and so f t t i s sue tum ors

Etiology:Genetic


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C LINICAL F EATURES :

onset early pubertypolyps of the colon ultimately change intoadenocarcinoma by the fourth decade of life.congenitally missing teeth, hypercementosis,

odontomas, dentigerous cysts, impacted teeth,supernumerary teeth, fused or unusually longroots, and multiple caries.osteomas most often develop first within the angle

of the mandible Abnormality of the retina of the eyeDevelopment of multiple epidermal cysts usuallyon face, scalp, and extremities


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R ADIOGRAPHIC F EATURES :

Usually impacted supernumerary teeth

osteomas in the mandible or paranasal sinuses;well delineated or spherical calcifications


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TREATMENT :

Colonectomy is recommended if 30 or morepolyps are detectedCutaneous findings do not require treatment.Genetic counsellingOsteomas may require excision if severelydeforming or interfering with function


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P ROGNOSIS :

Polyps have a risk of undergoing malignanttransformation

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Diseases of Bone