DISEASES OF BONE

Osteogenesis imperfecta Osteopetrosis Cleidocranial dysplasia Fibrous dysplasia Pagets disease Cherubism Gardners Syndrome

OSTEOGENESIS IMPERFECTA

Osteogenesis Imperfecta must be considered as a differential diagnosis in a child having multiple repeated fractures Heterogeneous group of heritable disorders characterized by impairment of collagen maturation

Heterozygosity for mutations in one of two genes that guide the formation of Type I collagen:

COL1A1 gene on chromosome 17 and COL1A2 gene on chromosome 7

Abnormal collagenous maturation results in bone with a thin cortex, fine trabeculation, and diffuse osteoporosis

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

OTHER NAMES
Brittle bones Fragilitas Ossium Osteopsathyrosis Lobsteins disease

CLINICAL AND RADIOGRAPHIC FEATURES

Affects 1 in 8000 individuals, with many being stillborn or dying shortly after birth Both AD & AR occur Bone fragility, blue sclera, altered teeth, hypoacusis (hearing loss), long bone and spine deformities, and joint hyperextensibility Radiographic hallmarks : osteopenia, bowing, angulation or deformity of the long bones, multiple fractures, and wormian bones ( Also seen in cleidocranial dysplasia)

CLINICAL AND RADIOGRAPHIC FEATURES

Oral findings: identical to dentinogenesis imperfecta, both dentitions are involved demonstrate blue to brown translucence Radiographs typically reveal premature pulpal obliteration, Although shell teeth rarely maybe seen Such dental defects in association with the systemic bone disease should be termed opalescent teeth, reserving the diagnosis of dentinogenesis imperfecta for those patients with alterations isolated to the teeth Increased prevalence of class III malocclusion that is caused by maxillary hypoplasia, with or without mandibular hyperplasia

Large number of impactions Unerupted first and second permanent molars

OSTEOPETROSIS
ALBERS-SCHONBERG DISEASE; MARBLE BONE DISEASE

OSTEOPETROSIS
Caused by inherent defect in osteoclasts Pathogenesis is expressed through failure of osteoclast-mediated resorption of the skeleton. Defective osteoclasts fail to resorb the bone in the normal resorption-remodeling cycle (0.7% per day)

 Consequently

primary spongiosa (calcified cartilage deposited during endochondral bone formation) persists and serves as histopathologic marker for these disorders

RG:

Erlenmeyer flask deformity

dense Ro and RL bands

Alternating

Rugger
Bone

jersey vertebrae

in bone: endobone

LAB

FINDINGS:

Hypocalcemia can occur and may be severe enough to cause rachitic changes in growth plates. Secondary hyperparathyroidism Acid phosphatase (ACP) activity raised in serum Biochemical marker: brain isoenzyme of creatine kinase (BB-CK) in serum ACP and BB-CK : originate from osteoclasts Immunoreactive PTH levels in serum are elevated

Osteopetrosis with neuronal storage disease (accumulation of ceroid lipofuscin) may involve a defect centered in the lysosomes Virus like inclusions have been found in the osteoclasts of a few sporadic cases of benign osteopetrosis Synthesis of abnormal PTH Defective production of IL-2 or superoxide: factors necessary for bone resorption

Abnormality in circulating monocytes and granulocytes Impaired bone resorption causes skeletal fragility because fewer collagen fibrils properly connect osteons, and there is defective remodeling of woven bone to compact bone

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

SCHEUTHAUERMARIESAINTON SYNDROME CLEIDOCRANIAL DYSPLASIA

Delayed ossification of skull, excessively large fontanelles, delayed closure of sutures Brachycephalic skull
Saggital suture ~ sunken, flat appearance to skull Bossing of frontal, parietal & occipital regions give skull a large globular shape ~Arnold Head

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

Etiology

Familial, autosomal dominant Translocation- chrom. 8(8q22) & long arm of chrom. 6 Mutations in core binding factor alpha-l (CBFA1) gene, located on chrom 6p21

Oral manifestations

High, narrow, arched palate, actual cleft palate Maxilla underdeveloped & smaller than mandible

Prolonged retention of deciduous teeth & subsequent delay in eruption of succedaneous teeth
Roots of teeth ~ shorter & thinner than usual, absence of cellular cementum Supernumerary teeth

FIBROUS DYSPLASIA

Skeletal developmental anomaly of the bone-forming mesenchyme that manifests as a defect in osteoblastic differentiation and maturation

Etiology :
Mutation in GNAS I, a-stimulating activity polypeptide I gene ~ encodes Gs-alpha subunit > cAMP to hormone receptors GTPase perturbations > prolonged Gs alpha activation & stimulation of endocrine receptors

Elevated intracellular cAMP in bone marrow osteoprogenitor cells > cell proliferation with differentiation defects

Mutation Undiff. stem cells~ early embryologic life Osteoblasts, 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

CLINICAL AND RADIOGRAPHIC FEATURES:

Monostotic FD of jaws:

Disease limited to single bone 80% to 85% of all cases, Jaws ~ most common Late 1st & early 2nd decades No gender/racial predilection Slow growing painless osseous expansion with facial asymmetry Maxilla > mandible Teeth involved ~ firm but may be displaced by bony mass

R/F ~ vary Early onset ~ R/L & later calcify > ground glass or mottled mixed R/L / R/O pattern Critical to diagnosis ~ fails to manifest 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

Craniofacial FD

Polyostotic fibrous dysplasia

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 ~ margins irregular, resembling a map of coastline of Maine (neurofibromatosis has smooth borders like coast of California)

HISTOPATHOLOGIC FEATURES

Irregularly shaped trabeculae of immature (woven) bone in cellular, loosely arranged fibrous stroma Trabeculae ~ not connected, curvilinear shapes ~ Chinese script writing, considered to arise by metaplasia & not surrounded by plump appositioned osteoblasts No capsule or line of demarcation

LABORATORY FINDINGS

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 PROGNOSIS

Surgical resection in their entirety 25% & 50% pt.s ~ regrowth after surgical shave down Osteosarcoma ~ rarely associated with FD Radiation therapy for FD is contraindicated because it carries risk for development of post irradiation bone sarcoma

OSTEITIS DEFORMANS/

PAGET

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 or B/RANKL/RANK pathway, a molecular regulator of osteoclastogenesis Mutations 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

CLINICAL AND RADIOGRAPHIC FEATURES:

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

ORAL MANIFESTATIONS
Maxilla > Mandible, 2.3:1, alv. Ridge ~ widened, Palate ~ flattened Teeth ~ loose, migrate, spacing Prominent dental finding ~ hypercementosis , on PM & M teeth Mouth remains open Edentulous pt.s ~ appliances remade

In early stages of disease, radiolucent coin shaped lesions appear in flat bones of skull ~ osteitis

circumscripta

With progression, sclerosis is seen radiographically yielding the so-called cotton

wool appearance

Bone scintigraphy: bone scan may demonstrate marked uptake throughout the entire mandible from condyle to condyle, a feature that has been termed Lincoln's sign

HISTOPATHOLOGIC FEATURES

Initial osteolytic phase ~ disordered areas of resorption, osteoclastic resorptive lacunae Osteoblastic phase ~ haphazard woven bone Resting & reversal lines Mosaic pattern Jigsaw puzzle Marrow spaces ~ loose vascularised tissue

LABORATORY FINDINGS

Serum calcium and phosphorus levels ~ within normal limits

Serum alkaline phosphatase level ~ elevated

Values 250 Bodansky units ~ osteoblastic phase, polyostotic Upto 50 Bodansky units ~ monostotic Serum acid phosphatase levels not increased Urinary hydroxyproline levels ~ elevated, N- telopeptide, alpha C telopeptide

TREATMENT AND PROGNOSIS

No specific treatment Calcitonin, parathormone antagonist which suppresses bone resorption Complications ~ pathological fractures, dvlpmnt of osteosarcoma

CHERUBISM
rare hereditary non-neoplastic bone disease characterized by clinically evident bilateral, painless enlargements of the jaws that are said to give the patient a cherubic appearance.

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"

ORAL MANIFESTATIONS
Absence of teeth, impacted or displaced teeth and Root resorption.

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

RADIOGRAPHIC FEATURES

multilocular, expansile RL

HISTOPATHOLOGIC FEATURES:
Similar to giant cell granulomas Vascular fibrous tissue containing variable numbers of multinucleated giant cells Stroma: more loosely arranged than that seen in giant cell granulomas Some cases reveals eosinophilic, cuff like deposits surrounding small blood vessels throughout the lesion. In older, resolving lesions of cherubism, the tissue becomes more fibrous, the number of giant cells decreases, and new bone formation is seen.

TREATMENT

self-limiting lesion and spontaneously regresses with age. Some authors point medical therapy in the form of calcitonin

GARDNER SYNDROME
Rare autosomal dominant disease characterized by GI polyps, Multiple osteomas, and soft tissue tumors

Etiology:

Genetic

CLINICAL FEATURES:
onset early puberty polyps of the colon ultimately change into adenocarcinoma by the fourth decade of life. congenitally missing teeth, hypercementosis, odontomas, dentigerous cysts, impacted teeth, supernumerary teeth, fused or unusually long roots, and multiple caries. osteomas most often develop first within the angle of the mandible Abnormality of the retina of the eye Development of multiple epidermal cysts usually on face, scalp, and extremities

RADIOGRAPHIC FEATURES:

Usually impacted supernumerary teeth osteomas in the mandible or paranasal sinuses; well delineated or spherical calcifications

TREATMENT:
Colonectomy is recommended if 30 or more polyps are detected Cutaneous findings do not require treatment. Genetic counselling Osteomas may require excision if severely deforming or interfering with function

PROGNOSIS:

Polyps have a risk of undergoing malignant transformation