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Bone diseases

CLASSIFICATIONIt is not easy to classify bone diseases since some of them are of unknownaetiology or their nature is imperfectly understood. Nevertheless, a classificationis necessary, and the one that follows may serve as a broad frameworkI. HereditaryAffecting all or any bones:Osteogenesis imperfecta.Osteopetrosis (marble bone disease; Albers Schonberg disease).Cherubism (familial fibrous dysplasia).Affecting mainly membrane-formed bones:Cleido-Cranial Dysplasia (dysostosis).Affecting bones formed in cartilage:AchondroplasiaII. AcquiredDevelopmental:Fibrous dysplasia.Dystrophic:Osteitis Deformans (Pagets disease of bone).Leonteasis Ossea.Inflammatory:Acute and chronic suppurative osteomyelitis.Chronic focal sclerosing osteomyelitis.Chronic diffuse sclerosing osteomyelitis.Chronic non-suppurative sclerosing osteomyelitis; Garres osteomyelitis.Osteoradionecrosis.Hormonal:Hyperparathyroidism (Von Recklinghausens disease of bone).Osteoporosis.Acromegaly (and Gigantism).Nutritional:Rickets.Osteomalacia.Reparative, representing failure in the normal reparative process:Traumatic (solitary) Bone Cyst.Aneurysmal Bone Cyst.Central Giant Cell Lesion.Cystic:Odontogenic Cysts.Fissural Cysts.Pseudocysts.Skeletal Reticuloendothelioses:Langerhan's cell histiocytosis.

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Unifocal Unisystem: Eosinophilic Granuloma. Multifocal Unisystem: Hand-Schuller-Christian disease. Multifocal Multisystem: Leterrer Siwes disease.Lysosomal storage diseases. Gauchers Disease. Niemann-Pick Disease.Neoplastic:Benign: Non-Ossifying Fibroma. Ossifying Fibroma (Calcifying Fibroma). Fibro-Osteoma. Cancellous Osteoma. Compact Osteoma. Chondroma. Giant Cell Tumour (sometimes malignant).Malignant: Fibrosarcoma. Chondrosarcoma. Osteogenic sarcoma (osteolytic, osteoblastic, telangiectatic).Myelogenic: Ewings Sarcoma (Tumour). Reticulum Cell Sarcoma. Plasma Cell Myeloma (multiple myeloma).Metastatic: Carcinoma of the Breast. Bronchogenic (lung) Carcinoma. Carcinoma of the Prostate. Carcinoma of the Kidney (hypernephroma). Carcinoma of the Thyroid Gland. Carcinoma of the Stomach. Carcinoma of the Colon.

HEREDITARY DISEASES OF BONEDiseases transmitted from one generation to another through genetic influences

OSTEOGENESIS IMPERFECTA

This is a rare hereditary disease transmitted by an autosomal dominant gene thatmay or may not show complete penetrance or expressivityAetiology

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The disease is most commonly caused by mutation to the COL1A1 and COL1A2genes.It may be transmitted as a dominant or a recessive disorder.Between 85 and 90 percent of osteogenesis imperfecta cases are dominant.People with osteogenesis imperfecta are born with defective connectivetissue, usually because of a quantitative or qualitative deficiency of Type-Icollagen.This deficiency arises from an amino acid substitution of glycine by bulkieramino acids in the collagen triple helix structure.The larger amino acid side-chains create a "bulge" in the collagen complex,which in turn influences the molecular mechanics and interaction betweenmolecules, which are compromised.Because of this, the body may respond by hydrolyzing the improperly formedcollagen structure.If the body does not remove the improper collagen, the relationship betweenthe collagen fibrils and hydroxyapatite crystals is altered, causing bonebrittleness.Failure of reticulin fibrils in the corium of the skin to become transformed intomature collagen fibres has been demonstrated.Presumably, a comparable defect may also be present in other connectivetissue structures affected by the disease such as ligaments and bone.Nature

The essential change in the skeleton predisposing to delicate, bent orotherwise deformed bones that are prone to fracture is deficient or defectivebone formation by osteoblasts. This is observed in both:

Bones formed in membrane at periosteal surfaces. At sites of endochondral ossification.

Osteoclastic activity is normal.There are eight different types of OI, Type I being the most common.

The symptoms may vary from one person to another. Type I osteogenesis imperfecta is mainly characterised by:

Autosomal dominant trait.Age at presentation: 2-6 years.Collagen is of normal quality but is produced in insufficient quantities:Bones fracture easily.Slight spinal curvature.Loose joints.Poor muscle tone.Discolouration of the sclera, usually giving them a bluish colour.The blue-gray colour of the sclera is due to the underlying choroidal veins,which show through the thin sclera.Early loss of hearing in some children.Slight protrusion of the eyes.Types "IA" and "IB" are distinguished by the absence or presence ofdentinogenesis imperfecta.Genetic FactorsMost cases of osteogenesis imperfecta are caused by a dominant geneticdefect.

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Some children with osteogenesis imperfecta inherit the disorder from aparent. Other children are born with osteogenesis imperfecta even though there isno family history of the disorder. In these children, the genetic defect occurred as a spontaneous mutation.Because the defect - whether inherited or due to a spontaneous mutation(prezygotic) - is usually dominant, a person with osteogenesis imperfecta hasa 50% chance of passing on the disorder to each of his or her children.Clinical FeaturesThe affected child may be born dead with multiple fractures sustained in utero.It may be born alive but die shortly afterwards from the many fracturessustained during delivery.It may be born in an apparently healthy condition and only show evidence ofbone weakness (tendency to fracture with mild trauma) during childhood andadolescence.There is a tendency for the condition to become gradually milder anddisappear as the affected person advances in age.A remarkable feature of the condition is for the patients to have blue or bluishsclera (patients are sometimes referred to as blue sclerotics).158The colour is due to partial visibility of the choroid through the abnormally thinsclera.Otosclerosis may develop after the age of 20 years.The patients suffer from many fractures sustained after relatively mild traumaduring their childhood and adolescence.The fractures heal readily and exuberantly.There may be bony swellings especially in the temporal region, andsometimes in the frontal and occipital regions.Ossification of the skull may be incomplete with the presence of manywormian bones.There may be looseness of the joints due to laxity of the ligaments supportingthem, with consequent easy dislocations.The skin may be thin.The parathyroid glands may be enlarged, but the serum calcium andphosphorus levels are normal.There may be associated dentinogenesis imperfecta.MicroscopicallyThe bone trabeculae are narrow and widely separated.Few osteoblasts are visible.Osteoclastic activity is normal.

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Osteogenesis imperfecta: Left: Many wormian bones between theoccipital and parietal bones; Right: Blue sclera.

OSTEOPETROSIS

A rare hereditary bone disease of heterogeneous pathogenesis in which failure ofosteoclastic bone resorption leads to increased bone mass. A Germanradiologist, Albers-Schon berg, first described the disease in 1904Nature of the Disease

Normal bone growth and remodelling is achieved by a balance between boneformation by osteoblasts and bone resorption by osteoclasts.

In osteopetrosis, the number of osteoclasts may be reduced or normal. The most notable feature mediating the pathogenesis of the disease,

however, is osteoclast dysfunction.The exact mechanism is only beginning to be understood.There are at least two types of osteopetrosis.In one type, deficiency of carbonic anhydrase II enzyme in osteoclasts isnoted.The absence of this enzyme causes defective hydrogen ion pumping byosteoclasts.This causes defective bone resorption, as a highly acidic environment isneeded for dissociation of calcium hydroxyapatite from bone matrix.The site for the other type has been identified to a locus on chromosome 1known as 1p21.The product of this gene belongs to the chloride channel family of proteins(CLCN7). This gene encodes chloride channel 7.Chloride channels play important roles in the plasma membrane and inintracellular organelles.Defects in this gene are one of the causes of osteopetrosis.This causes bone resorption to fail while its formation persists normally;excessive bone is thus formed

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This results in thickened sclerotic bones that have poor mechanical propertiesbecause of failure in remodelling to adjust to functional demands.Increased bone fragility results from: Failure of the collagen fibres to connect osteons properly. Defective or absent remodelling of woven bone to lamellar bone.The severity of the condition may vary within rather wide limits between differentaffected individuals.Milder forms are not incompatible with normal life expectancy.In the severest forms, on the other hand, death may occur in utero.There are at least nine types of osteopetrosis.Clinical FeaturesChildren with marked involvement who survive may show thickening andincreased density of the base of the skull, and sometimes of the facial bones.This may lead to optic atrophy, facial palsy and occasionally otherneurological manifestations due to narrowing of the foramina that transmit thenerves out of the cranial cavity.There is an accompanying aplastic anaemia due to narrowing of the marrowspaces and encroachment of bone on the myeloid tissue.There will be an accompanying hepato-splenomegally due to compensatoryextramedullary haematopoiesis.Symptoms and ComplicationsOsteopetrosis tends to comprise a very wide variety of symptoms andcomplications and a broad spectrum of severity of symptoms, including: Pain. Frequent fractures, especially of the long bones, which often do not heal. Nerve compression, leading to headache, blindness, deafness or facialpalsy. Haematological complications, including anaemia, thrombocytopenia,leucopoenia (pancytopaenia). Hepato-splenomegally. Osteomyelitis. Frontal bossing of the skull. Unusual dentition, including malformed and unerupted teeth. Infection, mainly due to the accompanying leucopoenia. Bleeding, mainly due to the accompanying thrombocytopenia.Radiographic FeaturesThere is widespread striking radiopacity of the affected bones.There is no distinction between bone cortex and trabeculae.Transverse bands of varying density producing a zebra-like effect may be seen.Histopathologic FeaturesThe affected bones may show the presence of persistent cores of cartilagewithin spongy trabeculae.Bone deposition is normal.There may be a deficiency in osteoclasts, bone resorption and remodelling.The number of osteoclasts, however, may be normal, but there is defectivefunction and lack of adhesion of osteoclasts to bony surfaces.

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CLEIDO-CRANIAL DYSPLASIA (Dysostosis)

This is a rare hereditary and congenital bone disease. Mutations involving thetranscription core-binding factor a1-subunit gene (CBFA1) cause the diseaseGenetic FeaturesThe disease is usually inherited as an autosomal dominant trait.It is due to a defective gene affecting osteoblast / osteoclast differentiation.The gene is located on chromosome 6p21. Mutation or loss of this gene result in Cleido-Cranial dysplasia.Clinical FeaturesCleido-Cranial dysplasia is a rare disease which can occur either spontaneouslyor through dominant autosomal inheritance.There is no sex or racial predilection.It is characterized by a generalized skeletal dysplasia: Absence of the clavicles, which occurs in about 10% of cases, or thepresence of hypoplastic clavicles that allow the patient to approximate theshoulders together in the midline of the body without any discomfort. These individuals are usually of short stature. They have relatively long necks with drooping shoulders. They have persistent or late closure of the fontanels. The sutures can also remain opened, and the sagittal suture is depressed,giving the cranium a flat appearance. In the typical case, the skull is larger than normal and the face is small. The mandible is relatively large and prognathic, but the maxilla is poorlydeveloped with a V-shaped high arched palate. There is imperfect ossification of membrane cranial bones, with thepresence of many wormian bones. The frontal, parietal and occipital bones are prominent. The paranasal sinuses are underdeveloped and many other cranialabnormalities may also be present. A number of dental anomalies are also frequently associated. The pelvic bones also show poor development with non-fusion of thesymphysis pubis and poor development of the sacrum.

There are also a number of associated dental anomalies including: Delayed or failure of shedding of many deciduous teeth. Failure of eruption of many permanent teeth. Presence of unerupted supernumerary and/or supplemental teeth. The unerupted teeth have hooked roots. The unerupted teeth show different degrees of enamel hypoplasia. Many conically shaped teeth. Multiple dentigerous cysts. Absence of cellular cementum.

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ACHONDROPLASIA

Achondroplasia is a genetic condition that results in abnormally short statureNatureAchondroplasia is a genetic (inherited) bone disorder that occurs in about onein 25,000 live births.Achondroplasia is inherited by an autosomal dominant gene that causesabnormal cartilage formation and maturation.It is the most common type of dwarfism, in which the patient's arms and legsare disproportionately short in relation to body length.The head is often large and the trunk is of normal size.The average height of adult males with the condition is about 130 centimetres.The average height of affected adult females is about 122 centimetres.In some cases, the child inherits the condition from an affected parent.The majority of cases, however, are the result of a new mutation in the family: The parents are of average height and do not have the abnormal gene.Mode of InheritanceAchondroplasia is inherited as an autosomal dominant trait whereby only asingle copy of the abnormal gene is required to cause the condition.The gene for achondroplasia is fully penetrant, meaning that everyone whopossesses it has achondroplasia. No one with the gene escapes the condition.However, there is some variation in expression of the gene.

Patient with cleidocranial dysplasia, Left: Relatively long neck and droopingshoulders; Centre: Absent clavicles; Right: Deep and narrow high arched palate.

This means that children with achondroplasia are not carbon copies of eachother, although they may look alike to the untrained eye.It is caused by a mutation in the gene for fibroblast growth factor receptor 3which causes an abnormality of cartilage formation.More then 97% of achondroplastics have a Gly380Arg mutation in thetransmembrane domain of the fibroblast growth factor receptor 3 gene.The mutation causes the receptor to send an inhibitory signal to developinggrowth plate cartilage cells even in the absence of the ligand.In only about an eighth of cases is the gene inherited from a parent who has

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achondroplasia.Conversely, about seven-eighths of cases are due to new mutations.This means that most cases of achondroplasia occur sporadically and are theresult of a new mutation in a sperm or ovum of one of the normal-appearingparents.It also means that it is a pre-zygotic mutation in contrast with fibrous dysplasiawhere there is a post-zygotic mutation.The chance of a new mutation rises with the age of the father.This suggests that de novo mutations are of paternal origin.As early as 1912, it was noted that sporadic (new) cases were more often lastbornthan first-born children.This fits with the fact that the chance of an achondroplastic birth has beenshown to increase with the age of the father.Clinical FeaturesThe following are the most common clinical features of achondroplasia; however,each child may experience symptoms differently, these may include:. Shortened arms and legs, with the upper arms and thighs relatively moreshortened than the forearms and lower legs.. Large head with prominent forehead and a flattened nasal bridge.. Crowded teeth with malocclusion.. Curved lower spine - a condition called lordosis, which may lead to kyphosis,or the development of a small hump near the shoulders that usuallydisappears after the child begins walking.. Bowed lower legs.. Flat feet that are short and broad.. The baby's fingers appear short and the ring and middle fingers divergegiving the hand a trident (three-pronged) appearance.. Poor muscle tone and loose joints..Frequent middle ear infections which may lead to hearing loss.. Delayed developmental milestones such as walking (which may occurbetween 18 to 24 months instead of around one year of age).The head is typically large with:.Prominence of the forehead (frontal bossing),. Underdevelopment of the midface with lack of prominence of cheek bones.. A low depressed nasal bridge with narrow nasal passages..This is due to the short base of the skull because of deficient growth atsphenoidal synchondroses, especially the spheno-occipital synchondrosis.. Most joints can extend more than normal.For example, the knees can be hyperextended beyond the normal stoppingpoint.. Not all joints are lax in this way.. On the contrary, extension and rotation of the elbow are abnormally limited;hip extension also tends to be limited..Normal intelligence.

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Achondroplasia, Left: Short stature, short arms and legs, bowed legs;Centre: Lordosis; Right: Flat face, depressed bridge of the nose.

ACQUIRED DISEASES OF BONE

Diseases of different aetiologies arising from causes acquired after fertilization ofthe ovum, either in utero or after birth

DEVELOPMENTALDiseases due to faulty development arising from genetic errors occurring postfertilization

FIBROUS DYSPLASIA OF BONE

Fibrous dysplasia is a skeletal developmental anomaly of the bone-formingmesenchyme that manifests as a defect in osteoblastic differentiation andmaturationFibrous dysplasia of bone is a genetic non-hereditary disease due to a postzygoticsomatic mutation in which abnormal fibro-osseous tissue develops inplace of normal bone during the normal process of bone remodelling.It has been shown that fibroblast-like cells in fibrotic areas of fibrous dysplasia,like committed osteogenic precursors and unlike soft tissue fibroblasts, exhibithigh levels of cell surface-associated alkaline phosphatase activity, indicatingthat it belongs to the preosteoblast lineage that expresses the earlyosteogenic markers.PathophysiologyCancellous bone maintenance is disturbed, and bone undergoing physiologic

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remodelling is replaced by an abnormal proliferation of fibro-osseous tissue.Trabeculae of woven bone are embedded largely in a collagenous fibrousmatrix.Reticulin fibrils run directly from the fibrous tissue stroma into the woven bonematrix at nearly right angles to the bone surface.Dysplastic lesions are thought to consist of an excess of pre-osteogenic cellsproducing a disorganized collagenous matrix.This matrix is rich in anti-adhesion molecules and poor in pro-adhesionmolecules, in direct contrast to normal lamellar bone.Though there may be repeated cycles of bone resorption and redeposition, thewoven bone trabeculae do not undergo lamellar remodelling.Instead, resorption of woven bone trabeculae, due to a several fold increase inthe rate of IL-6 production (also a consequence of raised levels of cAMP), isfollowed by deposition of new woven bone trabeculae.The bone trabeculae arise directly from fibroblast-like pre-osteoblast cells.The trabeculae are not rimmed by osteoblasts.They may be rimmed by fibroblast-like cells or they may not be rimmed at all.The mechanical quality of the affected bones is thus decreased.As a result of this bone fragility, there is an increased risk of pathological fracture.The incidence of fracture is around 50% of cases, especially in long bonesand in the mandible.The extent and pattern of the disease depend upon the stage of developmentand the location in the developing embryo at which the mutation occurred. Thus germ cell mutation is lethal. Early mutation produces widespread disease.While late mutation produces few or isolated lesions.

Osteoblast Differentiation Process.

Mutation-bearing cells occur in a mosaic pattern.Endocrine and skin involvements, when present, also follow embryologic linesof development.IncidenceAge: The initial manifestations of fibrous dysplasia are most commonly observed

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in persons aged 3-15 years.Sex: There is no sex predilection in the monostotic form. There is a definite female preponderance in the polyostotic form.Site: The maxilla is affected more often than the mandible at a ratio of about 2:1.Disease PatternsThree disease patterns are recognized:Monostotic form Cranio-facial form (when one cranial or facial bone is affected). Polyostotic form restricted to bone lesions. Polyostotic form with extra-skeletal manifestations.Approximately 70-80% of fibrous dysplasias are monostotic.The monostotic form most frequently occurs in the following bones indecreasing order of frequency:Cranio-Facial FormThis pattern of the disease occurs in 10-25% of patients with the monostoticform and in 50% of cases with the polyostotic form.

If lesional tissue reaches the suture between two bones, it pushes and displacesthe suture line distorting it, but it does not destroy or cross it.Clinical FeaturesThe disease usually first becomes manifest in childhood, and some casesmay be congenital.Solitary jaw lesions (monostotic) are the commonest form of the disease.The lesion is usually slowly growing.Growth usually decreases after puberty (early adulthood, 18-20 yrs) when thedisease process becomes quiescent.The facial affection produces facial deformity or disfigurement.It is painless, though pain may sometimes be the presenting feature.The affected bone is structurally weak and may undergo pathological fracture.Fibrous dysplasia may be associated with endocrinopathies in 2-3% of cases.These may include: Precocious puberty in girls. Precocious skeletal growth and early skeletal maturity in males. Hyperthyroidism. Hyperparathyroidism. Acromegaly. Diabetes mellitus. Cushing syndrome.Involvement of orbital and periorbital bones may also give rise to: Visual impairment. Exophthalmos. Blindness.

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Involvement of the sphenoid wing and temporal bones may result in Vestibular dysfunction. Tinnitus. Hearing loss.Distribution of the LesionsIn cases where only one bone is involved, it is most often a femur, tibia, rib ora facial bone.When a number of bones are involved, these are quite likely to be bones ofone limb, especially a lower limb (segmental distribution).When bones of an upper limb are involved, one or more skull bones areusually also involved.In a few cases, a limited number of trunk bones, e.g. several ribs, alone ortogether with several vertebrae (in a segmental manner) are involved.Cases in which a limited number of bones are affected merge without any sharpdistinction with cases in which skeletal involvement is relatively widespread.There are cases in which, though lesions are located predominantly in bonesof one limb on one side (mostly but not exclusively unilateral), there may alsobe some lesions in limb bones of the contralateral side, along with lesions insome skull bones, ribs and pelvis, especially on the side in which the limbbones are most severely affected.Altogether, segmental and predominantly unilateral distribution of lesions inpolyostotic cases is an important clinical and radiographic characteristic.Radiographic FeaturesDepending on the amount of bone present in the lesion, the radiographicpicture may be: An indistinct radiolucent lesion. Radiolucency mottled with radiopacities. Completely radiopaque..The radiographic picture of jaw lesions on periapical or occlusal views,especially those in the maxilla, is sometimes described as having:- An orange peel appearance.-A ground glass pattern On extra-oral films, especially in early lesions with little boneformationThe radiographic picture with more bone formation is often described as having a smoke-screen appearance.

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Fibrous dysplasia of the right maxilla in a 12 year old boy.

Histopathologic FeaturesThe histologic picture is characterized by the replacement of normal bonytrabeculae by a cellular fibro-osseous tissue.Lesional fibroblast-like cells (pre-osteoblasts) show a definite proclivity(tendency) to directly form new bone trabeculae.The newly formed bone trabeculae are characteristically thin, irregularly shapedand irregularly oriented, and remain mostly discreet (separate from each other),though much resorption and redeposition might have taken place.The bone trabeculae are of the coarse fibred or woven bone type.They are not rimmed by osteoblasts; sometimes they may be rimmed byfibroblast-like spindle-shaped cells, or they may not be rimmed at all.Silver staining for reticulin reveals that reticulin fibrils extend directly from thefibrous tissue into the newly formed woven bone, almost at right angles.Though bone trabeculae may undergo much resorption and redeposition, theydo not undergo lamellar remodelling.Rather, the newly formed bone trabeculae are also of the woven bone type.The histologic picture is closely similar to that of ossifying fibroma andcementifying fibroma, but in cases of fibrous dysplasia, the lesional bone iscontinuous with the cortex with no zone of fibrous tissue or a capsuleseparating them.As the lesion ages, it may become either: More fibrous, with thick collagen fibres. Its content of bony trabeculae may become more numerous.On aging, more numerous bone trabeculae develop in less-collagenizedrather than in well-collagenized lesions.

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Left: The diffuse ground glass appearance of the maxillary bone is striking.Note also, the absence of lamina dura around the teeth. Right: Ill defined, somewhatradiopaque lesion associated mainly with the second mola. Notice that the lamina duraof the second molar is involved and is inconspicuous.

Areas of haemorrhage and degeneration may occur, leading to accumulationof lipid-filled macrophages.Biochemical ValuesBoth serum calcium and serum phosphate are within normal limits.Alkaline phosphatase enzyme level may be normal or may be only slightlyelevated in monostotic form and in mild polyostotic cases.Serum alkaline phosphatase enzyme levels may be elevated in the polyostoticform, more so if many bones are affected.ComplicationsMalignant change occurs in 0.4% of cases, but the incidence increases in casesthat have been subjected to irradiation. Osteosarcoma may develop, this is evidenced by:- Rapid growth.- Pain.The affected bone may be weakened and may undergo pathological fracture,especially if a limb bone or the mandible is affected.Facial disfigurement follows lesions affecting facial bones.

Left: Metaplastic woven bone trabeculae developing directly from fibroblasts;Right: Cellular fibrous tissue containing irregular, partially calcified bone trabeculae with noosteoblastic rimming.

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Fig. 132: Left: Reticulin fibrils extending directly into metaplastic woven bone;Right: Trabeculae of lesional bone continuous with bone cortex.Differences between fibrous dysplasia and ossifying fibromaFibrous Dysplasia Ossifying FibromaAge at onset: < 25 years > 25 yearsGender Female predilection No sex differenceSize 60% > 4 cm 85% < 4 cmLocation About 25% in the head and neck 90% in mandible

ALBRIGHT SYNDROMEAlso known as the McCune-Albright SyndromeThe condition was first described in 1937 by Donovan James McCune and FullerAlbright.Evidence of the sporadic nature of the syndrome has included its occurrencein only one of monozygotic twins.In Albright Syndrome, the somatic mutation of Gs occurs during earlyembryonic development with mosaicism resulting from mixture of daughter cellsof one mutated stem cell among daughter cells of normal stem cells.The same GNASl arginine 201 mutation seen in fibrous dysplasia has beenfound in 49 patients with Albright Syndrome, with a net preponderance of thesubstitution by histidine (n = 34) as opposed to cysteine (n = 15).No difference in severity of manifestations of the disease was noted betweenthe two types of mutations.The proportion and distribution of affected cells in a tissue is determined bythe exact stage in development at which the mutation occurred.Thus, mutations that occur later in embryogenesis give rise to fewer mutantcells, milder phenotype, and fewer affected organs than mutations that occurearlier during embryonic development.Albright Syndrome consists of polyostotic fibrous dysplasia associated with: Sexual precocity in females. Precocious skeletal growth and early skeletal maturity in males, withultimate below average height. Caf au lait cutaneous pigmentation. This is the most common extraskeletal manifestation. It occurs in more than 50% of cases. The pigmentation in polyostotic fibrous dysplasia is ipsilateral to the

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side of bony lesions, a feature that differentiates this disease frompigmentation in von Recklinghausen's neurofibromatosis. The pigmented areas tend to be arranged in a linear or segmentalpattern near the midline of the body, usually overlying the lowerlumbar spine, sacrum, buttocks, upper back, neck, and shoulders. Often the spots are limited to one side of the body, which usuallycorresponds to the side with more severe bone involvement and they donot cross the midline. They are often arranged in a segmental pattern, which follows thedevelopmental lines of Blaschko (lines of ectodermal migration duringearly embryogenesis). Consistent with this pattern is the tendency of the macules to stop atand do not cross the midline. Similar lesions may occur on the lips and oral mucosa. Pigmentation may occur at birth and may occasionally precede thedevelopment of skeletal and endocrine abnormalities. The caf-au-lait spots in the syndrome are single or multiple tan-brownhyperpigmented flat macules with irregular borders. They become more obvious with advancing age or with sun orultraviolet light exposure. The lesions have irregular borders that have been described asresembling the "coast of Maine", in contrast to those ofneurofibromatosis in which the margins tend to be smoother, likenedto the "coast of California". However, the fact that the melanotic macules in Albright Syndromesometimes do not have the characteristic serrated or irregular bordershas been noted and was emphasized by Albright himself.

Albright Syndrome: Left: Precocious sexual development in a 5-yearoldfemale patient; Right: Caf au lait pigmentation.

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FAMILIAL FIBROUS DYSPLASIA (Cherubism)

This special variant of fibrous dysplasia is an autosomal-dominant disorder ofvariable penetrance. It occurs in children and is more severe in boysAetiologyThe lesion is an autosomal dominant hereditary condition.The mutated gene is called SH3BP2 and is located on chromosome 4p16.3.The gene shows variable expressivity according to the sex of the patient,usually being more severe in males.Some non-familial cases have been reported.The onset of the lesion is related to signals triggered by eruption of permanentteeth.IncidenceAge: Cherubism usually becomes manifest in young children. More severelyaffected persons manifest the disease at an earlier age.Sex: There is no sex predilection, but males are usually more severely affected.Site: The mandibular rami are always affected bilaterally and symmetrically. The maxillary tuberosities are the next most common site. The disease may affect any area of the jaws; bilaterally and symmetrically. The only parts of the jaws that have never been reported to be affected arethe mandibular condyles and coronoid processes.

ClassificationGrade 1: Affecting the mandible without showing root resorption.Grade 2: Affecting mandible and maxillary tuberosities without root resorption.Grade 3: Affecting both mandible and maxilla except mandibular condyle andcoronoid process; may show root resorption.Grade 4: Affecting both mandible and maxilla except mandibular condyle and coronoidprocess, as well as the floor of the orbit; may show root resorption.Grade 5: Rare aggressive form affecting both mandible and maxillae.Clinical FeaturesThis varies depending upon: The area of the mandible or maxilla affected. The severity of the involvement. The age of the patient.There is no typical picture that will fit every case or even the majority of cases.Cases exhibiting varying degrees of severity merge together with no clear

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dividing line.Both mandibular rami are invariably affected, with no case being reportedlacking their involvement.Any other part of the jaws, with the exception of the mandibular condyles andcoronoid processes, may be additionally affected, again symmetrically.The fact that both halves of the mandible and both halves of the maxilla areaffected in the same areas and approximately to the same extent is anoutstanding feature of the condition.There has never been any evidence of underdevelopment of either jaw.No case has been reported in which other facial bones than the mandible andthe maxilla have been involved.In minimally affected patients, the facial appearance is within the normal range.In slightly more severely affected patients, the angles of the jaw are definitelyenlarged and the face is broad with marked fullness of the rami.In more severely affected patients, with involvement of the body of themandible as well as the rami, patients present a broad face and a heavylookingjaw, and the mandible is thickened in every plane.Intra-orally, the alveolar process is broad and bossellated.On palpation, the surface feels as though it is covered by, hard, raised domes.Where the bone on the surface of the domes has been resorbed, a roundmass of a firm fibrous nature can be felt.The maxillae may also be involved.This usually occurs in cases where the mandible is grossly affected.The extent of maxillary involvement varies from involvement of the tuberositiesonly, to cases with gross maxillary involvement.Maxillary involvement exaggerates the deformity, and when extensive causesthe major part of the disfigurement.The normal contours of the maxillae are distorted.The anterior wall is thickened and bulges forwards, and the infra-orbitalmargins cannot be palpated as a definite ridge.The vault of the palate may be obliterated, or only a midline cleft may be left.Speech may be indistinct.Absence or premature loss of teeth has been reported when the tooth bearingpart of the jaw is involved.In severe cases, a rim of sclera is exposed between the iris and the lowereyelid (thus the cherubic look).This has been observed only in cases of involvement of the maxillae in the regionof the infra-orbital ridge and the maxillary antrum raising the orbital floor.The non-involved parts of the jaws have a normal contour.Course of the DiseaseFollowing early onset, rapid development takes place in the next 2 3 years.The dysplasia makes its appearance in all involved areas simultaneouslyproducing the above described clinical features.There follows a period during which no marked changes occur.At puberty or early adolescence, gradual improvement of the facial contourcommences.

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Fig. 134: Familial Fibrous Dysplasia: A 10year-old patient displaying marked fullnessof the face over both the maxilla andmandible.

Between 20 to 30 years of age, definite bone remodelling takes place and amore normal contour develops.There is always some residual enlargement.Radiographic FeaturesIn young patients, there are well-defined multilocular radiolucencies ofirregular shape.These are equal and identical on both sides.The lesions are always found in both mandibular rami.This causes expansion and widening of the rami, with thinning of the corticalplates. The cortex is reduced to a mere expanded shell of irregular contour.The inferior alveolar canal may be displaced.There is also displacement of unerupted teeth when the tooth-bearing area isinvolved.The coronoid process is often blunt, and the mandibular notch shallow.Dental AbnormalitiesThere may be missing, unerupted or displaced teeth.There may be early shedding of the deciduous dentition.This is often followed by early loss of permanent teeth, especially themandibular second and third molars.The dental abnormalities vary in severity depending upon the degree ofinvolvement of the tooth-bearing area of the jaws.In a reported case, calcification was normally advanced only in thosepermanent teeth whose calcification had commenced before clinical onset ofthe disease at 2 years.In those teeth commencing calcification after this time, i.e., second premolarsand second molars which would normally begin to calcify at 2 to 3 years, therewas no evidence of their presence at the age of 5 years.The dental abnormalities are not related to nor are they part of the condition.

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Fig. 135: Familial Fibrous Dysplasia: Note radiolucent lesions involvingthe mandibular rami with marked broadening of the rami.

Histopathologic FeaturesFibrous tissue consisting mainly of spindle-shaped fibroblasts replaces thebone in affected areas.There are large numbers of multinucleated giant cells distributed throughoutthe fibrous tissue.Mature collagen fibres may also be found.Giant cells tend to be grouped in foci, mainly around vascular areas and areasof extravasated red blood cells.New bone formation is rare within the fibrous tissue, and bone within thelesion is only conspicuous by its absence.In some cases, there may be perivascular cuffing of eosinophilic material, inwhich a few cells may be peripherally embedded.In the adult, the maxillae are normal and the multilocular rarefactions of themandible have become replaced by a moderate irregular sclerosis.

Fig. 136: Familial Fibrous Dysplasia: Left: Multilocular radiolucency involving theposterior part of the body of the mandible and the ramus; Right: Missing and displacedteeth, broadening of the alveolar process

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Fig. 137: Left: Giant cells in cellular connective tissue. Note absence of bone trabeculae;Right: Perivascular acidophilic material around small blood vessel and giant cell infibrous connective tissue..

DYSTROPHIC BONE DISEASESDiseases due to faulty bone metabolism and turnover

PAGETS DISEASE OF BONE (Osteitis Deformans)This is a condition of older individuals characterized by progressive skeletaldeformation due to regional breakdown in the process of remodeling

General FeaturesPagets disease of bone is the second most common bone disease afterosteoporosis, affecting up to 23% of adults over the age of 55.It is a chronic bone disease characterized by focal regions of increased boneresorption accompanied by increased formation of new, highly disorganizedbone.The aetiology of PDB has been difficult to determine, as it likely involves bothgenetic and environmental factors.Genetic factors play an important role in PDB and mutations or polymorphismshave been identified in four genes that cause classical Paget's disease.The mutations predispose to PDB by disrupting normal signalling, leading toosteoclast activation.Although Paget's has traditionally been considered a disease of the osteoclast,there is evidence that stromal cell and osteoblast function are also abnormal.The primary cellular defect in PDB is generally thought to reside in the OCL,since the bone lesions are characterized by large numbers of hypermultinucleatedosteoclasts, and inhibition of osteoclast activity in PDB patientsresults in prolonged clinical and histological remissions.Although osteoblasts and other cells in the bone microenvironment alsoparticipate in the disease, the increased bone formation has been thought torepresent a secondary response of osteoblasts to the elevated bone resorption.Environmental factors also contribute to Paget's disease.Most research has focused on paramyxovirus infection as a possibleenvironmental trigger but evidence in favour of the involvement of viruses inthe disease remains inconclusive.

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Recent evidence indicates that the disease is triggered by infection ofosteoclasts by a slow virus as the measles or respiratory syncytial virus (RSV)in patients with a genetic susceptibility for the disease.A striking feature of pagetic osteoclasts is the characteristic nuclear inclusionsthat are similar to nucleocapsids of paramyxoviruses.These nuclear inclusions are not present in other bone marrow cells in thePagetic lesion or in non-pagetic bone in patients with Paget's disease.

IncidenceAge: Pagets disease is recognized most commonly after age 40 years and israrely diagnosed in persons younger than 20 years. By the ninth decade of life, prevalence reaches nearly 10%.Sex: The male-to-female ratio is approximately 1:1.Site: The axial skeleton, the skull and leg bones are most frequently affected.PathophysiologyThe osteoclast is the primarily affected cell in Paget's disease.Osteoclasts in Pagetic lesions are increased in both number and size.In cross-section they are seen to contain up to 100 nuclei, in contrast tonormal osteoclasts, which contain 420 nucleiThe process of normal bone remodelling is disturbed.In the early years, osteoclastic resorption of normal bone is accelerated.Later, as bone is resorbed, new and abnormal bone is formed by increasedosteoblastic activity.This osteoblastic activity is triggered by stimulatory cytokines secreted by thehyperactive osteoclasts that recruit and activate osteoblasts.In the late phase, osteoclastic resorption slows down and osteoblasticapposition predominates.The disease may burn-out leaving enlarged dense sclerotic bone comprisedof atypical trabeculae of Pagetic bone with many reversal lines giving a mosaicappearance.The disease may affect a single bone (monostotic) or multiple bones(polyostotic form).General ConsiderationsMany individuals with Pagets disease are asymptomatic.The diagnosis is most commonly made incidentally during an unrelatedradiological or biochemical investigation.On occasion, the disease manifests with severe musculoskeletal impairmentwith neurological and cardiovascular complications.Pagets disease has a predilection for the axial skeleton and may bewidespread at the time of diagnosis.The condition commonly affects the pelvis and spine, particularly the lumbar

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spine with a frequency of 30-75%.The sacrum is involved in 30-60% of cases and the skull in up to 65% ofcases.The proximal long bones, especially the femur, are also frequently affected (in25-35% of cases).Though any bone may be affected, the fibula, ribs, and bones in the handsand feet are only infrequently involved.Pagets disease may affect one bone and then remain limited in its course, orit may progress from a few localized areas to the rest of the skeleton.Monostotic Pagets disease occurs in 10-35% of cases.The most common presenting complaint is pain.Other typical findings and complaints of patients with Pagets disease mayinclude the following: Pathologic fractures commonly result from weakened pagetic bone. Nonspecific headaches, impaired hearing, and tinnitus are commonsymptoms of Pagets disease with skull involvement. The patient's head dress size may increase or change due to skeletaldeformity and enlargement, especially of the skull and lower limbs. The most common cranial symptom is hearing loss, occurring in 30-50%of patients with skull involvement. Vertigo or tinnitus may also occur witha frequency of 25% of patients with cranial involvement. Nausea, dizziness, syncope, ataxia, incontinence, gait disturbances, anddementia can be observed with cerebellar or brainstem compressivesyndromes. Involvement of the jaw and facial bones is uncommon in Pagets disease,but it does occur. Facial disfigurement and malocclusion may occur following enlargementof either jaw. Tooth loss may occur with progressive root resorption. Absent periodontal membrane space and lamina dura are associated withexcessive cementum formation. Increased bone pain with an enlarging soft tissue mass and a lytic lesionis suggestive of a neoplastic transformation (osteosarcoma), especially ifa pathologic fracture is present.Clinical FeaturesClinical features are extremely variable and depend on which bones are affected.Typically, patients with Pagets disease present without any signs or symptoms.Visual inspection may reveal bone deformities, such as an enlarged skull,spinal kyphosis, and bowing of the long bones of the lower extremities.Localized pain and tenderness may be elicited with manual palpation.Superficial palpation reveals increased warmth of the skin over the affectedbones.Skin temperature may be correlated with both increased metabolic activity ofbone and bone pain.The legs are usually the first to be affected; but in many other cases, theearliest observable change may be in the skull.Persistent bone pains in the legs may be the first sign.Deformities of the bones of the legs (sabre tibia).and enlargement of the

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cranium are the next noticeable changes.The face may escape from the bony deformity.Occasionally, however, the bones of the face may become greatly thickened,especially the maxillae.The patient may need frequent remakes of his dentures, which become toosmall for the increased size of the jaws.The vault of the palate is flattened and obliterated.The increase in the size of the jaws may either be a part of a generalizedcondition or may occur alone (Leonteasis Ossea).The advanced stage of the disease is highly characteristic: The main feature is an enlarged head. Kyphosis. Bent shoulders. Sunken chest. Bowed legs, the femurs bowed outwards and the tibia bowed forwards. Out-turned toes.The above-mentioned features provide a living justification of the name OsteitisDeformans which Sir James Paget coined when he first described the condition.Radiographic FeaturesRadiographic features are diagnostic with an initial osteolytic phase, commonly inthe skull and tubular bones, followed by an osteoblastic and then anosteosclerotic phase that is most notable in the axial skeleton and pelvis.Osteolysis of the cranial vault is most frequent in the frontal or occipitalregions giving rise to the typical appearance of scattered circumscribedradiolucencies known as osteoporosis circumscripta.Lytic lesions may be the only finding in the early osteolytic stage.Later, as the osteoblastic stage supervenes, the irregular radiodensities of theskull vault give rise to what is known as a Cocks Comb or a hair on endappearance due to intermingling bone resorption and bone formation.Still later, in the mixed osteoblastic-osteosclerotic stage, focal radiodensitiesgive rise to what is known as a cotton-wool appearance.Areas of lysis and radiodensities may be separate or superimposed.An enlarged bone with increased radiodensity and trabeculations ischaracteristic.

Fig. 138: Pagets disease affecting themaxillae, marked expansion of themaxilla and separation of teeth, flattened palatal vault.

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Osteolytic stage, radiolucent areas with root resorption.Course of the DiseaseIn generalized Pagets disease, the blood flow to the bones is greatlyincreased, sometimes up to 20 times the normal.The first change is softening of the bones.This is brought about by both the excessive vascularity of the bones and, evenmore so, by intense osteoclastic activity.The resorbed bone is replaced by fibrous tissue in which new bone is laiddown by proliferating osteoblasts.This new bone in turn undergoes resorption and redeposition, and the cyclegoes on and on until eventually the bone presents a peculiar complex patterndescribed by Schmorl as a mosaic pattern.The bones are very hard and dense.The new bone is disordered, poorly mineralized, and lacks structural integrity.Histopathologic FeaturesThe initial osteolytic phase is marked by disordered areas of resorption by anincreased number of noticeably large osteoclasts.These abnormal osteoclasts may contain as many as 100 nuclei each.

Fig. 140: Sclerotic stage with extreme radiodensity andpronounced hypercementosis of roots.

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Fig. 141: Pagets disease; Left: Cock's comb appearance, multiple radiopacitiesradiating from the vault of the skull; Middle: Cotton wool appearance of the base of theskull and the maxilla; Right: Involved maxilla showing cotton wool appearance.

The subsequent osteoblastic phase follows with haphazard production of newbone matrix and formation of woven bone.Repeated episodes of bone resorption and bone formation result in theappearance of many small irregularly shaped bone fragments that appear tobe joined as if in a jigsaw or mosaic pattern.This pattern is the characteristic histologic feature of Pagets disease.As the disease progresses, the osteoblastic phase predominates.Excessive abnormal bone formation occurs, causing more compact anddense, though still finely porous bone.Marrow spaces are filled with loose highly vascularised connective tissue.The hypervascularity consists of an increased number of patent capillariesand dilated arterioles, as well as larger venous sinuses and numerous patentarterio-venous shunts.The normal trabecular appearance is distorted with a mosaic pattern ofprominent, irregularly scalloped and deeply staining cement lines (reversallines) joining areas of lamellar bone.Pagetic bone shows no tendency to form haversian systems.Biochemical FindingsThe following indices are increased in different phases of Pagets disease:Indices of Bone Resorption: Urinary hydroxyproline. Urinary collagen cross-links. Urinary calcium/creatinine (fasting).Indices of Bone Formation: Serum total or bone-specific alkaline phosphatase. Serum osteocalcin.General ComplicationsSkeletal pain.Skeletal deformities.Pathological fractures.Secondary osteoarthritis.Hearing deficit or loss.Other cranial nerve deficits.

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Congestive heart failure as a result of greatly increased cardiac output.Sarcomas: Osteogenic sarcoma. Chondrosarcoma. Fibrosarcoma.188Metastatic carcinomas.Haematologic malignancies.Giant cell tumours.Dental ComplicationsIn the osteolytic stage, there is root resorption, often pronounced.In the osteoblastic stage, the teeth show hypercementosis.Patchy osteosclerosis may affect the jawbones.Difficulty of tooth extraction mainly due to hypercementosis.Excessive haemorrhage following dental extractions due to the many patentarteriovenous shunts.Delayed healing of extraction sockets due to defective nourishment of thebone because the arteriovenous shunts divert blood from the capillary bedsaround the extraction socket (dry sockets).Need for frequent remaking of dentures due to continued enlargement ofaffected alveolar processes.

Fig. 142: Upper left: Early osteolyticstage, multinucleated osteoclasts ontrabecular surfaces immediatelyadjacent to rows of plump osteoblasts.-Upper right: Mixed phase,simultaneous bone resorption andbone deposition-Lower: Sclerotic phasefollowing continued resorption anddeposition, resulting in manyirregular

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reversal lines.

LEONTEASIS OSSEA (Localized Pagets Disease)In some instances of Pagets disease of bone, the skull, facial bones or themaxillae alone may be affected. Such instances are referred to by some authorsas Leonteasis Ossea

Leonteasis Ossea, greatlyenlarged maxillary alveolar process.

Nature of the DiseaseLeonteasis Ossea is no longer considered to represent an independentpathological entity.It appears rather to represent a miscellaneous category of which somecomponents are not well understood.Some cases appear to result from spreading, sclerosing osteoperiostitis.Others are associated with polyposis of the colon (Gardners syndrome).Some cases may represent a localised monostotic form of Paget's disease.Some have a familial pattern pointing to some ill-understood developmentaldisorder.In some instances, the thickened bones are rarefied rather than sclerotic.

INFLAMMATORY DISEASES OF BONEAcute and chronic bone diseases due to specific or nonspecific infectionsHealing of Extraction SocketsThe healing of a socket after an extraction is by essentially the same process asthe healing of a bone fracture and takes place in the following stages: Formation of a blood clot filling the socket. Organisation of the blood clot. Epithelialisation of the surface of the wound. Formation of woven bone in the connective tissue filling the socket. Replacement of the woven bone by lamellar bone and remodelling of thealveolus.

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Immediately after extraction, there is free bleeding which helps to wash debrisout of the socket.Torn vessels retract and, after a few minutes, the blood clots.Tissue damage provokes a mild, subclinical inflammatory reaction.Blood vessels of the bone surrounding the socket dilate and leucocytes andmacrophages invade the clot from its periphery.Macrophages and platelets present in a hypoxic state in the clot releaseangiogenic and growth factors such as acidic FGF (FGF-1) and basic FGF(FGF-2) which are important factors in wound healing, as well as vascularendothelial growth factor released by platelets.Endothelial cells of neighbouring capillary vessels are stimulated by angiogenicfactors released by macrophages and platelets when present in a low-oxygenenvironment in the clot, and are chemotactically attracted to the wound areaby fibronectin found on the fibrin network.These growth factors stimulate the proliferation of fibroblasts and endothelialcells that give rise to angiogenesis and developing granulation tissue.Capillaries in the surrounding tissue are stimulated to proliferate and sendsolid sprouts into the clot.Stem endothelial cells from uninjured blood vessels in the surrounding bonedevelop pseudopodia and push through the extracellular matrix into the clot toestablish new blood vessels.To migrate, endothelial cells need collagenases and plasminogen activator todegrade the clot and part of the extracellular matrix.Zinc-dependent metalloproteinases digest the basement membrane andextracellular matrix to allow cell migration, proliferation and angiogenesis.The sprouts later undergo canalization producing new capillary vessels withinthe clot.They are accompanied by proliferating fibroblasts from the surrounding marrow.Organisation is accompanied by gradual digestion of the clot by fibrinolysinenzyme released by leucocytes.Because the migration and proliferation of fibroblasts requires oxygen andnutrients, angiogenesis is necessary for later stages in wound healing, likefibroblast and epidermal migration.Fibroblasts and capillary buds continue to grow in from the surroundingconnective tissue until the clot is completely replaced by granulation tissue.When macrophages and other growth factor-producing cells are no longer in ahypoxic environment, they stop producing angiogenic factors.Thus, when the granulation tissue is adequately perfused, migration andproliferation of endothelial cells is reduced and ultimately ceases.Initially fibroblasts utilize the fibrin cross-linking fibres to migrate across thewound, subsequently adhering to fibronectin.Fibroblasts then deposit ground substance into the wound bed, and latercollagen, which they can adhere to for migration.Epithelium begins to proliferate over the surface during the second week andeventually forms a complete, protective covering.The increased blood supply to the socket is accompanied by resorption of thesurrounding dense lamina dura by osteoclasts.

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Small fragments of bone, which have been injured during extraction and havelost their blood supply are separated by osteoclasts and are eventually shed.In the connective tissue filling the socket, coarse, woven bone is laid down.In an adult, this starts about a month after the extraction and may be completein another month.During the following months woven bone is, in turn, resorbed and replaced bytrabeculae of lamellar bone until the normal bone pattern is restored.A layer of compact bone forms over the surface and the alveolus isremodelled.The alveolus becomes narrower and its surface sinks below the adjacent partsof the ridge where teeth are still standing.If all the teeth are lost, resorption goes on relatively rapidly at first then moreslowly for some years until the alveolar bone is entirely resorbed.Delayed Healing of Extraction WoundsFor normal healing to take place, the socket must fill with blood clot, and theclot must persist until it becomes organised.It is uncommon for the clot to fail to form unless the local blood supply is verypoor or an excessive amount of vasoconstrictor is injected near the socket. The functions of the clot are that it prevents infected debris from entering thesocket. It protects the underlying bone from oral bacteria and acts as a support forsubsequent organisation to occur and granulation tissue to grow.Delayed healing of extraction wounds may be due to: Infection is the most common cause of delayed healing and the usualresult is a painful, localised osteitis of the bone around the socket. This is called a "dry" socket because it is empty and does not contain ablood clot.

DRY SOCKET

Localised osteitis of the lamina dura lining an extracted tooth socketIt is a socket in which the blood clot disintegrates or fails to form, it produces afoul odour, with no pus formation and is accompanied by severe pain.Normally, a blood clot forms at the site of a tooth extraction.This blood clot serves as a protective layer over the underlying bone andnerve endings in the empty tooth socket.The clot provides the foundation for the growth of new tissue and bone.In some cases, the clot does not form properly or is physically dislodgedbefore undergoing organisation.With the blood clot gone, bone and nerves in the socket are exposed to air, foodand fluids.This can cause severe pain, not only in the socket, but is also referred alongthe nerves radiating to the ear and eye on the same side of the face.Severe pain following an extraction is usually due to this cause.Pain commonly begins the day after the extraction, but sometimes may bedelayed for up to a week.

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The pain is deep-seated, severe and throbbing in character.The cause is unknown but many possible causes have been blamed: Bacterial contamination of the socket. Difficult or traumatic tooth extraction surgery. Excessive use of vasoconstrictor in the anaesthetic drug used.Dry socket occurs in about 3% to 5% of all tooth extractions; it is much morecommon in the mandibular molar-premolar area.Nature of the ConditionFor this condition to be diagnosed there must be: Failure to form a blood clot in an extraction socket, or breakdown of theclot after its formation. Presence of bare bone of the socket. Presence of severe pain.Clinical FeaturesDry sockets tend to be more common in the mandible than in the maxilla andare more common in posterior teeth than in anterior teeth. This is because the cortical bone in the posterior mandibular area is thick. The vascularity of the mandible is not as good as that of the maxilla.The condition follows extractions done under local analgesia rather than thoseperformed under general anaesthesia.It has been demonstrated that the more difficult the extraction, the higher thechance of a dry socket.The condition occurs twice as often after single extractions as it does aftermultiple extractions completed during the same sitting.Bacteria, especially anaerobic bacteria, have been linked to its formation.Several investigators have found strains of streptococci, fusospirochaets,Treponema denticola, and bacteroides within extraction sites.Radiographic FeaturesDuring the first few days after extraction, there are no radiographic differencesbetween a dry socket and a normally healing socket.Ten to fourteen days following extraction, certain differences are observed: In the normally healing socket, the lamina dura is mostly resorbed abouttwo weeks after extraction in preparation for new bone formation toinvade the organising blood clot. In cases of dry socket, however, the lamina dura remains radiographicallydistinct two weeks following extraction. Later, resorption of normal living bone neighbouring and surrounding thelamina dura leads to its separation and eventual exfoliation. During that period of time, small bony spicules representing parts of thelamina dura may be seen in the socket. This is followed by loss of these spicules through their exfoliation.

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Dry socket, alveolar osteitis, Left: Clinical picture; Right: Radiographic picturedemonstrating sharply defined sclerotic lamina dura two weeks following extraction.

ACUTE SUPPURATIVE OSTEOMYELITIS

An acute inflammatory destructive process of bone, bone marrow and periosteumsecondary to infection with pyogenic organismsPredisposing Factors

Age Acute haematogenous osteomyelitis is primarily a disease of children. Direct trauma and contiguous focus osteomyelitis are more commonamong adults and adolescents than in children.Sex The disease is much more common in boys than in girls. Male-to-female ratio is approximately 2:1.Trauma A history of trauma is common. Jawbones, however, have a peculiar and unique position because of thepresence of teeth. In jawbones, the trauma may take the form of an extraction of a septictooth.PathogenesisHaematogenous osteomyelitis is an infection caused by bacterial seedingfrom the blood. Acute haematogenous osteomyelitis is characterised by an acute infectionof the bone and bone marrow caused by the seeding of bacteria withinthe bone from a remote source. This condition occurs primarily in children. The most common site is the rapidly growing and highly vascularmetaphysis of growing long bones.Direct or contiguous inoculation osteomyelitis is caused by direct contact ofbacteria and the tissue during trauma or surgery. Direct inoculation (contiguous-focus) osteomyelitis is an infection in the

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bone secondary to the inoculation of organisms from direct trauma, suchas cases of fracture of the mandible. Spread from a contiguous focus of infection such as a periapical infection,or sepsis after a surgical procedure such as extraction of a septic tooth orspread from a dry socket.BacteriologyAcute haematogenous osteomyelitis: Newborns (younger than 4 months): Staphylococcus aureus, Enterobacterspecies, and group A and B Streptococcus species. Children (aged 4 m to 4 yrs): Staph aureus, group A Streptococcusspecies, Haemophilus influenzae, and Enterobacter species. Children, adolescents (aged 4 yrs to adult): Staph aureus (80%), group AStreptococcus species, H influenzae, and Enterobacter species. Adult: Staph aureus and often Enterobacter or Streptococcus species.Direct contact osteomyelitis: Generally: Staph aureus, Enterobacter and Pseudomonas species. Puncture wound: Staph aureus and Pseudomonas species.Nature of the DiseaseClinical manifestations of direct inoculation osteomyelitis are more localizedthan those of haematogenous osteomyelitis.Infection of bone is accompanied by occlusion of blood vessels, which causeslocalised bone necrosis and local spread of infection.Infection may spread through the bone cortex and spread under the periosteum,with formation of subcutaneous abscesses that may drain through the skin.Haematogenous osteomyelitis usually presents with a slow insidiousprogression of symptoms.Direct osteomyelitis generally is more localized, with prominent signs andsymptoms.General symptoms of osteomyelitis include the following: Abrupt onset of high fever. Fatigue. Irritability. Malaise. Restriction of movement of the affected part. Local oedema, erythema, and tenderness.Patients with acute osteomyelitis of the jaws or peripheral bones usually are: Febrile. Show weight loss. Fatigue. Localized warmth. Swelling. Erythema. Tenderness.196If treatment of acute osteomyelitis is only partially successful, low-gradechronic osteomyelitis develops with:

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Intermittent bone pain lasting several months to many years. Local tenderness and sinus drainage.Chronic osteomyelitis is often polymicrobial.Radiographic FeaturesRadiographic changes are not evident for 14-21 days and initially manifest asperiosteal elevation followed by cortical or medullary radiolucencies.Approximately 40-50% of focal bone loss is necessary to cause detectableradiolucency on plain films.There are irregular radiolucencies described as moth-eaten appearance,intermingled with irregular radiopacities indicating unresorbed sequestra.There is peripheral new bone formation, which, in the mandible, is restricted tothe lower border.Histopathologic FeaturesThis is characterized by irregular masses of necrotic bone lying in a vast areaof acute, and later chronic, inflammatory cells.The necrotic bone is characterized by absence, due to death, of osteocytes,leaving empty lacunae.The dead bone is separated from the neighbouring living bone by osteoclasticresorption at the expense of the neighbouring living bone. Dead bone does not undergo resorption because osteoclasts need anavailable blood supply to live and function.There is subperiosteal new bone formation forming what is known as theinvolucrum in long bones. In the mandible, this new bone formation is mainlyrestricted to the lower border.

: Acute osteomyelitis of the mandible, moth-eaten appearance.

ComplicationsComplications of acute osteomyelitis of the jaws include: Unilateral numbness of the lower lip. Pathological fracture. Ankylosis of the TMJ if infection spreads to the joint. In the maxilla, infection may spread to the maxillary sinus. Pyaemia is very rare in oral osteomyelitis. Necrosis and exfoliation of developing tooth germs in children. Root resorption, loosening or exfoliation of erupted teeth.

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CHRONIC OSTEOMYELITIS

This is a persistent inflammation of bone characterized by a complex ofinflammatory processes including necrosis of bone and marrow tissue,suppuration, resorption, and sclerosis. It is a milder form than acute osteomyelitisTypesThere are several types of chronic osteomyelitis: Chronic suppurative osteomyelitis (CSO). Chronic focal sclerosing osteomyelitis. Chronic diffuse sclerosing osteomyelitis. Also known as chronic sclerosingor diffuse sclerosing osteomyelitis (DSOM). Chronic non-suppurative sclerosing osteomyelitis, also known as Garresosteomyelitis. Osteoradionecrosis.

CHRONIC SUPPURATIVE OSTEOMYELITISCases of osteomyelitis where the clinical manifestations are milder than in acuteosteomyelitis, but where the interaction between the virulence of the infectingorganisms and the patients resistance results in a protracted suppurative processPathogenesisThis may frequently develop as a sequel of untreated or inadequately treatedacute osteomyelitis resulting from Staphylococcal or Streptococcal infection.Occasionally, it may develop from dental infections as a low-gradeinflammatory reaction without a preceding acute stage such as in cases of: Periapical infection secondary to pulpitis. After tooth extraction, especially lower third molars. Infections secondary to fractures of the jaws.Clinical FeaturesThe mandibular molar area is the most frequently affected area of the jaws.The symptoms are usually of long duration.There is swelling of the affected area of the jaw.There is also looseness of related teeth.There is discomfort during mastication.Sinus tracts draining pus may be present.There is usually pain of varying intensity.There is mild fever.There is leukocytosis.There may be paraesthesia of the mental nerve (lower lip).Radiographic FeaturesRadiolucent lesion mottled with irregular areas of radiopacity.The appearance has been described as a "moth-eaten" appearance.Histopathologic Features

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Chronic inflammatory cells are seen infiltrating a fibrous bone marrow.Irregular bone trabeculae, with empty lacunae, are seen in the fibrous tissue.Both osteoblastic and osteoclastic activities may be seen in the surroundingbone frequently with many reversal lines.

Chronic suppurative osteomyelitis of the right side of themandible; Left: Clinical picture; Right: Radiographic picture.

CHRONIC FOCAL SCLEROSING OSTEOMYELITIS

An uncommon form of localized proliferative reaction of bone with high tissueresistance to mild prolonged bacterial infectionClinical FeaturesUsually affects young patients in the second or third decades of life.The mandible is usually involved where there may be a carious or heavilyfilled lower molar or premolar.There may be no signs or symptoms other than mild pain associated with thecarious tooth.Radiographic Features

Typically, a well-circumscribed radiopaque area of sclerotic bone surroundingthe apex or apices of a carious or heavily filled tooth.The border of the sclerotic area may be clearly distinguishable from the normalsurrounding bone.The radiopacity, however, may merge imperceptibly with the normalsurrounding bone.The lesion is clearly distinguishable from benign cementoblastoma by: Absence of radiolucent margin surrounding the lesion. The outline of the root is well demarcated with no root resorption.Histopathologic FeaturesThe lesion consists of a dense mass of bony trabeculae with little interveningmarrow.

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The marrow tissue present is fibrotic.The marrow tissue is infiltrated by a small number of chronic inflammatorycells, mainly lymphocytes.

Chronic focal sclerosing osteomyelitis, radiopacity at the apex of the distal root of heavily filledmandibular permanent first molar.

CHRONIC DIFFUSE SCLEROSING OSTEOMYELITIS

Similar to chronic focal sclerosing osteomyelitis except that the infection reachesthe bone through a wide area of entryClinical FeaturesThe condition may be met with at any age, but is more common in olderindividuals.It may be observed in edentulous areas, especially in the mandible.There may be some vague pain.There may also be a foul taste.Otherwise, the condition may remain symptomless for many years.It may undergo acute exacerbation with suppuration and draining sinuses.Radiographic FeaturesThe radiographic picture of chronic diffuse sclerosing osteomyelitis appears as: An area of diffuse bone sclerosis appearing as a diffuse radiopacity. The lesion may be extensive and is often bilateral. The border between lesional and normal bone is often indistinct. It may involve both the mandible and the maxilla.Histopathologic FeaturesThe histopathologic picture of chronic condensing osteomyelitis appears as: Dense, irregular bony trabeculae. Some trabeculae show active osteoblastic activity. There may be focal areas of osteoclastic activity. The alternation of osteoblastic and osteoclastic activities may result in a

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mosaic appearance, which, however, is not as extensive as that of Pagetsdisease of bone. The marrow is distinctly fibrous with focal areas of lymphocytic andplasma cell infiltration.

Chronic diffuse sclerosingosteomyelitis, diffuse radiopacity in themandible caused by periapical inflammation that spread (osteomyelitis).The inflammation caused bone production rather than bone destruction suggestingchronic rather than acute osteomyelitis.

CHRONIC NON-SUPPURATIVE SCLEROSING OSTEOMYELITIS(Garres Osteomyelitis)

Chronic osteomyelitis with proliferative periostitis. A focal thickening of theperiosteum with peripheral subperiosteal reactive bone formation resulting frommild chronic infectionClinical FeaturesThe disease occurs in children and young adults having high tissue vitality.It shows a definite predilection for the mandible.The presenting features are pain in the jaw and toothache.These are associated with a bony hard swelling of the outer surface of the jawof at least several weeks duration.Radiographic FeaturesLateral jaw radiographs fail to show the proliferative periosteal reaction.An occlusal radiograph, however, will show focal subperiosteal overgrowth ofbone on the outer surface of the cortex opposite the offending tooth.The mass of new bone is generally smooth and well calcified.It may show a thin cortical layer.

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Histopathologic FeaturesThe new mass of bone is composed of reactive bone with bordering osteoid.Many bony trabeculae are rimmed by active osteoblasts.The bone marrow is fibrous.There may be patchy diffuse areas of lymphocytic and plasma cell infiltrationin the intervening marrow.

Chronic osteomyelitis (Garres type) of the right side of the mandible, clinicaland occlusal radiographic pictures.

OSTEORADIONECROSIS

Osteoradionecrosis is generally recognised as the presence of exposed bone in apreviously irradiated field, which fails to heal within a three-month periodOsteoradionecrosis is bone necrosis in previously irradiated tissues.In 90% of cases, osteoradionecrosis is induced by secondary trauma; in theother 10%, it occurs spontaneously.The most prominent aetiological factor is the effect of radiation on theendothelial linings and fibrous coats of blood vessels resulting inhypocellularity and vasculitis followed by endarteritis obliterans (obliteration ofsmall arteries and arterioles), ischemia, fistula formation, and pathologicalfracture of the bone.There is an increased risk of developing the condition for those who receive acombination of both radiation therapy and chemotherapy.There is also mucositis with spontaneous breakdown of the oral mucosal liningfrom eating, tooth brushing, ingestion of hot food, or poor oral hygiene.The mucosa in the irradiated area tends to be thinner and telangiectatic.This makes it more susceptible to mechanical injury.Post-radiation tooth extraction results in poor healing due to compromisedvasculature and consequently poor blood supply of the tissues.The degree of damage is related to the severity of the surgical trauma.Bone injury can occur through direct trauma e.g. tooth extraction (84%),related cancer surgery or biopsy (12%), denture irritation (1%) or by exposure ofthe irradiated bone to the hostile environment of the oral cavity secondary tooverlying soft tissue necrosis.

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The irradiated mandible, periosteum, and overlying soft tissue undergohyperaemia, inflammation, and endarteritis.These conditions ultimately lead to thrombosis, cellular death, progressivehypovascularity, and fibrosis.The radiated bed is hypocellular and is devoid of fibroblasts, osteoblasts, andundifferentiated osteoprogenitor cells.Ninety-five percent of osteoradionecrosis cases in the head and neck regioninvolve the mandible.The most vulnerable areas are the buccal cortices of the premolar and molararea and the retromolar triangle supplied by the inferior alveolar artery.Predisposing factors for mandibular osteoradionecrosis include:Doses of < 65 Gray delivered in more than 6 weeks resulted in no cases ofosteoradionecrosis as compared to a 50% incidence when higher doses weredelivered in less than 6 weeks.Radiation damage in the oral soft tissues and jawbones makes the tissueenvironment favourable for anaerobic microorganisms especially actinomyces.Higher tissue density in the radiated area predisposes to osteoradionecrosis.Bone has a density 1.6 to 1.8 times greater than soft tissues and therefore ismore susceptible to the effects of radiation.The mandible has a higher density compared to the maxilla, which mayexplain the higher incidence of mandibular involvement.Severity of surgical trauma; technique of tooth extraction also contribute.PrecautionsPreventive measures should be taken to help reduce the risk and/or severityof osteoradionecrosis.The maxilla and mandible are unique in that they are the only bones directly incontact with the external environment through the gingival attachment of theteeth, which poses greater potential for disease and infection.The bacterial load of the mouth is greater than any other site of the body andconsequently, any changes to that environment can result in infection.During treatment, a patient is likely to develop mucositis and xerostomia thatcan change the oral environment and tissue resilience, which causes anincreased risk of dental caries and periodontal disease.Prior to radiation treatment, a patient should have a full dental examination bya dentist trained in dealing with the requirements of oral cancer patients.Each tooth should be carefully evaluated, charted and an individual treatmentplan should be developed for each tooth to ensure its long-term fitness so asnot to require extraction afterwards.Any teeth that are unsuitable for proper restoration should be extracted not lessthan 2-3 weeks before the start of radiation to allow sufficient time for healing.

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Left: The patient developed osteoradionecrosis following radiotherapy.Right: Lateral oblique radiograph of case of osteoradionecrosis. Bone necrosisand pathologic fracture are evident.

HORMONAL BONE DISEASES

The more common hormonal bone diseases include osteoporosis, the skeletalchanges of hyperparathyroidism and renal osteodystrophy

HYPERPARATHYROIDISM(Osteitis Fibrosa Cystica; Von-Recklinghausens Disease of Bone)

The disease is due to excessive secretion of parathormone.The parathyroid glands regulate serum calcium and phosphorus levels throughthe secretion of parathyroid hormone (PTH).Parathyroid hormone raises serum calcium levels while lowering the serumphosphorus concentration.The regulation of PTH secretion occurs through a negative feedback mechanismin which calcium-sensing receptors on the membranes of parathyroid cells triggerdecreased PTH production as serum calcium concentration rises and vice versa.AetiologyHyperparathyroidism, leading to increased secretion of parathormone may be: Primary. Secondary.Primary hyperparathyroidism is a metabolic disorder in which parathyroid cells,either neoplastic or hyperplastic secrete excessive amounts of PTH in theabsence of any known stimulus. Primary hyperparathyroidism is usually caused by a functioning adenomaof a single parathyroid gland. Less commonly, it may be caused by diffuse hyperplasia of all fourparathyroid glands, with no renal pathology. Rarely primary parathyroid carcinoma or multiple parathyroid adenomas.

The bone changes of primary hyperparathyroidism regress or disappear within a

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few weeks after surgical removal of the causative parathyroid lesion.The primary retention of phosphate by diseased kidneys results in hyperphosphataemia,which causes hypocalcaemia, resulting in secondaryhyperparathyroidism.The hyperparathyroidism increases bone resorption, which may normalizeserum calcium levels by releasing calcium deposited in bones.Secondary hyperparathyroidism is associated with many conditions that leadto hypocalcaemia and most often occurs as a consequence of: The hyperphosphataemia and hypocalcaemia of chronic renal failure. The complex bone changes in chronic renal failure are called renalosteodystrophy and include: Osteomalacia, Rickets "renal rickets", Osteitis fibrosa cystica and other bone changes associated with thedisease.In secondary hyperparathyroidism, elevated PTH levels do not result inhypercalcaemia.This has been attributed to excessive urinary excretion of calcium in patientswith chronic renal failure.IncidencePrimary hyperparathyroidism most frequently occurs in adults, and is rarelyseen in children less than 10 years of age.It has a peak incidence between the third and fifth decades.It has a female to male ratio of two or three to one.Clinical FeaturesThe symptoms of primary hyperparathyroidism may be minimal for many years,depending upon the extent of the metabolic disorder.The clinical presentations are divisible into three categories: Manifestations of hypercalcaemia, such as neuro-muscular weakness,fatigue, gastro-intestinal symptoms, and, rarely, coma in cases of severehypercalcaemic crisis. Renal stones (often bilateral); calcification of the kidneys (nephrocalcinosis);and metastatic calcification of other tissues. Bone resorption and fibrous replacement resulting in diffuse osteopenia(difficult to distinguish radiologically from osteoporosis).In some cases, "cystic" or tumour-like lesions of bone (brown tumours ofhyperparathyroidism) may occur.Although having a high prevalence in primary hyperparathyroidism, browntumours are frequently encountered in secondary hyperparathyroidism due tothe greater prevalence of this condition.Swellings and deformities may arise because of the bone lesions.Pathological fractures; the fractures heal readily, but other fractures occur.A complication that is rarely seen today is widespread alterations and deformitiesaffecting the demineralised and softened bones of the entire skeleton.The skull and jaws are sometimes affected.

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Radiographic FeaturesThe teeth are of normal density and radiopacity.The bone of the jaws, however, shows decreased density and radiopacity witha radiolucent honeycombed appearance.The trabecular pattern of bone is finer and exhibits trabecular mottling bestobserved in cranial bones.There is widespread or generalized loss of the lamina dura.Sometimes there are large radiolucent areas denoting areas of totaldestruction of bone corresponding to the sites of fibrous lesions.Histopathologic FeaturesThe characteristic feature is widespread osteoclastic activity in many bones.There is exuberant fibroblastic proliferation occupying the widened Haversiancanals and replacing the resorbed bone.The bone marrow is replaced by fibrous tissue as occurs in fibrous dysplasiaand in the early stage of Pagets disease of bone.Osteoid tissue may develop within the fibrous tissue with formation of newbone trabeculae rimmed by a row of osteoblasts.Bone resorption, however, invariably outstrips new bone formation.Groups of osteoclasts are seen actively engaged in resorbing bone.The bone stains weakly with eosin (pale) because of its decreased content ofcalcium salts.There are frequent areas of haemorrhage and extravasated red blood cells,imparting a dark reddish or brownish colour to the lesion.Multinucleated foreign body giant cells may also be seen aggregated aroundareas of extravasated blood cells.

Fig. 155: Brown tumour of hyperparathyroidism. Increased osteoclastic activity producingirregular bone resorption with hemorrhage, macrophage, multinucleated giant cells andfibrous connective tissue proliferation.

Biochemical FindingsPrimary hyperparathyroidism, in the absence of renal disease, isbiochemically characterized by: Hypercalcaemia. Hypophosphataemia.

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Hypercalciuria. Elevated serum alkaline phosphatase activity. Increased levels of PTH measured by radioimmunoassay.

OSTEOPOROSIS

Osteoporosis is defined as a decrease in bone density (bone mass per unitvolume) of normally mineralized bone, and an alteration of bone architectureresulting in thinning and increased porosity of the bone cortices and trabeculaewith an increased risk of fractureIncidenceOsteoporosis is a very common bone disease in most parts of the world and isincreasing in prevalence with the increased aging of the population.Presently, it has been estimated that ten million people, mainly postmenopausalwomen, in the U.S. have osteoporosis, and an additional 18million have low bone mass (osteopenia).Osteoporosis is also a broadly used clinical term for a generalized loss ofbone density resulting in skeletal fragility, bone pain, and pathologicalfractures (of the spine, wrist, hip, and ribs).This is particularly prevalent in postmenopausal women and in both sexeswith advancing age.Risk FactorsOf the potential predisposing risk factors in post-menopausal and senileosteoporosis, the most notable are: Low bone mass at maturity (early adult life). Oestrogen (and androgen in males) deficiency. Negative calcium balance. Steroid therapy or anticonvulsant medication. Smoking or frequent exposure to passive smoking. High alcohol intake. Lack of physical exercise.PathogenesisBone turnover and remodelling occurs throughout life and involves the tightlycoupled processes of bone formation by osteoblasts and bone resorption byosteoclasts.In the growing person, the total bone mass increases with skeletal growth asbone formation exceeds bone resorption.Bone mass then remains constant for several years during skeletal maturitywhen bone formation and bone resorption are nearly equal.Bone mass then begins to decline after the age of 40 to 50 years, at a faster ratein women than in men, as bone resorption exceeds bone formation.The progressive bone loss over the ensuing decades may amount to 30-50%,or more, of the initial skeletal mass.The detrimental effect of progressive bone loss tends to be greater in those

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who are genetically predisposed to have a smaller bone mass at maturity.Although not the only consideration in pathogenesis, sex hormone deficiencyis a major factor associated with the development of post-menopausal orsenile osteoporosis.Postmenopausal osteoporosis is mainly attributable to increased boneresorbing activity of osteoclasts caused by oestrogen deficiency,Senile osteoporosis, on the other hand, is attributed to inadequate osteoblasticfunction.Oestrogens normally react with and signal osteoblasts directly stimulatingthem to lay down bone through high-affinity oestrogen-receptors.With a deficiency of oestrogen (or of androgen in men), osteoclastic activitypredominates, resulting in an increased resorption and loss of bone mass.A large number of experimental studies indicate that, in osteoporoticconditions, osteoblasts are characterized by lower proliferation and defectivefunction compared with normal osteoblasts.Clinical FeaturesA 'silent' risk factor for bone fracture, osteoporosis is a major cause of thehundreds of thousands of fractures (of hip ~300,000, spine, and wrist)occurring annually in the U.S. in women over the age of 45 years.Estimates are that approximately 10-20% of women die within 1 year followingosteoporotic hip fracture.Osteopenia ("too little" bone) is a descriptive term for a loss of bone densityobserved radiologically.Osteopenia may be local (as in disuse atrophy of an immobilized limb) or itmay be generalized.Osteoporosis may be asymptomatic for a time, and may be only recognizedby clinical x-rays taken for some other purpose.At some critical point, the fracture threshold is reached, the fragile skeletonfails to meet mechanical demands, and Bone pain, Microfractures, and Overt fractures of the vertebrae and other bones occur.This condition of symptomatic osteoporosis occurs most frequently inpostmenopausal and aging white females, less commonly in white males, andrarely in blacks of either sex.PathologyThe excessive bone loss in postmenopausal and senile osteoporosisproduces thinning and increased porosity of the trabecular bone of the axialskeleton (vertebrae, ribs, and pelvis).The cortices of cylindrical bones are also thinned from the inside by endostealresorption, resulting in enlargement of the medullary cavity without acorresponding change in the outer diameter of the bone.The vertebral bodies, particularly in the thoracolumbar region, may beweakened by micro fractures and collapse anteriorly, resulting in compressionfractures and wedging of the vertebrae, loss of stature, and kyphotic deformityof the spine ("dowager's hump").

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213

HistopathologyHistologically, the amount of cortical and cancellous bone in osteoporosis isdecreased compared to the normal for a similar site, sex, and age.The remaining bone has a lamellar structure and osteoid seams of normal width.The bone cortices are thi