BDS10005 Bone Disease PDF

BDS10005 Bone disease [Paget's disease, fibro-osseous lesions, hyperparathyroidism] Aims: The aim of this lecture is to detail the clinical, histopathological and serological features of fibrosseous disease of the jaws as well as the impact of hyperparathyroid disease upon the maxilla and/or mandibl...

BDS10005 Bone disease [Paget's disease, fibro-osseous lesions, hyperparathyroidism] Aims: The aim of this lecture is to detail the clinical, histopathological and serological features of fibrosseous disease of the jaws as well as the impact of hyperparathyroid disease upon the maxilla and/or mandible Objectives: On completion of this lecture, the student should be able to: Understand the principle clinical and histopathological aspects of fibro-osseous disease of the jaws Understand the causes of hyperparathyroid disease and the possible implications of such disease upon the jaws Understand the relevance of serological investigations of Paget’s disease, fibrous dysplasia and hyperparathyroid disease Have an understanding of disease that may rarely manifest as boney swellings of the jaws Fibro-Osseous Lesions The term fibro-osseous lesion describes a group of jaw disorders, characterized by the replacement of normal bone by fibrous tissue containing a newly formed mineralized products. Bone resorption Proliferation of fibrous tissue Formation of mineralized products  Although lesions belonging to this category have different etiologies, they exhibit similar histopathologic features. [Therefore, correlation of histopathologic features with clinical and radiographic features is essential to reach final diagnosis] Fibro-Osseous Lesions According to the latest WHO classification of head and neck tumors (2017), fibro-osseous lesions can be classified as follows Developmental Fibrous dysplasia Reactive or dysplastic Neoplasms Cemento-osseous dysplasia [focalperiapical florid] Ossifying or cementoossifying fibroma Fibrous dysplasia Fibrous dysplasia is a developmental condition in which normal bone is replaced by an excessive proliferation of abnormal fibrous tissue with irregular bone trabeculae Bone resorption Proliferation of fibrous tissue Formation of bone trabeculae it is caused by postzygotic somatic mutation of GNAS1 gene The extent of disease depends on when the mutation of GNAS1 gene occurs If the mutation occurs During early embryonic development Pluripotent stem cell Cause abnormalities in Osteoblasts + melanocytes + endocrine cells Later, during embryonic development Skeletal progenitor cell Affcets Osteoblasts only Postnatal Osteoblasts in only a single bone Fibrous dysplasia Monostotic Involving one bone Polystotic Involving multiple bones example: Jaffe-Lichtenstein syndrome--McCuneAlbright syndrome Monostotic fibrous dysplasia It is fibrous dysplasia limited to a single bone Clinical features 2nd & 3rd decades of life females = males Maxilla is affected more than the mandible Unilateral slowly growing painless swelling that tends to stabilize with cessation of skeletal growth [♣] Maxillary lesions cause fullness of the cheek. Monostotic fibrous dysplasia Clinical features Intraorally, Buccal & palatal enlargement of the alveolar process Obliteration of canine fossa Downward slopping of the occlusal plane. The teeth may be displaced (due to expansion), but usually remain firm. Mandibular lesions result in expansion of the buccal & lingual plates Bulging of the lower border Monostotic fibrous dysplasia Radiographic features Depending on the amount of bone trabeculae in the lesion one of 3 patterns can be seen: Radiolucent area (early fibrous stage) Mixed radiolucent radiopaque Mainly radiopaque (more mature lesion)  Ground glass appearance is the chief radiographic feature which results from presence of poorly calcified bone trabeculae arranged in disorganized pattern within fibrous stroma Monostotic fibrous dysplasia Histopathology : The lesion consists of fibrous stroma containing irregularly shaped trabeculae of woven bone, which are thin, disconnected giving a Chinese letter appearance Bone trabeculae fuse directly to normal bone at the periphery of the lesion [that’s why limits of the lesion is difficult to define radiographically] In long standing lesions, woven bone is replaced by lamellar bone with parallel trabeculae Laboratory findings The blood serum calcium& alkaline phosphatase levels are within normal values [alkaline phosphatase levels may be elevated] Management Surgical procedures should be delayed after cessation of skeletal growth as the lesion tends to stabilize upon skeletal maturation [to avoid regrowth of the lesion] Disfiguring lesions are treated by surgical contouring (reduction of lesion) to improve esthetics, with no attempts to remove the entire lesion Polyostotic fibrous dysplasia Fibrous dysplasia involving 2 or more bones Usually diagnosed before 10 years of age There is female prediliction Some patients may exhibit polyostotic fibrous dysplasia with syndromes: Jaffe syndrome--McCune-Albright syndrome  Jaffe -Lichtenstein syndrome This syndrome is a genetic defect, characterized by: 1. Polyostotic fibrous dysplasia 2. Café au lait skin pigmentation Mc Cune-Albright Syndrome The syndrome is a genetic defect, characterized by : 1. Polystotic fibrous dysplasia [In skull & jaw bones, asymmetric growth of face takes place] 2. Café au lait skin pigmentation [limited to one side, never cross the midline & very irregular margins ≠ (that of neurofibromatosis)] 3. Endocrine abnormalities [premature sexual development in girls (sexual precocity)] Cemento-osseous dysplasia The most common fibro-osseous lesion Occurs in the tooth bearing areas of the jaw Based on clinical & radiographic features it includes the following variants Cemento-osseous dysplasia Focal Periapical Florid Focal cemento-osseous dysplasia Clinical features It involves a single site: most commonly the posterior area of mandible 90% of cases are females (3rd to 6th decades of life) Asymptomatic [detected incidentally by radiographic examination] Mostly smaller than 1.5 cm in diameter Focal cemento-osseous dysplasia Radiographic features It usually occurs around tooth apices and around extraction sites It occurs in one of 3 patterns: 1. Completely radiolucent 2. Mixed radiolucent & radiopaque 3. Densely radiopaque surrounded by a narrow radiolucent rim  The borders are well defined & slightly irregular Periapical cemento-osseous dysplasia Clinical features It involves periapical region of anterior mandible It typically occurs as multiple foci Female predilection [♀:♂ about 10:1] – 70% of the cases are blacks 3rd to 6th decades of life Associated teeth are usually vital Asymptomatic incidentally by examination] [detected radiographic Periapical cemento-osseous dysplasia Radiographic features It occurs in one of 3 patterns: 1. Early lesions appear as circumscribed periapical radiolucencies similar to periapical granuloma or cyst [adjacent lesions may fuse forming radiolucent area the envelops the apices of several teeth] 2. Mixed radiolucent & radiopaque Periapical cemento-osseous dysplasia Radiographic features It occurs in one of 3 patterns: 3. Densely radiopaque surrounded by a narrow radiolucent rim  Periodontal ligament space usually appears intact [no fusion to teeth] Florid cemento-osseous dysplasia Clinical features It exhibits multifocal involvement most commonly affects posterior areas of the jaws Middle aged black Female predilection  High tendency for bilateral symmetrical involvement of the mandible The lesion may be asymptomatic [detected incidentally by radiographic examination] OR with dull pain and exposure of yellowish avascular bone to the oral cavity Florid cemento-osseous dysplasia Radiographic features It occurs in the same maturation pattern of other cemento-osseous dysplasia: 1. Completely radiolucent 2. Mixed radiolucent & radiopaque 3. Densely radiopaque surrounded by a narrow radiolucent rim Florid cemento-osseous dysplasia Radiographic features It occurs in the same maturation pattern of other cemento-osseous dysplasia: 1. Completely radiolucent 2. Mixed radiolucent & radiopaque 3. Densely radiopaque surrounded by a narrow radiolucent rim Cemento-osseous dysplasia Histopathologic features All 3 patterns of cementoosseus dysplasia demonstrate similar histopathologic features: 1. Cellular connective tissue with scattered hemorrhage 2. A variable mixture of woven bone, lamellar bone and cementum like material Cemento-osseous dysplasia Histopathologic features As the lesion matures, the ratio of fibrous C.T. to mineralized material decreases Cemento-osseous dysplasia Histopathologic features  Bony trabeculae become thick resembling ginger roots  In the final radiopaque stage, the individual trabeculae fuse to form sheet of sclerotic, cementoosseous material Cemento-osseous dysplasia Management Generally doesn’t require removal as it isn’t neoplastic Lesions usually cause few problems during radiolucent phase ≠ sclerotic phase [as the lesions are hypovascular, prone to necrosis and secondary infection] Asymptomatic patients keeping good oral hygiene to avoid periodontal conditions and teeth loss Symptomatic patients surgical procedures should be avoided+ sequestration of cementum like masses occurs slowly & is followed by healing Familial gigantiform cementoma A rare hereditary disorder It is characterized by cemento-osseous proliferation involving multiple quadrants of the jaws and resulting in massive expansion  Tendency for progressive lesion growth suggests a neoplastic process Ossifying (cemento-ossifying) Fibroma It is a benign fibro-osseous neoplasm affecting jaws and craniofacial skeleton. It has two variants:  cemento-ossifying fibroma of odontogenic origin Juvenile ossifying fibroma Clinical features  Broad age range with peak incidence 3rd & 4th decades  female predilection  The molar/premolar region of the mandible is the most common site Ossifying (cemento-ossifying) Fibroma Clinical features  Appears as slow & painless expansion of the affected jaw  Small lesions are asymptomatic [detected by radiographic examination]  Larger tumors produce painless expansion of the affected jaws Ossifying (cemento-ossifying) Fibroma Radiographic features Depending on amount of calcification Radiolucent [little calcified material] Radiopaque [predominating calcified material] Intermediate degrees of radiolucency & radiopacity Ossifying (cemento-ossifying) Fibroma Radiographic features  The border of the tumor is usually sharply circumscribed [which helps in distinguishing this tumor from fibrous dysplasia which it may resemble microscopically]  Unilocular & multilocular forms may exist  Teeth in the area may exhibit root divergence or resorption Ossifying (cemento-ossifying) Fibroma Histopathology Cellular fibrous tissue with mineralized product: Osteoid tissue Bone trabeculae [ woven or lamellar with osteoblastic rimming] Cementum like material [brush borders] Ossifying (cemento-ossifying) Fibroma Management  The circumscribed nature of ossifying fibroma permits enucleation of tumor with relative ease.  Large lesions that cause bone destruction may need surgical resection & bone grafting. Juvenile Ossifying Fibroma Is differentiated by: 1. Patient age: children, adolescents & young adults 2. Site of predilection: Jaws [mostly maxilla], paranasal sinuses & orbital region 3. Behavior: rapid aggressive growth Hyperparathyroidism It is a condition characterized by overproduction of parathyroid hormone. PTH normally is produced by the parathyroid glands in response to a decrease in serum calcium levels. Two types exist: Hyperparathyroidism Primary Secondary There is uncontrolled production of PTH as a result of adenoma or hyperplasia of parathyroid gland, rarely parathyroid carcinoma Hyperparathyroidism It is a condition characterized by overproduction of parathyroid hormone. PTH normally is produced by the parathyroid glands in response to a decrease in serum calcium levels. Two types exist: Hyperparathyroidism Primary Secondary There is PTH is continuously produced in response to chronic low levels of serum calcium caused by a disease outside the gland such as chronic renal failure or vitamin D deficiency [because vitamin D is essential for calcium absorption from gut] Hyperparathyroidism Hyperparathyroidism Primary Secondary Tertiary hyperparathyroidism is observed in patients with chronic secondary hyperparathyroidism due to hypertrophy of parathyroid glands over time and continuous over-secretion of parathyroid hormone, despite serum calcium levels that are within the reference range or even elevated.. This type is particularly dangerous because it may cause diffuse calcinosis. Role of parathyroid hormone Normally, parathyroid hormone acts to maintain normal calcium levels in blood (8.5 to 10.2mg/dl) Overproduction of osteoclastic activity weakness of bone parathyroid hormone with excess bone increases resorption Hyperparathyroidism Clinical features The condition occurs above the age of 60, women >men Most patients are asymptomatic [diagnosed incidentally on routine serologic test showing abnormal rise in serum Ca]. Patients show the classic triad “stones, bones, abdominal groans” Hyperparathyroidism Clinical features Bone related symptoms The hallmark of hyperparathyroidism is excessive bone resorption causing osteoporosis with increased susceptibility to fracture Multiple lesions within bone known as brown tumors [this name is attributed to the dark red brown colour of tissue specimens from these tumors due to abundant haemorrhage & hemosidrin deposition The most severe complication of hyperparathyroidism is generalized osteitis fibrosa cystica, which develop from cystic degeneration & fibrosis of the brown tumors Hyperparathyroidism Clinical features Hypercalcemia related symptoms Kidney stones & metastatic calcification in walls of blood vessels & subcutaneous tissues [due to hypercalcemia] Muscle weakness & fragility Effects on central nervous system include confusion & depression Abdominal groans which refers to tendency for the development of duodenal ulcers Hyperparathyroidism Radiographic features Reduced bone density due to osteoporosis and thinner bone trabeculae Multilocular radiolucent areas Hyperparathyroidism Radiographic features Generalized loss of lamina dura around teeth Teeth are of normal density Hyperparathyroidism Histopathology Numerous multinucleated giant cells in granulation tissue, containing abundant hemosidrin deposition Differential Diagnosis Cherubism Hyperparathyroidism Central giant cell granuloma Aneurysmal bone cyst Paget's disease of bone Paget’s disease is a disturbance of bone turnover that is characterized by defect in both resorption & deposition resulting in distortion & weakening of the affected bone  It has geographic variance in its prevalence common in Britain, but rare in Africa & Asia [declines in incidence & severity of disease in last decades were observed].  The etiology is unknown, but both genetic and environmental factors are proposed, mainly mutations in SQSTM1 and RANK genes, both of which are important for osteoclast function. Paget's disease of bone Clinical features Most patients are asymptomatic [diagnosed incidentally on radiograph]. Some patients may experience severe bone pain joint pain, stiffness & limited mobility may develop [osteoarthritis] The affected bones become thickened, deformed & weakened with great susceptibility to fracture Paget's disease of bone Clinical features It often leads to bowing deformity of weight-bearing bones resulting in simian (monkey like) stance. Involvement of the skull produces increase in circumference of the head Paget's disease of bone Clinical features Jaw involvement (a) maxilla affected more than mandible, (b) enlargement of alveolar ridge [but remain symmetric] (c) Spacing of teeth (d) Edentulous patients usually complain that their denture no longer fit ♣ Paget's disease of bone Radiographic features Osteolytic phase: appear as large circumscribed areas of radiolucency in the skull vault, termed "osteoporosis circumscripta". Osteoblastic phase appears as patchy areas of sclerotic bone giving the "cotton wool" pattern. Paget's disease of bone Radiographic features  Teeth demonstrate extensive hypercementosis  They exhibit loss of lamina dura [can’t be distinguished from the surrounding sclerotic bone] D.D: cemento-osseus dysplasia!!!! Adjacent parts of the bone may show different stages of the disease; a common result is therefore patchy areas of osteoporosis and of sclerosis Paget’s disease of bone Histopathology  Uncontrolled resorption formation of bone and  In resorptive phase, numerous, enlarged osteoclasts surround bone trabeculae with evidence of bone resorption.  A highly vascular fibrous connective tissue replaces the marrow.  On the other hand, osteoblastic activity is also seen forming osteoid rims around bone trabeculae Paget’s disease of bone Histopathology  A characteristic feature is the presence of basophilic reversal lines in the bone.  These lines indicate the junction between alternating resorptive and formative phases of the bone and result in "mosaic" or jigsaw puzzle” appearance  The mosaic appearance is the hallmark of Paget’s disease Paget's disease of bone Laboratory findings Serum calcium levels are normal High elevation of serum alkaline phosphatase (index of active bone formation) [normal value 3-13KAU] Treatment Bisphosphonate therapy (IV or oral) which can reduce bone turnover, induce normalization of alkaline phosphatase levels, decrease, bone pain, and improve quality of life. Paget's disease of bone Complications 1. Neurologic complications headache, deafness or visual disturbances may occur due to encroachment on the various foramina, resulting in compression of the cranial nerves 2. Cardiovascular complications arterial calcification increased cardiac output & heart failure [due to, increased bone vascularity with multiple arterio-venous shunt during active disease] 3. Sarcomatous transformation [osteosarcoma in old age] Paget's disease of bone Complications 4. Severe involvement of maxilla is associated with enlargement of the middle face producing a lion-like facial appearance (liontiasis ossea) Mask movie 1985 based on a true story of Rocky Dennis Paget's disease of bone Complications 5. Difficult extraction of teeth due to hypercementosis or ankylosis, which may result into: Extensive haemorrhage of oral surgical procedures during vascular lytic phase Poor wound healing, dry socket or osteomyelitis may follow tooth extraction in avascular sclerotic phase Key points In fibrous dysplasia, surgical procedures should be delayed after cessation of skeletal growth with no attempts to remove the entire lesion Cemento-osseous dysplasia doesn’t require surgical removal The circumscribed nature of ossifying fibroma permits enucleation of tumor with relative ease. Hyperparathyroidism is a hormonal disturbance and one of giant cell lesions, microscopically. The mosaic or jigsaw puzzle appearance is the hallmark of Paget’s disease, microscopically. Aims: The aim of this lecture is to detail the clinical, histopathological and serological features of fibrosseous disease of the jaws as well as the impact of hyperparathyroid disease upon the maxilla and/or mandible Objectives: On completion of this lecture, the student should be able to: Understand the principle clinical and histopathological aspects of fibro-osseous disease of the jaws Understand the causes of hyperparathyroid disease and the possible implications of such disease upon the jaws Understand the relevance of serological investigations of Paget’s disease, fibrous dysplasia and hyperparathyroid disease Have an understanding of disease that may rarely manifest as boney swellings of the jaws Reading material: Students are advised to review any relevant teaching provided in the first year. In addition they are advised to read relevant sections of the following texts: Robinson M et al. Soames’ and Southam’s Oral Pathology. 5th edition. Oxford University Press, 2018 pp 180-183 Odell E.W. Cawson’s Essentials of Oral Pathology and Oral Medicine. 9th Edition. Elsevier, 2017 pp 179-182 Thank you