Dent 356-11 Disorders of Bone I

1. Dent 356-11Disorders of Bone I Inherited & Developmental Disorders of Bone Dr. Huda Hammad

2. Inherited & Developmental Disorders of Bone Osteogenesis Imperfecta Osteopetrosis (Marble Bone Disease) Cleidocranial Dysplasia (Cleidocranial Dysostosis) Achondroplasia Fibro-osseous Lesions Fibrous Dysplasia of Bone Cemento-osseous Dysplasia Cherubism

3. Osteogenesis Imperfecta A heterogeneous group of related hereditary disorders. The basic abnormality is a genetic defect in synthesis of type I collagen.

4. Osteogenesis Imperfecta:Clinical Features Characterized by weak bones with tendency to fracture. The slender, long bones have narrow, poorly formed cortices composed of immature woven bone. Fractures usually heal without trouble, but exuberant callus may form.

5. Osteogenesis Imperfecta:Clinical Features Sclerae may appear blue because they are so thin that the choroid shows through. There may be deafness due to distorted ear ossicles. Joint hypermobility with lax ligaments. Thin translucent skin. Heart valve defects.

6. Osteogenesis Imperfecta:Clinical Features Osteogenesis imperfecta is often associated with dentinogenesis imperfecta, especially in deciduous dentition. It is thought that the two defects are carried by separate but related genes.

7. Osteogenesis Imperfecta:Clinical Features Four main types: Type I (classic type): autosomal dominant, blue sclera, premature deafness, +/- dentinogenesis imperfecta. Type II (perinatal lethal): autosomal dominant. Type III (progressively deforming): autosomal dominant/ recessive, severely osteoporotic bone, progressive deformity, dentinogenesis imperfecta. Type IV: autosomal dominant. Similar to type I but more severe, white sclera, +/- dentinogenesis imperfecta.

8. Osteopetrosis (Marble Bone Disease):Clinical Features Rare disease characterized by excessive density of all bones with obliteration of marrow cavities. Secondary anemia, neutropenia, with susceptibility to infections.* Defect in osteoclast function results in failure of proper remodeling of developing bone. Abnormally dense bone is mechanically weak, so fractures are common.

9. Osteopetrosis (Marble Bone Disease):Clinical Features Jaws are composed of dense bone with reduced marrow spaces. There may be delayed eruption of teeth. Osteomyelitis is a common complication of tooth extraction.

10. Osteopetrosis (Marble Bone Disease):Clinical Features* Two basic patterns: 1. Malignant type: Progressive. Autosomal recessive. Occurs early in life. Severe bone fragility and malformations. Death usually before puberty. 2. Benign type: Autosomal dominant. Less severe. Diagnosis may not be made until late in life and incidentally. Repeated fractures following minor trauma.

11. Osteopetrosis (Marble Bone Disease)Radiographic Features Increased density of skeleton. Lack of distinction between cortical and medullar bone. Marked density of base of skull. Mandible more involved than maxilla. Roots of teeth may be invisible.

12. Osteopetrosis (Marble Bone Disease):Histopathologic Features* Thickened cortices. Reduced marrow cavities. Persistence of woven bone. Marked lack of mature lamellar bone.

13. Cleidocranial Dysplasia(Cleidocranial Dysostosis) Autosomal dominant inheritance. Abnormalities of many bones, particularly the skull, jaws, and clavicles. Dental abnormalities common.

14. Cleidocranial Dysplasia (Cleidocranial Dysostosis):Clinical Features Abnormalities of skull: Fontanelles and sutures tend to remain open. Skull appears flat with prominent frontal, parietal, and occipital bones. Nasal bridge is depressed. Partial or complete absence of clavicles allows shoulders to be approximated until they meet in the midline.

15. Cleidocranial Dysplasia (Cleidocranial Dysostosis):Clinical Features Dental abnormalities: Maxilla may be underdeveloped with a high, narrow arched palate. Deciduous dentition tends to be retained with delayed or non-eruption of permanent dentition because of multiple impactions. Supernumerary teeth and dentigerous cysts are common. Roots tend to be thinner than normal. Secondary cementum is sparse or absent on both dentitions.

16. Achondroplasia Autosomal dominant, but some cases appear to be due to spontaneous mutations. Most common form of dwarfism. Abnormality of endochondral ossification. Absent or defective zone of provisional calcification of cartilage in epiphyses and base of skull.

17. Achondroplasia:Clinical Features  Trunk and head of normal size. Limbs are excessively short. Middle part of face is retrusive due to defective growth of base of skull. Severe malocclusion.

18. Fibro-osseous Lesions The term encompasses a variety of disorders which are characterized histologically by replacement of normal bone by cellular fibrous tissue within which varying amounts of predominantly woven bone and acellular islands of mineralized tissue develop. They cannot be distinguished by histology alone; clinical and radiographic features must be considered.

19. Fibro-osseous Lesions They can be divided into lesions characterized by disorganized development of bone (osseous dysplasias), and benign fibro-osseous neoplasms of bone.

20. Fibro-osseous Lesions Within the jaws, fibro-osseous lesions include lesions previously considered to be derived from cementum, but since the latter is a modified form of bone, the distinction is somewhat artificial. Nevertheless, it is helpful to distinguish between dysplasias of bone that are generalized skeletal disorders, and those which appear to be localized to the tooth-bearing area of the jaws (cemento-osseous ) dysplasias.

21. Fibro-osseous Lesions: Classification A. Osseous dysplasia: Fibrous dysplasia - monostotic - polyostotic Cemento-osseous dysplasia: - periapical cemental dysplasia - focal cemento-osseous dysplasia - florid cemento-osseous dysplasia (gigantiform dysplasia) B. Benign neoplasia: Ossifying/ cemento-ossifying fibroma

22. Monostotic Fibrous Dysplasia of Bone Monostotic: involving one bone. Much more common than polyostotic forms (involving multiple bones). Any bone may be involved. Most frequent in limbs, ribs, skull bones, especially the jaws.

23. Monostotic Fibrous Dysplasia of Bone Jaw lesions are more common in the maxilla. When maxilla is involved, adjacent bones such as the zygoma and sphenoid may be involved, so it is not strictly monostotic. However, since the disease is restricted within a defined anatomic area, the pattern is not typical of polyostotic types. The term �craniofacial fibrous dysplasia� is appropriate in such circumstances.

24. Monostotic Fibrous Dysplasia of Bone:Clinical Features Majority present in childhood or adolescence. Occasionally not diagnosed until adult life, but usually with h/o quiescent bony enlargement. They may give h/o recent expansion of quiescent bony enlargement. Reactivation of quiescent lesions may occur for unknown reasons, and has been reported with pregnancy.

25. Monostotic Fibrous Dysplasia of Bone:Clinical Features 1st sign of disease is a gradually increasing, painless swelling causing facial asymmetry. Smooth, fusiform, and often more pronounced buccally than lingually or palatally.

26. Monostotic Fibrous Dysplasia of Bone:Clinical Features When maxilla is involved, there is usually prominence of the cheek and buccal expansion distal to the canine, which may extend to tuberosity. Canine fossa is obliterated. Maxillary lesions commonly involve the sinus, zygomatic process, and orbital floor, and may cause exophthalmos and proptosis.

27. Monostotic Fibrous Dysplasia of Bone:Clinical Features Mandibular lesions mostly involve molar-premolar areas. If the lower border is involved, there may be obvious protuberance and increase in depth of the jaw. In either jaw, there may be displacement or sometimes failure of eruption of teeth.

28. Monostotic Fibrous Dysplasia of Bone:Radiographic Features Jaw lesions are variable in appearance, reflecting differing amounts of metaplastic bone formed within fibrous tissue. Borders are difficult to define because of gradual transition to normal. Initially resemble cyst-like radiolucencies containing faint bony trabeculae. With increasing trabeculation, they become mottled and eventually opaque.

29. Monostotic Fibrous Dysplasia of Bone:Radiographic Features The many delicate trabeculae give a ground-glass or orange-peel-stippling effect. Roots of teeth in involved areas may be separated and teeth may be displaced. In the maxilla, lesions may extend up to and distort, but do not cross suture lines.

30. Polyostotic Fibrous Dysplasia of Bone:Clinical Features 2-3 times as common in females as males. Variable distribution of lesions. Frequently occur in bone of one limb, especially the lower, but skull, vertebrae, ribs, and pelvis are also often involved. Almost any combination can occur, but there is tendency for segmental involvement and localization to one limb or one side of body.

31. Polyostotic Fibrous Dysplasia of Bone:Clinical Features Severe cases are usually diagnosed in childhood because of associated deformities and pathological fractures. May be accompanied by caf�-au-lait melanotic spots on skin.* Serum alkaline phosphatase may be elevated depending on severity.*

32. Polyostotic Fibrous Dysplasia of Bone:Clinical Features May present as part of McCune-Albright syndrome: Rare, severe form. Caf�-au-lait skin pigmentation. Precocious puberty in females. Occasionally other endocrine abnormalities. Pigmentation of oral mucosa reported.

33. Fibrous Dysplasia of Bone:Histopathologic Features Replacement of normal bone by fibrous tissue containing islands and trabeculae of metaplastic woven bone. Fibrous tissue may be richly cellular or may consist of thick, interlacing collagen bundles. Newly formed bony trabeculae are delicate and irregular (likened to Chinese characters). They consist of immature, coarse-fibered woven bone.

34. Fibrous Dysplasia of Bone:Histopathologic Features Appearances of jaw lesions are more variable than in other bones. In jaw lesions, trabeculae may be thicker and blunter than in long bones. Spherical areas of calcification resembling cemetum may be present. Osteoblastic and osteoclastic activity may be seen in relationship to some trabeculae.

35. Fibrous Dysplasia of Bone:Histopathologic Features At the margins, lesional bone fuses with normal bone and this particular feature distinguishes FD from ossifying fibroma. Usually with increasing age, the amount and cellularity of fibrous tissue decreases and the amount of bone increases. As the lesion matures, there is progressive remodelling of woven bone to lamellar bone. Occasionally, the lesion may be associated with development of aneurysmal bone cyst.

36. Fibrous Dysplasia of Bone:Etiology & Behavior Pathogenesis is complex but is only beginning to be understood. It is not inherited but considered a developmental defect. Caused by mutation occurring in fetal (polyostotic) or postnatal (monostotic) life. Mutation in GNAS 1 gene which encodes for a stimulatory protein.

37. Fibrous Dysplasia of Bone:Etiology & Behavior A few cases of malignant transformation have been reported, usually to fibrosarcoma. Some of those cases followed radiotherapy which is now not an unacceptable treatment. Majority of cases are treated by conservative surgical removal to reduce deformity only. The lesions tend to expand mainly during the period of active skeletal growth and become quiescent in adult life.

38. Cemento-osseous Dysplasia Encompasses osseous dysplasias localized to the jaws, particularly tooth-bearing areas. It incorporates: - periapical Cemental Dysplasia - focal Cemento-osseous Dysplasia - florid Cemento-osseous Dysplasia They are considered to be different clinical presentations of the same disorder.

39. Cemento-osseous Dysplasia Shows the characteristic features of a fibro-osseous lesion, comprising fibrous tissue within which varying amounts of bone/calcified cellular tissue develops. The radiographic features reflect the extent of mineralization and may be radiolucent, mixed, or radiopaque. More prevalent in women than men. Majority of patients >30 years of age. Predominant in mandible.

40. Cemento-osseous Dysplasia Presents a range of appearances: Periapical cemental dysplasia: multiple small lesions associated with apical areas of mandibular incisors. Florid Cemento-osseous Dysplasia: Multiple large lesions involving one or more quadrants in one or both jaws.

41. Cherubism Rare disorder of bone, inherited in autosomal dominant pattern with variable expressivity. Thought to be related to a mutation in gene associated with fibroblast growth factor receptor 3 (FGFR3). Name relates to unusual clinical appearance and facial deformity which has been likened to appearance of cherubs.

42. Cherubism: Clinical Features Painless bilateral swellings of the jaws appear between ages 2-4 years. Swellings are usually symmetrical and always involve the mandible either alone or in combination with the maxilla. They enlarge rapidly up to age 7 years then become static and start to regress. Progressive reduction in deformity as the patient passes from puberty into adult life. Cosmetic surgery is often needed to deal with residual deformity.

43. Cherubism: Clinical Features Characteristic facial deformity is fullness of cheeks and jaws producing a typical chubby face. There is often a rim of sclera visible beneath the iris due to stretching of skin over swellings or upward displacement of orbit by maxillary lesions imparting the �eyes upturned to heaven� appearance. Reactive hyperplasia of submandibular lymph nodes adds to facial fullness. Dental abnormalities: premature loss of deciduous teeth and displacement, lack of eruption, and failure of development of many permanent teeth.

44. Cherubism: Radiographic Features Sharply defined, multilocular radiolucencies. Expansion and thinning of cortical plates, even perforation. Mandibular lesions appear to begin near the angle and spread to involve the body and ramus. Maxillary lesions are often confined to tuberosities, but sinus may be obliterated.

45. Cherubism: Histopathologic Features Cellular and vascular fibrous tissue containing varying amounts of multinucleated giant cells. The appearance is similar to other giant cell lesions of the jaws, and differentiation between them requires clinical and radiographic information. As the activity of the lesion decreases, it becomes more fibrous, giant cell number diminishes, metaplastic bone is deposited.