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The role of the condylar cartilage in mandibular growth. A study in thanatophoric dysplasia
The role of the condylar cartilage in mandibular growth. A study in thanatophoric dysplasia Rosario Berraquero, MD,* Josd Palaeios, MD, and Josd Ignacio Rodriguez, MD Madrid, Spain A new approach to evaluate the role of the condyle in mandibular growth could be its study in chondrodysplasias. The growth of the condylar cartilage and the mandible has not previously been reported in thanatophoric dysplasia (TD), a lethal osteochondrodysplasia. We have studied the light microscopic, histomorphometric, and radiologic findings in four infants affected by TD and in four control infants. The diagnosis was made on the basis of clinical, radiographic, and pathologic criteria. All the measured radiographic parameters of the patients' mandibles showed a normal longitudinal growth in TD, despite the severe disturbance of the condylar cartilages. The lesions in the chondroblastic cells and the extracellular matrix were similar to those observed in growth plate cartilages in TD. Marked membranous ossification spread from the cartilage canals of the condyles. The articular and prechondroblastic layers were histologically normal. Histomorphometry demonstrated that condylar cartilages were twice as thick as normal in TD, mainly because of the thickening by the chondroblastic layer. Present results support the hypothesis that condylar cartilage is a secondary growth site instead of being a primary growth center. (AM J ORTHODDENTOFAC ORTHOP 1992;102:220-6.)
T h e mandibular condyle is believed by some authors to be the main determinant to control the growth rate and the overall size of the mandible) This hypothesis is partially supported by the similar histologic appearance of the condylar cartilage and the epiphyseal growth plate cartilage, which is the pacemaker for long bone growth. However, other authors consider that condylar cartilage only provides regional adaptive growth, 2 3 which helps to maintain the proper anatomic relationship between the condylar region and the temporal bone, as the whole mandible is simultaneously being carried downward and forward. An intermediate point of view considers that the mandibular condylar cartilage serves as an important growth center for the developing mandible during the fetal and the early postnatal stages, but when functional activity increases, it functions as an articular cartilage. 4,5 The study of this structure in chondrodysplasias could be a new approach to evaluate the role of the condyle in mandibular growth. In these conditions, a severe disturbance of enchondral ossification at the growth plate produces a severe shortness of the long bones: If condylar cartilage structure and function in the mandible were similar to those in the long bone
growth plate, condylar lesions would be expected in chondrodysplasias. Therefore, if condylar cartilage plays an important role in mandibular growth, micro~ gnathia should occur in these disorders. Thanatophoric dysplasia (TD) is the most common, lethal neonatal chondrodysplasia in human beings: The clinical and radiographic manifestations of this disorder have been well establishedY The appearance at birth is characteristic and includes striking micromelia in association with a large head and a narrow thorax. The radiographic findings are diagnostic and include platyspondylisis, small iliac wing, diaphyseal bending, and flaring of the metaphyses of long bones. Histologically, the normal architecture of the growth plate is replaced-by a band of fibrous tissue, and the chondrocytes do not appear to proliferate or differentiate into hypertrophic cells: To the best of our knowledge, no prior histologic study has been reported of the mandibular condyle in TD. The aim of this study is to report the histologic changes of the condylar cartilage found in four newborns with TD. In addition, radiographic measurements of mandibles have been performed to evaluate the role of the condylar cartilage in mandibular growth. MATERIAL AND METHODS
Supported by the Fondo de InvestigacionesSanitarias de la Seguridad Social of Spain. From the Department of Pathology, La Paz Hospital, Madrid, Spain. *In private orthodontic practice. 8/1/30016
220
Diagnosis of TD in two male newboms and two female newborns of 36 to 38 weeks gestational age, who died in the first hour of life, was made according to clinical (Fig. 1), radiographic (Fig. 2), and histologic (Figs. 3 and 4) criteria.
Voh,me 102 Number 3
Condyle and mandible in thanatophoric dysplasia 221
Fig. 2. Lateral View of skull with shortening at its base.
Table I. Mandibular parameters in thanatophoric dysplasia (TD) Parameter (mm)
CO-ME CO-GO Ramus length GO-ME Gonial angle
TD (n = 4)
43.7 15.1 18.1 32.1 147.1
• • •
4.1 2.8 2.8 3.5 18.8
Control (n = 4)
44.9 17.5 18.3 30.3 145.7
• 3.8 ---2.4 - 3.2 --- 3.1 _ 18.8
co, Condylion; GO, gonion; AIE. menton. Fig. 1. Typical clinical features of thanatophoric dysplasia in patien.t no. 1. Note severe shortness of the limbs, narrow thorax, and large cranium with bulging forehead and prominent eyes.
At autopsy, the mandibles were obtained, and lateral x-ray films of each hemimandible were taken in a x-ray system (43805 N, Faxitron series, Hewlett-Packard, Oregon), with radiographic mammography film (Mammoray RP3, Agfa-Gevaert, Belgium). Quantitative measurements included total mandibular length (condylion-menton), ramus length (measured from condylion to the most mesial point of the first permanent molar), condylion-gonion length, corpus length (gonion-mention), and gonial angle (Fig. 5). Mandibular condyles were removed, sectioned sagittally, and fixed in buffered 10% formalin. After decalcification in 7% nitric acid, they were embedded in paraffin and sectioned at 6 p.m. The sections were stained with hematoxylin and eosin and Masson's trichrome. An IBAS 1 image analyzer (Kontron, Germany) was used to perform the histomorphometric study of the condylar cartilage. Measured parameters included the total thickness of the condylar cartilage and the thickness of the articular, prechondroblastic, and chondroblastic layers. Mandibles from four newborns of 36 to 38 weeks gestation, who had died from conditions other than malforma-
tions, were used as controls for the radiographic, histologic, and histomorphometrie studies.
RESULTS Radiology Thanatophoric and control mandibles showed a similar radiologic picture (Figs. 5 and 6). The radiographic measurements were also similar in both groups (Table I).
Histology Control group. The mandibular condyle o f control infants showed three distinctive tissue layers (Fig. 7): the articular layer, the proliferative or prechondroblastic layer, and the chondroblastic layer. The most superficial zone o f the condylar cartilage was the articular layer. This layer, which is continuous with the periosteum, was constituted by a connective tissue consisting mainly o f collagen bundles with a few fibroblasts. The proliferative layer was densely populated with undifferentiated mesenchymal cells surrounded by a small amount o f intercellular matrix. The chondroblastic layer had two distinctive levels, the most superficial one was com-
222
Am. J. Orthod. Dentofac. Orthop.
Berraquero, Palacios, and Rodriguez
September 1992
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posed by larger and more rounded chondrocytes than the cells in the adjacent upper layer of proliferation. The area of cell hypertrophy was the deep part of the chondroblastic layer and was composed of hypertrophic and haphazardly arranged chondrocytes surrounded by a small amount of extracellular matrix; the extracellular matrix was calcified, and the deepest part was invaded and eroded by capillaries and chondroclasts:'Theerosion line appeared parallel to the articular surface. The underlying cancellous bone was composed of short and
thin anastomosing trabeculae with a cartilaginous core. In some sections, the condylar cartilage appeared to be crossed perpendicularly by some vascular canals that connected with the erosion line. Direct or membranous ossification from the connective tissue that surrounded these vascular canals was usually seen (Fig. 8). P a t i e n t g r o u p . Histologically, the articular and the proliferative layers were normal (Fig. 9). However, the chondrocytes from the chondroblastic layer did not follow the normal process of cell differentiation and were
Condyle and mandible in thanatophoric dysp/asia 223
Volume 102 Number 3
Fig. 5. Lateral view of hemimandible from control infant illustrating points used for morphometric measurements. CO, condylion; GO, gonion; ME, menton. Open arrow indicates the most mesial point of the first permanent molar.
Fig. 6. Lateral view of hemimandible form patient no. 3.
smaller than those of the control group. Hypertrophic chondrocytes were absent and only a few cells underwent a partial maturation. There was an increase of intercellular matrix that had a marked fibrous appearance. The erosion line was very irregular (Fig. 10). Because there were no hypertrophic chondrocytes and the extracellular matrix was abnormal, capillary invasion and bone trabeculae formation were defective (Fig. 11). There seemed to be a large number of vascular canals crossing the condylar cartilage perpendicularly. Bone trabeculae were directly formed from these canals. The characteristic fibrous bands that replaced the growth plate in the long bones in TD were not observed in any of the condyles studied.
Histometry The results of the morphometric analysis of the condylar cartilage are shown in Table II. Condylar carti-
lage was thicker in TD than in control cases, mainly because of an increase of the chondroblastic layer thickness.
DISCUSSION The question of whether the condylar cartilage possesses a growth potential like that of the growth plate of the long bones has been the subject of contrasting viewpoints and much experimentation. According to some authors, ~ the condyle may be considered as the growth center that controls the overall length of the mandible and is not subjected to environmental factors. However, different clinical 9"~~ and experimental studies tH3 have demonstrated that the rate of condylar growth is modulated by extrinsic biomechanical influences. Moreover, it has also been demonstrated that the mandible can grow despite a condylar lesion, once normal muscular function is established? a't5 It has been
224
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Am. J. Orthod. Dentofac. Orthop. September 1992
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Fig. 7. Photomicrograph of condylar cartilage from control infant. Note the well-developed structure with the articular, prechondroblastic, and chondroblastic layer. Enchondral ossification takes place normally at the bottom.
Fig. 8. Condylar cartilage from control infant showing prominent vascular canals that cross cartilage perpendicularly 9 Note the membranous ossification (arrows).
Fig. 9. Photomicrograph of condylar cartilage from patient no. 4. Abnormal maturation and hypertrophy in the chondroblastic layer when compared with controls (Fig. 8).
suggested that mandibular condylar cartilage functions mainly as a growth cartilage during the fetal and the neonatal stages, when orofacial muscular structure and function are not completely developed, and when functional activity by the temporomandibular joint is scarce. Increase of the articular function is accompanied by a decrease of the growth activity of the condylar cartilage, which functions more as an articular cartilage. 4"5 Condylar cartilage differs in origin and histologic organization from the growth plate of the long bones. The condylar cartilage is a secondary or embryonic type of cartilage that develops from connective tissue to provide lower jaw articulation. 2J6 Whereas proliferating and hypertrophic chondrocytes in the growth plate differentiate from resting chondrocytes, condylar chondroblasts arise from undifferentiated connective cells (prechondroblast cells)) m7 Moreover, these chondroblasts are not aligned in those well-formed columns that characterizes growth plate.~6 The condyle also lacks the perichondrial ring, the supportive system of the growth plate. '8 Another histologic difference is the existence in the condyle of vascular canals that perpendicularly cross the cartilage, connect with the erosion line, '9"2~ and ossify directly by a membranous ossification process. As a consequence of the different histologic organization of the two structures, the condyle also differs
Vol,me 102 9 Number
Condyle and mandible i~, thanatophoric d)'splasia
225
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somewhat from the growth plate in its response to injuries. The different response of both cartilages to nutritional, hormonal, and metabolic factors has been well established; ~6however, despite the many studies on the growth plate cartilage in chondrodysplasias, little is known about the changes in condylar cartilage in these disorders. Johnson2m2 has reported that similar alterations have been found in chondrocytes of the condylar and rib growth plate cartilages in achondroblastic mice carrying the stumpy (stm) gene and in mice carrying the spondylometaphyseal chondrodysplasia (smc) gene. The present study has demonstrated that in TD there is a defective differentiation and maturation of the condylar chondrocytes that are similar to those observed
Table II. Histomorphometry of condylar cartilage in thanatophoric dysplasia (TD)
Condylar cartilage (I-on) Total thickness Articular layer Prechondroblastic Chondroblastic
I
TD (n = 4) 1908.2 185.5 63.7 1653.3
• • • •
278.4 57.1 7.1 205.3
I
Control (n = 4) 894.6 89.7 66.8 689.4
• 250.4 • 42.5 - 13.2 • 135.9
in the growth plate; 6'8 however, the bands of abnormal fibrous or mesenchyme-like tissue which disrupt the growth plate of the long bones in TD 2~ were absent from the condylar cartilage. This is probably due to the
226
Berraquero, Palacios, and Rodriguez
fact that this fibrous tissue arises from the perichondrial ring zone of the growth plate, s a structure that is not present in the condyle. Moreover, the membranous ossification that normally occurs around the condylar vascular canals seems to be increased in TD, probably as a compensetory mechanism for the decreased enchondral ossification in the condylar cartilage. Present histomorphometric results indicate that the condylar cartilage in TD is twice as thick as in controls. This increase in the thickness of the condylar cartilage is mainly due to the increase in the chondroblastic layer. The prechondroblastic layer had a normal histologic appearance, and its thickness did not differ from controis, indicating that cellular proliferation in this layer was unaffected in TD. However, because chondroblasts did not differentiate into hypertrophic chondrocytes and because there was an abnormal extracellular matrix, resorption of the chondroblastic layer was not normal, the formation of trabeculae was decreased, and, consequently, the chondroblastic layer was thicker. Long bone shortness secondary to defective endochondral ossification is a constant finding in TD. However, although the diagnosis seems to be on the basis of subjective criteria, micrognathia has been only occasionally diagnosed in TD. 24 We were unable to demonstrate a reduction in any of the longitudinal radiographic parameters measured in the mandible, including overall size, ramus length, CO-GO distance, and corpus length, as compared with those obtained in an agematched control group. Since TD is a lethal disorder, it is not possible to determine what postnatal mandibular growth potential exists in this condition. However, the coexistence of severe histologic and histomorphometric condylar lesions and a normal longitudinal growth of the mandible suggest that the condyle is not the main determinant to control the mandibular growth rate in the prenatal period. Hence, although the study was based on a small sample, the present results support the widely extended theory that the condylar cartilage is a secondary growth site rather than a primary growth center.
Am. J. Orthod. Dentofac. Orthop. September 1992
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REFERENCES 1. Mill JRE. A clinician looks at facial growth. Br J Orthod 1983;10:58-72. 2. Enlow DH. Facial growth. Philadelphia: WB Saunders, i 990:149-63. 3. Moss ML, Salentijn L. The capsular matrix. A.~t J ORTHOD 1969;56:474-90. 4. Livne E, Oliver C, Leapman RD, Rosenberg LC, Poole AR, Silbermann M. Age-related changes in the role of matrix vesicles in the mandibular condylar cartilage. J Anat 1987;150:6174. 5. Copray JCVM, Dibbets JMtt, Kantomaa T. The role of condylar cartilage in the development of the temporomandibular joint. Angle Orthod 1988;369-80. 6. Gilbert EF, Yang SS, Langer L, Opitz JM, Roskamp JO, Heil-
23.
24.
delberger KP. Pathologic changes of osteochondrodysplasias in infancy. Pathol Annu 1987;22:283-345. Maroteaux P, Lamy M, Robert J. Le nanisme thanatophore. PresseI Med 1967;75:2519-24. Stanescu V, Stanescu R, Maroteaux P. Etude morphologique et biochimique du cartilage de croissance dans les osteochondrodysplasies. Arch Fr Pt~diatr 1977;34(Supp 3):1-80. gloss ML, Rankow RM. The role of the functional matrix in mandibular growth. Angle Orthod 1968;38:95-103. Graber LW. The alterability of mandibular growth. In: McNamara JA Jr, ed. Determinants of mandibular form and growth. Mon~raph 4, Craniofacial Growth Series. Ann Arbor: Center of Human Growth and Development, University of Michigan, 1975:229-41. Petrovie AG, Stutzmann JJ, Oudet C. Control processes in the postnatal growth of the condylar cartilage of the mandible. In: McNamara JA Jr, ed. Determinants of mandibular form and growth. Monograph 4, Craniofacial Growth Series. Ann Arbor: Center of tluman Growth and Development, University of Michigan, 1975:101-53. McNamara JA Jr, Connelly TG, McBride MC. In: McNamara JA Jr, ed. Determinants of mandibular form and growth. Monograph 4, Craniofacial Growth Series. Ann Arbor: Center of ttuman Growth and Development, University of Michigan, 1975:209-27. Copray JCVM, Jansen tlWB, Duterloo HS. Growth and growth pressure of mandibular condylar and some primary cartilages of the rat in vitro. AM J OR'I'tIODDENTOFACORTttOP 1986;90:1928. Land K. Mandibular growth and remodelling processes after mandibular fractures. Acta Odontol Scand 1974;32(Supp 64). Melsen B, Bjerregard J, Bundgaard M. The effect of treatment with functional appliance on a pathol~ic growth pattern of the condyle. A.~IJ ORTttODDEN'I'OFACOR'l-HOP 1986;90:503-12. Durkin JF. Secondary cartilage: A misnomer? As! J OR'DtOD 1972;62:15-41. Livne E, Oliver C, Silbermann M. Further characterization of the chondroprogenitor zone in mandibular condyles of sickling mice. Acta Anat 1987;129:231-7. Shapiro F, Holtrop ME, Glimcher MJ. Organization and cellular biol~y of the perichondrial ossification groove of Ranvier. J Bone Joint Surg 1977;59A:703-23. Blackwood tlJJ. Vascularization of the condylar cartilage of the human mandible. J Anat 1965;99:551-63. Takenoshita Y. Development with age of the human mandibular condyle: histol~ical study. J Craniomandibular Pract 1987;5:317-23. Johnson DR. Abnormal cartilage from the mandibular condyle of stumpy (stm) mutant mice. J Anat 1983;137:715-28. Johnson DR. The ultrastructure of mandibular condylar and rib cartilage from mice carrying the spondylo-metaphyseal chondrodysplasia (smc) gene. J Anat 1984;138:463-70. Omoy A, Adomian GE, Eteson DJ, Burgeson RE, Rimoin DL. The role of mesenchyme-like tissue in the path~enesis of thanatophoric dysplasia. Am J Med Genet 1985;21:613-30. Elejalde BR, Elejalde MM. Thanatophoric dysplasia: fetal manifestations and prenatal diagnosis. Am J Med Genet 1985;22:66983.
Reprint requests to: Dr. Jos6 Ignacio Roddguez Departamento de Anatomfa Patolrgica Hospital La Paz Paseo Castellana 261 E-28046 Madrid, Spain
T h e mandibular condyle is believed by some authors to be the main determinant to control the growth rate and the overall size of the mandible) This hypothesis is partially supported by the similar histologic appearance of the condylar cartilage and the epiphyseal growth plate cartilage, which is the pacemaker for long bone growth. However, other authors consider that condylar cartilage only provides regional adaptive growth, 2 3 which helps to maintain the proper anatomic relationship between the condylar region and the temporal bone, as the whole mandible is simultaneously being carried downward and forward. An intermediate point of view considers that the mandibular condylar cartilage serves as an important growth center for the developing mandible during the fetal and the early postnatal stages, but when functional activity increases, it functions as an articular cartilage. 4,5 The study of this structure in chondrodysplasias could be a new approach to evaluate the role of the condyle in mandibular growth. In these conditions, a severe disturbance of enchondral ossification at the growth plate produces a severe shortness of the long bones: If condylar cartilage structure and function in the mandible were similar to those in the long bone
growth plate, condylar lesions would be expected in chondrodysplasias. Therefore, if condylar cartilage plays an important role in mandibular growth, micro~ gnathia should occur in these disorders. Thanatophoric dysplasia (TD) is the most common, lethal neonatal chondrodysplasia in human beings: The clinical and radiographic manifestations of this disorder have been well establishedY The appearance at birth is characteristic and includes striking micromelia in association with a large head and a narrow thorax. The radiographic findings are diagnostic and include platyspondylisis, small iliac wing, diaphyseal bending, and flaring of the metaphyses of long bones. Histologically, the normal architecture of the growth plate is replaced-by a band of fibrous tissue, and the chondrocytes do not appear to proliferate or differentiate into hypertrophic cells: To the best of our knowledge, no prior histologic study has been reported of the mandibular condyle in TD. The aim of this study is to report the histologic changes of the condylar cartilage found in four newborns with TD. In addition, radiographic measurements of mandibles have been performed to evaluate the role of the condylar cartilage in mandibular growth. MATERIAL AND METHODS
Supported by the Fondo de InvestigacionesSanitarias de la Seguridad Social of Spain. From the Department of Pathology, La Paz Hospital, Madrid, Spain. *In private orthodontic practice. 8/1/30016
220
Diagnosis of TD in two male newboms and two female newborns of 36 to 38 weeks gestational age, who died in the first hour of life, was made according to clinical (Fig. 1), radiographic (Fig. 2), and histologic (Figs. 3 and 4) criteria.
Voh,me 102 Number 3
Condyle and mandible in thanatophoric dysplasia 221
Fig. 2. Lateral View of skull with shortening at its base.
Table I. Mandibular parameters in thanatophoric dysplasia (TD) Parameter (mm)
CO-ME CO-GO Ramus length GO-ME Gonial angle
TD (n = 4)
43.7 15.1 18.1 32.1 147.1
• • •
4.1 2.8 2.8 3.5 18.8
Control (n = 4)
44.9 17.5 18.3 30.3 145.7
• 3.8 ---2.4 - 3.2 --- 3.1 _ 18.8
co, Condylion; GO, gonion; AIE. menton. Fig. 1. Typical clinical features of thanatophoric dysplasia in patien.t no. 1. Note severe shortness of the limbs, narrow thorax, and large cranium with bulging forehead and prominent eyes.
At autopsy, the mandibles were obtained, and lateral x-ray films of each hemimandible were taken in a x-ray system (43805 N, Faxitron series, Hewlett-Packard, Oregon), with radiographic mammography film (Mammoray RP3, Agfa-Gevaert, Belgium). Quantitative measurements included total mandibular length (condylion-menton), ramus length (measured from condylion to the most mesial point of the first permanent molar), condylion-gonion length, corpus length (gonion-mention), and gonial angle (Fig. 5). Mandibular condyles were removed, sectioned sagittally, and fixed in buffered 10% formalin. After decalcification in 7% nitric acid, they were embedded in paraffin and sectioned at 6 p.m. The sections were stained with hematoxylin and eosin and Masson's trichrome. An IBAS 1 image analyzer (Kontron, Germany) was used to perform the histomorphometric study of the condylar cartilage. Measured parameters included the total thickness of the condylar cartilage and the thickness of the articular, prechondroblastic, and chondroblastic layers. Mandibles from four newborns of 36 to 38 weeks gestation, who had died from conditions other than malforma-
tions, were used as controls for the radiographic, histologic, and histomorphometrie studies.
RESULTS Radiology Thanatophoric and control mandibles showed a similar radiologic picture (Figs. 5 and 6). The radiographic measurements were also similar in both groups (Table I).
Histology Control group. The mandibular condyle o f control infants showed three distinctive tissue layers (Fig. 7): the articular layer, the proliferative or prechondroblastic layer, and the chondroblastic layer. The most superficial zone o f the condylar cartilage was the articular layer. This layer, which is continuous with the periosteum, was constituted by a connective tissue consisting mainly o f collagen bundles with a few fibroblasts. The proliferative layer was densely populated with undifferentiated mesenchymal cells surrounded by a small amount o f intercellular matrix. The chondroblastic layer had two distinctive levels, the most superficial one was com-
222
Am. J. Orthod. Dentofac. Orthop.
Berraquero, Palacios, and Rodriguez
September 1992
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Fig. 3. Photomicrograph of tibial epiphyseal cartilage (upper right) and metaphyseal bone trabeculae (bottom left) from patient no. 2. Arrows show the typical fibrous tissue band interposed between cartilage and bone, occupying the growth plate site.
~-~'-f ~:----'"~ ' ~ ::'- - ~:.'; =-... ~. "z " . , ' : : " " : . , . " " ; ,.'.:~ .", ...,: --.'-",:,: ~-" ".',
Fig. 4. Tibial growth plate from patient no. 2 showing few and disorganized proliferative and hypertrophic chondrocytes. Asteris k marks an enlarged cartilage canal with membranous ossification crossing the growth plate.
posed by larger and more rounded chondrocytes than the cells in the adjacent upper layer of proliferation. The area of cell hypertrophy was the deep part of the chondroblastic layer and was composed of hypertrophic and haphazardly arranged chondrocytes surrounded by a small amount of extracellular matrix; the extracellular matrix was calcified, and the deepest part was invaded and eroded by capillaries and chondroclasts:'Theerosion line appeared parallel to the articular surface. The underlying cancellous bone was composed of short and
thin anastomosing trabeculae with a cartilaginous core. In some sections, the condylar cartilage appeared to be crossed perpendicularly by some vascular canals that connected with the erosion line. Direct or membranous ossification from the connective tissue that surrounded these vascular canals was usually seen (Fig. 8). P a t i e n t g r o u p . Histologically, the articular and the proliferative layers were normal (Fig. 9). However, the chondrocytes from the chondroblastic layer did not follow the normal process of cell differentiation and were
Condyle and mandible in thanatophoric dysp/asia 223
Volume 102 Number 3
Fig. 5. Lateral view of hemimandible from control infant illustrating points used for morphometric measurements. CO, condylion; GO, gonion; ME, menton. Open arrow indicates the most mesial point of the first permanent molar.
Fig. 6. Lateral view of hemimandible form patient no. 3.
smaller than those of the control group. Hypertrophic chondrocytes were absent and only a few cells underwent a partial maturation. There was an increase of intercellular matrix that had a marked fibrous appearance. The erosion line was very irregular (Fig. 10). Because there were no hypertrophic chondrocytes and the extracellular matrix was abnormal, capillary invasion and bone trabeculae formation were defective (Fig. 11). There seemed to be a large number of vascular canals crossing the condylar cartilage perpendicularly. Bone trabeculae were directly formed from these canals. The characteristic fibrous bands that replaced the growth plate in the long bones in TD were not observed in any of the condyles studied.
Histometry The results of the morphometric analysis of the condylar cartilage are shown in Table II. Condylar carti-
lage was thicker in TD than in control cases, mainly because of an increase of the chondroblastic layer thickness.
DISCUSSION The question of whether the condylar cartilage possesses a growth potential like that of the growth plate of the long bones has been the subject of contrasting viewpoints and much experimentation. According to some authors, ~ the condyle may be considered as the growth center that controls the overall length of the mandible and is not subjected to environmental factors. However, different clinical 9"~~ and experimental studies tH3 have demonstrated that the rate of condylar growth is modulated by extrinsic biomechanical influences. Moreover, it has also been demonstrated that the mandible can grow despite a condylar lesion, once normal muscular function is established? a't5 It has been
224
Berraquero, Palacios, and Rodriguez
Am. J. Orthod. Dentofac. Orthop. September 1992
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Fig. 7. Photomicrograph of condylar cartilage from control infant. Note the well-developed structure with the articular, prechondroblastic, and chondroblastic layer. Enchondral ossification takes place normally at the bottom.
Fig. 8. Condylar cartilage from control infant showing prominent vascular canals that cross cartilage perpendicularly 9 Note the membranous ossification (arrows).
Fig. 9. Photomicrograph of condylar cartilage from patient no. 4. Abnormal maturation and hypertrophy in the chondroblastic layer when compared with controls (Fig. 8).
suggested that mandibular condylar cartilage functions mainly as a growth cartilage during the fetal and the neonatal stages, when orofacial muscular structure and function are not completely developed, and when functional activity by the temporomandibular joint is scarce. Increase of the articular function is accompanied by a decrease of the growth activity of the condylar cartilage, which functions more as an articular cartilage. 4"5 Condylar cartilage differs in origin and histologic organization from the growth plate of the long bones. The condylar cartilage is a secondary or embryonic type of cartilage that develops from connective tissue to provide lower jaw articulation. 2J6 Whereas proliferating and hypertrophic chondrocytes in the growth plate differentiate from resting chondrocytes, condylar chondroblasts arise from undifferentiated connective cells (prechondroblast cells)) m7 Moreover, these chondroblasts are not aligned in those well-formed columns that characterizes growth plate.~6 The condyle also lacks the perichondrial ring, the supportive system of the growth plate. '8 Another histologic difference is the existence in the condyle of vascular canals that perpendicularly cross the cartilage, connect with the erosion line, '9"2~ and ossify directly by a membranous ossification process. As a consequence of the different histologic organization of the two structures, the condyle also differs
Vol,me 102 9 Number
Condyle and mandible i~, thanatophoric d)'splasia
225
3
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Fig. 10. Absence of enchondral ossification from condylar cartilage in same patient. Bone trabecufae formation is related with vascular canals.
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Fig. 11, Higher magnification from Fig. 10. Abnormal chondroblastic cells and matdx in condylar cartilage.
somewhat from the growth plate in its response to injuries. The different response of both cartilages to nutritional, hormonal, and metabolic factors has been well established; ~6however, despite the many studies on the growth plate cartilage in chondrodysplasias, little is known about the changes in condylar cartilage in these disorders. Johnson2m2 has reported that similar alterations have been found in chondrocytes of the condylar and rib growth plate cartilages in achondroblastic mice carrying the stumpy (stm) gene and in mice carrying the spondylometaphyseal chondrodysplasia (smc) gene. The present study has demonstrated that in TD there is a defective differentiation and maturation of the condylar chondrocytes that are similar to those observed
Table II. Histomorphometry of condylar cartilage in thanatophoric dysplasia (TD)
Condylar cartilage (I-on) Total thickness Articular layer Prechondroblastic Chondroblastic
I
TD (n = 4) 1908.2 185.5 63.7 1653.3
• • • •
278.4 57.1 7.1 205.3
I
Control (n = 4) 894.6 89.7 66.8 689.4
• 250.4 • 42.5 - 13.2 • 135.9
in the growth plate; 6'8 however, the bands of abnormal fibrous or mesenchyme-like tissue which disrupt the growth plate of the long bones in TD 2~ were absent from the condylar cartilage. This is probably due to the
226
Berraquero, Palacios, and Rodriguez
fact that this fibrous tissue arises from the perichondrial ring zone of the growth plate, s a structure that is not present in the condyle. Moreover, the membranous ossification that normally occurs around the condylar vascular canals seems to be increased in TD, probably as a compensetory mechanism for the decreased enchondral ossification in the condylar cartilage. Present histomorphometric results indicate that the condylar cartilage in TD is twice as thick as in controls. This increase in the thickness of the condylar cartilage is mainly due to the increase in the chondroblastic layer. The prechondroblastic layer had a normal histologic appearance, and its thickness did not differ from controis, indicating that cellular proliferation in this layer was unaffected in TD. However, because chondroblasts did not differentiate into hypertrophic chondrocytes and because there was an abnormal extracellular matrix, resorption of the chondroblastic layer was not normal, the formation of trabeculae was decreased, and, consequently, the chondroblastic layer was thicker. Long bone shortness secondary to defective endochondral ossification is a constant finding in TD. However, although the diagnosis seems to be on the basis of subjective criteria, micrognathia has been only occasionally diagnosed in TD. 24 We were unable to demonstrate a reduction in any of the longitudinal radiographic parameters measured in the mandible, including overall size, ramus length, CO-GO distance, and corpus length, as compared with those obtained in an agematched control group. Since TD is a lethal disorder, it is not possible to determine what postnatal mandibular growth potential exists in this condition. However, the coexistence of severe histologic and histomorphometric condylar lesions and a normal longitudinal growth of the mandible suggest that the condyle is not the main determinant to control the mandibular growth rate in the prenatal period. Hence, although the study was based on a small sample, the present results support the widely extended theory that the condylar cartilage is a secondary growth site rather than a primary growth center.
Am. J. Orthod. Dentofac. Orthop. September 1992
7. 8.
9. 10.
i 1.
12.
13.
14. 15.
16. 17.
18.
19. 20.
21. 22.
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delberger KP. Pathologic changes of osteochondrodysplasias in infancy. Pathol Annu 1987;22:283-345. Maroteaux P, Lamy M, Robert J. Le nanisme thanatophore. PresseI Med 1967;75:2519-24. Stanescu V, Stanescu R, Maroteaux P. Etude morphologique et biochimique du cartilage de croissance dans les osteochondrodysplasies. Arch Fr Pt~diatr 1977;34(Supp 3):1-80. gloss ML, Rankow RM. The role of the functional matrix in mandibular growth. Angle Orthod 1968;38:95-103. Graber LW. The alterability of mandibular growth. In: McNamara JA Jr, ed. Determinants of mandibular form and growth. Mon~raph 4, Craniofacial Growth Series. Ann Arbor: Center of Human Growth and Development, University of Michigan, 1975:229-41. Petrovie AG, Stutzmann JJ, Oudet C. Control processes in the postnatal growth of the condylar cartilage of the mandible. In: McNamara JA Jr, ed. Determinants of mandibular form and growth. Monograph 4, Craniofacial Growth Series. Ann Arbor: Center of tluman Growth and Development, University of Michigan, 1975:101-53. McNamara JA Jr, Connelly TG, McBride MC. In: McNamara JA Jr, ed. Determinants of mandibular form and growth. Monograph 4, Craniofacial Growth Series. Ann Arbor: Center of ttuman Growth and Development, University of Michigan, 1975:209-27. Copray JCVM, Jansen tlWB, Duterloo HS. Growth and growth pressure of mandibular condylar and some primary cartilages of the rat in vitro. AM J OR'I'tIODDENTOFACORTttOP 1986;90:1928. Land K. Mandibular growth and remodelling processes after mandibular fractures. Acta Odontol Scand 1974;32(Supp 64). Melsen B, Bjerregard J, Bundgaard M. The effect of treatment with functional appliance on a pathol~ic growth pattern of the condyle. A.~IJ ORTttODDEN'I'OFACOR'l-HOP 1986;90:503-12. Durkin JF. Secondary cartilage: A misnomer? As! J OR'DtOD 1972;62:15-41. Livne E, Oliver C, Silbermann M. Further characterization of the chondroprogenitor zone in mandibular condyles of sickling mice. Acta Anat 1987;129:231-7. Shapiro F, Holtrop ME, Glimcher MJ. Organization and cellular biol~y of the perichondrial ossification groove of Ranvier. J Bone Joint Surg 1977;59A:703-23. Blackwood tlJJ. Vascularization of the condylar cartilage of the human mandible. J Anat 1965;99:551-63. Takenoshita Y. Development with age of the human mandibular condyle: histol~ical study. J Craniomandibular Pract 1987;5:317-23. Johnson DR. Abnormal cartilage from the mandibular condyle of stumpy (stm) mutant mice. J Anat 1983;137:715-28. Johnson DR. The ultrastructure of mandibular condylar and rib cartilage from mice carrying the spondylo-metaphyseal chondrodysplasia (smc) gene. J Anat 1984;138:463-70. Omoy A, Adomian GE, Eteson DJ, Burgeson RE, Rimoin DL. The role of mesenchyme-like tissue in the path~enesis of thanatophoric dysplasia. Am J Med Genet 1985;21:613-30. Elejalde BR, Elejalde MM. Thanatophoric dysplasia: fetal manifestations and prenatal diagnosis. Am J Med Genet 1985;22:66983.
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