Secondary cartilage: A misnomer?

James F. Durkin, D.D.S., MS.

Boston, Mass.

I t has been said that the intelligent practice of orthodontics has as one
of its basic requirements a knowledge and an awareness of the biologic basis for
diagnosis and therapy. Nowhere is this statement more true than in the treatment
and management of the developing skeletal orthodontic problem. It is with the
idea of applying some basic biologic information to such clinical problems that
the discussion of cartilage is undertaken.
Cartilage is a term readily associated with the process of skeletal growth and,
from the point of view of the orthodontist, brings to mind a type of tissue which,
in the growing child, is intimately involved with the development of craniofacial
abnormalities. The term secondary cartilage, although familiar to the ortho-
dontist, is probably less appreciated as a distinct type of tissue.
Does this special type of cartilage exist as a separate entity? If so, where do
we find it and what are its identifying characteristics? Does it differ from other
cartilages, such as that seen in the growth plate, and does it react differently
to growth demands”2 If so, how does it differ and how would these differences
affect our approach to the management of developing skeletal orthodontic prob-
lems? These are some of the questions that one might ask when a discussion of
secondary cartilages is undertaken, as well as those which the present discussion
is intended to answer.
The term secondary cartilage, as used in the literature, is a descriptive term
for those cartilage sites which do not fall into the same category as that of the
growth plate cartilage. The criteria by which a cartilaginous area is judged
secondary in nature appear to be based originally on the work by Schafferl and
DeBeer.? Both authors used the term to describe certain cartilages associated
with membranous bones which have no topographic connection with, and appear
later in development than, the primary cartilaginous skeleton. Since then, in
most works dealing with secondary cartilages the identification of this type of
cartilage has been based on this definition. With but a few exceptions, very little

This work was supported in part by Research Grant Nos. DE-1592 and DE-03061
from the National Institute for Dental Research, National Institutes of Health.
Winner of the 1971 Milo Hellman Award of the American Association of Orthodontists.

15
Figs. 1 to 4. For legend, see opposite page.
 Secondary cartilage 17

attempt has been made to further clarify the true nature of secondary cartilages,
and in spite of the contributions made since the work of Schaffer and DeBeer,
the term seco&ary cartilage still remains somewhat nebulous.
Since there is obviously a lack of correlated information about the basic char-
acter of this form of cartilage, it might prove beneficial to explore further the
nature of a known secondary cartilage, such as the mandibular condylar carti-
lage, at a morphohistologic level in the hope of putting forth additional criteria
by which to judge any cartilaginous site as being truly secondary in nature.
This report will not only describe the nature of condylar cartilage, as well as
additional sites which heretofore had not been mentioned or considered as
secondary cartilages, but it will also suggest a more accurate term to label these
types of cartilages.

Method and materials

The material used in this report incorporates data collected from four
separate investigations. In two of these, a histologic comparison and bone label-
ing techniques were used to observe changes during normal maturation in the
cartilages of the growth plate, epiphysis, and mandibular condyle in addition
to those in the cartilaginous anlage of the rat long bone. In two other studies,
a histologic comparison of the cartilages of the growth plate, epiphysis, and
mandibular condyle of both the guinea pig and the rat were made under the
conditions of ascorbic acid and vitamin D deficiencies, respectively. Both the
Von Kossa and the Gomori methods were used in these studies to demonstrate
sites of calcification. The three cartilaginous areas of the early analage, epiphy-
sis, and mandibular condyle are compared with each other as well as with the
growth plate, with the objective of using all the data collectively as a basis for
a better appreciation of the relationships between the growth and function of a
particular area and the type of cartilage found at that site. Although both the
guinea pig and the rat have been involved in these past investigations, and prob-
ably some small differences do exist between these species, I do not believe that
these differences are sufficient to negate the collective use of the information
from both species.

Fig. 1. The tibia1 anlage of a rat 151/z days in utero, stained with Von Kossa’s method for
calcification. Note arrangement of chondrocytes and circular calcification pattern. (Mag-
nification, Xl 0.) [Sections shown in this and subsequent illustrations were stained or
counterstained with hematoxylin and eosin.)
Fig. 2. A high-power view of the previous section of multinucleated chondroclasts eroding
the calcified bars of matrix (arrows) in the region of the eroding cartilage. [Magnification,
X40.)
Fig. 3. Section of the tibia of a rot 17 days in utero, stained by the Von Kossa method for
calcification. Note the scanty trabecular network beneath the cartilage as well as the
identical cellular arrangement and calcification pattern seen in Fig. 1. (Magnification, X10.)
Fig. 4. Section of the tibia of a rat 201/z days in utero, stained by the Von Kossa method
for calcification. Note the change in calcification pattern, cellular organization, and increase
in the amount of trabecular network. (Magnification, X10.)
18 Durkin

Histologic comparison of cartilage

Cartilaginous a&age. Despite t,he tremendous amount of material availahlc

on the development of cartilaginous anlage of Ion g bones, a proportionally small
amount has been devoted to the histologic events and character of cartilage cells
contained within these cartilaginous models. VW- little attention has heretofore
been given to the details of the cellular activities and t,he calcification pattern
involved with the initial and continued erosion of the calcified cartilage ma,tris
within the early anlage. The histologic appearance of the early cartilaginous
anlage reveals several noteworthy fea.turcs which are not usually given in the
standard textbook description of its tra.nsit.ion from a strict cartilage model to
a true replica of the long bone. The cellular organization of this early anlagr,
both prior to and just after the initial capillary invasion, exhibits a rather hap-
hazard arrangement of cells. The entire central third of the anlage is made up
of hypertrophic chondrocytes enclosed in t,hin capsules of matrix. The matrix
making up the individual chondrocytic capsules demonstrates a pericellular
pattern of mineralization that completely circumscribes the hypertrophic cells.
The entire hypertrophic zone rcreals this pattern of calcification (Fig. 1).
Coincident with the initial penetration of capillaries, there is an appearance
of multinucleated chondroclast,s (Fig. 2). These can be obselTTec1in the regions
of resorbing calcified matrix As the calcified matrix around the hypcrtrophic
chondrocytes is actively resorbed by the chondroclasts and capillary penetration
takes place, the embryonic marrow cavity is initiated by bhe coalescing of these
eroding capsules. At around 17 days in utero, the anlage of the fetal rat shows
a slight increase in width and length, but the cha,racter of the cartilage is still
embryonic, with its cells still arranged in the same haphazard fashion and
separated by a scanty amount of matrix with its circular pattern of mineraliza-
tion still present. The marrow cavity has enlarged, but there is very little endo-
chondral bone formation and trabecular network being formed at this stage of
development (Fig. 3). From this point on, the cartilage of the anlage begins
to change in character and the establishment of the growth plate begins. This
reorganization of the cartilage cells becomes apparent at around 18 to 20 days
in utero, as a definite change in t,he arrangement of the chondrocytcs and mine]*-
alization pattern can be seen (Fig. 4). The wlls now begin to organize into
columns, with thick bars of matrix separating one column from the nrst. AS-
sociated with this change in cellular arrangement is an alteration in the mincr-
alization pattern, which has changed from a pericellular one to one which has
become prominent along these vertical bars of matrix (Fig. 5).
Coincident with the change in the pattern of calcification is the evidence
that the zone of erosion, at the lower end of the columns of chondrocytes, has
become more organized, with capillary penetration t,akilrg place by eroding the
unmineralized horizontal portions of matrix between the mineralized vertical
partitions (Fig. 5). The increase in endochondral bone formation anil resulting
trabecular network is obvious at this stage (compare Figs. 3 and 4).
It is readily apparent that different forms of cartilage are present during
the two distinct phases of development of the long bone. The indications are
that the first phase ends when the character of the cartilage of the early anlage
 Secondary cartilage 19

Fig. 5. A high-power view of the growth plate of a postnatal guinea pig. Note the
calcification pattern as revealed by the Gomori stain. The vertical bars of matrix are
calcified, while the horizontal partitions of the chondrocytic capsules are uncalcified.
(Magnification, X40.)
Fig. 6. Section of the tibia1 articular cartilage in a 20-day-old rat. Note the embryonic
characteristics, the presence of hypertrophic chondrocytes across the entire marrow surface,
and the minimal trabecular network. (Magnification, Xl 0.)

changes and the establishment of the growth plate begins. This distinction has
also been made in a recent histochemical study of the developing tibia1 anlage
by Heeley, Durkin, and Irving.3
During the initial phase of development, the cartilage is embedded in an
environment of developing mesenchymal tissue, and its growth response to this
changing environment is one of an increase in both width and length. It is logical
to assume that at this stage the growth in length probably occurs at a much more
reduced rate than that seen after the establishment of the growth plate, and this
20 Durkin

seems to suggest that the two distinct phases of development take place in t,WcJ
different environments, involving two distinct types of cartilage.
Ha11,4 as well as Riinning, Paunio, and Noski,” has stressed that secondary
cartilage appears to be more involved with mineralization and less wit,h endo-
chrondral bone formation. This certainly seems to be the case with the early
developmental phase of the cartilaginous anlage. It is only after the initial for-
mation of the growth plate that this emphasis begins t.o change. Since that form
of cartilage seen in the early anlage, prior to the est~ablishment of the growth
plate, is the first to appear in development, it truly can be classified as embryonic
in character (see diagram in Fig. 26). In view of the morphohistologic features,
calcification pattern, and mechanism of erosion just demonstrated in this embry-
onic form of cartilage, it is probable t,hat during its early phase of tlevelopmellt,
the anlage is capable only of adaptive changes dictated in part by the surround-
ing muscular blastema.
Epiphyseal and articulclr cartilage. Recently, attempts hare been made to
separate the anatomic and functional identity of the epiphysis and its cartilage
by using the term growth plate for the commonly referred to epiphyseal plate.
The term epiphyseal is reserved for that cartilage contained within the epiphy-
sis, while the term growth plate clarifies the anatomy and function of the growth
plate, which has very little to do with the epiphysis. McKibbin and Holdsworth’
have attempted to separate the two cartilaginous sites by putting forth the
hypothesis that articular and growth plate cartilages are fundamentally differ-
ent on the basis of their embryologic derivation and ultrastructure. Duterloo7
has pointed out that the articular surfaces in vitro are capable of developing even
in the absence of adjacent structures. It has also been noted that the epiphyses
of the limb bones can develop independently from the shaft and that the normal
ossification of the epiphysis is not conditioned by the normal development of the
diaphysis.
On the basis of this evidence, the term epiphyyseal cartilage is used here to
refer to that cartilage which is located in the proximal epiphyseal head above
the growth plate of the tibia. Articulnr cartilage is used to denote that epiphyseal
cartilage found lining the articular surfaces after the initial marrow cavity for-
mation.
The cartilage within the epiphysis varies considerably with age and does not
have a single histologic appearance when viewed over its entire span of matura-
tion. In the developing epiphysis just prior to initial erosion, as one would ex-
pect, the similarity between t,his cartilage and that just described for the early
anlage is quite obvious. In the central zone the chondrocytes of the epiphyseal
cartilage have undergone hypertrophy and are arranged in a haphazard fashion,
while the thin capsules of matrix surrounding the hypertrophic cells are calcified
pericellularly. Multinucleated chondroclasts can be observed as erosion takes
place in the areas of the resorbing calcified matrix, thus initiating the formation
of the marrow cavity in the epiphysis.
This embryonic character persists even after the marrow cavity of the
epiphysis is fully formed and only a hemispherical area of immature articular
cartilage remains (Fig. 6). The haphazardly arranged cells of the entire mar-
 Secodary cartilage 21

Fig. 7. Section of the tibia1 articular cartilage in a 19-day-old rat stained for calcification
by the Von Kossa method. Note the circular pattern of calcification and the small amount
of trabecular network. (Magnification, Xl 0.)
Fig. 8. A high-power view of the articular cartilage at a site of chondroclastic erosion at the
face of the cartilage (arrows) in a 20-day-old rat. (Magnification, X40.)

row surface of this cartilage are in a state of hypertrophy and the sparse
amount of matrix surrounding these cells is calcified circumferentially (Fig. 7).
The calcified matrix around the lowest level of hypertrophic chondrocytes is
actively resorbed by chondroclasts (Fig. 8). Very little trabecular network can
be observed at this point, beneath the zone of erosion and within the marrow
cavity in general (Figs. 6 and 7).
The histologic appearance of this hypertrophic form of cartilage begins to
change in the middle superior portion of articular surface in the proximal
tibia1 epiphysis at around 35 days of age (Fig. 9). The cellular organization of
the articular cartilage in this area is noticeably different from the rest in that
the intermediate zone of cells now shows evidence of some polarity with the long
axis of these cells being perpendicular to the surface. The amount of matrix
surrounding the cells has definitely increased, and this is especially so in the lower
zone where the cells are rounded in shape and farther apart. The most prominent
22 Durkin

Fig. 9. Section of the tibia1 cartilage of a 35day-old rat. Note the sharp line of demarca-
tion between the hypertrophic and nonhypertrophic forms of cartilage. (Magnification, X10.)
Fig. 10. Section of the tibia1 articular cartilage of a 35-day-old rat. Note the difference in
calcification patterns as revealed by the Gomori stain. (Magnification, X10.)

feature of this new form of articular cartilage is the absence of the zone of hyper-
trophic cells. The lower border of t,his nonhypertrophic form of cartilage reveals
no cartilage erosion but, rather, merges directly with compact boric. The dif-
ference between these coexisting forms of articular cartilage present at this inter-
mediate stage of development is further illustratecl by their mineralization pat-
terns (Fig. 10).
In more fully mature animals, all the cartilage in the epiphysis is nonhypor-
trophic and bears very little resemblance to the hypertrophic form present in
the early stages of maturation (Fig. 11). As seen in the nonhypertrophic portion
at the intermediate stage, the cells are fewer and farther apart, with the matrix
being much more elaborate, and the lower noneroding border is a smoothly
scalloped area which is in direct contact with a broad margin of bone. The tra-
becular network within the epiphysis, beneath this type of articular cartilage,
is much more elaborate than that seen during the immature or hypertrophic
stage. The change in calcification pattern in this nonhypertrophic form of artic-
ular cartilage corresponds to the change in type of bone formation (Fig. 12).
It is evident that after the formation of the marrow cavity of the epiphysis
the articular cartilage continues to maintain its embryonic cellular arrange-
ment and calcification pattern (see diagram in Fig. 26). Even the mechanism
of erosion is reminiscent of the embryonic type seen in the pregrowth plate phase
 Secondary cartilage 23

Fig. 11. Section of the tibia1 articular cartilage of a 55-day-old rat. Note the absence of :a
hw xtro bphic zone as well as the appearance of the bone beneath the cartilage. [Ma ‘9-
nificc 3tiol 7, X10.)
Fig. 12. Section of the tibia1 articular cartilage of a 55day-old rat. Note the change in
ca Ici ficai iion pattern as revealed by the Gomori stain [see Fig. 7). (Magnification, Xl’ 0.1
Fig. 13. Section of the condyle of a 20-day-old guinea pig. Note arrangement of the ce ‘IIS
and the trabecular network. (Magnification, X10.)
 of development in the cartilaginous anlagt. This embryonic charactor has }NY~~I
referred to by other workers8 and is maintained up to the age when the trans-
formation from hypertrophic to t,he nonhyprrtrophic form of cartilage is ~lll-
plete.
It appears, then, that the epiphysis can be considered distinct in it,s anatom!,,
embryology, and function from the rest of the long bonej and its articular carti-
lage varies considerably from the growth plate cartilage from both a morpho-
logic and a histologic point of view. The histologic events and changes leading
to full maturation of the articular cartilage seems to be the key to the functional
role that it plays at any particular time. On this basis, it appears that the growth
of the immature hypertrophic form of articular cartilage occurs in an adapt,i\-(1
manner throughout the entire epiphysis and appears to be merely enough to as-
sure the proper modeling of the extremities of the bone. In view of the presort
evidence, it is thought that, up to the stage when the nonhypertrophic form ot
caartilage first appears, the adaptive remodeling process in the epiphysis is uni-
form throughout and therefore is made up entirely of the hypertrophic form of
cartilage. During the intermediate stage of development, when t,hc middle portion
of the cartilage changes to the nonhypertrophic form, adaptive remodeling
ceases in a superior direction and occurs only in a lateral direction, increasing
the width and altering the form of the epiphysis (see diagram in Fig. 17). When
the demand for adaptive remodeling ceases at these sites, all cartilages become
nonhypertrophic and its fun&ion is mainly articular and surface cell replace-
ment.
Condylar cartilage. The cartilage of the condyle has long been considered
to be to the mandible what the growth plate is to the long bones. This concept
still persists in the orthodontic literature, in spite of the fact that concepts
as to the role of the condyle in mandibular growth have recently undergone
changes. s-11Histologic examination of the condylar cartilage reveals an architec-
tural arrangement of the cells quite unlike that observed in the growth plates.l?-‘*
From the histologic sections of the early phase of development of t,he cartilagi-
nous anlage and the immature or hypertrophic form of articular cartilage, it is
quite clear, when one examines the cartilage of the mandibular condyle, that a
marked similarity in the histologic organization exists between all three sites.
The condylar cartilage also demonstrates chondrocytcs which are arranged in
a haphazard fashion and separated by a scanty amount of matrix (Fig. 13).
These thin partitions around the lower level of hypertrophic cells tlemonstrat,e
a pattern of mineralization identical to that seen in the previous cartilaginous
sites, in that the calcified partitions completely circumscribe the hypertrophic
chondrocytes (Fig. 14). Chondroclasts are seen in the active zone of erosion of
condylar cartilage, closely associated with the terminal ends of the penetrating
vessels. These cells can be observed eroding the mineralized matrix surrounding
the hypertrophic chondrocytes (E’ig. 15). The trabecnlar network beneath this
zone of erosion is not very extensive (Fiqs. 13 and 14). This embryonic cellular
organization, pattern of calcification, an6 mechanism of erosion persist even dur-
ing later stages of development of the cotidyle until sometime between the ages of
200 and 250 days in the rat, when the character of the condylar cartilage begins
Fig. 14. Section of the condylar cartilage of a 20-day-old guinea pig stair led by Go n 7ori’s
method for calcification. Note the pattern of calcification, the cellular OI ‘gar iizatior and
the scanty amount of trabecular network. (Magnification, Xl 0.)
Fig. 15. A high-power view of the chondroclasts (arrows) at the face of the er )ding
condylar cartilage. (Magnification, X40.)
Fig. 16. Section of the nonhypertrophic form of condylar cartilage of a rc rt a pproxil rr lately
150 days old. Note the dramatic increase in bone formation beneath the car tilage. Mag-
nification, Xl 0.)
to change from hypertrophic to nonhypertrophic simultaneously across its entire
width. By about 250 days the entire width ol’ the cartilage takes on an appear-
ance very similar to that seen in the nonhypc~rtrophic type of articular cartilngt:
(Fig. 16). The lower border of this form of cartilage also shows the absence of a
hypertrophic zone as well as a, lack of active resorption. Just as was the case in
the nonhypertrophic form of articular cartilage, the lower border merges directly
with the compact zone of the trabecular network, which is now much more es-
tensive than that seen in the early stages of devclopmcnt. In some areas the tra-
beculae are so wide that they occupy a large portion of the marrow cavity.
(Compare Fig. 16 with Figs. 13 and 14.)
Once again, then, the histologic evidence points to the fact that the irnmatur~~
or hypertrophic form of cartilage in the condyle also displays the embryonic
character described in the previous two sites (Fig. 26). The cells of all three 01
these sites, during their immature stage, are arranged in a more or less haphaz-
ard fashion and not in a vertical pattern, such as is seen in the growth plate
cartilage. The thin partitions around the cells in t,he embryonic types of cartilage
are calcified pericellularly, while calcification in the growth plate takes place
only on the thick vertical partition between the columns of cells (Fig. 26). In
the condylar as well as the articular cartilages, where all partitions at the ero-
sion front are calcified, the initial factor in erosion is the chondroclast. This also
appears to be the cast in the early cartilaginous anlage. In the growth plates,
the uncalcified horizontal partitions are the avenues of erosion by the penetrating
capillariesl”s I32I5 This capillary erosion of the unmineralized partitions in the
growth plates is by far the more rapid of the two means of erosion just described
and, by the very nature of the growth occurring in the growth plate areas, is
the type necessary to keep pace with the rate of proliferation taking place there.
By the same t,oken, the chondroclastic resorption of the calcified matrix taking
place in the condyle is the type necessary to accommodate the slow adaptive type
of changes occurring in this area. This probably holds true for the cartilages of
the early anlage and epiphpsis as well. Therefore, in view of these basic differ-
ences between the embryonic types of cartilage and the primary type of cartilage
in the growth plate, it becomes apparent that the needs, dictated by the growth
changes taking place in these respective areas are inherent in their basic histol-
ogy. That is, the basic morphologic arrangement of the chondrocytes, the manner
of calcification, and the resulting mechanisms of erosion, all point to the different
types of growth response occurring at each sit,e.
The changes brought on by the process of maturation in the mandibular con-
dyle strongly suggest that a transformation similar to that seen in the epiphysis
takes place in the cartilage of the condyle as well. 14-16The only difference is that
because the transformation from the hypertrophic to the nonhypertrophic form
of cartilage takes place gradually and simultaneously across its entire width,
the condyle does not pass t,hrough an intermediate stage of development as seen
in the epiphysis where both forms of cartilage exist at the same time (Fig. 17).
Although the transformation from the hypertrophic to the nonhypertrophic
form of cartilage takes place sooner in the region of the epiphysis than in the area
 Xecondar?y cartilage 27

Fig. 17. A diagram comparing the stages of development and the direction of adaptive
remodeling in the epiphysis and the condyle. There is no intermediate stage of develop-
ment in the condyle.

of the mandibular condyle, the changes leading to the complete transformation

correspond at both sites to the changes in the location and type of bone formation
occurring beneath the cartilages. This observation has been substantiated with
autoradiographic studies utilizing tritiated proline to observe and correlate
these changes in the condyle and epiphysis during maturation.14 Indirectly, then,
it appears that this conversion from hypertrophic to nonhypertrophic cartilage
takes place in both regions when the demands for the adaptive remodeling pro-
cess characteristic of these cartilages ceases. Therefore, while we can conclude
that the condylar and articular cartilages are truly comparable, there are some
slight variations between the two sites during maturation. These probably reflect,
differences in the adaptive remodeling demands placed on each site during
development in their respective environments.
28 Durkin

Fig. 18. Section of the growth plate of the tibia of a 35day-old guinea pig. (Magnification,
Xl 0.)
Fig. 19. Section of the growth plate of the tibia of a 35.day-old guinea pig on a
scorbutigenic diet for 22 days. Note the displacement of the marrow by the enlarging
gerustmark zone (G). (Magnification, Xl 0.)

Nutritional deficiencies and cartilages

The differential response of the condylwr and growth plate cartilages to
nutritional, hormonal, metabolic, and pathologic factors have been emphasized
in a variety of studies. The collective findings of these st,udies have given rise to
a fair amount of cvidencc that further illustrates the inherent differences be-
tween the type of cartilage found in the mandibular condyle and that found in
the growth plates of the long bones. On the basis of this evidence, as well as the
present material, there is little doubt that the growth plate cartilage varies
considerably from the cartilage of the cxondyle. The differcncc has not been as
well documented for the cartilages of the early anlage and epiphysis. Since the
evidence presented thus far suggests that, these cartilagrs, as well as that of the
condyle, also vary greatly from the growth plat,c, a. brief description of some
of the pertinent findings in the study of nutritional effects on cartilage seems
warranted.
Evidence which seems to reinforce the suggestion that the cartilage of not
only the condyle but also of the epiphysis and the early anlage as well is a dif-
ferent type from that seen in the growth plate has been observed under the ex-
perimental conditions of ascorbic acid and vitamin 1) deficicncies.‘l, 12jI51*7
Ascorbic ncid deficiency. In general, the scorbutic studies using young guinea
pigs on a scorbutigenic diet have demonstrated a minimal response in both the
condylar and articular cartilages,ll! I22IT while the onset of scurvy produced the
classic picture in the growth plate region of the tibia. To fully appreciate the
Volume 62 Secondary cartilage 29
Number 1

difference found in the condyle and epiphysis, one must first examine some of
t,he more prominent changes in the growth plate of the scorbutic long bone
(Figs. 18 and 19). These changes include a lengthening of the cartilage cell
columns as a result of lack of capillary erosion and osteogenesis. Directly below
the cell columns, the formation of an area with a tremendous accumulation of
fibroblast-like cells replacing the primary spongiosa can be seen. This area is
known as the geriistmurk zofle, and the cells in this area are considered to be
inactive osteoblasts. As these cells accumulate during the onset of scurvy, the
geriistmark zone enlarges and displaces the marrow further down into the shaft
(Fig. 19).
In both the condylar and articular cartilages of the scorbutic animals, the
c*hanges brought on by the deficiency were entirely different from those observed
in the growth plate cartilages of the same animals (Figs. 50 and 21). The most.
ob\-ious and probably the most important finding was the fact that although
these cartilages did become thicker, especially the condylar cartilage, there was
no geriistmark zone formed at any time in either site during the experimental
period. The chondroclasts, normally present in large numbers in the region of
cartilage erosion, became fewer and fewer and finally disappeared during the
late stages of scurvy when the erosive activities came to a standstill.
Both the condylar and articular cartilages showed a faster rate of healing,
both histologically and vascularly, following injections of ascorbic acid during
different stages of scurvy. The presence or absence of a geriistmark zone played
an important role in the rate at which the healing events occurred at a par-
ticular site. Since the scorubtic growth plate always developed a geriistmark
zone, the rate of histologic changes and vascular reconstruction in this cartilage
was always slower than that seen in the cartilage of the condyle and epiphysis.
It is of significance to note here that since a geriistmark zone does not form
in the scorbutic articular and condylar cartilage, and since this area is con-
sidered to be made up of inactive or immature osteoblasts accumulating in an
area of former extensive endochondral bone formation, it is most likely
that the areas directly beneath the cartilages of the epiphysis and condyle are
not comparable to the primary spongiosa region of the growth plate in long
bones and therefore not primarily involved in the ordinary process of endochon-
dral bone formation. This point has also been stressed in previous reports, which
have considered the condylar cartilage to be more involved with the process of
mineralization and less with endochondral bone formation.4j 5l gl X11I29l7
If the concept that the condyle and epiphysis are remodeling centers is ac-
cepted, it can be seen why in scurvy both sites should react differently from the
growth plate cartilage. In all other bony areas where remodeling is normally
occurring, this process is stopped in scurvy. This cessation of remodeling was
evident in both the scorbutic articular and condylar cartilages where, as the
chondroclasts gradually disappeared, there was a decrease in cartilage erosion
and a resulting increase in the thickness of cartilage.
Vitamin I) deficiency. Further evidence which points to the articular and
condylar cartilages as being inherently different from the growth plate cartilage
and basically similar to the cartilage of the early cartilaginous anlage is brought
Fig. 20. Section of the condylar cartilage of a 35day-old guinea pig on a scorbutigs :nic
diei t for 22 days. Note absence of gerustmark zone and lack of erosion at face of
ca ri .ilage. (Magnification, X 10.)
Fig. 21. Section of the tibia1 articular cartilage of a 35-day-old guinea pig on a
SC01.butigenic diet for 22 days. Note absence of gerustmark zone and decrease in cartilc rge
era: Con. (Magnification, Xl 0.)
Fig. 22. Section of the growth plate of a %-day-old rat on a rachitogenic diet for 28 dc IYS.
Noi ‘e increased width of cartilage, the areas of capillary erosion, and elaborate oste oid
trak secular network. (Magnification, Xl 0.)
 Secondary cartilage 31

out in a study of vitamin D deficiency in young rats.15 The use of rickets as

another means of comparing these cartilaginous areas was prompted by the
differences observed in their respective normal calcification patterns. Since in
all areas being studied, the pattern of calcification and the mechanisms of
erosion appear to be somewhat dependent on each other, and since rickets is
known to cause an upset in the normal calcification process, a study of this
nature seemed germane to these findings. The onset of rickets, as was the case
in scurvy, produced less severe effects in both the articular and condylar car-
tilages than those seen in the growth plate (Fig. 22). The greatest change
seen in either the articular or the condylar cartilages was an increase in cartilage
thickness as a result of the increased number of hypertrophic cells (Figs. 23 and
21). While both sites demonstrated an increase in the thickness of the cartilage,
the condyle showed the greater increase, resulting in the formation of an elabo-
rate tongue of cartilage extending into the ramus and merging directly with the
elaborate osteoid trabecular network. This difference between the two sites was
due to the significant finding that the normal transformation from the hyper-
trophic to the nonhypertrophic articular cartilage was greatly retarded, so that
after the onset of rickets, there was disproportionately more of the former than
of the latter, while, on the other hand, the nonhypertrophic cartilage present
in the epiphysis prior to the onset of rickets was essentially unchanged. Since
maturation in the mandibular condyle has been seen to occur much later than in
the articular cartilage, only the hypertrophic form of cartilage was seen in the
condyle during the period of this study.
One of the most interesting observations, in light of our present discussion,
was the fact that the rachitic state apparently brought about a more embryonic
character to all cartilage sites studied. This alteration was especially prominent
in the condylar cartilage (Fig. 24). As a result of the fact that the nonhyper-
trophic form of cartilage did not appear in the condyle during the period of this
study, the changes in the mandibular condyle during rickets occurred over the
entire surface of cartilage and thus reverted to a “carrot-wedge” shape which
was reminiscent of that form described by Sarnat18 during embryonic develop-
ment of the condyle (compare Fig. 24 with Fig. 25). The onset of a more em-
bryonic character is understandable in light of the fact that the condylar carti-
lage has been considered to be a secondary cartilage and is, in its normal state,
as we have seen, more embryonic in character. In a discussion of a recent paper
by Baume, Mos#~ stated that the condylar cartilage is an articular cartilage
and that it will react in precisely the same way as articular cartilage elsewhere
in the body. He does not believe either site to be a primary growth center. The
preceding evidence appears to add credence not only to Dr. Moss’s statements
but to the idea being proposed here that the immature articular head of the long
bone is also an adaptive remodeling center and that its cartilage can also be
considered ‘a so-called secondary cartilage.
The type of response in the articular as well as the condylar cartilage to
the onset and healing of rickets appears to be governed by the specific form of
cartilage being studied. That is, the vitamin D deficiency affected only the hyper-
trophic form or immature stage of the cartilage, thus increasing the over-all
thickness of the hypertrophic form of cartilage. Since rickets is primarily a defect
Fig. 23. Section of the tibia1 articular cartilage of a %-day-old rat on a rachitogenic diet
for 28 days. Note lack of resumed cartilage removal and the persistence of the
he bertrophic type of cartilage in spite of the age of the animal. [Magnification, X:lo.)
Fig. 24. Section of the condylar cartilage of a 55day-old rat on a rachitogenic diet for
28 days. Note lack of cartilage erosion and resulting elaborate tongue of cartilc 3ge.
(Co1 mpare with Fig. 25.) (Magnification, X25.)
Fig. 25. Section of the mandibular condyle of a newborn rat. Note the carrot-sha lped
wet Ige of cartilage. (Compare with Fig. 24.) (Magnification, X25.)
Fig. 26. A diagram classifying the different cartilages according to their respective forms
and growth response.

in calcification, this finding, along with the absence of a geriistmark zone dur-
ing scurvy, appears to re-emphasize the fact that the hypertrophic forms
of both articular and condylar cartilages are concerned chiefly with mineraliza-
tion and are not involved in an ordinary cndochondral growth process. The car-
rot-wedge shape of the cartilage, which is invariably found during rickets, is
thought to be specific to and characteristic of this cartilage. The effect of rickets
impresses one more with the resemblance between the early anlage, articular,
and condylar cartilages and does not confirm the idea that the condyle is the
most important growth center in the mandible.
Discussion

It would seem, then, from the foregoin g discussion, that the striking simi-
larities in the basic morphohistologic features of the cartilaginous anlage and
the hypertrophic forms of both the articular and condylar cartilages are indica-
tive of the inherent embryonic character present in all three sites and that these
cartilages respond to changes in the relationship of their surrounding structures
during development by a process of adaptive remodeling. This character certain-
ly is not to be found in the growth plate cartilages and appears to be one of the
underlying factors which differentiate the growth cartilages from others. The
activities during normal maturation as well as the reactions to pathologic situa-
tions, such as the nutritional upsets reviewed in this report, are reflections that
indicate the embryonic nature of these cartilages, while the growth plate car-
34 Lhcrkin

tilage reflects its postembryonic nature in its reactions to similar situations.

In view of evidence demonstrating the resemblanc~e of the articular and UHI-
dylar cartilages 60 the early cartilaginous anlagc, whicdh is tAc very first type
of cartilage to be seen in development, the term P)H~,Y~~o)L~c appears to be more
valid than secondmy cwtilagc. The growth plate, on the other hand, is not.
embryonic in character but is a highly specialized and unique type of cartilage
specifically adapted to meet the demands of the primary growth requirement
of an area. R,ather than being regarded as a model to which all other cartilages
are compared, the growth plate cartilage should be considered at,ypical (Fig.
26).
Moss’s breakdown of secondary cartilage into definitive and intarmediate js
quite interesting, at least as far as the present cartilaginous sites are concerned,
since in several respects his two types coincide nicely with the hypertrophic and
nonhypertrophic forms of cartilage described in this article. Moss’s description
of the definitive type of secondary cartilage appears, for the most part, to coin-
cide with the hypertrophic form of cartilage while his intermediate type of
secondary cartilages appears to correlate w&h the nonhypertrophic form of
embryonic cartilages described in this report,. IIe stabes that the intermediate
type of secondary cartilage is not replaced by endochondral bone formation but
is transformed directly into bone. The nonhypertrophic form of the embryonic
type of cartilage also demonstrates an area directly beneath the cartilage where
bone merges directly with the smooth scalloped border of the cartilage.

Therapeutic implications

How, then, might the knowledge and awareness of these specific cellular ac-
tivities, involved in the development and responses of these embryonic-type
cartilages, be of help to us in the diagnosis and treatment of skeletal orthodontic
problems. Primarily, such awareness affords one the necessary understanding
for the proper assessment of not only the skeletal malocclusion but also the ab-
normal pattern of development associated with craniofacial deformities. It is
much more likely that a correct diagnosis as well as an accurate det,ermination
of the limitations and prognosis of a particular treatment procedure will result
from this kind of knowledge.
Transplantation procedures. In the area of congenital malformations, a basic
understanding of sucl~ cellular activities as described in this report may form
the foundation toward a better understanding and improved treatment measures
in these progressive growth aberrations. This knowledge becomes even more im-
portant when such procedures as transplants are considered as a possible means
of treatment for these malformations and may form the basis for determining
the best conditions in which transplantation may be undertaken in those birth de-
fects where such a procedure might prove useful.
The fact that the cartilages, such as the embryonic type described here,
undergo a transformation in their cellular characteristics and activities during
normal development (Fig. 27) would appear to have particular significance
when one is considering a transplant, as in early corrective procedures for any
one of the extensive list of syndromes involving either or both of the cartilages
 Fig. 27. A diagram of both forms of the embryonic type of cartilage.

of the mandibular condyle or epiphysis of the long bone. To date such attempts
have been approached on a rather hit-or-miss basis, with unpredictable re-
sults.21p 22 From the present study, it would seem that the success or failure of a
transplant approach to such problems would no doubt depend heavily on the
type of cartilage involved (see diagram in Fig. 28). If, for example, the affected
area in a particular congenital deformity is considered to be an adaptive re-
modeling center, such as the mandibular condylt or long bone cpiphysis, then
a donor site with embryonic, not primary, cartilage would have the greatest
potential for successful adaptation and adjustment in its new environment,.
Since we have seen that the nonhypertrophic form of embryonic cartilages was
essentially nonreactive during normal maturation as well as under the condi-
tions of nutritional deficiencies, it is reasonable to assume that it would not have
the adaptive potential necessary for a successful transplant in a site whrrc
growth changes are still occurring. Therefore, it is apparent that when we arc
dealing with an adaptive remodelin g cartilaginous site, that is, an embryonic
or secondary cartilage, an important consideration would be whether the donor
or recipient site is in its hypertrophic or nonhypertrophic form. Such discrim-
inatory selection has been alluded to, but only in a general way, by Ware and
TayloP in their condylar cartilage transplantation studies. It is easy to SW,
then, when the recipient site is an area where the adaptive remodeling type of
growth response is in demand, why the hypertrophic form of embryonic cartilage
would have the greatest potential for success in its new environment.
It would appear, on the basis of Moss’s10 work on ankylosis of the temporo-
mandibular joints in growing children, that such procedures as transplants
Fig. 28. A diagram of the possible transplantation potential in both forms of embryonic
cartilage.

in the region of the mandibular condylc would bc -11sc1ess. Moss has tlemonstratetl
in these studies that removal of the condyle does not affect the over-all growth
of the mandible. This idea is likewise being rc-enforced by the present work,
but I do not believe that the efficacy of cartilage transplantation is affected
by this fact. The condition of ankylosis, if not actually destructive, places a
physical restriction on the hypertrophic cartilage of the condyle and thereby
either destroys or restricts its adaptive remodeling potent,ial. This fact alone
dictates that early r&oration or replacement of the hypertrophic form of
cartilage be undertaken. This point has also been made recently by Morscher
and associatesz3 in their studies on function and mandibular growlh. Although
the cartilage of the condyle can bc thought of only in terms of an adjustment
mechanism and therefore is not necessary for the over-all growth of the mandible
it is thought that the condylar cartilage is indeed essential for the maintenance
of the normal anatomic integrity of the t,cmporomandibular joint. JVe know
that with loss or absence of a condylc, there is produced a deviation of the man-
dible and a resulting facial asymmetry. We also know that this facial asym-
metry is not primarily a result of altered growth of the mandible but, rather,
a direct result of the altered direction in the pull of muscles and ligaments in
the region of the missing condylc. This altered musculature produces compen-
satory changes in adjacent structures in an attempt to allow for better function
under the conditions of the deformity. Ware and Taylor believe that these com-
pensatory changes give merit to attempts at early restitution or substitution
of a growth force to replace the condylar center. While I take esccption to
 Secondary cartilage 37

Fig. 29. A diagram illustrating how the knowledge of the form of cartilage present in the
mandible might be useful in the selection of the correct approach to skeletal orthodontic
problems.

Ware and Taylor’s use of the term growth force, it is nevertheless thought that
the efficacy of transplantation procedures in such conditions as congenitally
malformed or traumatically injured condyles is indeed based on the need to
restore the adjustment mechanism in this region. If normal anatomic integrity
is to be maintained without periodic surgical intervention during a period
when growth changes are occurring, this adjustment mechanism must be re-
stored.
Surgical orthodontics and dentofacial orthopaedics. The two most perplexing
types of skeletal problems which confront the orthodontist, as well as the oral
surgeon, are the Class III and Class II cases. In the light of the preceding dis-
cussion, it would appear that, because of its embryonic nature and properties
during the growing years, surgical treatment and/or orthopedic forces should
be able to influence the nature of the response to its changing environment.
This, indeed, appears to be the case in view of the result obtained both clini-
cally and experimentally in recent years.
One of the considerations with the surgical orthodontic approach to skeletal
problems today is whether to use one or a combination of both approaches.
One treatment plan may consider surgical corrections to be undertaken only
after the failure of orthodontic procedures and at the completion of facial
growth, while others may prefer a series of surgical procedures at selected times
during the growing years, with or without orthodontic treatment.
 - 2”
ADAPTIVE REMODELLING RESPONSE

IN THE HYPERTROPHIC CONDYLAR CARTILAGL

TREATMENT FORCES ADVERSE ENVIRONMENTAL FORCES

Fig. 30. A diagram illustrating how certain treatment procedures or adverse conditions
utilize the same adaptive remodeling potentials in the hypertrophic condylar cartilage to
bring about the correction or production, respectively, of a skeletal orthodontic problem.

On the basis of the fundamental knowledge of the cellular activities taking

place in the cartilaginous areas involved, one is more likely to determine the
best conditions in which tither an orthodontic and/or a surgical approach
might be undertaken in each particular case (Fig. 29). To consider a surgical
procedure as the treatment of choice for such conditions as postpubertal prog-
nathic mandibles is to imply, in a general way, that, surgical intervention is
the best approach to these problems once the condylar cartilage is in its no11-
hypertrophic form. By the same criteria, if the cartilage of the condyle is
still in its hypertrophic form, a strict orthopedic approach sho-tlld prove suc-
cessful in triggering and maintaining the proper adaptive response in this
cartilage necessary for the ultimate correcbion of such a developing skeletal
problem. The responsiveness of the hypertrophic form of the condylar cartilage
to such an orthopedic approach has already been documented by such studies
as those by Folke and Stallard,Y4 Graber and his colleagues,25 and Charliet
and associates.2F
Deciduous and mixed-deniition problem md therapy. The orthodontic
literature is replete with reasons and indications for early intervention in
incipient skeletal orthodontic problems. In most of these reports, four major
problems which may involve the condylar cartilage are emphasized as being
Volume 62 Secondary cartilage 39
Number 1

amenable to early orthodontic treatment: (1) the retrognathic and (2) prog-
nathic mandibular growth problems, (3) open-bite, and (4) functional cross-
bites. The success of treatment, by whatever mechanical means, in these mixed-
dentition problems can be attributed, at least in part, to the following factors:
(1) a favorable genetic tendency in the functional matrices, (2) removal of
unfavorable environmental conditions or tendencies, and, most important, (3)
maintenance of a favorable environment for the adaptive remodeling process
within the hypertrophic form of condylar cartilage.
The point to be emphasized here is that those developing skeletal problems
which are brought about by adverse conditions or tendencies are produced
and maintained by the same adaptive remodeling process characteristic of the
hypertrophic form of the condylar cartilage that can and should be utilized
to correct them (Fig. 30). The same functional adaptability of this embryonic
or secondary type of cartilage that produces these kinds of skeletal orthodontic
problems can also be used in their correction.
While the title and text of this article emphasize that enzbryonic cartilage
appears to be a more appropriate term for secondary cartilage, it is not my
intention to alter or change the terminology but, rather, to point out the true
nature and character of these cartilages. Definite concepts about orofacial
growth are fundamental to the diagnosis and treatment of clinical orthodontic
problems, but such concepts can be postulated only with the knowledge of the
specific cellular activity and the precise mechanisms involved in both the
cartilaginous and osseous changes occurring during growth.

Conclusions

The histologic evidence at hand reveals that the term secondary cartilage
is a misnomer and that the nature of this type of cartilage resembles that of
the early cartilaginous anlagc. A more appropriate term for these cartilages
would appear to be embryonic cartilages. The criteria by which one may classify
a site as being on embryonic cartilage follow:
1. Cellular organization. These cartilages are less well organized cellu-
larly, and their chondrocytes are arranged rather haphazardly.
2. Matrix formation. These cartilages have a scanty amount of inter-
cellular matrix in their immature or hypertrophic form.
3. Calcification pattern. These cartilages present a pericellular type
of calcification circumscribing the hypertrophic chondrocytes.
4. Uechanism of erosion. In the hypertrophic form of these cartilages,
erosion of the calcified matrix takes place by chondroclastic resorp-
tion.
5. Trabecular network formation. In their hypertrophic form, these
cartilages are chiefly undergoing mineralization and are not involved
in an ordinary endochondral growth process; t,herefore, a primary
spongiosa is practically nonexistent.
6. Growth mechanism. These cartilages arc remodeling centers, and
their growth responac is adaptive in nature.
7. Pathologic response. These cartilages demonstrate a lesser degree
 of reactivity to hormonal, enzymat.ic, alltl clietilq, clisturkwilcw tlla7L
the primary growth cartilages.
I wish to express my sincere thanks to Dr. J. ‘I’. 1 rving an11 .J. I). Heeley Tar f.heir wise
counsel and guidance, to Miss .T. Reddirrg and Miss .J. J)obec*l< for their technical assistance.
and to Miss Leslie Levitt for her secretarial assistancfl.

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