has reduced the complement to fewer, the adult condition is usually attained by fetal regression

of
some digits. Creases formed in the proximal part of the bud soon allow recognition of segments
corresponding to the arm and forearm (or thigh and leg) regions of the adult.
The first indication of the future limb skeleton is provided by an axial condensation of the
mesoderm to produce a denser core. In the early stages of development (but not always later) a
definite proximodistal gradient of differentiation occurs. This gradient establishes and then
maintains the girdle elements in advance of those of the arm or thigh and the latter in advance of
more distal parts.
In the next stage of development, the mesoderm is locally transformed to create a series of
cartilaginous models in the pattern of the adult bones. These precursors soon come to resemble
the
final forms in broad outline; they remain ensheathed by thin coverings of the unmodified
mesoderm, now appropriately known as perichondrium. Dense mesoderm also remains between
the
cartilages where the joints will develop.
The cartilage models grow mainly by interstitial growth, in which each part expands more or less
uniformly to maintain the general form. The next stage involves the replacement of the cartilage
by
bone tissue—not its transformation into bone, a distinction that deserves to be emphasized. The
process does not occur identically or synchronously in different bones, and the remarks that
follow
concern that hypothetical concept, the “typical long bone.”
The initial ossification involves two processes. In one, the perichondrium around the middle of
the shaft lays bone down on the cartilage. This process of bone formation is known as
intramembranous ossification because it occurs within the connective tissue membrane. Its
details
must be sought in textbooks of histology. A tubular bony sheath, the periosteal collar, is thus
formed about the center of the shaft; it is gradually extended toward each extremity (Fig. 2.43). In
the other process, the cartilage of the center of the shaft shows aging or degenerative changes;
its
cells hypertrophy, come to occupy enlarged lacunae (spaces) in the matrix, and then die, while the
matrix becomes impregnated with calcium salts. This central patch of dead cartilage is now
invaded
by a connective tissue sprout that pushes in from the periosteum (as the perichondrium is now
more appropriately known in the region of the collar). The progress of this sprout, which is rather
cellular and well vascularized, is facilitated by the spongy texture given to the dead cartilage by
the
enlarged lacunae. Some of the cells that are carried inward have the capacity to engulf and
remove
calcified matrix, others have the capacity to lay bone down on the surviving framework, and a third
group are precursors of marrow cells. The processes of construction and destruction continue in
parallel and transform the whole middle portion of the shaft into a parcel of bone known as the
primary or diaphysial center of ossification.
Later (much later in some species and mainly after birth in humans), similar sprouts from the
perichondrium invade the centers of the two extremities to establish secondary or epiphysial
centers of ossification. The secondary centers are not preceded by the formation of any
equivalent to
the periosteal collar of the shaft. The general stage of development of the long bone at this time is
shown in Fig. 2.43/8. This drawing demonstrates that the original cartilage now survives only as
two plates, the epiphysial or growth cartilages, that intervene between the primary and secondary
centers. These have a special significance since they are responsible for the growth in length of
the
bone. They are clearly polarized, with cell division and matrix expansion confined to the
epiphyseal
aspect and degeneration, calcification, and replacement occurring at the central or diaphyseal
side
(Fig. 2.44). The replacement adds continuously to the length