periosteum deposit a layer or layers of fibrous lamellæ upon the surface of the cartilage, and these lamellæ also become calcified (fig. 64, im). As they are formed some of the osteoblasts (o) are included between them and become bone-corpuscles.

FIG. 64.-SECTION OF PHALANGEAL BONE OF HUMAN FETUS, AT THE TIME OF COMMENCING OSSIFICATION. (Magnified about 75 diameters.)

The cartilage-cells in the centre are enlarged and separated from one another by dark-looking calcified matrix; im, layer of bone deposited underneath the periosteum; o, layer of osteoblasts by which this layer has been formed. Some of the osteoblasts are already embedded in the new bone as lacunæ. The cartilage-cells are becoming enlarged and flattened and arranged in rows above and below the calcified centre. At the ends of the cartilage the cells are small and the groups are irregularly arranged; the fibrous periosteum is not sharply marked off from the cartilage.

In the second stage some of the subperiosteal tissue eats its way through the newly formed layer of bone and into the centre of the calcified cartilage (fig. 65, ir). This is freely absorbed before it, so that large spaces are produced which are filled with osteoblasts and contain

numerous blood-vessels which have grown in at the same time. The spaces are termed medullary spaces, and this second stage may be termed the stage of irruption.

FIG. 65.--SECTION OF PART OF
ONE OF THE LIMB-BONES OF
A FETAL CAT, AT A MORE
ADVANCED STAGE OF OSSIFI-
CATION THAN IS REPRE-
SENTED IN FIG. 64, AND
SOMEWHAT MORE HIGHLY
MAGNIFIED.

The calcification of the cartilage-
matrix has advanced from the
centre, and is extending between
the groups of cartilage-cells
which are arranged in character-
istic rows. The subperiosteal
bony deposit (im) has extended
pari passu with the calcification
of the cartilage-matrix. The
cartilage-cells in the primary
areolæ are mostly shrunken and
stellate; in some cases they have
dropped out of the space. At ir
and in two other places an irrup-
tion of the subperiosteal tissue,
composed of ramified cells with
osteoblasts and growing blood-
vessels, has penetrated the sub-
periosteal bony crust, and has
begun to excavate the secondary
areolæ or medullary spaces; P,
fibrous layer of the periosteum;
o, layer of osteoblasts, some of
them are embedded in the osseous
layer as bone-corpuscles in la-
cunæ; bl, blood-vessels occupied
by blood-corpuscles. Beyond the
line of ossific advance the perios-
teum may be noticed to be dis-
tinctly incurved. This incurva-
tion is gradually moved on, the
cartilage expanding behind it
until the head of the bone is
reached, when it forms the peri-
osteal notch or groove represented
in fig. 66, p. 57.

ы

In the third stage of endochondral ossification there is a gradual advance of the ossification towards the extremities of the cartilage, and at the same time a gradual deposition of fresh bony lamellæ and spicules on the walls of the medullary spaces, and on the surface of the new bone under the periosteum. The advance into the cartilage always takes place by a repetition of the same changes, the cartilagecells first enlarging and becoming arranged in rows, the matrix between the rows becoming calcified, and then the calcified cartilage becoming excavated from behind by the osteoblastic tissue so as to form new medullary spaces (fig. 67). The walls of these are at first formed

only by remains of the calcified cartilage-matrix (fig. 67, c), but they soon become thickened by lamellæ of fibrous bone (b) which are

DIAMETERS.

30

ic, the part of the shaft which was
primarily ossified in cartilage;
what remains of the primary
bone is represented as dark, en-
veloped by the clear secondary
deposit. The areolæ of the bone
are occupied by embryonic mar-
row with osteoblasts, and blood-
vessels variously cut, represented P
as dark lines. One long straight
vessel (bv) passes in advance of
the line of ossification far into
the cartilaginous head, most of
the others loop round close to the
cartilage. At one or two places
in the older parts of the bone
elongated groups of cartilage-
cells (c) may still be seen, which
have escaped absorption. im, the
part of the bone that has been
ossified in membrane, that is to
say, in the osteoblastic tissue
under the periosteum. It is well
marked off from the central por-
tion, and is bounded, peripherally,
by a jagged edge, the projections
of which are indistinctly seen to
be prolonged by bunches of osteo-
genic fibres. A row of osteoblasts
covers the superficial layer of the
bone. The subperiosteal layer is
prolonged above into the thicken-
ing (p), which encroaches upon
the cartilage of the head of the
bone, and in which are seen,
amongst numerous osteoblasts
and a few blood-vessels, the
straight longitudinal osteogenic
fibres (of), and some other fibres
(pf) crossing them, and perhaps
representing fibres of Sharpey.
The calcareous salts having been
removed by an acid, the granular
ossific deposit passing up between
the rows of cartilage-cells is not
seen in this specimen; it would
have extended as far as a line
joining the marks x x. Observe
the general tendency of the osse-
ous trabeculæ and the vascular
channels between them to radiate
from the original centre of ossifi-
cation. This is found to prevail
more or less in all bones when
they are first formed, although
the direction of the trabeculæ
may afterwards become modified
in relation with varying physio-
logical conditions, and especially
as the result of pressure in dif-
ferent directions.

deposited by the osteoblasts, and between which bone-corpuscles become included, as in the case of the subperiosteal bone. The latter

advances pari passu with the endochondral calcification, but beyond this the uncalcified cartilage grows both in length and breadth, so that the ossification is always advancing into larger and larger portions of cartilage; hence the endochondral bone as it forms assumes the shape of an hour-glass, the cylindrical shape of the whole bone being maintained by additions of periosteal bone to the outside (see fig. 66). The

FIG. 67.-PART OF A LONGI

TUDINAL SECTION OF THE
DEVELOPING FEMUR OF THE

RABBIT. (Drawn under a
magnifying power of 350
diameters.)

a, rows of flattened cartilage-cells;
b, greatly enlarged cartilage-
cells close to the advancing bone,
the matrix between is partly
calcified; c, d, already formed
bone, the Osseous trabeculæ
being covered with osteoblasts
(e), except here and there,
where an osteoclast () is seen,
eroding parts of the trabeculæ ;
9, h, cartilage-cells which have
become shrunken and irregular
in shape. From the middle of
the figure downwards the dark
trabeculæ, which are formed of
calcified cartilage-matrix, are be-
coming covered with secondary
osseous substance deposited by
the osteoblasts. The vascular
loops at the extreme limit of the
bone are well shown, as well as
the abrupt disappearance of the
cartilage-cells.

absorption of the calcified cartilage-matrix appears to be effected, as is the case with absorption of bony matter wherever it occurs, by large multinucleated cells (fig. 67, f, f) which are termed osteoclasts. They are the same as the myeloplaxes of the marrow.

The bone which is first formed is more reticular and less regularly lamellar than that of the adult, and contains no Haversian systems. The regular lamellæ are not deposited until some little time after birth, and their deposition is generally preceded by a considerable amount of absorption. It is about this time also that the medullary canal of the long bones is formed by the absorption of the bony tissue which originally occupies the centre of the shaft.

After a time the cartilage in one or both ends of the long bones begins to ossify independently, and the epiphyses are formed. These are not joined to the shaft until the growth of the bone is completed. Growth takes place in length by an expansion of the cartilage (intermediate cartilage) which intervenes between the shaft and the epiphyses, and by the gradual extension of the ossification into it; in width entirely by the deposition of fresh bony layers under the periosteum. In the terminal phalanges of the digits the ossification starts, not from the middle of the cartilage, but from its distal extremity.

For the regeneration of portions of bone which have been removed by disease or operation it is essential that the periosteum be left.

FIG. 68.-PART OF THE GROWING EDGE OF THE DEVELOPING PARIETAL BONE OF A FETAL CAT, 1 INCH LONG.

sp, bony spicules, with some of the osteoblasts embedded in them, producing the lacunæ; of, osteogenic fibres prolonging the spicules, with osteoblasts (ost) between them and applied to them.

Intramembranous ossification. In this variety of ossification, the bone is not preceded by cartilage at all, and therefore no endochondral bone is formed, but the calcification occurs in a sort of embryonic fibrous tissue which contains numerous osteoblasts and blood-vessels (fig. 68). The fibres of this tissue (osteogenic fibres), which, like those of fibrous tissue, are collected into small bundles, become enclosed in a calcareous matrix; and as the fibres grow, the calcification extends further and further, so that bony spicules are formed, which, as they become thickened, run together to form reticular layers, leaving spaces filled with osteoblasts around the blood-vessels. The osteogenic