Prenatal Growth and Maturation of a Long Bone

The following description is appropriate for most long bones, although the timing of
changes differs among these bones. Timing before birth is expressed as
postconceptional age. Some alternative schemes are based on either crown-rump
length or the maturity horizons of Streeter ( 1951 ); all these classification criteria are
closely correlated. The term "gestational age" is common in the obstetrical literature.
In some reports, gestational age equates with postconceptional age, but it is usually
calculated without adjustment from the date of either the last menstrual period or the
last normal menstrual period. The latter ages are systematically less than
postconceptional ages.
Where a long bone is destined to develop, the first visible change is a condensation of
mesenchyme. This packing of loosely arranged cells occurs at about 7 weeks of fetal
life; soon afterward, the cells secrete compounds characteristic of cartilage. This
occurs first in the central part of the condensed area; it is associated with a separation
of the central cells and compression of the marginal cells into a membrane called the
perichondrium. The cells of the inner layer of this membrane remain undifferentiated
and retain the potential to form cartilage. The cells in the outer, more obvious, layer
change to fibroblasts and sharply define the shape and size of the model of the future
bone (Oliver, 1962). Even when first formed, this model resembles the adult bone in
shape (Lewis, 1902; Hesser, 1926), although its ends are relatively wider and there are
differences in structural details (Oliver and Pineau, 1959; Gardner and Gray, 1970).
For example, the linea aspera of the femur is not present until the third prenatal month
(Gardner and Gray, 1970). With chondrification, there is an indication of future joints
in areas in which the mesenchyme persists as homogeneous interzones.

The model of a long bone enlarges by apposition from the deep layer of the
perichondrium that surrounds it completely. This apposition involves the formation of
chondrocytes (cartilage cells). The bone grows also by the division of chondrocytes
within the model and by an increase in the intercellular material. Newly formed
chondrocytes are concentrated at each end of the model, where the cells are densely
packed. Rapid growth in these areas results in elongation of the model and increase in
its width. The increase in width is more rapid at the ends than in the central part of
themodel, partly because the central cells do not divide. These central cells grow old,
enlarge, develop vesicles and later vacuoles in their cytoplasm, and finally disintegrate.
While these changes occur, the older chondrocytes secrete alkaline phosphatase, and
the intercellular substance around them becomes calcified (Niven and Robison, 1934;
Fell and Robison, 1934) (Figure lA). This calcified area is usually too small to be
visible radiographically, but exceptions occur in the vertebral bodies (Hadley,1956).
Ossification begins around the central part of the model after this area of cartilage is
calcified (Figure lB). At first, osteoid tissue (uncalcified bone matrix) forms deep to
the perichondrium as a collar. This osteoid tissue calcifies quickly to form periosteal
bone in contact with the cartilage. The membrane external to this bone is called the
periosteum; the deep cells in the periosteum are osteoblasts (bone-forming cells) that
can become osteocytes (bone cells).
The calcified cartilage in the central part of the model is now vascularized by masses
of cells that extend quickly from the periosteum through the periosteal bone. These
masses contain osteoclasts (bone-removing cells) and undifferentiated cells. The
cartilage cells are destroyed and blood vessels.

Fig. I. Diagram of the maturation of a long bone in which the length of the bone has
been kept constant. (AG) Approximate age scale: (A) sixth prenatal week, (B) seventh
prenatal week, (C) twelfth prenatal week, (D) sixteenth prenatal week to 2 years, (E)
2-6 years, (F) 6-16 years, and (G) adulthood. The clear area in (D-G) represents
the marrow cavity. (Based on Roche, 1967.)