2)

Development and growth of the bones. Histogenesis - types of bone formation. Factors,
influencing bone formation. Increase of the bones in length and thickness - the growth
cartilage, periosteum - structure.

 Bone is the basic unit of the human skeletal system and provides the framework for
and bears the weight of the body, protects the vital organs, supports mechanical
movement, hosts hematopoietic cells, and maintains iron homeostasis.
 Bones can be classified on the basis of their position, shape, size, or structure.
 With regard to location, bones can be classified as follows:

 Axial skeleton – Bones of the skull, vertebral column, sternum, and ribs
 Appendicular skeleton – Bones of the pectoral girdle, pelvis girdle, and limbs; the
acral skeleton is the part of the appendicular skeleton that includes the bones of the
hands and feet
 Bone tissue arises either through intramembranous ossification or through
endochondral ossification.
 In either case, the original or model tissue is gradually destroyed and replaced with
bone tissue.
 Bone forms only by appositional deposition of matrix on the surface of a preformed
tissue. Woven bone is initially formed and is then later converted to lamellar bone by
subsequent remodeling.
 The direct conversion of mesenchymal tissue into bone is called intramembranous
ossification.
 Although intramembranous ossification is the source of flat bones, this process also
contributes to the growth of short bones and thickening of long bones.
 Interstitial membranous ossification takes place within a condensation of
mesenchymal tissue. The process begins when multiple groups of cells differentiate
into osteoblasts in a primary ossification centre.
 Osteoid is synthesized and then mineralized surrounding the osteoblasts, which then
become osteocytes.
 When these ossification centres fuse, a loose trabecular structure known as primary
spongiosa is formed.
 Subsequently, blood vessels grow into the connective tissue between the
trabeculae. Bone marrow stem cells from the circulating blood then give rise to
hematopoietic cells.
 Growth and fusion of several ossification centres eventually replace the original
mesenchymal tissue.
 In flat bones, compact bone is formed at both the internal and external surfaces due
to a marked predominance of bone deposition over bone resorption, whereas a
spongy pattern remains in the central portion.
 The endosteum and periosteum are formed from layers of connective tissue that are
not undergoing ossification.
 Membranous ossification: flat bones of the skull, clavicle, periosteum
 Unlike endochondral ossification, which is the other process by which bone tissue is
created during fetal development, cartilage is not present during intramembranous
ossification.
 The process by which a cartilage intermediate is formed and replaced by bone cells is
called endochondral ossification.
 Endochondral ossification is responsible for the formation of short and long bones.
This process takes place within a hyaline cartilage model, which provides a template
of the shape of the bone to be formed.
 Endrochondral ossification axial and appendicular skeleton, some bones in the skull.
 This type of bone formation occurs in pre-existing cartilaginous models.
 Endochondral ossification can be divided into two phases. In the first phase,
chondrocytes of the model are hypertrophic and degenerated, and then the
intervening chondroid matrix is calcified.
 In the second phase, osteogenic buds, composed of osteoprogenitor cells and blood
capillaries, invade the spaces left by the degenerating chondrocytes.
 Osteoblasts arise from osteoprogenitor cells and lay down a layer of rapidly
mineralized osteoid on the surface of calcified cartilage.
 The complex structure of calcified cartilage with overlying newly bone thus formed is
known as the primary spongiosa, which is later remodeled to become lamellar bone
(secondary spongiosa).
 Calcified cartilage remnants are resorbed by chondroclasts, which are structurally
and functionally equivalent to osteoclasts, except that chondroclasts work on
cartilage rather than bone. Thus, the cartilage model is gradually replaced by bone
and marrow cavities.
 Long bones are formed from cartilaginous models.
 The primary ossification centre is initiated by intramembranous ossification that is
produced by the deep portions of the perichondrium that surround the diaphysis. A
bone collar is thus formed, blocking the nutrient diffusion and leading to the
degeneration of internal chondrocytes.
 The perichondrium then becomes the periosteum, from which the osteogenic bud
arises and penetrates the calcified cartilage matrix through passages that are created
in the bone collar by osteoclasts.
 The primary ossification center expands longitudinally and is associated with the
growth of the periosteal bone collar. Osteoclasts are activated at the beginning of
the process, resorb the bone at the center, and hence create the marrow cavity.
 At a later stage of bone development, a secondary ossification center arises at the
center of each epiphysis.
 Unlike primary ossification, which expands in a longitudinal fashion, the secondary
ossification center grows in a radial fashion.
 Furthermore, a bone collar is not formed in the area of articular cartilage due to the
absence of perichondrium in this area. Thus, the epiphysis of the chondroid model is
replaced by bone tissue, except the articular cartilage and the epiphyseal cartilage.
Epiphyseal cartilage is located between the epiphysis and the metaphysis and is responsible
for the longitudinal growth of bone. It can be divided into the following five zones, starting
from the epiphyseal side of cartilage:

 Resting zone – This zone consists of small chondrocytes

 Proliferative zone – The proliferative zone consists of rapidly dividing chondrocytes
in columns that are parallel to the long axis of the bone, resulting in interstitial
growth of cartilage; the chondroid matrix is laid down, and mitotic figures may be
detected
 Hypertrophic zone – This zone consists of large chondrocytes that contain abundant
cytoplasmic glycogen; here, chondrocytes mature and degenerate, with associated
chondroid matrix resorption
 Calcified cartilage zone (zone of provisional calcification) – This zone is where
chondrocytes die; chondrocyte death is followed by blood vessel invasion and bone
deposition on the calcified cartilage
 Ossification zone – The ossification zone is where primary spongiosa forms by rapidly
mineralized osteoid that is laid down on the calcified cartilage septa

 During growth, the epiphyseal plate normally does not change in thickness, because
the rates of proliferation and destruction are approximately equal.
 It is simply replaced away from the middle of the diaphysis, resulting in longitudinal
growth of the bone.
 When the epiphyseal plate closes, between ages 16 and 20 years, longitudinal
growth of bones becomes impossible, though widening may still occur through
appositional growth.
 Upon completion of growth, this plate is replaced by spongy bone; the epiphyses and
diaphyses are fused and no more elongation of the bone occurs.

 Much as in development, bone also grows by either endochondral ossification or

intramembranous ossification.
 Whereas endochondral ossification of the epiphyseal plate is responsible for
longitudinal growth of the long bones, periosteal deposition contributes to both the
length and thickness of long bones, as well as the overall growth of flat bones.
 A number of factors influence bone development, growth, and repair. These include
nutrition, exposure to sunlight, hormonal secretions, and physical exercise.
 For example, vitamin D is necessary for proper absorption of calcium in the small
intestine.
 In the absence of this vitamin, calcium is poorly absorbed, and the inorganic salt
portion of bone matrix lacks calcium, softening and thereby deforming bones. In
children, this condition is called rickets, and in adults, it is called osteomalacia.