BONE REMODELING:

Bone remodeling (or bone metabolism) is a life-long process where mature bone tissue is
removed from the skeleton (a process called bone resorption) and new bone tissue is formed (a
process called ossification or new bone formation). These processes also control the reshaping
or replacement of bone during growth and following injuries like fractures but also micro-
damage, which occurs during normal activity. Remodeling responds also to functional demands
of the mechanical loading. As a result, bone is added where needed and removed where it is
not required.
In the first year of life, almost 100% of the skeleton is replaced. In adults, remodeling proceeds
at about 10% per year.
An imbalance in the regulation of bone remodeling's two sub-processes, bone resorption and
bone formation, results in many metabolic bone diseases, such as osteoporosis.
BONE TISSUE:
Osseous tissue, or bone tissue, is the major structural and supportive connective tissue of the
body. Osseous tissue forms the rigid part of the bone organs that make up the skeletal system.
There are two types of osseous tissue, compact and spongy. Compact bone forms the
extremely hard exterior while spongy bone fills the hollow interior. The tissues are biologically
identical; the difference is in how the microstructure is arranged.
BONE RESORPTION:
Bone resorption is the process by which osteoclasts break down bone and release the minerals,
resulting in a transfer of calcium from bone fluid to the blood.
The osteoclasts are multi-nucleated cells that contain numerous mitochondria and lysosomes.
These are the cells responsible for the resorption of bone. Attachment of the osteoclast to the
osteon begins the process. The osteoclast then induces an infolding of its cell membrane and
secretes collagenase and other enzymes important in the resorption process. High levels of
calcium, magnesium, phosphate and products of collagen will be released into the extracellular
fluid as the osteoclasts tunnel into the mineralized bone. Osteoclasts are also prominent in the
tissue destruction commonly found in psoriatic arthritis and other rheumatology related
disorders.
Bone resorption can also be the result of disuse and the lack of stimulus for bone maintenance.
Astronauts, for instance will undergo a certain amount of bone resorption due to the lack of
gravity, providing the proper stimulus for bone maintenance.
During childhood, bone formation exceeds resorption, but as the aging process occurs,
resorption exceeds formation.
Bone resorption is highly constructable stimulated or inhibited by signals from other parts of
the body, depending on the demand for calcium.
Calcium-sensing membrane receptors in the parathyroid gland monitor calcium levels in the
extracellular fluid. Low levels of calcium stimulates the release of parathyroid hormone (PTH)
from chief cells of the parathyroid gland.
OSSIFICATION:
Ossification (or osteogenesis) is the process of laying down new bone material by cells called
osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in
the formation of normal, healthy bone tissue:
[1]
Intramembranous ossification is the direct
laying down of bone into the primitive connective tissue (mesenchyme), while endochondral
ossification involves cartilage as a precursor.
In fracture healing, endochondral osteogenesis is the most commonly occurring process, for
example in fractures of long bones treated by plaster of Paris, whereas fractures treated by
open reduction and stabilization by metal plate and screws may heal by intramembranous
osteogenesis.
Intramembranous ossification:
Mesenchymal stem cells, or MSCs, within human mesenchyme or the medullary cavity of a
bone fracture initiate the process of intramembranous ossification. A MSC is an unspecialized
cell whose morphology undergoes characteristic changes as it develops into an osteoblast.
Mesenchyme cell in the membrane become osteochondral progenitor cell
osteochondral progenitor cell specialized to become osteoblast
Osteoblast produce bone matrix and surrounded collagen fiber and become osteocyte.


Endochondral ossification:

Endochondral ossification
[1][2]
is one of the two essential processes during fetal development of
the mammalian skeletal system resulting in the creation of bone tissue. Unlike
intramembranous ossification, which is the other process, cartilage is present during
endochondral ossification.

The cartilage model will grow in length by continuous cell division of chondrocytes, which is
accompanied by further secretion of extracellular matrix. This is called interstitial growth. The
process of appositional growth occurs when the cartilage model would also grow in thickness
which is due to the addition of more extracellular matrix on the periphery cartilage surface,
which is accompanied by new chondroblasts that develop from the perichondrium.
Physiology
The cells responsible for bone metabolism are known as osteoblasts, which secrete new bone,
and osteoclasts which break bone down. The structure of bones as well as adequate supply of
calcium requires close cooperation between these two types of cells. It relies on complex
signaling pathways to achieve proper rates of growth and differentiation. These signaling
pathways include the action of several hormones, including parathyroid hormone (PTH),
vitamin D, growth hormone, steroids, and calcitonin, as well as several cytokines. It is in this
way that the body is able to maintain proper levels of calcium required for physiological
processes.
Osteoblasts:
Osteoblasts (from the Greek words for "bone" and "germ" or embryonic) are mononucleate
cells that are responsible for bone formation; in essence, osteoblasts are sophisticated
fibroblasts that express all genes that fibroblasts express, with the addition of the genes for
bone sialoprotein and osteocalcin.
[1]

Osteoblasts produce osteoid, which is composed mainly of Type I collagen. Osteoblasts are also
responsible for mineralization of the osteoid matrix. Zinc, copper and sodium are some of the
many minerals produced. Bone is a dynamic tissue that is constantly being reshaped by
osteoblasts, which build bone, and osteoclasts, which resorb bone. Osteoblast cells tend to
decrease as individuals become elderly, thus decreasing the natural renovation of the bone
tissue.
[2]

Osteoclast:
An osteoclast (from the Greek words for "bone" () and "broken" ()) is a type of
bone cell that removes bone tissue by removing its mineralized matrix and breaking up the
organic bone (organic dry weight is 90% collagen). This process is known as bone resorption.
Osteoclasts were discovered by Kolliker in 1873.
[1]
Osteoclasts and osteoblasts are instrumental
in controlling the amount of bone tissue: osteoblasts form bone, osteoclasts resorb bone.
Osteoclasts are formed by the fusion of cells of the monocyte-macrophage cell line.
[2]

Osteoclasts are characterized by high expression of tartrate resistant acid phosphatase (TRAP)
and cathepsin K.