Figure 1
Figure 2: Histologic
slide of the different stages of osteoblast.
Overlying these cells is the periosteum.
Bones
Introduction
Bones have multiple functions that include structural support and protection for vital organs, support and leverage for movement and manipulation, repository for essential minerals and housing for the hematopoietic system.
Thirty-five percent of bone is composed of a flexible
extracellular matrix consisting mostly of collagen. The remaining sixty-five percent is composed of harder, more
rigid materials. These mainly consist
of calcium and phosphorous (mostly in the form of hydroxyapatite). The cellular components of bones include
osteoprogenitor cells, osteoblasts, osteocytes, and osteoclasts (Figure 1). Osteoprogenitor
cells are unspecialized bone cells with a mesenchymal origin that possess
mitotic ability and can differentiate into osteoblasts. These cells are found throughout the bone
with heavy concentrations around the endosteum and periosteum. Osteoblasts are cells that produce the
extracellular substances of bone tissue.
Osteoblasts lack mitotic capacity and are derived strictly from
osteoprogenitor cells. Often a transitional
cell called a pre-osteoblast can be seen on micrographs (Figure 2).
They are found throughout the bone and concentrate on the surfaces of
the bone where their activity is stimulated by calcitonin produced within the
thyroid gland. Osteoblasts that become
encased in extracellular substances are known as osteocytes. Osteocytes lose capacity for bone production
and function in a bone maintenance role where they support the existing
extracellular environment. Finally,
osteoclasts are multinucleate cells that function to break down existing
bone. They are usually found on bone
surfaces and lead the tips of “cutting cones” (Figure 3), which are
required to remodel existing bone. They
are derived from monocytes and are positively regulated by parathyroid hormone.
Figure 1
Figure 2: Histologic
slide of the different stages of osteoblast.
Overlying these cells is the periosteum.
Figure 3: Below
is pictured a cutting cone with an osteoclast at it’s leading edge (left). See
the section on remodeling for more details.
There are two basic forms of bone. The first is called woven bone (also known as primary bone), which describes an immature, disordered bone that is often formed rapidly. This bone is found in the early stages of fracture healing and is the primary component of early callus (Figure 4). It has a low mineral content and disordered composition. Woven bone will remodel to a mature form of bone called lamellar bone. There is a highly ordered structure to the lamellar bone, called an osteon. Within a bone there are two configurations for osteons that include the cortical and cancellous regions. These configurations are distributed in variable amounts thru the three regions and are called the epiphysis, metaphysis and diaphysis (Figure 5). High-density cortical regions are found within the metaphysis and diaphysis of bones and are typically arranged into hollow cylinders that are adapted to resisting bending forces. Within the metaphysis, the cortical regions begin to thin out and the lower density cancellous regions predominate. These regions are particularly adapted to supporting weight bearing by flaring out to provide a larger surface area and increasing porosity to help resist strain. This helps distribute the forces of impact to the bulk of the bony structure during activities such as walking or running. The epiphysis describes the most distal aspect of the bone that contains the articular cartilage and subchondral bone.
Figure 4: Note the callus formation thru the healed 3rd metatarsal fracture.
Figure 5: Idealized bone anatomy
There are
two types of bone formation that occur during development. The first is called intramembranous
ossification and is the primary method of forming the clavicles and skull
bones. In this process, osteoblasts
cluster within fibrous membranes to form a center of ossification. They begin secreting collagenous fibers that
are subsequently calcified until trabeculae are formed. Eventually the osteoblasts are surrounded by
their secretions and become osteocytes.
Trabeculae grow together and form a complex lattice structure with the
spaces between trabeculae acting as the repository for marrow cells. In time, the bone surfaces are remodeled to
form compact bone.
The
second method is called endochondral ossification. This method describes the formation of most bones in the
body. It begins with the precursory
formation of a cartilage model covered with a perichondrium. Multiple blood vessels penetrate the
cartilage to initiate bone formation and growth. The first blood vessel penetrates about mid-shaft and sends
vessels to both ends of the cartilage model (Figure 6).
This will set up the primary center of ossification. In addition, the vessel penetration causes
osteoprogenitor cells to differentiate into osteoblasts and begin forming the
periosteal collar and eventually the cortex of the diaphysis. The central regions form spongy trabecular
patterns and are populated with red marrow.
Second, the epiphyseal vessels penetrate the ends of the cartilage
enlage and will form the secondary ossification centers. The vessels help arrange an environment
around the growth plate that allows longitudinal growth. (Figure 7)
Figure 6
Figure 7
The growth plate is divided into multiple zones (Figure 8). These
zones include the reserve zone, proliferative zone, and the hypertrophic zone.
The reserve zone is the area closest to the secondary center of ossification. It has epiphyseal vessels the pass through
this area but do not provide it with oxygen and keeps the oxygen tension low
in this area. It has no known function
with respect to longitudinal growth.
Figure 8
The proliferative
zone contains a progenitor cell at the top of each flattened column of cells
that is not derived from a cell within the reserve zone. These cells have large amounts of glycogen
storage and highly active endoplasmic reticulum for protein synthesis. This region is responsive to hormones and mechanical
factors. This region is affected in
achondroplasia and a single mutation in the FGFR3 receptor will cause proliferative
zone not to divide and subsequent failure of longitudinal growth.
The hypertrophic zone is divided into three regions including: the
zone of maturation, the zone of degeneration and the zone of provisional calcification. Throughout these zones the large quantities
of glycogen stored in the proliferative zone are consumed while the cells
transition from a high oxygen tension to low oxygen tension. The role of mitochondria change from one of
energy production to calcium storage and eventual release. (Figure 9)
Figure 9
The nutrient artery that pierces the central region of the bone bifurcates
and branches to form multiple metaphyseal arteries at the ends of the growth
plate. These arteries have capillaries
that perform a hairpin loop back upon themselves to provide venous return
for this low-flow system. These vessels
approach but do not penetrate the hypertrophic zone.
Blood vessels penetrate the epiphyses and form secondary centers of
ossification through a similar process. When
growth is complete, the progenitor cell stops dividing and the cartilage is
entirely replaced by bone leaving only an epiphyseal “scar” (Figure 10).
Figure 10: Open epiphyses top picture
with closed epiphyses below leaving a “scar”.
