BME/ME 456 Biomechanics
Bone Physiology
I. Overview
In this section we discuss aspects of bone physiology that are most relevant to the study of mechanically mediated bone adaptation. These aspects include bone cells and what they do, the different aspects of bone adaptation including osteogenesis, modeling and remodeling, and description of surfaces on which remodeling can occur. We basically will describe what potential exists for alterations of bone structure based on whether the bone is undergoing osteogenesis, modeling and remodeling. This physiologic potential will determine how mechanics may affect bone structure.
II. Bone Cells
Bone cells may be divided into two broad classifications depending on whether they make bone or resorb it. Osteoblasts make bone, while osteoclasts resorb or take away bone. However, there are actually three different sub-categories of bone cells related to osteoblasts: 1) the osteoblasts themselves, 2) bone lining cells, and 3) osteocytes. bone lining cells are basically inactive osteoblasts (in terms of making bone) that line bone surfaces. Osteocytes are osteoblasts that have becomes encased in bone matrix during bone tissue production. Many believe that osteocytes serve as sensors of mechanical stimuli within bone tissue. Specific characteristic of bone cells are detailed below:
Osteoclasts:
1. Giant multi-nucleated cells typically 20-100 microns in diameter
2. Secret acids and enzymes (collagenase) to break down bone matrix
3. Derived from macrophage lineage
Osteoblasts
1. Plump cuboidal single nucleated cells that synthesize and deposit bone matrix
2. Derived from mesenchymal stem cell lineage
3. Typically ~10 microns in diameter
Bone Lining Cells
1. Cover all available bone surfaces
2. Inactive osteoblasts
Osteocytes
1. A derivative of osteoblasts created when osteoblasts are encased in bone
matrix
2. Typically have much less bone deposition capability than active osteoblasts
3. Believed to be sensor cells within bone, sensing mechanical deformation
4. Connected to other osteocytes in a network via cell processes running through
canaliculi
III. Bone Surfaces
There are four major bone surfaces:
1.
Periosteal (outer surface of all bones)
2. Endosteal
(inner surface of cortical bone)
3. Haversian
(inner surface of haversian canals within osteons)
4. Trabecular
(outer surface of all individual trabeculae)
All activity that changes bone by direction operation on bone tissue occurs on one of these four surfaces. These four surfaces can be seen in the figure below:
The periosteum in the picture is the same as the periosteal surface. Likewise, endosteum in the picture is the same as the endosteal surface. The trabeculae have their own surface. Inside the cylindrical haversian systems are the haversian surfaces.
IV Osteogenesis: Production of Bone on Soft Tissue
Now that we know the players in bone adaptation, we will look at the ways in which bone may be created and modified. There are three major ways bone tissue may be altered: 1) osteogenesis, 2) modeling and 3) remodling. The alterations differ basically in the tissue on which bone is placed and the way in which osteoblasts and osteoclasts work together. Osteogenesis is the production of bone on soft tissues, either soft fibrous tissue or cartilage. It is the way in which bones are formed during embryonic development and how bone is initially formed at the site of injury, for example in fracture healing. Osteogenesis may divided into two sub-classifications depending on the mechanism and soft tissue base for bone formatin.
The first type is intramembranous ossification, which is the process
by which flat bones like the skull, mandible and clavicle are formed. It occurs
in the following steps.
1. Condensation of mesenchymal cells in well-vascularized primitive connective
tissue.
2. Appearance of dense eosinophilic osteoid matrix and simultaneous transformation
of mesenchymal cells to larger, more basophilic osteoblasts.
3. Initial production of bone spicules (trabeculae) with random collagen organization
(woven bone).
4. Compaction of trabeculae to form cortical bone
This process is illustrated in the schematic below:
The spindle shape objects with the dark circles are the initial mesenchymal cells, the cross hatched area is the initial bone formation, and the square shaped objects with dark circles are the differentiated osteoblasts.
The second type of osteogenesis is endochondral ossification. This process is different from intramembranous ossification in that it occurs with a cartilage base. Endochondral ossification is responsible for a good deal of formation of the long bones and vertebrae. It occurs in the following steps:
1. Hypertrophy (swelling) of chondrocytes (cartilage cells) in central portion
of cartilage model. These enlarged chondrocytes cease production of type II
collagen and proteoglycan aggregates and begin to produce matrix vesicles, alkaline
phosphatase, and type X (ten) collagen. They initiate the matrix changes that
lead to their ultimate death.
2. Formation of bone collar between the periosteum and the shaft of the cartilage
model.
3. Cartilage matrix calcification; because oxygen, nutrients and cellular wastes
can no longer diffuse through the matrix the chondrocytes degenerate and leave
behind a scaffolding of calcified cartilage.
4. Blood vessel invasion by a periosteal bud of blood vessels that penetrates
the primary marrow cavity through the bone collar. Osteoprogenitor cells and
hemopoietic cells enter the cartilage model. The hemopoietic cells will form
bone marrow.
5. Bone matrix layed down on scaffolding of calcified cartilage by cells of
the periosteal bud that transform into osteoblasts.
The process of endochondral ossification is illustrated below:
A in the illustration corresponds to steps 1 and 2. B corresponds to step 3. C corresponds to step 4 and D corresponds to step 5.
In osteogenesis, large amounts of woven bone can be formed very rapidly. This bone is believed to be much more compliant than organized lamellar bone. In osteogenesis, osteoblasts and osteoclasts generally act independently, that is, they are not coupled in their actions.
V. Bone Modeling: Reshaping of bone by independent action of osteoblasts and osteoclasts
Once we have initial bone formation in the embryonic or initial healing stage, large changes in the bone shape may be needed. This for example may occur because the child is growing rapidly, or because the initial fracture callus must be chaned to a shape that is more functional. The defining characteristics of bone modeling are 1). Changes in bone structure occur on existing bone structure and 2) bone structure alterations occur by independent action of osteoblasts and osteoclasts. This means that bone resorption and formation may occur on different surfaces. In addition, modeling may cause large changes in bone structure.
VI. Bone Remodeling
Bone remodeling differs from the other two means of bone structure alteration in that osteoblasts and osteoblasts do not act independently but are coupled and bone resorption and formation occur at the same spot on a bone surface. As with modeling, bone remodeling occurs on existing bone surfaces. However, unlike modeling, remodeling cannot cause large changes in bone structure at a given site. At best, remodeling maintains the current amount of bone structure. However, as we all age past 35, the amount of bone that is deposited starts to slightly lag the amount of bone that is resorb leading to a gradual decline in bone mass.
There are five stages in bone remodeling:
1.
Quiescence
2. Activation
3. Resorption
4. Reversal
5. Formation
Quiescence refers to the resting state of the bone surface. This includes all of the bone surfaces. Activation is the recruitment of osteclasts to a bone surface and signal coupling of osteoblasts. Resorption is the removal of bone by osteoclasts. Reversal is the process by which osteoclasts stop removing bone and osteoblasts fill the defect. Formation is the laying down of bone by osteoblasts. The entire process is illustrated below:
In the above illustration, LC refers to lining cells, POC refers to osteoclast precursors, OC refers to osteoclasts, HL refers to Howship lacunae (the name of a resorption pit), OB refers to osteoblast, CL refers to closed lacunae, and BSU refers to bone structural unit, the newly created piece of bone. The scenario illustrated above is most relevant to trabecular bone surface remodeling. In cortical bone the same steps occur in remodeling, but the remodeling occurs in a different shape, known as a cutting cone. A cutting cone is diagrammed below:
The same steps occur in cutting cone remodeling as in general surface remodeling. The only difference is in the geometry of the remodeling zone.
VII Summary
In summary, there are three major ways in which bone structure may be changed. These are summarized below:
1. Osteogenesis
a.
Bone formed on soft tissue
b. Occurs
during embryonic development, early stages of growth, and during healing
c. Two
major subclassifications: intramembranous ossification and endochondral ossification
d. Intramembranous:
bone formed on soft fibrous tissue
e. Endochondral:
bone formed on cartilage
f. Osteoblasts
derived from mesenchymal cells act indepdendent of osteoclasts
g. Potential
to create large amounts of bone
2. Modeling
a.
Bone formed on existing bone tissue
b. Occurs
during growth, and during healing
c. Osteoblasts
and osteoclasts act independently at different sites
d. Potential
to create or resorb large amounts of bone
3. Remodeling
a.
Bone both resorbed and formed at the same site
b. Occurs
from growth through death.
c. The
only normal physiologic mechanism for chaning bone in adult skeleton
d. At
best leads to maintenance of bone; however as we age leads to net loss of bone