Bone growth and healing Flashcards
Describe the anatomical regions of a normal tubular bone
A normal tubular bone has an epiphysis, physis (growth plate), metaphysis and diaphysis. The epiphysis extends from the base of the articular surface to the region of the growth plate. The metaphysis extends from the growth plate to where the diameter of the bone becomes narrow and the diaphysis or shaft extends from the base of one metaphysis to the base of the opposing one. In immature or growing bones the metaphysis is separated from the epiphysis by a cartilaginous growth plate or physis.
What are the differences between woven bone and lamellar bone?
Woven bone is bone which is made rapidly such as in the unborn child, a healing fracture or in some diseases. Type I collagen fibres are laid down and then mineralised as criss-cross woven bone which is able to withstand stress equally well in all directions. In lamellar bone, the collagen fibres are nearly parallel and this takes longer to make but is much stronger. The collagen fibres run in opposite directions in alternating layers of lamellar bone, helping the bone to resist torsion forces. Normally the entire mature skeleton is composed solely of lamellar bone.
What is osteoid?
Osteoid is unmineralized bone matrix and is composed of type I collagen and glycosaminoglycans (GAGs). Calcium hydroxyapatite, a calcium salt crystal is then deposited which gives bone its strength and rigidity.
What are the two ossification methods by which bone normally forms?
Intramembranous ossification and endochondral ossification.
Describe intramembranous ossification and give an example of bones which form by this method.
During intramembranous ossification bone develops directly from sheets of mesenchymal (undifferentiated) connective tissue. The flat bones of the face, most of the cranial bones and the clavicles (collarbones) are formed via intramembranous ossification.
Describe endochondral ossification and give some examples of bones which form by this method.
In endochondral ossification, bone develops by replacing hyaline cartilage. Cartilage serves as a template to be completely replaced by new bone and this takes much longer than intramembranous ossification. Bones at the base of the skull and long bones form via endochondral ossification.
Describe the layers of a long bone beginning at the external surface and moving towards the centre of the bone.
The layers of a long bone, beginning at the external surface are:
- Periosteum.
- Outer circumferential lamellae.
- Compact bone (Haversian systems).
- Inner circumferential lamellae.
- Endosteal surface of compact bone.
- Trabecular bone.
Describe the structure of an osteon/Haversian system.
Compact bone is organized as parallel columns known as Haversian systems or osteons which run lengthwise down the axis of long bones. These columns are composed of lamellae - concentric rings of bone surrounding a central channel or Haversian canal that contains nerves blood vessels and the lymphatic system of bone. The parallel Haversian canals are connected to one another by the perpendicular Volkmann’s canals.
Describe the process of bone remodelling.
Bone remodelling begins when mononuclear osteoclast-precursors (derived from haematopoietic stem cells) arrive at a bone surface and differentiate into functional osteoclasts. Remodelling is regulated by cell-to-cell interactions and cytokines. Mature osteoclasts secrete acid and proteases (matrix metalloproteinases) onto the bone surface, excavating a pit known as Howship’s lacuna. The resorption phase ends with osteoclast apoptosis and a reversal phase follows characterised by activation of osteoblasts (of mesenchymal origin) to replace the excavated bone.
The activity of osteoclasts and osteoblasts is normally tightly coupled, and the amount of bone synthesized matches the amount resorbed. The newly secreted matrix called osteoid becomes mineralised to form mature bone.
The remodelling cycle ends where new bone formation is complete and the osteoblasts are either incorporated into the new bone matrix as osteocytes or become quiescent surface bone lining cells.
The net result of each cycle is a formation of a new osteon - a packet of bone in which the collagen fibres are aligned.
Describe the regulation of osteoclast activity by the Receptor Activator of Nuclear Factor Kappa Beta (RANK) and Osteoprotegrin (OPG).
Osteoclasts are derived from the same mononuclear cells that differentiate into macrophages. Osteoblast/stromal cell membrane-associated RANK ligand (Receptor Activator of Nuclear Factor Kappa Beta ligand) binds to its receptor RANK located on the cell surface of osteoclast precursors. This interaction, in the background of macrophage colony-stimulating factor (M-CSF), causes the precursor cells to produce functional osteoclasts. Stromal cells also secrete osteoprotegrin (OPG) which acts as a decoy for RANKL, preventing it from binding the RANK receptor on osteoclast precursors. Consequently OPG prevents bone resorption by inhibiting osteoclast differentiation. Bone resorption or bone formation can be favoured by altering the RANK:OPG ratio. Parathyroid hormone and steroids promote osteoclast differentiation and bone turnover. In contrast, bone morphogenetic proteins and sex hormones block osteoclast differentiation or activity by favouring OPG expression.
List and define the various fracture types (7 types).
- Simple - bone fracture without skin penetration.
- Compound - bone fracture with skin penetration.
- Comminuted - bone fracture with fragmentation.
- Displaced - bone fracture where the ends are not aligned properly.
- Stress - a fracture caused by increased physical activity and repetitive loads.
- Greenstick - a fracture seen in infants when the bone is soft, which extends only partially through the bone.
- Pathological - a fracture of a bone which is weakened by an underlying process such as a tumour.
What would you see if you examined a fracture under the microscope on day 1?
An organising haematoma.
What would you see if you examined a fracture after 2-3 weeks?
After about 2 weeks the soft callus is transformed into bony callus. The activated osteoprogenitor cells deposit woven bone. In some cases the activated mesenchymal cells in the soft tissues and bone surrounding the fracture line also differentiate into chondrocytes that make fibrocartilage and hyaline cartilage. The newly formed cartilage along the fracture line undergoes endochondral ossification forming a contiguous network of bone with newly deposited bone trabeculae in the medulla and beneath the periosteum. In this fashion the fractured ends are bridged.
What would you see after 12 weeks?
As the callus matures and as it is subjected to weight-bearing forces, portions that are not physically stressed are resorbed. This remodelling reduces the size of the callus until the shape and outline of the fractured bone are re-established as lamellar bone. The healing process is complete with restoration of the medullary cavity.
List five factors which can impair fracture healing.
- Displaced/comminuted fractures - can lead to deformity.
- Inadequate immobilisation - prevents normal callus maturation causing delayed or non-union.
- Open fractures - can become infected.
- Malnutrition.
- Skeletal dysplasia (congenital abnormalities).
