Lecture 3

Bone Modelling

Modelling occurs as a result of:

• formation through osteoblastic activity on selective bone surfaces

• resorption through osteoclastic activity on other bone surfaces

Growth of Flat Bones

Flat bones grow due to bone formation on their leading outer surfaces and resorption from the inside

• This is how the cranial cavity enlarges to accommodate the growing brain and other elements of the head

Growth of Long Bones

During growth, long bones need to grow both in length and girth. Growth in length is achieved via the process of endochondral ossification; by chondrocyte proliferation in the growth plate and hypertrophy which is then followed by osteogenesis. Epiphyses expand and grow similarly; through proliferation of chondrocytes in articular-epiphyseal growth cartilage.

Growth in girth occurs by a net accrual of new bone (formation – resorption > 0) on the outer surfaces (intramembranous ossification) while bone from the inner surfaces is subjected to a net loss (formation – resorption < 0)

Bone Remodelling

Trabecular Bone

1. During the quiescent phase, bone lining cells normally form the endosteum covering the surface of bony spicules.

2. Following the activation of signalling pathways that initiate remodelling, osteoclasts form (=osteoclastogenesis) and replace bone lining cells

   • RANKL assists with osteoclastogenesis through up regulation via PTH

3. They then establish a sealing zone and start digesting and removing bone to form a resorption pit.

4. As they do so, growth factors previously locked in the bone matrix are released which stimulate osteoblastogenesis of mesenchymal precursors or perhaps re-activation of some of the bone lining cells.

5. Osteoclasts as well produce factors that further facilitates recruitment of osteoblasts to the exposed bone matrix. This is called the reversal phase and is followed by deposition of osteoid by osteoblasts.

6. Next is matrix mineralisation followed by formation of a new layer of bone lining cells. At this stage, the new bone surface enters the quiescent phase which may last days or years.

Cortical Bone

1. Osteoclasts displace bone lining cells that invest the haversian canal and start to tunnel through bone longitudinally. The resorption cavity (instead of a resorption pit in trabecular bone) that results is often conical in shape at the active resorption front which is called a ‘cutting cone’.

2. Blood vessels can invade the cutting cone and “follow it”

3. The reversal zone initiates mesenchymal cells into osteoblasts

4. This is followed by osteoblasts which deposit concentric lamellae of bone to fill in the tunnel, leaving space for blood vessels, thus forming a new osteon. The trailing end of the resorption pit where bone formation takes place is called a ‘closing cone’

Regulation of Modelling/Remodelling

Osteoblast activity is stimulated by:

• Hormones such as sex steroid hormones (oestrogen, testosterone), BMPs, other growth factors

• mechanical load

• inflammatory cytokines and prostaglandins

Osteoclast activity is stimulated by:

• PTH (calcium homeostasis, especially during pregnancy and lactation)

• mechanical unloading (e.g. rest periods following training – horses)

• inflammatory cytokines and prostaglandins

• most of these effects mediated by osteoblasts – hormones and cytokines stimulate RANKL expression in osteoblasts

Fractures

Fracture is defined as a break in the continuity of bone or cartilage that could be either complete or partial. The resulting pieces of bone are referred to as fracture fragments; a single complete fracture line results in two bone fragments, two lines three fragments, etc

Forces that affect the bones are either non-physiological or physiological in nature

Non-physiological forces

• motor vehicle accidents (MVA)

• falls

• gunshot trauma

Physiological forces

• weight bearing

• muscle contraction and physical activity

Fracture Gap

Following a fracture, fragments move and gaps form. Eventually, these gaps need to be filled in with bone for the fracture to heal fully

The tissue that fills in the fracture gap and its surrounding area is called the bridging callus. The larger the gap, the more work that needs to be done in order to bridge the fracture fragments

• Usually gets filled with granulation tissue first then fibrous tissue then towards cartilage and then bone

Larger than a certain size and gaps never heal; such a gap is called a critical-sized defect

Concept of Interfragmentary Strain

Following a fracture, bone fragments are unstable and move often

Movement, as discussed earlier, leads to strain. The bridging callus should be able to survive this strain in order for the fracture to heal

The smaller the gaps, the larger the strain (potentially due to the increased compliance of the tissue in larger gaps compared to smaller gaps)→ This is why body resorbs the edges of a fracture gap that is smaller than 0.3 mm or when fragments are mobile; it enlarges that gap in order to decrease interfragmentary strain.

Fracture Healing

Indirect Union

A large gap (formed through body resorption + minimally mobile → indirect (secondary) union

Indirect union occurs through the following stages:

1. Inflammation and oedema

   Disruption of vascular integrity leads to formation of a haematoma → granulation tissue forms → recruitment of mesenchymal stem cells

2. Soft callus formation

   Mesenchymal stem cells differentiate into chondrocytes and fibroblasts, which generate a cartilage and fibrous tissue mix

3. Hard callus formation

   Soft tissue is modified to turn into cartilage and bone → generally woven and trabecular bone and then can be remodelled in step 4

4. Callus remodelling

Direct Union

Small gap (less than 0.1mm) + limited mobility → direct (primary) bone healing

Occurs via direct osteonal remodelling or new osteon formation without resorption of the fracture surfaces. No callus forms in this mode nor do any intermediate fibrous or cartilage tissues.

If gaps are absent, cutting cones form and run through the fracture line from one fragment to the next which are then followed by lamellar bone formation to establish continuity across the fracture gap and bridge the fragments

Mechanical Forces

Mechanical forces produce internal force intensities known as internal stress/strain which leads to deformation of the bone

Stress is the force applied divided by the area

Strain is the change in length of the bone as a result of the stress, divided by the original length of the bone

Axial Compression

= the act of putting pressure on bone as in trying to make it shorter

• Putting the bone under weight

Concentric axial compression refers to the presence of compressive forces around the central axis of a bone, e.g. weight bearing of the equine metatarsus.

• Causes compressive stress, shear stress and tensile strain (lateral displacement)

Eccentric axial compression refers to axial compressive forces that act some distance away from the central axis e.g. weight bearing of canine radius

• Results in bending and therefore compression stress on the near side and tensile strength on the far side

Tension

= the act of stretching a bone as in pulling an object tight

Bending Moment of Force

= a force that tends to bend a bone about an axis perpendicular to its long axis

Results from eccentric compression → Bending creates compressive stress on the concave side of the bone and tensile stress on the convex side

Has been seen when the position of the joint is eccentric (not central) and when the bone has normal curvature

Torsion Moment of Force (Torque)

= a force that tends to twist a bone about its long axis

Muscle contraction too contributes to torque when the point of insertion of the muscle is offset from the central axis of rotation of bone

Definitions

Modelling - the shaping of bones during their development (embryonic) and growth, in response to changing mechanical loads or bone injury.

Normal stresses and strains - internal stresses and strains that are perpendicular to a surface

Shear stresses and strains - oblique or parallel (as in pushing a part of bone to the left and the part just below that to the right) internal stresses/strains

Axial force - refers to a force that acts parallel to the long axis of bone.

Radial force - refers to a force that acts perpendicular to the long axis