2. COMPONENTS OF FRACTURE
HEALING
1. Progenitor cells (Periosteum and Endosteum):
Bone surfaces are covered by tissue layers called the periosteum and endosteum (fibrous layers rich in cells
and blood vessels)
Periosteum responds to bone fracture through extensive cellular proliferation
The resulting pluripotent cells differentiate into either osteoblasts or chondrocytes, depending on
inflammatory signals and the local mechanical and vascular environment, with increased mechanical
stability favouring osteogenic differentiation.
Periosteum provides a supply of osteoblasts, and is the primary source of chondrocytes
3. Endosteum primarily give rise to osteoblasts during fracture healing
Disruption of the periosteum leads to failures of healing through the invasion of fibrous tissue and loss of
fracture hematoma contents into the surrounding soft tissues.
2. Chondrocytes:
Play an important role in the healing of fracture
Function is to produce extracellular matrix proteins such as proteoglycans and collagen
During fracture healing, hypertrophic chondrocytes participate in endochondral ossification through the
synthesis of matrix and the deposition of intracellular calcium.
Chondrocytes subsequently undergoes apoptosis, leaving a bed of woven bone that is invaded by new blood
vessels and remodelled by osteoblasts and osteoclasts.
4. 3. Osteoblasts:
Defines by its ability to produce osteoid (the organic component of bone composed primarily of type I
collagen)
Line the surfaces of bone
Function is to form bone matrix and regulating the process of bone turnover by influencing osteoclast
activity.
Osteoblasts primarily produce type I collage osteocalcin, bone sialoprotien, other matrix proteins associated
with bone
Express alkaline phosphatase, a membrane- bound enzyme responsible for dephosphorylation, an enzyme
activity.
4. Osteoclasts:
Cell population responsible for the resorption of bone enabling the remodelling of fractures.
5. Express tartrate- resistant acid phosphatase (TRAP) and cathepsin K.
Large, multinucleated cells that are formed by the fusion of mononuclear cells.
On bone surfaces, osteoclasts reside in Howship lacunae, or resorption pits in the bone surface.
5. Inflammatory cells:
Associated with the cell mediated and humoral responses to bone injury.
Platelets, neutrophils, macrophages and leukocytes are all found at the fracture site within the first hour after
fracture.
a. Platelets:
Small cell fragments that are derived from megakaryocytes
Present in circulating blood and spleen.
6. Activated after fracture by encountering injured epithelial cells with exposed collagen and von Willebrand
Factor (vWF)
Results in the aggregation of platelets, blood coagulation, and the excretion of granule contents (platelet
derived growth factor- PDGF; vascular endothelial growth factor-VEGF; transforming growth factor beta-
TGF-ß; fibroblast growth factor- FGF; insulin- like growth factor- 1 IGF- 1; platelet derived endothelial
growth factor- PEGF)
Role in both hemostasis and the early local fracture healing process.
b. PMNs or neutrophils:
Most abundant form of granulocytes in the peripheral blood.
Circulate in the bloodstream making up 75% of the white blood cell mas.
After tissue trauma, PMNs arrive immediately, and their number continue to increase at 4 hours after injury
7. PMNs invade traumatized tissue in response to chemotactic signals and vessel endothelium cell surface
capture mechanisms at the site of injury.
Their life span is only 1 to 2 days
Activated PMNs perform both phagocytic and degranulation functions at the site of trauma
c. Macrophages:
Follow PMNs, arriving at the fracture site after several hours.
Derived from the hematopoietic stem cell lineage
Play a role in the debridement of tissue injury sites, activation of the adaptive immune system through the
presentation of antigens on the cell surface and the secretion of cytokines
8. d. Lymphocytes:
Including various subpopulation of B- cells and T- cells, form the adaptive immune system
As granulation tissue develops at the fracture site about 7 days after fracture, the number of T- cells eclipses
that of macrophages
Lymphocytes are responsible for production of cytokines (Inhibitory effect)
6. Scaffold:
Bone healing is a three- dimensional process that requires a scaffold to allow the cellular components of the
healing process to perform their function
Responsible for conferring the structural properties of bone and cartilage and in some cell regulatory
functions
9. The ECM of bone is composed of inorganic and organic materials
Inorganic- mineral cysts (calcium, phosphate, sodium, magnesium and carbonate)
Organic material- primarily type I collagen
Fracture → fibrinogen → converted to fibrin → semisolid blood clot → provides initial scaffold for
inflammatory cell migration
Absence of MMPs (metal metalloproteinases) particularly MMP9, results in non-union associated with the
failure to replace cartilage with osteoid at the fracture site
7. Blood supply:
Fracture → local blood vessels disrupted → avascular and hypoxic area→ hypoxia- inducible factor (HIF)-
1→ promotes production of VEGF→ promotes revascularization
10. TYPES OF BONE HEALING
1. Healing by callus:
Stages:
i. Haematoma formation:
Vessels are torn and a hematoma forms around and within the fracture
Lasts upto 7 days
Fracture →periosteum and local soft tissues are stripped from the fracture- ends →ischaemic necrosis of the
fracture ends over a variable length (few mm) →osteocytes differentiate into daughter cells → contribute to
the healing process
11. ii. Stage of granulation tissue:
Inflammation and cellular proliferation
Lasts for 2-3 weeks
The sensitised precursor cells (daughter cells) produce cells which differentiate and organise to provide
blood vessels, fibroblasts, osteoblasts etc
Gives a soft tissue anchorage to the fracture, without any structural rigidity
Blood clot gives rise to a loose fibrous mesh which serves as a framework for the ingrowth of fibroblasts and
new capillaries
The clot is eventually removed by macrophages, giant- cells and other cells arising in the granulation tissue.
12. iii. Stage of callus:
Lasts for about 4-12 weeks
Granulation tissue differentiate further and creates osteoblasts
These cells lay down an intracellular matrix which soon becomes impregnated with calcium salts
Formulation of the callus also known as woven bone
First sign of union visible on X-rays
Slower in adults than children and in cortical bones than in cancellous bone
iv. Stage of remodelling:
Also known as the stage of consolidation
1- 4 years
Woven bone is replaced by mature bone with a typical lamellar structure
13. This process of change is multicellular unit based, whereby a pocket of cells is replaced by pocket of
lamellar bone
Slow process
v. Stage of modelling:
Formerly called the stage of remodelling
Bone is gradually strengthened
Shapening of cortices occurs at the endosteal and periosteal surfaces
Stimulus to this process is from the weight bearing stresses
2. Healing by direct union:
If the fracture site is absolutely immobile there is no stimulus for callus
Instead, osteoblastic new bone formation occurs directly between the fragments
14. Gaps between the fracture surfaces are invaded by new capillaries and osteoprogenitor cells growing in from
the edges, and new bone is laid down on the exposed surface (gap healing)
Where the crevices are narrow (less than 200 mm), osteogensis produces lamellar bone; wider gaps are filled
with woven bone first, which is then remodelled to lamellar bone
By 3-4 weeks the fracture is solid enough to allow penetration and bridging of the area by bone remodelling
units, i.e. osteoclastic ‘cutting cones’ followed by osteoblasts
Where the exposed fracture surfaces are in intimate contact and held rigidly from the outset, internal
bridging may occasionally occur without any intermediate stages (contact healing)
15. FACTORS AFFECTING FRACTURE
HEALING
i. Age:
Unite faster in children
Callus is often visible on X-rays as early as 2 weeks after the fracture
Failure of non union is uncommon
ii. Sex: no difference in fracture healing between males and females
iii. Type of bone: flat and cancellous bone unite faster than tubular and cortical bone
iv. Pattern of fracture: spiral fracture > oblique fracture > transverse fracture
16. v. Type of reduction: good apposition = faster union
vi. Immobilization: not necessary for all fractures; some need restrict immobilization
vii. Compounding: open fracture = delayed and non – union
viii. Compression at fracture site: enhances the rate of union in cancellous bone
ix. Electrical stimulation: electro- negativity enhances union
Dephosphorylation is the process by which phosphate groups are removed from a molecule by a phosphatase. Removal of phosphate groups from a DNA fragment can prevent ligation.
Cathepsin K is protease, which is defined by its high specificity for kinins, that is involved in bone resorption. The enzyme’s ability to catabolize elastin, collagen and gelatin allow it to break down bone and cartilage.
Howship’s lacunae, a groove or cavity usually containing osteoclasts that occurs in bone which is undergoing reabsorption.
vWF is a blood glycoprotein involved in hemostasis