Proximal fractures of the humerus

X ray AP and lateral you knee and lower femur show a recent green stick fracture that starts healing after 2 weeks in a one years old child.

X ray AP and lateral views of left leg of a 20 years old case of fracture tibia show evidence of healing after 3 months

Fracture healing stages 

Fracture is a break in the structural continuity of the bone cortex, with a degree of injury to the surrounding soft tissues. Following the fracture, bone healing begins, which consists of four stages: However, these stages have considerable overlap.

1. Hematoma formation.
2. Fibrocartilaginous callus formation.
3. Bony callus formation.
4. Bone remodeling and addition of compact bone.

Delayed fracture healing occurs in up to ten percent of all fractures.

 Some authors summarize fracture healing stages into three stages of bone healing:

1-inflammatory.

2-reparative.

3-remodeling.

Some authors describe fracture healing as a five stages process:

1- Stage one, fracture and inflammatory phase, lasts for 5 days:

The blood vessels that supply the bone and the periosteum rupture during the fracture. Bleeding initially occurs between edges of  bone fracture. That causes a hematoma to form around the fracture site. The hematoma clots, and forms the temporary frame for subsequent healing. 

Hematoma develops during first few hours and days. The injury to bone results in the secretion of cytokines. Tumor necrosis factor-alpha (TNF-α), bone morphogenetic proteins (BMPs), and interleukins (IL-1, IL-6, IL-11, IL-23) are examples of pro-inflammatory cytokines. Inflammation in the area causes vascular permeability and attraction of WBCS.

2- Stage two, granulation tissue formation: it lasts for two weeks. Fibroblasts are attracted to area of injury. There is a growth of vascular tissue, nutrient and oxygen supply. Cytokines act to stimulate and attract macrophages, monocytes, and lymphocytes. These cells act together to remove necrotic tissue and secrete cytokines like vascular endothelial growth factor (VEGF) to stimulate healing at the site.

3- Stage three, callus formation: it lasts four to fifteen weeks. Callus consists of osteoblasts and chondroblasts, cells syntehsize matrix of woven bone and cartilage. 

The release of VEGF leads to angiogenesis at the site of fracture. Within the hematoma fibrin-rich granulation tissue, begins to develop. Mesenchymal stem cells are recruited to the area and begin to differentiate (driven by BMPs) to fibroblasts, chondroblasts, and osteoblasts. Chondrogenesis begins to occur and a collagen-rich fibrocartilaginous network span the fracture ends with a surrounding hyaline cartilage sleeve. At the same time, osteoprogenitor cells lay down a layer of woven bone.

During this preliminary stage of repair and soft callus formation, pain and swelling subside as the bone fragments become united by a fibrocartilagenous tissue.

4- Stage four, lamellar bone deposition:

Ossification is mineralized. The meshlike callus of woven bone is replaced by sheets of mineralized bone. They are organized parallel to axis of the bone and are mechanically stronger than woven bone.

Lamellar bone is a mature bone which results from the remodeling of immature woven bone. Lamellar bone is highly organized bone structure in which stress-oriented collagen of lamellar bone gives its anisotropic properties.

At the end of this phase, a hard, calcified callus of mature bone forms.

5- Stage five, bone remodelling:

It begins from day 18 onwards, lasting months-years. Osteoblasts and osteoclasts continue their migration and the hard callus undergoes repeated remodeling. It is better termed 'coupled remodeling.' This 'coupled remodeling' is a continuous balance of resorption by osteoclasts and new bone formation by osteoblasts. The center of the callus is ultimately replaced by compact bone, while the callus edges become replaced by lamellar bone. Remodeling of the vasculature occurs at the same time of these changes. The process of bone remodeling lasts for many months, ultimately resulting in regeneration of the normal bone structure.

 Types of bone healing

Bone can heal without forming a fibrous scar. There are two types of fracture healing 

 - indirect (secondary). It occurs when the bony fragments are not fixed together with compression.

 - direct healing (primary). It occurs when the bony fragments are fixed together with compression.

Types of ossification 

1- Endochondral ossification is the process of conversion of cartilage to bone. As described above, this occurs during the formation of bony callus. The newly formed collagen-rich immature cartilaginous callus is replaced by immature bone. Endochondral ossification is also the key to the formation of long bones in the fetus, in which the bony skeleton replaces the hyaline cartilage model. 

2- The second type of ossification also occurs in the fetus. This is intramembranous ossification; this is the process by which mesenchymal tissue (primitive connective tissue) is converted directly to the bone, with no cartilage intermediate. intramembranous ossification takes place in the flat bones of the skull. 

Clinical picture and Treatment 

 -If a fracture is adequately fixed, primary bone healing occurs. It is the reestablishment of the cortex without the formation of a callus.

-Secondary bone healing, which is described above, occurs through the formation of callus and subsequent remodeling.

- Reducing and fixating the fracture by moving the two ends of the fracture into close apposition results in minimal formation of granulation tissue and callus. Reduction of a fracture can be either open or closed. Closed reduction is done without the need to make an incision into the skin. Open reduction is done with opening the skin with a surgical incision.

- Closed reduction is used, if a fracture pattern appears stable. Options for this are by cast (e.g., plaster of Paris), a brace or a splint. 

- Open reduction is used if a fracture appears unstable and commonly occurs alongside internal fixation. The term ORIF means open reduction and internal fixation. 

- Internal fixation is the use of surgical implants to fix the two ends of the fracture. Methods of internal fixation are plating, wires, screws and intramedullary nails. 

- External fixation is the placing of pins through the skin, which are then held in place by an external 'scaffold.' External fixator tends to be used in complex fractures and it may be as a temporary option before internal fixation.[9]

Factors that delay fracture healing

 These factors are divided into local and systemic categories.

• General
• Age
• Infection
• Radiation
• Chemical or thermal burns
• Anaemia & hypoxia
• Nutrition (Vitamen C required for normal collagen)
  
• Drugs (corticosteriods inhibit osteoblast differentiation)
• Endocrine conditions - Diabetes mellitus, Parathyroid disease, and Menopause
  
• Smoking
  
• Obesity

• Local
• Interposed soft tissue
• Distraction of the fracture 
• Inadequate fixation or compliance
  
• Intact fellow bone
  
• Excessive Movement at the fracture site 
• Soft tissue trauma
• Denervation
• Excessive compression

Factors stimulate and promote fracture healing:

• Dietary supplements - calcium, protein, vitamin C and vitamin D
• Bone graft - this means the use of bone to provide a scaffold to the newly forming bone. This graft can be from the patient's body (autograft) or from a cadaver donor (allograft).
• Bone stimulators - which can be electromagnetic, electric and ultrasound. The effectiveness of these methods is still equivocal and this area requires more future research.