Bone healing

Definition
Proliferative physiological process in which the body facilitates the repair of bone fracture
Generally bone fracture treatment consist reduce displaced bone and waiting natural
healing process to occur

Factore integrity fracture healing :

- Adequate nutrient
- Age
- Bone type
- Drug therapy
- Pre existing bone pathology

Healing process is mainly determined by periosteum (connective tissue membrane covering

the bone). periosteum one source of precursor cells develop into chondroblast – osteoblast
that essential to healing bone.
Other source : bone marrow, endosteum, small blood vessel, fibroblast

Primary healing (direct healing)

- Require anatomical reduction which is stable
- Without any gap formation
- Require remodeling lamellar bone, haversian canal and blood vessel
- Without callus formation
- Intramembranous healing
- Occurs with absolute stability construct

Contact healing
- When the gap between bone end less than 0.01 mm
- Interfragmentary strain less than 2 %
Contact healing can occur
- Cutting cone (consist of osteoclast, form across the fracture line, generating cavities
at rate 50-100 micro/day
- Osteoblast fill up the cavities with haversian system

Gap healing
If fracture gap 800 mikro – 1mm fx filled by osteoclast then by lamellar bone oriented
perpendicular axis of bone. orientation lamellar bone is weak. Secondary healing required
to re orient lamellar bone longitudinally. This process 3-8 weeks
Secondary healing (indirect healing)
- Most common
- Consist endochondral ossification
- Sometimes intramembranous ossification
Mediated by periosteal layer bone, without callus formation
- endochondral ossification
deposition bone only occurs after mineralized cartilage
- involves response in the periosteum and external soft tissue
- occurs with non rigid fixation, external fixation, bridge plating, intramedullary nailing

3 major phases fracture healing

1. Reaction
- inflammation
- granulation tissue formation
2. Repair
- cartilage callus formation
- lamellar bone deposition
3. Remodelling

Reaction
Fracture  blood vessel constrict  stop bleeding  few hours extravascular blood cells
form clot (hematom)  that act template for callus formation

Including macrophage  release inflammatory mediator :

- Cytokine ( tumor necrosis factor alpha)  TNF
- IL 1, 6, 11,18
Increase blood capillary permeability

Inflammation peak 24 hours  complete 7 days

IL 1 promotes formation callus & blood vessel
IL 6 promote differentiation osteoblast & osteoclast

Within this area  fibroblast replicate

7-14 days they form aggregate of cells  interspersed small blood vessel (granulation
tissue)  osteoclast move into reabsorb dead bone ends  other necrotic tissue is
removed
Fracture  inflammation process start rapidly  hematoma formation + inflammatory
exudation from rupture blood vessel
Bone necrosis seen at the end of fracture fragments  injury of soft tissue and
degranulation platelet  release powerful cytokine  produce inflammatory response 
(vasodilatation, hyperemia, migration proliferationof PMN, macrophage)

Repair
- 7-9 days after fracture cells of periosteum replicate & transform
- periosteal cells proximal to(on the near side) fracture gap  develop chondroblast
 which form hyaline cartilage
- periosteal cells distal (at the far end of) fracture gap  develop osteoblast  which
form woven bone
- fibroblast within granulation tissue  develop into chondroblast
- 2 new tissue grow in size until they unite each other  (new mass heterogenous) 
callus
- callus formation peak 14 days
- next phase endochondrial ossification  (replacement hyaline cartilage woven bone
into lamellar bone
- lamellar bone begins forming after collagen matrix become mineralized (the process
induced IL 1 & TNF
- mineralized matrix penetrated by microvessel and numerous osteoblast
- osteoblast form  new lamellar bone
- new lamellar bone form  trabecular bone
- woven bone & cartilage original fracture callus  replaced by trabecular bone 
restoring bone original strength
Remodelling
- begin 3-4 weeks after fracture, take 3-5 years to complete
- trabecular bone resorbed by osteoclast  creating shallow resorption pit “howship
lacuna”
- osteoblast deposit compact bone within resorption pit
- fracture callus remodeled into new shape  duplicate bone original shape and
strength
- this process can achieved by formation electrical polarity during partial weight
bearing

Obstruction – variables that influence healing

Internal variable
1. poor blood supply
- leads to dead of osteocyte
- depends on degree of fracture & disruption haversian system
2. head injury
increase osteogenic response
3. condition of soft tissue
4. infection
5. age
6. pre existing bone malignancy
7. mechanical factors
- poor alignment
- less movement
- excess mobility can disrupt bridging callus
- slight biomechanical motion  improve callus formation
- bony soft tissue attachment
external variable
1. nutrition
 - Vitamin D & calcium
- 84% patient non union found metabolic issue (66% these patient had vitamin D
deficiency)
2. DM
- affect repair & remodeling bone
- decrease cellularity facture callus
- delayed enchondral ossification
- diminished strength fracture callus
- fracture healing takes 1.6 times longer in diabetic patients
3. Nicotine
- decrease rate fracture healing
- inhibit growth new blood vessel
- smoker can take 70% longer to heal

4. NSAID
prolonged healing time because of COX enzyme inhibition
5. Quinolone
Toxic chondrocyte and diminished fracture repair

Complication
1. infection
2. non union
- no progression healing within six months
- leave the limb with pain and instability
3. malunion
- healing bone with deformed position (angular, translation, rotational)
4. delayed union
- persistence fracture line
- absence callus formation on xray
- healing still occur but slower than normal

Source :
 Brighton, Carl T. and Robert M. Hunt (1991), "Early histologic and ultrastructural changes
in medullary fracture callus", Journal of Bone and Joint Surgery, 73-A (6): 832-847
 Brighton, Carl T. and Robert M. Hunt (1997), "Early histologic and ultrastructural changes
in microvessels of periosteal callus", Journal of Orthopaedic Trauma, 11 (4): 244-253