Non Union

Definition

 

Non-union

- arrest of progression to union at fracture site 

- > 6-9 /12

- no visible progressive signs of healing for at least three consecutive months

- individualise for each fracture

- when the surgeon believes the fracture has little or no chance to heal

 

Delayed union

- failure of fracture to unite within expected time

- still may spontaneously unite

 

Fracture Healing

 

Phases

- haematoma / inflammation / neoangiogenesis

- soft callus

- hard callus

- remodelling 

 

Haematoma

- immediate at site of injury

 

Inflammation

- vasodilation & exudation of plasma &  leucocytes

- polymorphs, histiocytes, & mast cells appear

- process of removing debris begins

 

Neoangiogenesis

- rapid development of an extra-osseous blood  supply

- derived from surrounding soft tissue

- invasion of fibrovascular tissue that replaces the haematoma

- lays down collagen & matrix that later becomes mineralised to form woven bone (provisional/ primary/ soft callus)

 

Soft callus

- primary callus response within days / weeks

- inner cambrial layer (as opposed to outer fibrous layer) of periosteum

- surrounding soft issue fibroblasts

- forms fibrocartilage matrix

 

Hard callus

- external bridging callus within weeks

- woven bone formed by mineralisation of fibrocartilage matrix

- arises most probably from osteoinduction of cells which do not have direct connection with bone

- blood supply reliant on surrounding soft tissue

- primary purpose is to arrest movement between bone fragments

- strong evidence it arises from by bioelectric feedback (piezoelectric effect)

 

Remodelling

 

Bone remodelling in response to local stress / strain in accordance to Wolff's Law

 

Bone Healing

 

Primary Bone Healing

 

Anatomical reduction and absolute fixation

- no gap, no strain

- no callous is form

- intramembranous ossification (osteoid onto CT membrane)

 

Creeping substitution

- advancing front of osteoclasts

- osteoclasts form cutting cones across cortical bone allowing revascularisation

- followed by osteoblasts laying down bone matrix

- endosteal callous is formed

 

Secondary Bone healing

 

Normal phases of bone healing

- endochondral ossification

- mineralisation of fibrocartilaginous matrix

- soft and hard callous

 

Mechanobiology of Skeletal Regeneration

 

Differentiation of mesenchymal tissue into bone, cartilage or fibrous tissue

 

A.  Intramembranous ossification 

- in areas of low stress / strain

- mesenchymal stem cells

- no cartilage stage

- osteoid secreted onto CT

- woven bone

- eventually becomes lamellar bone

 

B.  Endochondral ossification 

- low to moderate tensile strain & hydrostatic tensile stress

- chondrocytes make cartilage

- osteoprogenitor cells become osteoblasts and secrete osteoid onto calcified cartilage matrix

 

C.  Chondrogenesis 

- if hydrostatic compressive stress or poor vascularity

 

D.  Fibrous tissue 

-  if high tensile strain

 

E.  Fibrocartilage 

- if tensile strain with hydrostatic compressive stress

 

Concept Interfragmentary Strain

 

Different tissue can tolerate different amounts of strain 

- Fibrous ~ 100% strain

- Chondroid ~ 20% strain

- Bone < 2% strain

 

Interfragmentary strain (motion) is inversely proportional to the fracture gap

- small gap with small motion --> large strain

- large gap with small motion --> small strain

 

Bone resorption may decrease strain & hence allow granulation tissue to form

- then the callus will stabilize the fracture enough to allow the next stage to progress

- hence amount callus proportional to stability

 

Aetiological factors

 

Patient factors

Injury

Treatment

 

Patient factors

 

Age

Activity 

Immoderate, noncompliant patient

Nutrition / catabolic states

Anaemia 

Smoking

- decreases peripheral O2 tension

- dampens peripheral blood flow

Alcohol

DM

Peripheral Neuropathy

Immunocomprimise 

Osteomalacia

- failure to mineralise callous

- correct abnormality

 

Pharmacological agents

- Steroids

- Cytotoxics

- Ciproflaxacin

- NSAIDS

- Irradiation

 

Giannoidin et al JBJSB 2000

- 32 unions and 67 non-unions

- NSAID use significant

- delayed healing in united group also

 

Injury

 

Open fracture 

Significant soft tissue trauma

Soft tissue interposition

Infection

- inflammatory response

- disrupts callous, increases fracture gap and motion

Pathological fracture 

Malignant tissue

Osteoporosis 

Anatomic Location

- Poor vascularity / NOF / scaphoid / 5th MT 

Intact fellow bone

Excessive bone loss

Segmental injury

Comminution

Displacement

- shown to be important in the tibia

Synovial fluid / Intra-articular

 

Treatment

 

Distraction of fracture

Inadequate stability with excessive movement 

Extensive approach with vascular compromise

No axial load 

 

Classification Non-union

 

1.  Hypertrophic

- elephant foot (abundant callous)

- horse hoof (less abundant callous)

- adequate vascularity, poor mechanical environment for healing

- predominantly fibrocartilage in gap 

- inadequate stabilization / excessive strain

- 92-95% non-infected non-unions tibia & fibula

 

2.  Oligotrophic

- no callous on x-ray

- vascularity on bone scan

 

3.  Atrophic / avascular

- pencilling of bone ends

- avascular 

- no vascularity on bone scan

- fibrous or cartilage interposition

- needs osteoinduction + stabilization

- debride non-union / rigid fixation / compress / bone graft

 

4.  Pseudarthrosis

- non-union with fluid-filled cavity

- synovial-like membrane & pseudocapsule formation

- new joint at fracture site

- usually painless motion

- needs excision of pseudoarthrosis / rigid fixation / compression / bone graft

 

Management

 

Options

 

1.  Rigid stabilization

 

2.  Autograft / allograft

 

3.  Other modalities

- Electrical stimulation

- US therapy

- BMP 

- Bone marrow aspirate

 

Electrical Stimulation

 

Science

 

Based on principle that bone healing primarily occurs as a result of strain-generated electrical potentials

- no effect on fully fibrous non-union

- must have some biological process occurring

 

Three types

 

1.  DC

- negative pole (cathode) has to be implanted into fracture site

- produces sustained injury potential that increases inflammatory respons

- invasive / risk infection

 

2.  AC

- use conductive medium

- paste electrode either side of affected extremity

- only work on soft & hard callus

- increase cAMP, collagen synthesis & calcification during soft & hard callus stages of healing

 

3.  Pulsed Electromagnetic Fields

- most used clinically

- placed externally without need for inductive media

- electrodes either side of non-union in cast or brace (no need to contact skin)

- can be symmetrical or asymmetrical pulse 

- help convert soft to hard callus

 

Results

 

Simonis et al Injury 2003

- RCT of electrical stimulation v placebo in tibial non union

- increased union rate in smokers from 67% to 100%

 

Sharrard JBJS Br

- RCT of 45 tibial delayed union

- significantly improved union rate c.f. control

 

Pulsed US 

 

Science

 

Ultrasound is acoustic radiation at frequency above human hearing

- mechanical energy that can be transmitted into the body as high-frequency pressure waves

- micromechanical strains may promote bone formation in same manner as postulated by Wolff's Law

 

Exact mechanism unknown but may be

- enhanced production of osteoinductive agents

- direct stimulatory effect on osteoblasts

- increased blood supply

 

Results

 

Exogen Registry

- 1700 delayed unions 91% healing rate

- 700 non-unions 85% healing rate

 

Heckman JBJS 1994

- prospective, double-blind, randomised, placebo-controlled trial

- closed or grade 1 open tibial diaphyseal fractures

- all US patients healed (average 96 days) vs some nonunions in placebo group (average 150 days)

- healing times reduced in smokers 

 

BMP

 

Science

 

See Miscellaneous / Bone graft

 

Results

 

Friedlaender et al JBJS Am 2001

- as efficacious as autograft in established tibial non union

 

Govender et al JBJS Am 2002

- RCT of control v BMP in open tibial fractures

– less secondary interventions, accelerated time to union, reduced infection rates

 

Jones et al JBJS Am 2006

- RCT allograft + BMP2 v autograft in tibial diaphyseal cortical defects

- similar rates of healing, reduced blood loss in BMP group

 

Garrison et al Cochrance Database Review 2010

- limited evidence for BMP in acute fracture

- unclear evidence in non union

- likely economically viable in severe open tibial fractures

 

Bone Marrow Aspirate

 

Results

 

Hernigou et al JBJS Am 2006

- 20mls BMA injected percutaneously into 60 atrophic tibial non unions

- union obtained in 53 cases