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Non-Union Current Treatment Concept

ArticleinShafa Orthopedic Journal · February 2016

DOI: 10.17795/soj-4546

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Shafa Ortho J. In Press(InPress):e4546. doi: 10.17795/soj-4546

Published online 2016 February 20. Review Article

Non-Union Current Treatment Concept

Arash Moghaddam,1,* Claudia Ermisch,1 and Gerhard Schmidmaier1

1Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany

*Corresponding author: Arash Moghaddam, Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany. Tel: +49-62215635394, Fax:

+49-62215629123, E-mail: Arash.Moghaddam@med.uni-heidelberg.de

Received 2015 October 31 ; Accepted 2015 December 25.

Abstract

Context: This article wants to give a current concept for the challenging decision for conservative or operative treatment strategies of non-

unions according to the principles of ‘diamond concept’ and aspects that have to be attended.

Evidence Acquisition: Between February 2010 and March 2014, 424 patients with non-unions were treated at Heidelberg university

hospital. This database has been analyzed at least one year after the treatment. The analysis and the experience in surgery and treatment

of non-unions as well as present literature were prepared for this review as a current concept.

Results: If an atrophic non-union is suggested, reosteosynthesis and biological stimulation is required. A revision surgery of autologous

transplantation of cancellous bone from the iliac crest is often enough. Alternatively, reamer-irrigator-aspirator (RIA) can be taken out

of the femur with lower complications and pain in the extraction area and be combined with growth factors like bone morphogenetic

proteins (BMPs), if consolidation after cancellous bone is still absent. In complex cases, consequential and radical removal of the infection

often improved circulation through interventional angiography and use of the two-step procedure (the Masquelet technique) as well as

a tissue covering are required.

Conclusions: By using the ‘diamond concept’ as a complex concept, non-unions can be treated in different stages in a targeted manner.

Keywords: Diamond Concept, Reamer-Irrigator-Aspirator, Non-Union, Masquelet Technique

cial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages,

provided the original work is properly cited.

1. Context

The percentage of delayed or non-union after fractures of

long bones is approximately 10%, but depends on patient’s

risk profile. The current definition states that a non-union

is a fracture that will not consolidate without any further

intervention, independent of the treatment time. With

adequate stability, conservative treatment in the early

stages of a non-union is possible. The operative treatment

depends on the type of non-union. There are one-step or

two-step procedures according to the principles of the ‘di–

amond concept’. This involves the improvement of the me–

chanical situation (in most cases with a reosteosynthesis)

and vascularization, local application of osteoconductive

carriers e.g. tricalciumphosphate, vital cells from autolo–

gous bone, and osteoinductive substances like bone mor–

phogenetic proteins (BMP-2 or BMP-7).

Hypertrophic and atrophic non-unions without large

defect gaps or signs of infection can be treated with a

one-step procedure. For treating infected non-unions or

non-unions with large defect gaps, the Masquelet tech-

nique is recommended.

2. Evidence Acquisition

University of Heidelberg hospital is the major center

for orthopaedic treatments in Germany. This database

has been analyzed at least one year after treatment. Our

results were on one hand based on a collective of 424

patients with non-unions who were treated in our cen-

ter between February 2010 and March 2014, and on the

other hand they were based on the current literature on

e.g. PubMed. The analysis and the experience in surgery

and treatment of non-unions as well as present literature

were prepared for this review as a current concept.

3. Results

3.1. Epidemiology

In general, non-union as a complication of fracture

healing occurs in 5% – 10% of cases (1) and can be as high as

30% in high-risk groups (2-5).

The high incidence on the tibia can be explained by poor

tissue covering and therefore poor blood circulation. In ad–

dition, there is more often 2° – 3° of open injuries with com–

plex damage of the bone and the surrounding soft tissue (5).

The incidence of non-unions in bones of the extremi-

ties is as follows: the tibia has on average an occurrence

of 8.7% (6, 7), the femur only slightly less at 6.1% (8-10), the

humerus 3% – 5%, and the lower arm 5% (11-18).

According to the data in our non-union register, there

is a greater presence of non-unions in male patients be-

tween the ages of 30 and 50 years.

Uncorrected Proof

Moghaddam A et al.

Shafa Ortho J. In Press( InPress):e4546

3.2. Risk Factors

Besides the type of fracture and the soft tissue damage,

there are other risk factors for the development of non-

unions (19). Smoking increases the risk of delayed heal-

ing or non-unions (5, 20). In addition, advanced age has a

negative effect on physiological fracture healing (21, 22).

Other factors such as diabetes mellitus, the use of non-

steroidal anti-inflammatory drugs (NSAIDs) and previous

fractures of the same extremity also have negative effects

(23, 24). In the risk score according to Moghaddam et al.

all of these risk factors have their relative importance for

measuring the individual risk of a patient for developing

a non-union (5) (Table 1).

3.3. Diagnosis

The diagnosis begins with extensive history taking and

includes the individual risk profile of the patient, taking

into account previous illnesses and medications as well

as all previous conservative and operative treatments.

History of previous infections should be taken into ac-

count as well as the analysis of previous clinical and ra-

diological findings. Blood circulation and soft tissue at

the site of injury should also be evaluated.

Clinical indications of non-union include pain on weight

bearing, limitations to the mobility of an extremity, or in–

stability. In addition, there are clinical signs of infection to

be aware of, such as redness, swelling and warmth or de–

velopment of a fistula. One should especially look out for

local, systemic or anamnestic signs of osteitis.

Conventional radiological imaging of the affected ex-

tremity in two levels with inclusion of joints is standard

for diagnosing faulty positioning or instability. One

should note that defects cannot be completely observed

with native X-rays due to summation and covering. An

additional computed tomography (CT) can be used to

evaluate whether there is partial or entire bridging of the

defect gap. In addition, a contrast magnetic resonance

imaging (MRI) can be used to evaluate vascularization of

the bone and separate vital and non-vital areas (25) (A CT

scan is considered the gold standard for evaluating non-

unions and providing information for treatment).

3.4. Classification

According to the current definition from European society

of tissue regeneration in orthopedics and traumatology (ES–

TROT), a non-union is a fracture that does not heal without

further intervention, independent of the length of treatment.

Non-unions are classically divided into four types: hy-

pertrophic due to mechanical causes, atrophic due to

biological causes, defect, and infection non-unions.

Hypertrophic non-unions develop due to insuffcient

mechanical stability and can lead to formation of a callus

in the area of fracture. Bone consolidation does not occur.

If therapy is delayed, atrophic non-unions can develop

(26). Atrophic non-unions often involve reduced vascu-

larity of the defect gap and surrounding bone, which can

lead to atrophy of the fracture ends. Defect non-unions

usually occur due to high-speed trauma and higher grade

open fractures, which can cause loss of bone through nu-

merous fragments. Furthermore, infected non-unions

develop primarily in open fractures after traumas in

which germs can get into the wound.

Besides the purely morphological classification, there is

a new classification system according to the non-union

scoring system (NUSS) which incorporates bone quality,

soft tissue damage, and the individual patient risk (e.g.

smoking) into a score (27). From this NUSS-score, there

are therapy considerations that can be adapted to the pa-

tient (28-30). The higher the score, the more specialized

and custom the therapy concept must be to offer the pos-

sibility of consolidation (Table 2).

3.5. Therapy

The goal of non-union therapy is the consolidation of bone

defects with correction of the axis and leg length as well as

reaching weight bearing stability. A suffcient tissue covering

as well as removal of the infection are the basic prerequisites.

Independent of the type of non-union and localiza-

tion, therapy can differ in conservative and operative ap-

proaches.

3.5.1. Conservative

Conservative approaches are especially useful in the early

phase of non-union treatment and require suffcient me–

chanical stability as well as bone regeneration potential.

The newest methods in conservative treatment in delayed

fracture healing of the lower extremity are consequential

weight bearing until full weight bearing can be mustered.

The most common methods of conservative treatment in

delayed fracture healing in the area of the lower extremity

are consequential weight bearing to full weight bearing.

Additionally, fractures are treated with daily lower ener-

gy ultrasound (a possibility of conservative therapy is the

application of low energy ultrasound to the defect gap),

over a defined interval of three to six months.

The deciding criteria for successful treatment with low

energy ultrasound are suffcient stability as well as a de-

fect gap of under 10 mm, free of infection in the previous

history, start of therapy in less than five months after the

fracture, and a NUSS-score less than 35 (31).

3.5.2. Operative Treatment Diamond Concept

The multi-factorial causes of delayed fracture healing

make an individual patient’s specific therapy noteworthy.

In this way, the so-called diamond concept (Figure 1) has

become evermore established (3, 32). Therapy consists of

an optimized combination of biological and biomechani–

cal factors (29, 33-38) (The diamond concept has five differ–

ent factors that must be analyzed for therapy) (39).

Non-unions are analyzed according to the following criteria:

– Biomechanical stability; example: through angle sta-

ble implants, dynamized medulla nailing.

Uncorrected Proof

Moghaddam A et al.

– Osteogenic cells: in form of mesenchymal stem cells

(MSCs), autologous cancellous bone (iliac crest or reamer

irrigator aspirator (RIA)).

– Osteoconductive structures; example: autologous can-

cellous bone, synthetic bone replacement material (ex-

ample: tricalcium phosphate).

– Growth hormones; examples: bone morphogenetic

protein (BMP)-2 and BMP-7.

– Vascularization: through improving the macro-circu-

lation and local induction of a Masquelet membrane re-

newal of the fracture ends.

In looking at individual clinical and radiological param-

eters, there are a number of factors lacking in a combi-

nation treatment and therefore, systemic optimization

of the biological and biomechanical treatment of non-

unions should be looked at (29, 34, 40, 41).

3.5.3. Isolation of Bone Replacement Material

The iliac crest often serves as the source of autologous

cancellous bone. The method involved is widely used and

is considered the gold standard in the surgical treatment

of non-unions. It has the optimal consistency and can es–

tablish good primary stability as a tricortical graft. Prob–

lematic is the limited availability and differing quality and

quantity as well as a high extraction morbidity (25, 42-46).

An alternative to autologous cancellous bone extraction

is the use of RIA (Depuy-Synthes, USA) (Figure 2). In this

procedure, the percutaneous opening of the medullary

cavity is performed with a combination of drilling, clean–

ing and vacuum extraction of MSCs out of long bones. This

method is primarily performed on the femur, but can also

be done on the tibia. In this way, it is possible to extract 80

cm of the autologous bone material for transplantation

ture healing and bone regeneration. Currently, there are

two growth hormones permitted for use in orthopedics

and trauma surgery. These include BMP 2 for open lower

leg fractures and BMP-7 for non-unions of the tibia.

Studies over the past years have shown that the use of

BMP-7 is at least equal to a single cancellous bone graft (52).

Furthermore, there are adequate indications in everyday

clinical routine to suggest increases in the healing rate of

non-unions (18). The combination of autologous cancellous

bone with BMPs is clearly superior to a single cancellous

bone graft (53).

BMP-7 is not currently commercially available; so, increased

BMP-2 (Medtronic) can be used in non-union therapy.

The authors recommend the additional use of BMPs in a

failed therapy with autologous cancellous bone. In addi–

tion, when the effect is clearly proven by clinical studies, we

recommend receiving approval of costs from the insurance

company and approval of its use from a panel of experts.

3.6. Bone Marrow Drilling in Hypertrophic Non-

Unions

According to the diamond concept, optimizing mechani–

cal stability is indicated in hypertrophic non-unions. In the

case of an instable osteosynthesis, a reosteosynthesis is nec–

essary. In simple cases, the dynamization of an adjoining

nail with full weight bearing is possible. In complex cases, a

reosteosynthesis with medullary cavity drilling and medul–

lary nail osteosynthesis with a thick nail is necessary (54) (in

hypertrophic non-unions in the tibia shaft area, medullary

cavity drilling and nail osteosynthesis has been indicated).

3.6.1. Positioning

A patient is positioned on the back and the x-ray beam is po–