General Principles in the Assessment

and Treatment of Nonunions

Matthew J. Weresh, MD
Original Author: Peter Cole, MD; March 2004
New Author: Matthew J. Weresh, MD; Revised August 2006

Definitions
Nonunion: A fracture that has not and is not
going to heal
Delayed union: A fracture that requires
more time than is usual and ordinary to heal

Previous Definitions of Nonunion

Nonunion: A fracture that is a minimum of
9 months post occurrence and is not healed
and has not shown radiographic progression
for 3 months
Orthopaedic Advisory Panel:
Food & Drug Administration, 1986

 Waiting 9 months or more is often

inappropriate:

Prolonged morbidity
Inability to return to work
Narcotic dependence
Emotional impairment

 Definition of nonunion should not limit or

prevent appropriate and timely intervention

The best treatment for

nonunions is prevention
Sir John Charnley

The designation of a delayed union

or nonunion is currently made
when the surgeon believes the
fracture has little or no potential to
heal.
Donald Wiss M.D. & William Stetson M.D.
Journal American and Orthopedic Surgery 1996

Classification of Nonunions
Two important factors for consideration
(1) Presence or absence of infection
(2) Vascularity of fracture site

Classification
(1) Hypertrophic
(2) Oligotrophic
(3) Avascular

Weber and Cech, 1976

Hypertrophic

Vascularized
Callus formation present on x-ray
Elephant foot - abundant callus
Horse hoof - less abundant callus (see diagram)

Oligotrophic
No callus on x-ray
Vascularity is present on bone scan

Avascular
Atrophic or similar to oligotrophic on x-ray
Ischemic or cold on bone scan

Hypertrophic
(elephant foot)

Hypertrophic
(horse hoof)

Oligotrophic
or atrophic

Incidence of Nonunion
Tibia
Femur
Humerus
Forearm
Clavicle

Boyd et.al

Connolly

No. 842(1965)

No.602 (1981)

35 %
19%
17.5%
15.5%
2%

62%
23%
7%
7%
1%

*Increasing frequency of tibial nonunion over time

Increasing relative incidence of

tibial and femoral nonunion most
likely secondary to improved
limb salvage techniques

Etiology of Nonunion:
Systemic
Malnutrition
Diabetes (neurovascular)
Smoking

Malnutrition
Adequate protein and energy is required for
wound healing
Screening test:
serum albumin
total lymphocyte count

Albumin less than 3.5 and lymphocytes less

than 1,500 cells/ml is significant
Seltzer et.al. JPEN 1981

Diabetes
(Neuropathic Fractures)
Neuro arthropathy is not entirely the result of
unprotected weight bearing on an insensate joint
Inability to control response to trauma can result
in hyperemia, osteopenia, and osteoclastic bone
resorption

Neuropathic Fracture Nonunions

Treatment, conservative (bracing) and operative, are
fought with complications
No currently accepted algorithm
Consider use of biphosphonates to decrease
osteolytic response
Shelby et.al. Diab. Med. 1994
Connolly J.F. and Csencsitz T.A. CORR #348 1998
Young e.t. al. Diab. Care 1995
McCormack R.G. e.t. al. JBJS 1998

Smoking
Decreases peripheral oxygen tension
Dampens peripheral blood flow
Well documented difficulties in wound
healing in patients who smoke
Schmite, M.A. e.t. al. Corr 1999
Jensen J.A. e.t. al. Arch Surg 1991

Smoking vs. Fracture Healing

Most information is anecdotal
No prospective randomize studies on humans
Retrospective studies show
time to union
69% delay in radiographic union with smoker (2 of 44
nonunions in smokers vs. 0 of 59 nonunion in
nonsmokers) increased incidence of nonunion with
smokers
Schmitz, M.A. e.t.al. CORR 1999

Etiology of Nonunion
(Local Factors)
Infection
Energy of fracture mechanism
Mechanical factors of fracture configuration
Increased motion between fracture fragments
Inadequate fixation
Wolfs Law - lack of physiologic stresses to bone

Anatomic location

Infection
Of all prognostic factors in tibia
fracture care, that implying the
worst prognosis was infection
Nicoll E.A. CORR 1974

The inflammatory response to bacteria at

the site of the fracture disrupts callus,
increases gap between fragments, and
increases motion between fragments.

Energy of Fracture Mechanism

Initial fracture displacement
Fracture pattern i.e:
comminution
bone loss
segmental patterns

Soft tissue disruption (vascularity and oxygen

delivery)

Initial Fracture Displacement

Nicoll E.A., 705 cases, 1964

Delayed union and nonunion were nearly

three times as frequent in tibia fractures with
moderate to severe displacement as
compared to fractures with slight
displacement.

Fracture Pattern
Fracture patterns in higher energy injuries
(i.e.: comminution, bone loss, or segmental
patterns) have a higher degree of soft tissue
and bone ischemia

Soft Tissue Disruption

1. Introgenic
2. Traumatic

Traumatic Soft Tissue Disruption

Incidence of nonunion is increased with open
fractures
More severe open fracture (i.e. Gustillo III B vs
Grade I) have higher incidence of nonunion
Gustilo et.al.Jol 1984
Widenfalk et.al.Injury 1979
Edwards et.al. Ortho Trans 1979
Velazco et.al. TBJS 1983

Introgenic
Excessive soft tissue dissection and
periosteal stripping at time of previous
fixation

Tscherne Soft Tissue Classification

Not all high energy fractures are open
fractures. This classification emphasizes
the importance of viability of the soft tissue
envelope at the zone of injury.
Fractures with Soft Tissue Injuries
Springer Verlag 1984

Soft Tissue Classification

Grade 0: Soft tissue damage is absent or negligible
Grade I: Superficial abrasion or contusion caused
by fragment pressure from within
Grade II: Deep, contaminated abrasion associated
with localized skin or muscle contusion from
direct trauma
Grade III: Skin extensively contused or crushed,
muscle damage may be severe. Subcutaneous
avulsion, possible artery injury, compartment
syndrome

Revascularization of ischemic bone fragments in

fractures is derived from the soft tissue. If the soft
tissue (skin, muscle, adipose) is ischemic, it must
first recover prior to revascularizing the bone.

E.A. Holden, JBJS 1972

Mechanical Factors
Excessive motion at fracture secondary to
poor fixation, failed fixation, or inadequate
immobilization
Lack of physiologic mechanical stimulation
to fracture area (i.e. nonweight bearing,
fracture fixed in distraction, adynamic
environment with external fixation)

Anatomic Location of Fractures

Some areas of skeleton are at risk for nonunion
due to anatomic vascular considerations i.e.:
Proximal 5th metatarsal, femoral neck, carpal
scaphoid

Diagnosis of Nonunion- History

Nature of original injury (high or low energy)

Previous open wounds of injury site
Pain present at fracture site
Symptoms of infection i.e.
Antalgic gait or decrease use secondary to pain

History of any drainage or wound healing

difficulties

Examination

Alignment
Deformity
Soft tissue integrity
Erythema, warm, drainage
Vascularity of limb
Pulses, transcutaneous oximetry

Stability at fracture site

Pain assessed during this portion of examination

X-rays
AP, lateral, and oblique (45degree internal and 45
degree external)
In majority of cases, this is all that is required to
confirm nonunion
Examination under fluoroscopy to check for
motion can occasionally be helpful also

Tomography
Linear tomograms
Helpful if metallic hardware present

Helps to identify persistent fracture line in:

Hyptrophic nonunions in which x-rays are not
diagnostic and pain persists at fracture site

Computed tomography and MRI are

replacing linear tomography if no hardware
present

Subclinical Undetected Infection

The main diagnostic dilemma in evaluation
of nonunions

Radionuclide Scanning
Technetium - 99 diphosphonate
Detects repairable process in bone ( not specific)

Gallium - 67 citrate
Accumulate at site of inflammation (not specific)

Sequential technetium or gallium scintigraphy

Only 50-60% accuracy in subclinical ostoemyelitis
Esterhai et.al. J Ortho Res. 1985
Smith MA et.al. JBJS Br 1987

Indium III - Labeled Leukocyte Scan

Good with acute osteomyelitis, but less
effective in diagnosing chronic or subacute
bone infections
Sensitivity 83-86%, specificity 84-86%
Technique is superior to technetium and
gallium to identify infection
Nepola JV e.t. al. JBJS 1993
Merkel KD e.t. al. JBJS 1985

MRI
Abnormal marrow with increased signal on T2
and low signal on T1
Can identify and follow sinus tacts and
sequestrum
Mason study- diagnostic sensitivity of 100%,
specificity 63%, accuracy 93%
Berquist TH et.al. Magn Res Img
Modic MT et.al. Rad. Clin Nur Am 1986
Mason MD et.al. Rad. 1989

Tissue Biopsy
Antibiotic discontinued for 72 hours prior to
biopsy
Multiple representative biopsy specimens should
be obtained
Cultures sent for gram stain, aerobic, anerobic,
fungal, and acid fast studies
Open biopsy techniques can be inconclusive due
to problem of detecting bacteria protected by an
external glycocalyx
Gristina AG el.al
Inst Con Lect 1990

Treatment
Nonoperative
Operative

Nonoperative
Ultrasound
Electric stimulator
Bone marrow injection

Ultrasound
Ultrasound fracture stimulation devices
have shown ability to increase callus
response in fresh fractures (shortens time
for visible callus on x-ray)
Prospective randomized trial in nonunion
population has not been done
Use in nonunions remains theoretical
Goodship & Kenwright JBJS
1985

Electric Stimulation
Piezoelectric nature of bone - stress generated
electric potentials exist in bone and are related to
callus formation
Phys Soc Jpn 1957
Science 1962

Fukada & Yasuda,J

Busse H CAL e.t. al.

Electromagnetic fields influence vascularization

of fibrocartilage, cell proliferation & matrix
production
Monograph Series,AAOS

Three Modalities of Electric bone

Growth Stimulators
1. Direct current - percutaneous or implanted
electrodes
2. Electromagnetic stimulation - uses time
varying magnetic fields (noninvasive)
3. Capacitive coupling - uses electrodes placed
on skin (noninvasive)

Two Attempts at Well Controlled Double

Blind (placebo) Studies on Nonunion
Healing with Electric Stimulation
1. Pulsed electromagnetic fields
Tibial delayed unions 16-32 weeks from injury
45% united in active device group
14% united in placebo group
0.02)
Sharrard JBJS e.t. al 1990

(P <

2. Capacitive coupling
6 of 10 with active device healed
0 of 11 with placebo device healed
(P < 0.004)
and King JBJS 1994

Scott G

Contraindication to Electric
Stimulation
Synovial pseudoarthrosis
Electric stimulation does not address
associated problems of angulation,
malrotation and shortening

Unanswered Questions

When is electric stimulation indicated

Which fracture types are indicated
What are the efficacy rates
What time after injury is best for
application
Ryaby JT Corr 1998

Bone Marrow Injection

Percutaneous bone marrow injected to level of
fracture
9 of 10 delayed tibia fractures united
80% of 100 tibial fracture patients united when
in conjunction with adequate fixation
*Nonradomized and anecdotal studies
Connolly J., CORR. 1995

Surgical Treatment

Fibular osteotomy
Bone graft
Plate osteosynthesis
Intramedullary nailing
External fixation

Fibular Osteotomy
Fibula can distract or unweight physiologic
forces seen in the tibia
Teitz, C.C. e.t.al.JBJS 1980
Often used as adjunctive procedure to assist
with deformity correction and surgical
stabilization of tibia
Dynamizes tibial to augment healing
environment

Bone Grafting
Osteoinductive - contain proteins or
chemotactic factors that attract vascular
ingrowth and healing
i.e.. demineralized bone matrix & BMPs

Osteoconductive - contains a scaffolding for

which new bone growth can occur
i.e. allograft bone, calcium hydroxyappatite

Bone Grafting
Used to stimulate biologic response of healing
in nonunions (usually atrophic nonunions)
Also used to fill defects in fracture zone
i.e. up to 6 cm intercalary defects of long bones)
Bosse, MJ e.t.al. JBJS 1989

rhBMP-2
44% reduction in need for secondary
intervention in the treatment of acute open
tibial fractures

Gorender,S e.t.al. JBJS 2002

rhBMP-2
Reduces incidence of nonunion in high risk
fractures
Believed to reduce the need for autologous
bone grafting
Theoretically makes sense in the operative
treatment of nonunions

Plate Osteosynthesis
Corrects malalignment
Restores function & stabilizes fracture fragments
directly
Compresses fragments in some circumstances to
augment healing
Allows patients to mobilize surrounding joints
and dynamize fracture environment
Requires adequate skin and soft tissue coverage
Often used with adjunctive bone graft

Locking Plate Technology

Will give better fixation in pathologic bone
Most likely will prevent early failure
Occasionally seen with traditional compression
plating techniques

Intramedullary Nailing
Mechanically stabilizes long bone nonunions as a
load sharing implant
Corrects malalignment
Reaming is initially detrimental to intramedullary
blood supply, but it does recover and is believed
to stimulate biologic healing at fracture
Allow patient to mobilize surrounding joints and
dynamize fracture environment

Intramedullary Nailing
Can be performed without direct exposure or
dissection of the fracture soft tissue envelope
Nonapplicable in articular fractures

External Fixation
Correct malalignment
Used primarily in management of infected nonunions
Allows for repeated debridements, soft tissue
reconstructive procedures, and adjunctive bone-grafting
Small wire ring fixators can also allow for bone
transport into large intercalary defects
Ring fixators can also generate large compressive
forces at fracture to allow mobilization of joints and
improve fracture healing environment
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