General Principles in the Assessment and Treatment of Nonunions

1
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

2
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

3
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

4

• Waiting 9 months or more is often inappropriate
• Prolonged morbidity
• Inability to return to work
• Narcotic dependence
• Emotional impairment

5

• Definition of nonunion should not limit or
  prevent appropriate and timely intervention
• The best treatment for nonunions is prevention
• Sir John Charnley

6

• 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

7
Classification of Nonunions

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

8
Classification

• (1) Hypertrophic
• (2) Oligotrophic
• (3) Avascular
• 
  Weber and Cech, 1976

9
Hypertrophic

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

10
Oligotrophic

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

11
Avascular

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

12
Hypertrophic (elephant foot)
Hypertrophic (horse hoof)
Oligotrophic or atrophic
13
Incidence of Nonunion

• Boyd et.al Connolly
• No. 842(1965) No.602
  (1981)
• Tibia 35 62
• Femur 19 23
• Humerus 17.5 7
• Forearm 15.5 7
• Clavicle 2 1 Increasing frequency
  of tibial nonunion over time

14
Increasing relative incidence of tibial and
femoral nonunion most likely secondary to
improved limb salvage techniques
15
Etiology of Nonunion Systemic

• Malnutrition
• Diabetes (neurovascular)
• Smoking

16
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

17
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

18
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

19
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

20
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

21
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

22
Infection

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

23
The inflammatory response to bacteria at the site
of the fracture disrupts callus, increases gap
between fragments, and increases motion between
fragments.
24
Energy of Fracture Mechanism

• Initial fracture displacement
• Fracture pattern i.e
• comminution
• bone loss
• segmental patterns
• Soft tissue disruption (vascularity and oxygen
  delivery)

25
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.

26
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

27
Soft Tissue Disruption

• 1. Introgenic
• 2. Traumatic

28
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

29
Introgenic

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

30
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

31
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

32
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
33
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)

34
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

35
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

36
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

37
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

38
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

39
Subclinical Undetected Infection

• The main diagnostic dilemma in evaluation of
  nonunions

40
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

41
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

42
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

43
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

44
Treatment

• Nonoperative
• Operative

45
Nonoperative

• Ultrasound
• Electric stimulator
• Bone marrow injection

46
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

47
Electric Stimulation

• Piezoelectric nature of bone - stress generated
  electric potentials exist in bone and are related
  to callus formation
  
  Fukada Yasuda,J
  Phys Soc Jpn 1957
  Busse H CAL e.t. al.
  Science 1962
• Electromagnetic fields influence vascularization
  of fibrocartilage, cell proliferation matrix
  production Monograph
  Series,AAOS

48
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)

49
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
  (P lt 0.02)
  Sharrard JBJS e.t. al 1990
• 2. Capacitive coupling
• 6 of 10 with active device healed
• 0 of 11 with placebo device healed
  
  (P lt 0.004)
  Scott G and King JBJS 1994

50
Contraindication to Electric Stimulation

• Synovial pseudoarthrosis
• Electric stimulation does not address associated
  problems of angulation, malrotation and shortening

51
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

52
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

53
Surgical Treatment

• Fibular osteotomy
• Bone graft
• Plate osteosynthesis
• Intramedullary nailing
• External fixation

54
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

55
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

56
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

57
rhBMP-2

• 44 reduction in need for secondary intervention
  in the treatment of acute open tibial fractures
• Gorender,S
  e.t.al. JBJS 2002

58
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

59
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

60
Locking Plate Technology

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

61
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

62
Intramedullary Nailing

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

63
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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