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

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 Wolf’s 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 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 < 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 < 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 & BMP’s 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