Nonunions of Long Bones

Robert Probe, MD

Scott & White Memorial HospitalTexas A&M University Health Science Center

Original Author: Matthew J. Weresh, MD; March 2004;

New Author: Robert Probe, MD; Revised January 2007

Outline

Definition

Epidemiology

Etiology

Evaluation

Classification

Treatment Principles– Stabilization

– Biologic

Specific Bones– Clavicle

– Humerus

– Forearm

– Femur

– Tibia

Definition

FDA: 9 months elapsed time with no healing progress for 3 months. Problems– Subjective– Arbitrary

Pragmatic: A fracture that has no potential to heal without further intervention

Incidence

Between 5% and 10% of long bone fractures

Relative Risk depends upon:– Injury– Bone– Patient – Treatment

Nonunion under conditions of Absolute Stability

Fracture gaps that exceed the allowable distances for primary or gap healing

Construct instability that prevents primary healing

Nonunion under Conditionsof Relative Stability

Sufficient stability is not imparted at the soft callus stage to allow for mineralization of the chondroid matrix.

Instability prevents bringing bone formation despite biologic activity

Local Risk Factors

Open FracturesHigh energy fractures with bone devitalizationSevere associated soft tissue injuryBone lossInfection

Systemic Risk Factors

Malnutrition

Smoking

NSAIDs

Systemic Medical Conditions

Smoking and Tibial Fractures

Smokers Non-smokers

Healing Time 32 wk 28 wk

Bone Graft Required

26% 18%

Exchange Nail Required

38% 26%

Adams Injury 2001

Non-steroidals and Healing

32 femoral nonunions compared with 67 that healed uneventfullyNo difference:– Smoking– Reaming– Locking

NSAIDs– Significant to P< 0.000001

Giannoudis JBJS-B 2000

Iatrogenic

Poor Reduction

Unstable fixation

Bone Devitalization

Iatrogenic Stripping

Indiscriminate devitalization (1)Leads to limited healing potential and implant failure (2,3)Occasionally requiring resection and reconstruction prior to healing (4,5)

1 2 3 4 5

Diagnosis Suspected When:

Persistent Pain

Non physiologic motion

Progressive deformity

No radiographic evidence of healing

Failing implants

Clinical ExamLimb Stability

Limb alignment and length

Condition of the soft-tissue envelope

Neurovascular exam

Radiologic Evaluation

Standard radiographs are often diagnostic

45 degree oblique films can increase diagnostic accuracy

Despite additional projections, the potential for false-positive results for fracture healing remains

Varus Valgus

Clinical diagnosis can be confirmed and information about stability obtained with

stress radiographs.

Computed Tomography

Clarity when implants or fracture obliquity produce doubt

Classification

Is there infection?

Is there deformity?

Define the biologic activity and stability

InfectionMRI can play a role in identifying soft tissue component; however, bone edema is too sensitive to be accurate

Reliance on clinical diagnosis augmented by CRP

Low virulence infection may require aspirate or operative culture for diagnosis

Indium scan carries only moderate sensitivity and specificity

Determine Deviations in:

Angulation

Length

Rotation

translation

Define the Level of Osteogenesis along the Spectrum of Biologic Activity

Weber & Cech: Pseudarthosis, 1976Inherent Biology

hypertrophic oligotrophic atrophic

Nonoperative Treatment

Electromagnetic– Direct Current– Inductive coupling (PEMF, CMF)– Capacitive coupling

Ultrasound– mechanical energy in the form of low frequency

acoustic waves 30 mW/cm2

Role of Nonoperative Modalities

All have clinical evidence to support effectiveness

Few comparative studies between modalities

Few comparative studies between nonoperative and operative methods

Best suited for hypertrophic nonunions with good inherent stability

Does nothing to correct deformity or provide immediate stability

Surgical Treatment:Algorithm

Cure infection if present

Correct Deformity if significant

Provide stability through implants

Add biologic stimulus when necessary

Infected Nonunions

Contaminated implants and devitalized implants must be removed

Infection treated:– Temporary stabilization (external fixation)– Culture specific antibiotics– +/- local antibiotic delivery (antibiobic beads)

Secondary stabilization with augmentation of osteogenesis (cancellous grafting)

24 year male with continued distal osteolysis after debridement,

antibiotics and local beads

Hardware removed andInfected bone debrided.

Once the infectionWas resolved, bone

Graft was applied andHealing ensued.

Persistent drainage And gross motion afterMultiple attempts atSurgical treatment

Treatment consistedOf resection of Infected bone, acuteShortening and External fixation

Followed by proximalCorticotomy andDistraction to restorelength

Methods of Adding Stability

Cast/Brace – rarely sufficient in nonunions

External Fixation

Plates

Intramedullary Devices

External Fixation

Largest indication is a temporary stabilization following infection debridement

Also useful in correction of stiff deformity and lengthening

Plate StabilizationPlates provide a powerful reduction toolSurgical technique should strive for absolute stabilityLocking plates have improved stability and fixation strengthOther relative indications:– Absent medullary canal– Metaphyseal nonunions– When open reduction or removal of prior implants

is required

Plate Stabilization

Multiple Indications for plate– Broken implants require that

removal

– Metaphyseal nonunion

– Significant deformity

Technique– Blade properly positioned in the

distal fragment

– Reduction obtained by bringing plate to the shaft

– Absolute stability with lag screw

– Nonunion was not exposed

Brokenplate

Nail Stabilization

Ideal case – Femur or tibia with an existing canal and no prior implants

Exchange nailing provides a good option for the tibia and femur

Special equipment is often necessary to traverse sclerotic canals

Adding Biology

Often unnecessary in hypertrophic cases with sufficient inherent biologic activityOptions– Aspirated stem cells (with or without expansion)– Demineralized Bone Matrix– Autogenous Cancellous Graft– Growth Factors

Platelet derivedRecombinant BMPsGene Therapy

Autogenous Cancellous Bone

Sites– Posterior Iliac Crest (20 cc)– Anterior Iliac Crest (10cc)– Proximal Tibia (7cc)– Distal Radius, Calcaneus, Olecronon (?)

All series suggest some incidence of donor morbidity dependent upon harvest site and volume requiredStill considered by many to be the most osteogenic graft material

Demineralized Bone Matrix

Osteoinduction has been experimentally demonstrated*

Osteoinductive ability appears variable between products and donors

A consecutive series with historic controls has demonstrated effectiveness in humeral shaft nonunions

Avoids the morbidity of iliac crest graft

As effective as iliac crest ????? (doubtful in the authors opinion)

*Hierholzer et al J Bone Joint Surg 2006

Stem Cells

Aspirated iliac crest stem cells has been shown to enhance the activity of osteoconductive grafts

Has been studied as an isolated technique with limited success

Role of expansion and delayed implantation may play a future role

Recombinant Bone Morphogenic Proteins

BMP-2Infuse™

Demonstrated effective in acute open tibial fractures

FDA approved in acute fractures

BMP-7– OP-1™– Comparable to autograft in tibia

nonunions– FDA approved under HD exemption

Results

– High dose BMP-2 treatment led to

44% reduction in risk of

nonunion/delayed union

– Significantly fewer invasive interventions

– Significantly faster fracture healing

– Significantly fewer hardware failures and fewer infections

BMP-2 for Open Tibial Fractures:Prospective & Randomized with 450 Patients

BESTT Study Group, et al. J Bone Joint Surg 84A: 2123, 2002.

OP-1 in Tibial Nonunions

TreatmentTreatment

• IM nailIM nail

• 70 % exchange nail70 % exchange nail

• 20 % new 120 % new 1ºº nail nail

• 10 % maintained 10 % maintained prior nailprior nail

• OP-1/collagen vs. ICBCOP-1/collagen vs. ICBC

• Clinical success:Clinical success:

• 81% BMP781% BMP7

• 85% ICBG85% ICBG

Friedlaender GE et al, J Bone Joint Surg, 2001: 83A, Suppl 1; S1-151.

• Prospective, Prospective, randomized studyrandomized study

• 122 patients with 124 122 patients with 124 tibial nonunionstibial nonunions

adenoviralvector carryinggrowth factorgene

cell

ribosomesmakinggrowth factors

growth factor releasedfrom cell

DNA coding for growth factor

nucleus

Ongoing Osteoinductive Research will likely change the future-

Improved understanding of BMPs

Optimize BMP carriers

Explore role of expanded stem cell lines

Role of gene therapy

Reduce the cost of production of inductive agents

Osteoinduction Summary

The diversity and limited numbers of nonunions make Level 1 studies rarePersonal Opinion:– Nothing in hypertrophic or rodded nonunions– DBM in biologically friendly environments (humerus)– Autologous cancellous graft in challenging cases– BMP when ABG has failed or is not feasible

Specific Anatomic Sites

Clavicle

Humerus

Forearm

Femur

Tibia

Metaphyseal

Clavicle Nonunions

Middle 1/3 treated with compression plating +/- graftAnterior or superior plate position95% union reported*Lateral 1/3 treated with ORIF or excision and ligament reconstruction

*Ballmer J Shoulder Elbow Surg 1998

HUMERAL NONUNION

24 patients age 52-86yrs (ave 72yrs)– Locking compression

plate with bone graft or DBM

– All healed – 2 of the DBM cases needed secondary surgery for bone grafting

Ring et al, CORR 425, 2004Ring et al, CORR 425, 2004

Humeral Failed Intramedullary Treatment

•Avoid the temptation toAvoid the temptation to Perform exchange nailingPerform exchange nailing

•Union rates with exchange nailingUnion rates with exchange nailingMcKeeMcKee 60%60%RobinsonRobinson 40%40%FlinkkillaFlinkkilla 46%46%

•Recommended treatment isRecommended treatment is rod removal and platingrod removal and plating

Forearm

Compression plating for hypertrophic nonunions

Critical attention to preservation of radial bow and radio-ulnar relationship

Cancellous graft for atrophic nonunion or bone loss

Forearm Nonunion with Bone Loss

35 patients, both bones 8, ulna 11, radius 16

All with segmental defects

Treatment– 3.5 plates, autologous

cancellous bone graft– All nonunions healed– Improved function

•Ring et al. JBJS 86A 2004

Grafted defect

Femoral Nonunions

Low incidence with good primary surgery

Stabilization may be performed with either plate or rod

Despite the rarity, cases can become challenging as evidenced by this case

Primary surgery. A shortNail was chosen becauseof intertrochanteric fracture.

Dynamization failed to workPlating failed to workRevision platingFailed to workFemoral nailing andGrafting has failed to

work

Exchange Nailing

12 series in English Literature between 1975 and 2006 (462 pts)

Success Rates– Average succcess of 89%

– Range of 53%-100%

Necessary to change from retrograde to antegrade?

Retrogradenail

Antegradeexchage

Healed

Jackson, 2001 - 13/14 (93%) Jackson, 2001 - 13/14 (93%) healed healed

Wu et al., Arch Ortho Trauma Wu et al., Arch Ortho Trauma Surg 1999Surg 199921 nailings after failed plating21 nailings after failed plating

21 / 21 healed21 / 21 healed

Plate to Nail

Plating of Femoral Nonunion

10 English series between 1969 and 2006 (195 patients)

Success Rate– Average 89%– Range 63% to 100%

PLATING FEMORAL NONUNIONS AFTER FAILED

NAILING23 NONUNIONSBLADE PLATE4.5 LCDCPBONE GRAFT21 HEALED BY 12 WEEKS2 REQUIRED REVISION

Bellabarba et al.J Ortho Trauma 2001; 254-63Bellabarba et al.J Ortho Trauma 2001; 254-63

Plate

Nail

Plate

Nail

All Paths are Reasonable under Clinical Circumstances

Femoral Nonunion Guidelines

ORIF and bone graft– Deformity

– Absent medullary canal

– Atrophic

Exchange nailing– well aligned

– Hypertrophic

– Limited concern over infection

Tibial Intramedullary Nailingfor Nonunion

Indications:– Correctable alignment

– Demonstrated biology

– Reconstructable canal

Relative Contraindications– Previous infected pin sites

– History of infection

Exchange Nailing for Tibial Nonunion

Indicated for isthmic fractures that are not infected

Increase nail diameter by 2mm

95% success rate*

Bone loss >50 circumference is a relative contraindication

*Zelle et al J Trauma 2004

Addition of Posterolateral ICBG when there is Substantial Bone Loss

2 years post fracture Exchange nail with ICBG Healed

Plating Tibial Nonunions

Indications– No canal

– Stiff deformity

– Prior external fixation

– Need for graft

Relative Contraindications– Poor soft-tissues

Note the plate used as a reduction tool in this case

Compression Plating for Tibial Nonunions

50 patients with nonunion following external fixationExternal fixation averaged 8 weeksInjury to plating averaged 8 monthsAverage deformity of 15 degreesPost-op– 92% union– 4 deg angulation

Wiss JBJS-A 1992

Unique Challengesof Metaphyseal Nonunions

Small articular segmentsJoint contracturePost-traumatic chondral changesResidua from prior surgery– Devitalized bone– Infection– Fractured implants– Implant tracts

This implant isThis implant isfailing under thefailing under the

high bending high bending forces in the forces in the

subtrochanteric zonesubtrochanteric zone.

An intramedullaryAn intramedullaryimplant was chosenimplant was chosen

because of the reducedbecause of the reducedbending moment.bending moment.

Hypertrophic nonunionHypertrophic nonunionWith 30 degree sagitalWith 30 degree sagital

deformitydeformity

Correction ofCorrection ofDeformity withDeformity with

Absolute stability.Absolute stability.

No graft was usedNo graft was usedIn this hypertrophic In this hypertrophic

casecase

however, theyhowever, theymay be successfullymay be successfully

reconstructed if reconstructed if satisfactory cartilagesatisfactory cartilage

remains.remains.

Articular nonunionsArticular nonunionspresent challengespresent challengesof arthrofibrosis andof arthrofibrosis and

small fragmentssmall fragments

Metaphyseal nonunionMetaphyseal nonunionwith significant with significant chondral losschondral loss

Both the post-Both the post-Traumatic arthritisTraumatic arthritis

And nonunion treatedAnd nonunion treatedsimultaneouslysimultaneously

In certain nonunions,In certain nonunions,a deleteriousa deleterious

mechanical environmentmechanical environmentmay lead to nonunionmay lead to nonunion

In this case of femoralIn this case of femoralneck nonunion, shearneck nonunion, shearforces are converted forces are converted into compressive onesinto compressive ones

by closing wedge by closing wedge osteotomy.osteotomy.

In other instances, boneIn other instances, boneloss and osteopenia may loss and osteopenia may

make prosthetic replacementmake prosthetic replacementa preferable option. This is a preferable option. This is

particularly true in theparticularly true in theproximal femurproximal femur

..and increasingly..and increasinglyin other joints asin other joints as

prosthetic replacementsprosthetic replacementscontinue to improve.continue to improve.

Traumatic Bone Loss

Reconstructive planning and intervention should begin prior to meeting the time requirements for nonunions

Options– Distraction osteogenesis

– Iliac crest bone grafting

– BMP reconstruction

Tibial Bone Defects Tx withIlizarov Techniques

27 tibial defects ave size 8.3 cm

Docking grafting in 25

Acute shortening in 10

Ave time of fixation was 8 months

Bone union in all cases

Song International Orthopaedics 1998

Diaphyseal Nonunion SummaryCareful assessment– Infection

– Deformity

– Biologic activity

Create viable bone and soft tissue

Correct the deformity

Provide stability

Osteoinduction when necessary

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