NONUNION OF LONG BONESNONUNION OF LONG BONES&&

INFECTED NONUNIONINFECTED NONUNION

Dr Mohammed Akbar KhanDr Mohammed Akbar Khan

DefinitionDefinition Healing process come to halt - clinically/radiologically Healing process come to halt - clinically/radiologically

–beyond stipulated period of healing – mechanical or –beyond stipulated period of healing – mechanical or biological failure with a gap being filled with fibrous or biological failure with a gap being filled with fibrous or fibro-cartilagenous tissue usually requiring a change in fibro-cartilagenous tissue usually requiring a change in treatmenttreatment

FDA: FDA: Minimum of 9 months since injury and fracture Minimum of 9 months since injury and fracture shows no visible progressive signs of healing for 3 shows no visible progressive signs of healing for 3 monthsmonths

Fracture that has no potential to heal without further Fracture that has no potential to heal without further interventionintervention

Definition of nonunion should not limit or Definition of nonunion should not limit or prevent appropriate and timely interventionprevent appropriate and timely intervention

– “ “The best treatment for nonunions is The best treatment for nonunions is prevention”prevention”

Sir Sir

John CharnleyJohn Charnley

Waiting 9 months or more is often Waiting 9 months or more is often inappropriate:inappropriate:– Prolonged morbidityProlonged morbidity– Inability to return to workInability to return to work– Narcotic dependenceNarcotic dependence– Emotional impairmentEmotional impairment

Mechanisms for Bone Mechanisms for Bone HealingHealing

Indirect (secondary) - Callus Direct (primary)

Indirect Bone HealingIndirect Bone Healing Mechanism for healing in fractures that are not

rigidly fixed. Bridging periosteal (soft) callus and medullary (hard)

callus re-establish structural continuity Callus - undergoes endochondral ossification Process fairly rapid - weeks

Direct Bone HealingDirect Bone Healing Mechanism of bone healing seen when there is no

motion at the fracture site (i.e. rigid internal fixation) Osteoblasts originate from endothelial & perivascular

cells– lay down lamellar bone behind osteoclasts forming lay down lamellar bone behind osteoclasts forming

a secondary osteona secondary osteon– Healed by formation of numerous secondary Healed by formation of numerous secondary

osteonsosteons Slow process – months to yearsSlow process – months to years

Direct Bone HealingDirect Bone Healing

LOCAL REGULATION OF BONE HEALING

Growth factors Cytokines Prostaglandins/Leukotrienes Hormones Growth factor antagonists

GROWTH FACTORSGROWTH FACTORS

Transforming growth factor Bone morphogenetic proteins Fibroblast growth factors Platelet-derived growth factors Insulin-like growth factors

Transforming Growth FactorTransforming Growth Factor

Serine/Threonine kinase cell wall receptorsSerine/Threonine kinase cell wall receptors Proliferation & differentiation of mesenchymal Proliferation & differentiation of mesenchymal

precursors for osteoblasts, osteoclasts & precursors for osteoblasts, osteoclasts & chondrocyteschondrocytes

Endochondral & intramembranous bone Endochondral & intramembranous bone formationformation

Bone Morphogenetic Proteins Bone Morphogenetic Proteins

Included in the TGF-β family– Except BMP-1

BMP 2-7,9 - Osteoinductive BMP 2,6 & 9 - Osteoblastic Work through the intracellular Smad pathway Follow a dose/response ratio Osteoinductive proteins isolated from Osteoinductive proteins isolated from

demineralized bone matrixdemineralized bone matrix

Bone Morphogenetic ProteinsBone Morphogenetic Proteins Induce cell mesenchymal Induce cell mesenchymal

differentiationdifferentiation– BMP-3 (osteogenin) - boneBMP-3 (osteogenin) - bone

Promote endochondral ossificationPromote endochondral ossification– BMP-2 & BMP-7 - segmental defectsBMP-2 & BMP-7 - segmental defects

Regulate extracellular matrix Regulate extracellular matrix productionproduction– BMP-1 is an enzyme that cleaves the BMP-1 is an enzyme that cleaves the

carboxy termini of procollagens I, II and IIIcarboxy termini of procollagens I, II and III

Fibroblast Growth FactorsFibroblast Growth Factors

Both acidic (FGF-1) and basic (FGF-2) forms Both acidic (FGF-1) and basic (FGF-2) forms Increase proliferation of chondrocytes & Increase proliferation of chondrocytes &

osteoblastsosteoblasts Enhance callus formationEnhance callus formation FGF-2 stimulates angiogenesisFGF-2 stimulates angiogenesis

Platelet-Derived Growth FactorPlatelet-Derived Growth Factor

Dimer of products of two genes PDGF-A & Dimer of products of two genes PDGF-A & PDGF-BPDGF-B

Stimulates bone cell growthStimulates bone cell growth Increases type I collagen synthesis by Increases type I collagen synthesis by

increasing the number of osteoblastsincreasing the number of osteoblasts PDGF-BB stimulates bone resorption by PDGF-BB stimulates bone resorption by

increasing number of osteoclastsincreasing number of osteoclasts

Insulin-like Growth FactorInsulin-like Growth Factor

Two types: IGF-I and IGF-IITwo types: IGF-I and IGF-II– Synthesized by multiple tissuesSynthesized by multiple tissues– IGF-I production in the liver is stimulated IGF-I production in the liver is stimulated

by Growth Hormoneby Growth Hormone Stimulates bone collagen and matrix Stimulates bone collagen and matrix

synthesissynthesis Stimulates replication of osteoblastsStimulates replication of osteoblasts Inhibits bone collagen degradationInhibits bone collagen degradation

CytokinesCytokines Interleukin-1, 4, 6, 11, macrophage and Interleukin-1, 4, 6, 11, macrophage and

granulocyte/macrophage (GM) colony-granulocyte/macrophage (GM) colony-stimulating factors (CSFs) & Tumor Necrosis stimulating factors (CSFs) & Tumor Necrosis FactorFactor

Stimulate bone resorptionStimulate bone resorption– IL-1 is the most potentIL-1 is the most potent

IL-1 and IL-6 synthesis is decreased by estrogenIL-1 and IL-6 synthesis is decreased by estrogen Peak during 1Peak during 1stst 24 hours then again during 24 hours then again during

remodelingremodeling Regulate endochondral bone formationRegulate endochondral bone formation

Specific Factor Stimulation of Specific Factor Stimulation of Osteoblasts and OsteoclastsOsteoblasts and Osteoclasts

CytokineCytokine Bone Formation Bone Formation Bone Bone ResorptionResorption

IL-1IL-1 ++ ++++++TNF-TNF-αα ++ ++++++TNF-TNF-ββ ++ ++++++TGF-TGF-αα ---- ++++++TGF-TGF-ββ ++++ ++++PDGFPDGF ++++ ++++IGF-1IGF-1 ++++++ 00IGF-2IGF-2 ++++++ 00FGFFGF ++++++ 00

Prostaglandins / LeukotrienesProstaglandins / Leukotrienes Effect on bone resorption is species Effect on bone resorption is species

dependent and their overall effects in dependent and their overall effects in humans unknownhumans unknown

Prostaglandins of the E seriesProstaglandins of the E series– Stimulate osteoblastic bone formationStimulate osteoblastic bone formation– Inhibit activity of isolated osteoclastsInhibit activity of isolated osteoclasts

LeukotrienesLeukotrienes– Stimulate osteoblastic bone formationStimulate osteoblastic bone formation– Enhance capacity of isolated osteoclasts Enhance capacity of isolated osteoclasts

to form resorption pitsto form resorption pits

HormonesHormones EstrogenEstrogen

– Stimulates fracture healing - receptor mediated Stimulates fracture healing - receptor mediated mechanismmechanism

– Modulates release of a specific inhibitor of IL-1Modulates release of a specific inhibitor of IL-1 Thyroid hormonesThyroid hormones

– Thyroxine and triiodothyronine - osteoclastic bone Thyroxine and triiodothyronine - osteoclastic bone resorptionresorption

GlucocorticoidsGlucocorticoids– Inhibit calcium absorption from gut - increased PTH Inhibit calcium absorption from gut - increased PTH – increased osteoclastic bone resorptionincreased osteoclastic bone resorption

Parathyroid Hormone -Intermittent exposure Parathyroid Hormone -Intermittent exposure – OsteoblastsOsteoblasts– Increased bone formationIncreased bone formation

Growth HormoneGrowth Hormone– Mediated through IGF-1 (Somatomedin-C)Mediated through IGF-1 (Somatomedin-C)– Increases callus formation and fracture strengthIncreases callus formation and fracture strength

Vascular FactorsVascular Factors

MetalloproteinasesMetalloproteinases– Degrade cartilage & bones to allow invasion of Degrade cartilage & bones to allow invasion of

vesselsvessels Angiogenic factorsAngiogenic factors

– Vascular-endothelial growth factorsVascular-endothelial growth factors Mediate neo-angiogenesis & endothelial-cell Mediate neo-angiogenesis & endothelial-cell

specific mitogensspecific mitogens– Angiopoietin (1&2)Angiopoietin (1&2)

Regulate formation of larger vessels & Regulate formation of larger vessels & branches branches

IncidenceIncidence

Between 5% and 10% of long bone fracturesBetween 5% and 10% of long bone fractures Relative Risk depends upon:Relative Risk depends upon:

– InjuryInjury– BoneBone– Patient Patient – TreatmentTreatment

Metabolic & Nutritional statusMetabolic & Nutritional status Generalized health & activity levelGeneralized health & activity level SmokingSmoking NSAIDsNSAIDs Systemic Medical ConditionsSystemic Medical Conditions

Systemic Risk FactorsSystemic Risk Factors

Local factorsLocal factors – OpenOpen– InfectedInfected– Segmental -impaired blood supply -Middle Segmental -impaired blood supply -Middle

fragment fragment – Comminuted by severe traumaComminuted by severe trauma– Insecurely fixed Insecurely fixed – Immobilized for an insufficient time Immobilized for an insufficient time – Treated by ill-advised open reduction Treated by ill-advised open reduction – Distracted - Traction or Plate and screws Distracted - Traction or Plate and screws – Irradiated bone Irradiated bone

MalnutritionMalnutrition

Adequate protein and energy is required for Adequate protein and energy is required for wound healingwound healing

Causes reduced activity & proliferation of Causes reduced activity & proliferation of osteochondral cellsosteochondral cells

Decreased callus formationDecreased callus formation Albumin less than 3.5 and lymphocytes less Albumin less than 3.5 and lymphocytes less

than 1,500 cells/ml is significantthan 1,500 cells/ml is significant

Diabetes Mellitus

Associated with collagen defects Decreased collagen content Defective cross-linking Alterations in collagen sub-type ratios

SMOKINGSMOKING

Cigarette smoke inhibits osteoblastsCigarette smoke inhibits osteoblasts Nicotine causes vasoconstriction diminishing Nicotine causes vasoconstriction diminishing

blood flow at fracture siteblood flow at fracture site Decreases peripheral oxygen tension & Decreases peripheral oxygen tension &

Dampens peripheral blood flowDampens peripheral blood flow Well documented difficulties in wound healing Well documented difficulties in wound healing

in patients who smokein patients who smoke

Infection

““Of all prognostic factors in tibia fracture care, Of all prognostic factors in tibia fracture care, that implying the worst prognosis was that implying the worst prognosis was infectioninfection””

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

IatrogenicIatrogenic

Poor ReductionPoor Reduction Unstable fixationUnstable fixation Bone DevitalizationBone Devitalization

– Excessive soft tissue dissection and Excessive soft tissue dissection and periosteal stripping at time of previous periosteal stripping at time of previous fixationfixation

Energy of Fracture Energy of Fracture MechanismMechanism

Initial fracture displacementInitial fracture displacement Fracture pattern Fracture pattern

– comminutioncomminution– bone lossbone loss– segmental patternssegmental patterns

Soft tissue disruption (vascularity and oxygen Soft tissue disruption (vascularity and oxygen delivery)delivery)

CausesCausesMechanical FailureMechanical Failure

Inadequate immobilization & internal fixationInadequate immobilization & internal fixation Hypertrophic type with mobility & pain Hypertrophic type with mobility & pain Stability restored – fracture heals quicklyStability restored – fracture heals quickly Fragments have good blood supplyFragments have good blood supply

CausesCausesBiological FailureBiological Failure

Loss of blood supply to fracture site/ infection/loss of Loss of blood supply to fracture site/ infection/loss of healing factors- BMP / evacuation of haematoma in healing factors- BMP / evacuation of haematoma in ORIFORIF

Addition to restoring stability + stimulation of healing- Addition to restoring stability + stimulation of healing- bone grafting / electrical stimulation / low intensity ultra bone grafting / electrical stimulation / low intensity ultra soundsound

Bone ends are atrophic, with no callus and presence Bone ends are atrophic, with no callus and presence of mobilityof mobility

CLASSIFICATIONCLASSIFICATION Judet and Judet, Müller (AO), Weber and Cech

Hypervascular (Hypertrophic) or viable - Capable of biological reaction.

Avascular (Atrophic) or inert

- Not capable of uniting without intervention.

Hypervascular nonunionsHypervascular nonunions

Elephant foot. Horse hoof Oligotrophic

Torsion wedge Comminuted Defect Atrophic

Avascular nonunions

Classification of Nonunions of TibiaClassification of Nonunions of Tibia Paley et al. Paley et al. Applied to nonunions of other bones Applied to nonunions of other bones Type A - Nonunions with bone loss of less than 1 cm Type A - Nonunions with bone loss of less than 1 cm

– Type A1 - mobile deformityType A1 - mobile deformity– Type A2 - fixed deformity Type A2 - fixed deformity

Type A2-1 - Stiff nonunion without deformity, Type A2-1 - Stiff nonunion without deformity, Type A2-2 - Stiff nonunion with a fixed deformity.Type A2-2 - Stiff nonunion with a fixed deformity.

Type B - Nonunions with bone loss of more than 1 Type B - Nonunions with bone loss of more than 1 cmcm– Type B1 - Bony defect Type B1 - Bony defect – Type B2 - Loss of bone length Type B2 - Loss of bone length – Type B3 - BothType B3 - Both

Modified further by presence or absence of Modified further by presence or absence of infection. infection.

Type AType A

A1-Lax (mobile) A2-1-Fixed+No deformity

A2-2-Fixed deformity

Type B

Bony defect + no shortening Shortening+ no bony defect

Bony defect and shortening

Diagnosis of Nonunion- Diagnosis of Nonunion- HistoryHistory

Nature of original injury (high or low energy)Nature of original injury (high or low energy) Previous open wounds of injury sitePrevious open wounds of injury site Pain present at fracture sitePain present at fracture site Symptoms of infection i.e. Symptoms of infection i.e.

– Antalgic gait or decrease use secondary to Antalgic gait or decrease use secondary to painpain

History of any drainage or wound healing History of any drainage or wound healing difficultiesdifficulties

ExaminationExamination AlignmentAlignment DeformityDeformity Soft tissue integritySoft tissue integrity Erythema, warm, drainageErythema, warm, drainage Vascularity of limbVascularity of limb

– Pulses, transcutaneous oximetryPulses, transcutaneous oximetry Stability at fracture siteStability at fracture site

– Pain assessed during this portion of Pain assessed during this portion of examinationexamination

X-raysX-rays

AP, lateral, and oblique (45degree internal AP, lateral, and oblique (45degree internal and 45 degree external)and 45 degree external)

In majority of cases, this is all that is required In majority of cases, this is all that is required to confirm nonunionto confirm nonunion

Examination under fluoroscopy to check for Examination under fluoroscopy to check for motion can occasionally be helpful alsomotion can occasionally be helpful also

TomographyTomography

Linear tomogramsLinear tomograms– Helpful if metallic hardware presentHelpful if metallic hardware present

Helps to identify persistent fracture line in:Helps to identify persistent fracture line in:– Hyptrophic nonunions in which x-rays are not Hyptrophic nonunions in which x-rays are not

diagnostic and pain persists at fracture sitediagnostic and pain persists at fracture site Computed tomography and MRI are replacing Computed tomography and MRI are replacing

linear tomography if no hardware presentlinear tomography if no hardware present

Computed TomographyComputed Tomography

Radionuclide ScanningRadionuclide Scanning Technetium - 99 diphosphonateTechnetium - 99 diphosphonate

– Detects repairable process in bone ( not specific)Detects repairable process in bone ( not specific) Gallium - 67 citrateGallium - 67 citrate

– Accumulate at site of inflammation (not specific)Accumulate at site of inflammation (not specific) Sequential technetium or gallium scintigraphySequential technetium or gallium scintigraphy

– Only 50-60% accuracy in subclinical ostoemyelitisOnly 50-60% accuracy in subclinical ostoemyelitis Indium III - Labeled Leukocyte ScanIndium III - Labeled Leukocyte Scan

– Good with acute osteomyelitis, but less effective Good with acute osteomyelitis, but less effective chronic or subacute bone infectionschronic or subacute bone infections

– Sensitivity 83-86%, specificity 84-86%Sensitivity 83-86%, specificity 84-86%– superior to technetium and gallium to identify superior to technetium and gallium to identify

infectioninfection

MRIMRI

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%

Tissue BiopsyTissue Biopsy Antibiotic discontinued for 72 hours prior to Antibiotic discontinued for 72 hours prior to

biopsybiopsy Multiple representative biopsy specimens Multiple representative biopsy specimens

should be obtainedshould be obtained Cultures sent for gram stain, aerobic, anerobic, Cultures sent for gram stain, aerobic, anerobic,

fungal, and acid fast studiesfungal, and acid fast studies Open biopsy techniques can be inconclusive Open biopsy techniques can be inconclusive

due to problem of detecting bacteria protected due to problem of detecting bacteria protected by an external glycocalyxby an external glycocalyx

TreatmentTreatment

NonoperativeNonoperative OperativeOperative

Nonoperative TreatmentNonoperative Treatment

Mechanical stimulationMechanical stimulation UltrasoundUltrasound

– mechanical energy in the form of low frequency mechanical energy in the form of low frequency acoustic waves 30 mW/cmacoustic waves 30 mW/cm22

ElectromagneticElectromagnetic– Direct CurrentDirect Current– Inductive coupling (PEMF, CMF)Inductive coupling (PEMF, CMF)– Capacitive couplingCapacitive coupling

Bone marrow injectionBone marrow injection

Mechanical StimulationMechanical Stimulation

Early weight bearingEarly weight bearing– Facilitate maturation of callus Facilitate maturation of callus – – endochondral ossification in cast braceendochondral ossification in cast brace

Axial MicromotionAxial Micromotion– Acclerates healingAcclerates healing

Low intensity pulsed ultrasound (lipus)Low intensity pulsed ultrasound (lipus)

Dose – low intensity Dose – low intensity

– – 30 m W/cm2 30 m W/cm2

– – 20 minutes a day20 minutes a day

Electric StimulationElectric Stimulation Piezoelectric nature of bone - stress generated

electric potentials exist in bone & are related to callus formation

Electromagnetic fields influence vascularization of fibrocartilage, cell proliferation & matrix production

Three Modalities of Electric bone Growth Stimulators– 1. Direct current - percutaneous or implanted electrodes1. Direct current - percutaneous or implanted electrodes– 2. Electromagnetic stimulation - time varying magnetic 2. Electromagnetic stimulation - time varying magnetic

fieldsfields– 3. Capacitive coupling - electrodes placed on skin3. Capacitive coupling - electrodes placed on skin

ContraindicationContraindication– Synovial pseudoarthrosisSynovial pseudoarthrosis

Surgical TreatmentSurgical Treatment

Cure infection if presentCure infection if present Correct Deformity if significantCorrect Deformity if significant Provide stability through implantsProvide stability through implants Add biologic stimulus when necessaryAdd biologic stimulus when necessary

Surgical TreatmentSurgical Treatment Fibular osteotomyFibular osteotomy Bone graftBone graft Plate osteosynthesisPlate osteosynthesis Intramedullary nailingIntramedullary nailing External fixationExternal fixation

Infected NonunionsInfected Nonunions

Contaminated implants and devitalized implants must Contaminated implants and devitalized implants must be removedbe removed

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

Secondary stabilization with augmentation of Secondary stabilization with augmentation of osteogenesis (cancellous grafting)osteogenesis (cancellous grafting)

Methods of Adding StabilityMethods of Adding Stability

Cast/Brace – rarely sufficient in nonunions External Fixation Plates Intramedullary Devices

External FixationExternal Fixation Correct malalignmentCorrect malalignment Used primarily in management of infected Used primarily in management of infected

nonunionsnonunions Allows for repeated debridements, soft tissue Allows for repeated debridements, soft tissue

reconstructive procedures, and adjunctive bone-reconstructive procedures, and adjunctive bone-graftinggrafting

Small wire ring fixators can also allow for bone Small wire ring fixators can also allow for bone transport into large intercalary defectstransport into large intercalary defects

Ring fixators can also generate large compressive Ring fixators can also generate large compressive forces at fracture to allow mobilization of joints forces at fracture to allow mobilization of joints and improve fracture healing environmentand improve fracture healing environment

Plate OsteosynthesisPlate Osteosynthesis Corrects malalignmentCorrects malalignment Restores function & stabilizes fracture Restores function & stabilizes fracture

fragments directlyfragments directly Compresses fragments in some circumstances Compresses fragments in some circumstances

to augment healingto augment healing Allows patients to mobilize surrounding joints Allows patients to mobilize surrounding joints Locking plates - improved stability & fixation strengthLocking plates - improved stability & fixation strength Requires adequate skin and soft tissue Requires adequate skin and soft tissue

coveragecoverage Often used with adjunctive bone graftOften used with adjunctive bone graft

Intramedullary NailingIntramedullary Nailing Mechanically stabilizes long bone nonunions as a Mechanically stabilizes long bone nonunions as a

load sharing implantload sharing implant Corrects malalignmentCorrects malalignment Reaming is initially detrimental to intramedullary Reaming is initially detrimental to intramedullary

blood supply, but it does recover and is believed blood supply, but it does recover and is believed to stimulate biologic healing at fractureto stimulate biologic healing at fracture

Allow patient to mobilize surrounding joints and Allow patient to mobilize surrounding joints and dynamize fracture environmentdynamize fracture environment

Can be performed without direct exposure or Can be performed without direct exposure or dissection of the fracture soft tissue envelopedissection of the fracture soft tissue envelope

Nonapplicable in articular fracturesNonapplicable in articular fractures

Adding BiologyAdding Biology Often unnecessary in hypertrophic cases with Often unnecessary in hypertrophic cases with

sufficient inherent biologic activitysufficient inherent biologic activity OptionsOptions

– Aspirated stem cells (with or without expansion) stem cells (with or without expansion)– Demineralized Bone MatrixDemineralized Bone Matrix– Autogenous Cancellous GraftAutogenous Cancellous Graft– Growth FactorsGrowth Factors

Platelet derivedPlatelet derived Recombinant BMPsRecombinant BMPs Gene TherapyGene Therapy

Stem CellsStem Cells

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

Has been studied as an Has been studied as an isolated technique with isolated technique with limited successlimited success

Role of expansion and Role of expansion and delayed implantation may delayed implantation may play a future roleplay a future role

Demineralized Bone MatrixDemineralized Bone Matrix Osteoinduction has been experimentally demonstratedOsteoinduction has been experimentally demonstrated Produced by acid extraction of allograft boneProduced by acid extraction of allograft bone Contains type I collagen, noncollagenous protein & Contains type I collagen, noncollagenous protein &

osteoinductive growth factorsosteoinductive growth factors Effective in humeral shaft nonunionsEffective in humeral shaft nonunions Avoids the morbidity of iliac crest graftAvoids the morbidity of iliac crest graft As effective as iliac crestAs effective as iliac crest

Autogenous Cancellous BoneAutogenous Cancellous Bone SitesSites

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

incidence of donor morbidity dependent upon harvest incidence of donor morbidity dependent upon harvest site and volume requiredsite and volume required

Still considered by many to be the most osteogenic Still considered by many to be the most osteogenic graft materialgraft material

Bone GraftingBone Grafting Most frequently used method of treatment of

nonunions Used to stimulate biologic response of healing in

nonunions -usually atrophic nonunions Autogenous bone graft, allograft bone, or synthetic

bone substitute, used alone or in conjunction with internal fixation, may help to stimulate bone formation.

Autogenous cancellous bone - gold standard grafting material

osteoconductive (matrix) and osteoinductive (protein) properties and its osteoprogenitor cells make it an ideal substance for nonstructural grafting

Bone Grafting Bone Grafting

Onlay Bone Graft Dual Onlay Graft Cancellous Insert Grafts Massive Sliding Graft Whole Fibular Transplants Vascularized Free Fibular Graft Intramedullary Fibular Allografts

Onlay Bone GraftOnlay Bone Graft Massive cortical grafts combine fixation Massive cortical grafts combine fixation

&osteogenesis&osteogenesis Massive sliding graft - Gill Massive sliding graft - Gill Campbell originated the term onlay graft -Campbell originated the term onlay graft -

modification of Henderson's technique modification of Henderson's technique Phemister - graft is placed subperiosteally Phemister - graft is placed subperiosteally

across the fragments without mobilizing the across the fragments without mobilizing the fragments. fragments. – Blood supply of the fragments and the normal Blood supply of the fragments and the normal

impacting forces of the fracture were not disturbedimpacting forces of the fracture were not disturbed Forbes described a modification of the Forbes described a modification of the

Phemister technique. Phemister technique.

Dual Onlay Graft 1941 Boyd - dual grafts are used. 1941 Boyd - dual grafts are used. Two cortical onlay grafts are placed opposite Two cortical onlay grafts are placed opposite

each other on the host bone across the nonunion each other on the host bone across the nonunion and are fixed with the same set of screwsand are fixed with the same set of screws

Any intervening space at the bone ends is filled Any intervening space at the bone ends is filled with cancellous chips. with cancellous chips.

Dual grafts have been used to fix a nonunited Dual grafts have been used to fix a nonunited fracture near a joint firmly with a short, fracture near a joint firmly with a short, osteoporotic fragment. osteoporotic fragment.

Nonunions near a joint now often are treated by Nonunions near a joint now often are treated by plating and autogenous cancellous bone grafting plating and autogenous cancellous bone grafting or by the application of a circular external or by the application of a circular external fixator. fixator.

Boyd dual onlay grafts

Cancellous Insert Grafts Nicoll - Bridging gaps in long bones with solid Nicoll - Bridging gaps in long bones with solid

blocks of cancellous bone & fixing fragments blocks of cancellous bone & fixing fragments with metal plates.with metal plates.

Defects less than 2.5 cm long.Defects less than 2.5 cm long. Ordinary plates are used but compression Ordinary plates are used but compression

plates are preferable.plates are preferable. Aftertreatment Aftertreatment

– cast is applied and worn for 2 or 3 months,

Massive Sliding Graft

Gill - uses a sliding graft about one half the Gill - uses a sliding graft about one half the circumference of the bone and 10 to 15 cm long circumference of the bone and 10 to 15 cm long

Flanagan and Burem revised and improved this Flanagan and Burem revised and improved this technique for nonunion of the tibia and femurtechnique for nonunion of the tibia and femur

Useful for bridging bone defects, but when a Useful for bridging bone defects, but when a massive sliding graft fails, later grafting is massive sliding graft fails, later grafting is difficult. difficult.

Gill massive sliding graft

Whole Fibular Transplants

whole fibular transplant may be useful for bridging defects in the radius or ulna

As it is tubular, it is stronger than a tibial graft with same amount of cortical bone and need not be as large

used to bridge defects in the humeral shaft & Distal radius

Vascularized Free Fibular Graft Treatment of osteonecrosis of the femoral head Treat defects associated with tumor resections Duffy et al. - vascularized free fibular grafting for

nonunions of shaft fractures of bones that had been irradiated to treat a malignancy

Used the graft in an “onlay” manner in association with other forms of fixation, such as intramedullary nailing or plating.

Bone graft substitutesBone graft substitutes

Osteoconductive propertyOsteoconductive property Calcium phosphate, calcium sulphate, Calcium phosphate, calcium sulphate,

hydroxyapatite, other calcium based ceramicshydroxyapatite, other calcium based ceramics

Recombinant Bone Morphogenic Recombinant Bone Morphogenic ProteinsProteins

BMP-2BMP-2

Infuse™Infuse™

Demonstrated effective in acute open tibial Demonstrated effective in acute open tibial fracturesfractures

FDA approved in acute fracturesFDA approved in acute fractures BMP-7BMP-7

–OP-1™OP-1™–Comparable to autograft in tibia nonunionsComparable to autograft in tibia nonunions–FDA approved under HD exemptionFDA approved under HD exemption

INFECTED NON UNION

Sir Reginald Watson JonesSir Reginald Watson Jones

Infection is not a cause of nonunions If nonunions allowed to occur, it is due not

infections, but to adequate immobilization permitted by reason of infection

Mobility at fracture site is more likely to promote or sustain infection than a metal foreign body

DefinitionDefinition

Fracture un-united for less than 6 months with Fracture un-united for less than 6 months with wound is open & infected with exposed dead wound is open & infected with exposed dead bone or metalbone or metal

Fracture un-united for more than 6 months with Fracture un-united for more than 6 months with apparent clinical motion at fracture site, apparent clinical motion at fracture site, formation of sinus, indicating sequestration or formation of sinus, indicating sequestration or extensive osteomyelitisextensive osteomyelitis

-Dendrinos 1995-Dendrinos 1995

IncidenceIncidence

Gustilo’s study – 44% of open segmental Gustilo’s study – 44% of open segmental fracture with periosteal stripping and fracture with periosteal stripping and fragmentation of bone developed infectionsfragmentation of bone developed infections

Commonest in tibia followed by femur, humerus Commonest in tibia followed by femur, humerus & forearm bones& forearm bones

Rosen’s ClassificationRosen’s Classification

Non-draningNon-draning– Quiescent dry for three monthsQuiescent dry for three months– Active abscessActive abscess

Draining - Sinus with sequestrum or cavityDraining - Sinus with sequestrum or cavity

Cierny and Mader StagingCierny and Mader StagingAnatomical Type I Medullary Endosteal disease II Superficial Cortical surface infected because of

coverage defect III Localized Cortical sequestrum that can be excised

without compromising stability IV Diffuse Features of I, II, and III plus mechanical

instability before or after débridement

Physiological Class A host Normal Immunocompetent with good local

vascularity B host Compromised Local (L) or systemic (S) factors that

compromise immunity or healing C host Prohibitive Minimal disability, prohibitive morbidity

anticipated, or poor prognosis for cure

PathogenesisPathogenesis Microbial adhesion to the damaged tissue or metal

implants Occurs in open fractures with implant applied has

become loose Necrotic bone or implants are covered by avascular

material – glycocalyx(slime) – hydrated mucopolysaccharide layer

Slime protects bacteria in a sessile state increasing their resistance to destruction by a factor of 500

Increased bacterial surface adherence isolating them from effects of antibiotics, antibodies & immune directed phagocytosis

Infection persist due to thrombosis of Haversian canal– avascular zone of fibrosis of local tissue & bone

marrow– causing reduction in antibiotic perfusion and

protecting the microorganisms Inadequate perfusion

– leads to inadequate supply of antibiotics – resulting in failure of antibiotic action & resistance of

organisms

InvestigationsInvestigations Routine blood investigation including ESR & CRPRoutine blood investigation including ESR & CRP X- Rays – helpful in identifying necrotic areas & X- Rays – helpful in identifying necrotic areas &

sequestrasequestra CT scan – extent of sequestration underneath a CT scan – extent of sequestration underneath a

periosteal new bone formationperiosteal new bone formation MRI – information on soft tissue & marrow MRI – information on soft tissue & marrow

involvementinvolvement Skeletal scintigraphy – sub-clinical infectionSkeletal scintigraphy – sub-clinical infection

– 111 Indium labeled leukocyte imaging111 Indium labeled leukocyte imaging– Te 99m methylene diphosphonate imagingTe 99m methylene diphosphonate imaging– Gallium -67 scanGallium -67 scan– Sulphane blue – identify infected areas of bone while Sulphane blue – identify infected areas of bone while

doing debridementdoing debridement

PRINCIPLES OF TREATMENT

Conversion of infected into asceptic nonunion– Debridement, local antibiotics

Stabilisation of fracture by internal or ext. fixation Adequate soft tissue coverage

DEBRIDEMENT Devitalized bone and soft tissue – barriers for

eradication of infection Intramedullary debridement - Reaming I M Canal Removal of implant Carcinogenic resection of infected bone

– Wide resection of entire infected bone with infected scarred soft tissue with clearence of margin of 5 mm in bone

Resect bony ends till punctuate bleeding(Paprika sign)

Lautenbach’s principles of infection control

Radical resection & removal of infected marrow – gentle reaming & washing marrow out

Antiobiotic solution are instilled 4 th hourly, kept for 4 hours and sucked out for 4 weeks

Irrigation solution contains chlorhexidine(antiseptic) teicoplanin(antibiotic) & streptokinase(anticoagulant)

Local Antibiotic delivery system

Treatment by AB impregnated intramedullary nail & beads

kill bacteria protected in Biofilm local concentration > 100 times serum conc.

IDEAL LOCAL DRUG DELIVERY SYSTEM

High concentration locallyHigh concentration locally No systematic toxicityNo systematic toxicity Satisfactory elution Satisfactory elution Easily placed, removed & changedEasily placed, removed & changed InexpensiveInexpensive Broad spectrumBroad spectrum ThermostableThermostable

AntibioticsAntibiotics Antibiotic Commonly UsedAntibiotic Commonly Used

– VancomycinVancomycin– GentamycinGentamycin– TobramycinTobramycin

Other antibioticsOther antibiotics– CefazolinCefazolin– CiprofloxacinCiprofloxacin– ClindamycinClindamycin– TicarcillinTicarcillin– TeicoplaninTeicoplanin– ErythromycincolistinErythromycincolistin– CefotaximeCefotaxime– Amphoteracin BAmphoteracin B

Preparation of Dough for Beads and Rod

40 gm. Cement plus– Tobramycin 3.6 gm.– Vancomycin 4 gm. – Cefepime 4 gm. – Cefezolin 4 gm.– Nafcillin 4 gm.– Brittle Beads size 7 mm.

ADVANTAGES OF AB ROD & BEADS Local high concentration -AB Primary wound closure – reduced post operative

morbidity No systemic toxicity Painful inflammatory response subsides rapidly –

increased patient comfort. No daily dressing. No secondary infection Gram negative over growth (wet Germs) seen with

irrigation suction drainage are avoided Bacterial cross seeding avoided (Hospital infections) Hospitalization is shortened Cost effective

DISADVANTAGES OF AB ROD & BEADS

Cannot adjust antibiotic when wound flora changes Not as effective as irrigation Spent beads may act as nide for infection Only limited number of antibiotics are available in the

form in which it can be used in beads Requires surgery for removal Complications have occurred with use of PMMA

beads when they were left too long or placed near major places

STABILIZATION & RECONSTRUCTION STABILIZATION & RECONSTRUCTION METHODSMETHODS

Aim of stabilization– Bring about bony bridging– Allow functional after treatment– Allow easy wound care & to support eradication of

infection– Allow later reconstructive surgery if necessary

STABILIZATION & RECONSTRUCTION STABILIZATION & RECONSTRUCTION METHODSMETHODS

Skeletal Reconstruction– Ilizarov’s method– Vascularised bone graft– Corticocancellous bone graft– Papineau cancellous bone graft– Bypass graft (tibiofibular grafting)– Tibio fibular synostosis

ILIZAROV’S CONCEPT FOR INFECTED ILIZAROV’S CONCEPT FOR INFECTED NONUNIONNONUNION

Osteomylitis burns in the fire of regenerationOsteomylitis burns in the fire of regeneration Cyclic axial telescoping mobility, not rigidity, at Cyclic axial telescoping mobility, not rigidity, at

the union site is important for formation of the union site is important for formation of reparative callusreparative callus

Activate biosynthetic process, increasing local Activate biosynthetic process, increasing local resistant to infectionresistant to infection

Three ways of elimination of Three ways of elimination of infection in Ilizarov methodinfection in Ilizarov method

Controlled osteogenesis, filling of cavities by Controlled osteogenesis, filling of cavities by newly formed tissuenewly formed tissue

Resection of infected bone and subsequent Resection of infected bone and subsequent intercalary bone lengtheningintercalary bone lengthening

Gradual bone transport of one wall of the cavityGradual bone transport of one wall of the cavity

Ilizarov methodIlizarov method Distraction osteogenesisDistraction osteogenesis Tension-stress effectTension-stress effect Mechanical induction of new bone formationMechanical induction of new bone formation NeovascularizationNeovascularization Stimulation of biosynthetic activityStimulation of biosynthetic activity Activation and recruitment of osteoprogenitor Activation and recruitment of osteoprogenitor

cellscells Intramembranous ossificationIntramembranous ossification

Ilizarov`s plan depends on Ilizarov`s plan depends on

Size and thickness of bone fragmentSize and thickness of bone fragment Degree and type of displacementDegree and type of displacement The extent of mobilityThe extent of mobility Amount and character of scar tissueAmount and character of scar tissue Prevalence of purulent processPrevalence of purulent process Characteristics of the individual caseCharacteristics of the individual case

Ilizarov Treatment ModesIlizarov Treatment Modes Monofocal

– Compression– Sequential distraction-compression Distraction– Sequential compression-distraction

Bifocal –  Compression-distraction lengthening– Distraction-compression transport (bone transport)

Trifocal – Various combinations

Monofocal longitudinal Monofocal longitudinal compressioncompression

Hypertrophic nonunion Hypertrophic nonunion Minimal infectionMinimal infection No sequestrum, smallest sequester left in place, No sequestrum, smallest sequester left in place,

they are assimilated in the process of active they are assimilated in the process of active osteogenesisosteogenesis

spontaneous eradication of infection and spontaneous eradication of infection and achievement of unionachievement of union

Monofocal osteosynthesis with Ilizarov fixator for hypertrophic nonunions with minimal infection, as recommended by Catagni.

Bifocal MethodBifocal Method

Atrophic nonunion with diffuse infection & Atrophic nonunion with diffuse infection & sequestrum sequestrum

Infected segment should be resectedInfected segment should be resected Creating an intercalary defectCreating an intercalary defect Acute shortening, opposing ends under Acute shortening, opposing ends under

compression; 1-2 Cm defectcompression; 1-2 Cm defect Poor skinPoor skin Big necrotic bone Big necrotic bone Numerous fistulaNumerous fistula

Bilocal simultaneous compression-Bilocal simultaneous compression-distraction osteosynthesisdistraction osteosynthesis

Small gap & substantial bone shorteningSmall gap & substantial bone shortening

Treatment consistedOf resection of Infected bone, acuteShortening and External fixation

Followed by proximalCorticotomy andDistraction to restorelength

Bifocal osteosynthesis with Ilizarov fixator after débridement of necrotic segments, as recommended by Catagni

Bilocal consecutive distraction-Bilocal consecutive distraction-compression osteosynthesiscompression osteosynthesis

Large gapLarge gap

ADVANTAGES ADVANTAGES Surgical morbidity is minimalSurgical morbidity is minimal Soft tissue reconstruction is rarely requiredSoft tissue reconstruction is rarely required Functional weight bearing is started earlyFunctional weight bearing is started early Progressive correction of angulatory & torsional Progressive correction of angulatory & torsional

deformitiesdeformities Ability to apply compression distraction or Ability to apply compression distraction or

angulatory correctionat multiple levelsangulatory correctionat multiple levels Diffuse osteoporosis is minimal – early Diffuse osteoporosis is minimal – early

functional wt bearingfunctional wt bearing Near bloodless & minimally invasive methodNear bloodless & minimally invasive method Eliminates secondary bone harvestingEliminates secondary bone harvesting

CONTRAINDICATIONS CONTRAINDICATIONS

Severe damage of tibial nerve with motor & Severe damage of tibial nerve with motor & sensory losssensory loss

Mental disease including senile dementiaMental disease including senile dementia Anticipated poor co- operation by patientAnticipated poor co- operation by patient

Ilizarov is a golden method for the Ilizarov is a golden method for the management of nonunion management of nonunion osteomylitis for both achieving union osteomylitis for both achieving union and eradication of infection, however and eradication of infection, however generous, careful sequential generous, careful sequential debridement and hardware/dead debridement and hardware/dead tissue removal and bone grafting is tissue removal and bone grafting is also an option for some selected also an option for some selected cases.cases.

Four basic methods of immediate, Four basic methods of immediate, biological management of dead space biological management of dead space using living tissue or cancellous bone using living tissue or cancellous bone grafts grafts

TREATMENT OF DEAD SPACE

Four basic methods of immediate, biological management of Four basic methods of immediate, biological management of

dead space using living tissue or cancellous bone graftsdead space using living tissue or cancellous bone grafts

Open Bone Grafting Papineau et al - open bone grafting - Papineau et al - open bone grafting -

chronic osteomyelitis.chronic osteomyelitis. principles:principles:

– granulation tissue markedly resists infection granulation tissue markedly resists infection – autogenous cancellous bone grafts are autogenous cancellous bone grafts are

rapidly revascularized and are resistant to rapidly revascularized and are resistant to infection infection

– infected area is completely excised infected area is completely excised – adequate drainage is provided adequate drainage is provided – adequate immobilization is provided adequate immobilization is provided – antibiotics are used for prolonged periods.antibiotics are used for prolonged periods.

Chronic osteomyelitis.

After débridement and development of granulation tissue.

Open bone graft.

Blood clot in place

Other treatment optionsOther treatment options

Free vascularized bone graftFree vascularized bone graft Posterolateral bone grafting (harmon’s Posterolateral bone grafting (harmon’s

technique)technique) Tibiofibular synostosisTibiofibular synostosis Free microvascular soft tissue flaps for Free microvascular soft tissue flaps for

coveragecoverage Local soft tissue rotational flapLocal soft tissue rotational flap Monolateral external fixatorMonolateral external fixator

Tibia and fibula have been approached posterolaterally. Tibia and fibula have been approached posterolaterally. Posterior aspect of tibia (or tibia and fibula) is roughened and grafted Posterior aspect of tibia (or tibia and fibula) is roughened and grafted with autogenous iliac bonewith autogenous iliac bone

Bone is approached anteriorly and is Bone is approached anteriorly and is saucerized, incision is closed,saucerized, incision is closed, and infection is treated with antibiotics by and infection is treated with antibiotics by irrigation and suctionirrigation and suction

Tibia is grafted posteriorly-Skin incision.Tibia is grafted posteriorly-Skin incision.

Treatment of nonunion of tibia in which sequestration or gross infection is presentTreatment of nonunion of tibia in which sequestration or gross infection is present

BIBILOGRAPHYBIBILOGRAPHY

CAMPBELL’S OPERATIVE ORTHOPAEDICSCAMPBELL’S OPERATIVE ORTHOPAEDICS APLEY’S ORTHOPAEDICSAPLEY’S ORTHOPAEDICS ORTHOPAEDIC TRAUMA ASSOCIATIONORTHOPAEDIC TRAUMA ASSOCIATION Prof. Mani & Prof Sudhkar Shetty, Prof. Mani & Prof Sudhkar Shetty,

Mangalore Orthopaedic CourseMangalore Orthopaedic Course

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