Bone Healing and Non Unions[1]

Bone Healing and Non-Unions

Felicia Bock –TUSPM 2011

Bone Healing and Non Unions

• Non-union will occur in 10% to 30% of long bone fractures (Zimmerman)

• 733.82

Incidence of Non Union in Foot and Ankle*Location/Procedure

Incidence of Non Union

# of Pts (n)

Reference

Triple Arthrodesis

22% (MC was

TNJ)80

(Angus)

Ankle Arthrodesis w/ IM rod

26% 19(Moore)

STJ Arthrodesis (bone block distraction)

13% 37(Trnka)

* Liporace et al. Bioadjuvants for Complex Ankle and Hindfoot Recon. Foot Ankle Clin N Amer

Types of Bone Healing

• Primary Healing– Bone heals without callus formation– Occurs with “absolute stability”

• Secondary Healing– Bone heals with callus formation– Occurs with “relative stability”

• Due to effect of mechanical environment on differentiation of stem cells *

Jagodzinski M, Krettek C. Effect of mechanical stability on fracture healing. Injury 2007. 38: S3-10

Essential Components for Bone Healing

1. Osteogenesis – presence of mesenchymal cells to differentiate into osteogenic cells

2. Osteoconduction – ability of the graft to create a structural framework for growth

3. Osteoinduction - the recruitment of stem cells from the host bone into the graft site where they differ into osteoblasts

• Stability• Vascularity

Harwood PJ, Michael AL, Newman JB. An Update on Fracture Healing and Nonunion. Orthopaedics and Trauma. 2010; 24: 10 23

Perren’s Strain Theory of Fracture Healing*

• Low fracture strain (<2%) results in no callus formation and primary healing (Strain = length/original length)

• Higher fracture strains between 10 to 20% result in secondary healing with callus formation.

• The loss of fixation creates strains exceeding 30% and subsequently yields nonunion results.

*Walter J.H. and L. Goss. Traumatology of the Foot and Ankle. TUSPM

3 Types of Healing Complications

• Delayed Union

• Non Union

• Pseudoarthrosis – end stage of Non Union

Delayed Unions vs. Non Unions• Healing that takes

longer then it should for a certain area of bone, type of fracture or age of patient

• Still capable of healing on their own (still have biologic properties of healing)

• No signs of healing progression at 6 months or more?

• FDA defines a non union as an osseous discontinuity of 9 months duration, in which there has been no radiographic evidence of healing for 3 consecutive months?

Weber and Czech Types of Non Unions

• Hypertrophic (Hypervascular)

• Atrophic (Avascular)

Hypertrophic Non Unions

Olsen S., Hahn D. Surgical treatment of non unions: a case for internal fixation. Injury (2006) 37, 681-690Harwood PJ, Michael AL, Newman JB. An Update on Fracture Healing and Nonunion. Orthopaedics and Trauma. 2010; 24: 10 23

Atrophic Non Unions

Olsen S., Hahn D. Surgical treatment of non unions: a case for internal fixation. Injury (2006) 37, 681-690

Paley and Herzenberg

• Classify non-unions according to clinical mobility

1.Stiff (<5º mobility)

2.Partially mobile (5-20º mobility)

3.Flail (>20 ºmobility)

Identify the Cause (Etiologies of Non Unions)

1. Lack of stability2. Failure to reduce the fracture gap3. Lack of Blood Supply4. Infection (OM and Systemic)5. Location of the fracture 6. Compromised Host (DM, RA, nutrition,

osteoporosis)7. Smoking8. Drugs

Blood Supply and Non-unions

• Long bones have three blood supplies– Nutrient artery

(intramedullary)– Periosteal vessels– Metaphyseal

vessels

Nutrient artery

Metaphysealvessels

Periosteal vessels

Figure adapted from Rockwood and Green, 5th Ed

Nutrition and Non-Union

• 40% of patients who underwent orthopaedic surgery had evidence of malnutrition

• Jensen recommended albumin >3.5 and lymphocyte > 1000 for surgery

• Pt with major fracture; 25% in energy requirements

• Pt with multiple traumas and/or infection; 30-55% in energy requirements– Severe trauma pt undergoing multiple

procedures has the energy consumption of a marathon runner

Jensen J et al. Nutrition in Orthopaedic Surgery. Journal of Bone Joint Surgery. 1982 (64-A)

Nutrition (continued)

• Study of fracture healing and protein in mice

• Low Protein Diet (< 5.0 gm/dL)– At 3 months post fracture: fibrous non

union (minimal osseous formation)

• Normal Protein Diet (8 gm/dL)– At 1 month; new bone and cartilage

present at fracture sight– At 3 months; fracture line was indistinct

Rodrigues L. Healing of displaced condylar process fracture in rats submitted to protein undernutrition. J of Cranio-Maxillo-Facial Surgery. 2010 (1-6)

Smoking and Non-Unions• Carbon Monoxide reduces O2 carrying

capacity of blood (stronger affinity for Hb)• Nicotine causes vasoconstriction

• Smokers w/ hindfoot fusions were 2.7 times more likely to develop non-union (Ishikawa)

• Smokers took 1.73 times longer to heal s/p Austin Bunionectomy vs. non smokers (Krannitz)

Haverstock, B. Vincent J. Mandracchia. Cigarette Smoking and Bone Healing: Implications in Foot and Ankle Surgery. The Journal of Foot & Ankle Surgery 37(1):69-74, 1998

Krannitz C, Fong H et al. The Effect of Cigarette Smoking on Radiographic Bone Healing After Elective Foot Surgery. The Journal of Foot & Ankle Surgery 48(5):525–527, 2009

Ishikawa S, Murphy A, Richardson G. The Effect of Cigarette Smoking on Hindfoot Fusions. Foot Ankle Int. 23(11), 2002.

NSAID’s and Non-unions*• Inhibit COX-2, which inhibit Prostaglandin-

E2 (PGE-2 is needed by osteoblasts)• NSAID’s also thought to inhibit

angiogenesis via VEGF

• In a study on mice with osteotomies, found that those on Vioxx had a decreased in blood flow at the osteotomy site as well as an increase in soft callus and slower progression to bone healing as compared to the control osteotomy group.

*Murnaghan M. et al. NSAID induced fracture nonunion; an inhibition of angiogenesis. JBJS. 2006 Vol 88-A

Is it a Non Union?

Clinical Signs • pain and

tenderness• edema• joint stiffness and

impaired function• pain is often

present before radiographic signs

Radiographic Signs• Radiolucent void

• Zone of fibrous or cartilage

• Lab Values– Prolonged

elevation of ALP levels

– TGF decreaseZimmerman G. et al. The value of laboratory and imaging studies in the evaluation of long-bone non-unions  Original Research Article Injury, Volume 38, Supplement 2, May 2007, Pages S33-S37

Management of Non Unions

• Hypertrophic

– Immobilization– Electrical Bone

Stimulation

• Atrophic

– Debridement– Graft or other

biologic– Immobilization– Electrical Bone

Stimulation

Management of Non Unions (cont’d)

• Conservative/Non Surgical– WB in functional

cast (cyclic loading induces the healing process)

– Electrical Stimulation

– Ultrasound– Bone Marrow

Injection

• Surgical– External Fixation– Internal Fixation

(Plates, IM Nail)– Bone Graft

• Auto/Allograft

– Other Orthobiologics

Internal Fixation of Non-Unions

• Plates

• IM Nail– For tibial non-unions

*usually combined with bone graft or orthobiologic if gap or defect present

Distraction for Non-Unions

• Ilizavrov technique– Basically a method of auto graft– Form new bone by distracting at

1mm/day– Used instead of a bone graft

• Paley*: In 25 tibial non-unions w/ defect (23A/3H); all went to fusion

• Sveshnikov**: distraction doubles perfusion to the limb and 11.8 times increase perfusion to non union site

*Paley D, Catagni M. Ilizarov treatment of tibial nonunions with bone loss. Clin Orthop. 1989; 241:146-65**Sveshnikov A, Barabash A, Cheplenko T. Radionuclide studies of osteogenesis and circulation in substitution of large defects of the leg bones in experiment. Ortop Travmatol Protez 1984;11:33—9.

Distraction Osteogenesis (cont’d)

• Hypertrophic Non-Union, <7 degrees mobility– Immediate distraction

• > 7 degrees mobility– 2-3 weeks of compression prior to

distraction (crush fibrous tissue)

• Atrophic Non-Union– Corticotomy distraction to encourage

perfusion

Kanellopoulos A. Soucacos P. Management of nonunion with distraction osteogenesis. Injury. (2006) 37S, S51-S55

Bone Graft

• Autogenous – satisfies all 3 properties– “Gold Standard”

• Allograft (freeze dried, demineralized)

• Synthetic (Hydroxyapatite- CHAG, CHAP, etc)– Predominantly osteoconductive, but can be

mixed with inductive agents like bone marrow

Comparative Properties of Bone Grafts

BONE-GRAFT SUBSTITUTES:FACTS, FICTIONS &APPLICATIONS,AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS

Bone Grafting Techniques

• Cortical Onlay

• Inlay

• Peg In Hole

• Shingling (chisel is used to lift thin strips of cortex with periosteum attached to create a vascular bed for bone graft )

Bone Graft Substitutes (Osteoconductive)

• Coralline Hydroxyapatite

• Calcium Sulfate (plaster of paris)– Osteocet®

• Calcium Phosphate cement– Norian® (injectable past that hardens)

Calcium phosphate cement (injected into STJ for arthrodesis)

Trinity Evolution™

• Demonstrates all 3 bone-forming characteristics (MSC, cancellous and cortical component)

Rush S. Trinity Evolution ; mesenchymal stem cell allografting in foot and ankle surgery. Foot and Ankle Specialist. June 2010

Bone Growth Electrical Stimulation

• Direct Current (DC)

• Capacitative Coupling (CC)

• Pulsed Electromagnetic Field (PEMF)

• Low Intensity Pulsed Ultrasound (LIPUS)

Electrical Stimulation

• Based on Yusuda’s Piezoelectricity of Bone Theory– Areas of bone growth and fracture exhibit

electronegativity which signals the regulation of cellular processes of bone healing

• Contraindicated in pregnancy, OM, malignancy, gaps greater then 1 cm, cold bone scan, only the invasive can be used with pacemakers

Direct Current• Osteogen® (Biomet)• Cathode and anode placed directly on the bone• (+) Constant stimulation and increased

compliance (24 hour use)• (-) Need for retrieval surgery of device, irritation

Direct Current (cont’d)

Capacitative Coupling

• Bioelectron Orthopak ® (EBI Medical Systems)• 2 skin electrodes placed on opposite sides of the

bone • (+) Continuous use (24 hours)• (-) Possible irritation from percutaneous placement

of electrodes

Pulsed Electromagnetic Field

• EBI Bone Healing System ®

• Physio Stim Lite ® (Orthofix)

• Use for 3-10 hrs/day

• (+) Non invasive, can be used over a cast

• (-) Requires long period of use

Combined Magnetic Field

• DonJoy OL1000 ® (dj Orthopedics)• 30 minutes/day• (+) Can be used over a cast

Low Intensity Pulsed Ultrasound

• Exogen ® (Smith and Nephew)• Placed over non union sight, 20 mins/day• (+) Non invasive, short periods of use• (-) Pt must be compliant

Comparison of Healing % for E StimTechnology Product

manufacturerNon Union Heal Rate

LIPU (ultrasound)

Exogen (Smith and Newphew)

86%

Capacitive Coupling

Orthopack 2 (Biomet)

72.5%

Direct Current (implant)

Osteogen (Biomet)

66%, 38.8%

PEMF (pulsed magnetic)

EBI System (Biomet)

63.5%

Combined magnetic field

DonJoy OL1000 (dj Orthopedics)

60.7%

www.exogen.com

Electrical Bone Stim in Charcot

• CMF for consolidation of Phase 1 Charcot (Hanft et al)– Decreased from 23.8 wks to 11 wks (n=30)

• Implantable Stim w/ autograft in hindfoot arthrodesis of Charcot Pts (Hockenbury et al)– Fusion rate of 90% in an average of 3.7

months (n=10)

• Ultrasound in Charcot (Strauss)– STJ and ankle fusion 162 days (n=1)

Orthobiologics

• Bone Marrow Aspirates (BMA)

• Platelet Rich Plasma (PRP)

• Bone Morphogenic Protein (BMP)

Bone Marrow Injections

• Bone marrow can be drawn from the iliac crest/femur and injected into the non union under flouroscopy

• Contains both osteoinductive and osteogenic properties (so can be combined with allograft or similar- making it similar to cancellous autograft)

• Integra Mozaik™ - osteoconductive putty or strip that can be combined with BMA

Platelet Rich Plasma

• Platelets act as reservoirs for growth factors – PDGF, IGF, TGF play role in healing

process

• Symphony ™ Platelet Concentration System

• F&A nonunions treated with PRP and autogenous bone graft – resolved in 60 days*

• *Ghandi A et al. The Role of PRP in Foot and Ankle Surgery. Foot Ankle Clin N Am. 10 (2005)

Bone Morphogenic Protein (BMP)

• INFUSE® Bone Graft (BMP on collagen sponge)• OP-1 Implant and Putty® (BMP on Type 1 collagen)

• In tibial fractures treated with IM nails and overlay of BMP on collagen sponge at fracture sight: s/p 6 months, showed 20% faster healing rate then the control

BESTT Study. Govender S et al. Recombinant human BMP-2 for treatment of open tibial fractures. Bone Joint Surg Am 2002; 84A

Summary of Essential Components of Bone Healing

• Osteoconduction: Allogenic Bone Graft

• Osteoinduction: Demineralized Bone Matrix (PRP etc)

• Mechanical Stability: internal fixation

• Biophysical application: E stim

AAOS 2010 Bone Graft Substitutes

• Commerically available product

• Mechanism of Action

• Types of Studies performed

• FDA Status

Giannoudis’s Diamond Concept of Fracture Healing and Polytherapy

Goals of Treatment of Non-UnionsThe 4 S

• Sterilize

• Straighten

• Stabilize

• Stimulate

Works Cited• Walter J.H. and L. Goss. Traumatology of the Foot and Ankle• Aaron RK, Ciombar DM. The Role of Electrical Stimulation in Bone Repair. Foot Ankle Clin N Am. 2005; 10:

579 93• DiGiovanni W, Koh EY, et al. Tibial Nonunion. Foot Ankle Clin N Am. 2006; 11: 1 18• Harwood PJ, Michael AL, Newman JB. An Update on Fracture Healing and Nonunion. Orthopaedics and

Trauma. 2010; 24: 10 23• Nolte PA, van der Krans A, Patka P, Janssen IM, Ryaby JP, Albers GH. Low-intensity pulsed ultrasound in the

treatment of nonunions. J Trauma. 2001 Oct;51(4):693–703.• Heckman JD, Ryaby JP, McCabe J, Frey JJ, Kilcoyne RF. Acceleration of tibial fracture-healing by non-invasive,

low-intensity pulsed ultrasound. J Bone Joint Surg Am. 1994 Jan;76(1):26–34.• Kristopher W. Krannitz, Hon W. Fong, Lawrence M. Fallat, John Kish The Effect of Cigarette Smoking on

Radiographic Bone Healing After Elective Foot Surgery The Journal of Foot and Ankle Surgery, Volume 48, Issue 5, September-October 2009, Pages 525-527

• Einhorn TA. Enhancement of fracture healing. J Bone Joint Surg 1995;77:940– 56.• Weinraub GM. Orthobiologics: A Survey of Materials and Techniques. Department of Orthopaedic Surgery,

Lewis-Gale Clinic, 1802 Braeburn Drive, Salem, VA 24153, USA• Fracture healing: The diamond concept

Injury, Volume 38, Supplement 4, September 2007, Pages S3-S6Peter V. Giannoudis, Thomas A. Einhorn, David Marsh

• The value of laboratory and imaging studies in the evaluation of long-bone non-unionsInjury, Volume 38, Supplement 2, May 2007, Pages S33-S37G. Zimmermann, U. Müller, A. Wentzensen

• Kobata Y, Shigematsu K, Yajima H. Vascularized fibular grafting in the treatment of methicillin-resistant Staphylococcus Aureus osteomyelitis and infected nonunion. J Reconstr Microsurg 2004;20:1—12.

• Strauss E, Gonya G. Adjunct low intensity ultrasound in Charcot neuroarthropathy. Clin Orthop. Apr 1998;(349):132-8.

• Hockenbury RT, gruttadauria M, McKinney I. Use of implantable bone growth stimulation in charcot ankle arthrodesis. Foot Ankle Int 2007; 28(9); 971-976

• Hanft JR, Goggin JP, Landsman A, et al. The role of combined magnetic field bone growth stimulation as an adjunct in the treatment of Charcot joint. J Foot Ankle Surg 1998; 37)6);510-5.

• Murnaghan M. et al. NSAID induced fracture nonunion; an inhibition of angiogenesis. JBJS. 2006 Vol 88-A• Liporace F, Bibbo C, et al. Bioadjuvants for Complex Ankle and Hindfoot Reconstruction. Foot Ankle Clin N Am

12 (2007) 75-106• Ramanujam C, Belczyk R. et al. Bone Growth Stimulation for Foot and Ankle Nonunions. Clin Podiatric Med

Surg 26(2009) 607-618• Haverstock, B. Vincent J. Mandracchia. Cigarette Smoking and Bone Healing: Implications in Foot and Ankle

Surgery. The Journal of Foot & Ankle Surgery 37(1):69-74, 1998

THANKS for a great month!