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/Procedur Incidence of # of Pts Reference
e Non Union (n)
Triple Arthrodesis 22% 80 (Angus)
(MC was TNJ)

Ankle Arthrodesis 26% 19 (Moore)

w/ IM rod

STJ Arthrodesis 13% 37 (Trnka)

(bone block
distraction)

* 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 • No signs of healing
longer then it should progression at 6 months
or more?
for a certain area of
bone, type of
fracture or age of • FDA defines a non union
as an osseous
patient
discontinuity of 9 months
duration, in which there
• Still capable of has been no radiographic
evidence of healing for 3
healing on their own consecutive months?
(still have biologic
properties of
healing)
 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, 681-690
Harwood PJ, Michael AL, Newman JB. An Update on Fracture Healing and Nonunion.
 Atrophic Non Unions

Olsen S., Hahn D. Surgical treatment of non unions: a case for internal fixation. Injury (2006) 37, 681-69
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 stability
2. Failure to reduce the fracture gap
3. Lack of Blood Supply
4. Infection (OM and Systemic)
5. Location of the fracture
6. Compromised Host (DM, RA, nutrition,
osteoporosis)
7. Smoking
8. Drugs
Blood Supply and Non-unions

• Long bones have

three blood Periosteal
supplies vessels

– Nutrient artery
(intramedullary)
Nutrient
– Periosteal vessels artery
– Metaphyseal
vessels Metaphyseal
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.
 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.

naghan M. et al. NSAID induced fracture nonunion; an inhibition of angiogenesis. JBJS. 2006 Vol 88-A
 Is it a Non Union?
Clinical Signs Radiographic Signs
• pain and • Radiolucent void
tenderness
• edema • Zone of fibrous or
cartilage
• joint stiffness and
impaired function
• Lab Values
• pain is often
– Prolonged
present before elevation of ALP
radiographic signs levels
– TGF decrease
Zimmerman G. et al.
The value of laboratory and imaging studies in the evaluation of long-bone non-union
  Original Research Article Injury, Volume 38, Supplement 2, May 2007, Pages S33-S37
 Management of Non Unions

• Hypertrophic • Atrophic

– Immobilization – Debridement
– Electrical Bone – Graft or other
Stimulation biologic
– Immobilization
– Electrical Bone
Stimulation
Management of Non Unions
(cont’d)
• Conservative/Non • Surgical
Surgical – External Fixation
– WB in functional – Internal Fixation
cast (cyclic loading (Plates, IM Nail)
induces the healing – Bone Graft
process) • Auto/Allograft
– Electrical – Other Orthobiologics
Stimulation
– Ultrasound
– Bone Marrow
Injection
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
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
Stim
Technology Product Non Union Heal
manufacturer Rate
LIPU (ultrasound) Exogen (Smith 86%
and Newphew)
Capacitive Orthopack 2 72.5%
Coupling (Biomet)
Direct Current Osteogen 66%, 38.8%
(implant) (Biomet)
PEMF (pulsed EBI System 63.5%
magnetic) (Biomet)
Combined DonJoy OL1000 60.7%
magnetic field (dj Orthopedics)

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-Unions
The 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-S6
Peter V. Giannoudis, Thomas A. Einhorn, David Marsh
• The value of laboratory and imaging studies in the evaluation of long-bone non-unions
Injury, Volume 38, Supplement 2, May 2007, Pages S33-S37
G. 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!