PERSONAL DATA

Name : Prof. Dr. H. Errol U. Hutagalung, SpB, SpOT

Place/Date of Birth : Tanjung Karang, May 15, 1942
Married to : Anita Errol Hutagalung
Children : 4 childrens
Office/Institution : Div. of Orthopaedic & Traumatology, Faculty of Medicine
University of Indonesia/Dr. Cipto Mangunkusumo
Jl. Diponegoro 71, Jakarta 10430

Telephone : (62-21) 392 9655 Fax : (62-21) 390 5894 HP : 0816 808054 Email : [email protected]
Home Address : Jl. H. Buang No. 27, Ulujami, Kebayoran Lama, Jakarta Selatan
Education : - Medical Doctor : FKUI – 1967
- Surgeon : FKUI – 1973
- Orthopaedic Surgeon : FKUI – 1975
Current Position : Chairman of Division of Orthopaedic & Traumatology FKUI/RSCM
Academic Appointment and Activities :
- Chairman of Division of Orthopaedic & Traumatology FKUI/RSCM, since 1990 – now
- Chairman of Advisory Board, Dept. of Surgery, FKUI/RSCM
- Chairman of Education Committee, Academic Senate FKUI
Professional Activities :
- Chairman of the Indonesian College of Orthopaedic & Traumatology,
PABOI (2006 – now)
- Chairman of Steering Committee, PERTUMSI
- Chairman of Elect of PEROSI
Awards and Qualifications :
Society Memberships : PABOI, IKABI, POI, PERTUMSI, IRA, PEROSI
FRACTURE HEALING :
-BIOLOGY
-INHIBITION FACTORS.

ERROL U. HUTAGALUNG

Div. of Orthopaedic & Traumatology

Faculty of Medicine, Univ. of Indonesia
Dr. Cipto Mangunkusumo Hospital - Jakarta

COE-54, Pontianak
1-3 Mei 2008
Healing of a fracture – most remarkable of all repair
processes in the body since the result NOT in scar Æ
actual reconstitution of the injured tissue

Fractures unite by :
1. Primary bone healing
2. Secondary bone healing

Primary occur when there is rigid int. fixation,

while secondary bone healing occur when there is
NON RIGID internal fixation

Majority of fractures unite by secondary bone healing

which progress in five stages
5 Stages as describe by Mc Kibbin (1978) :

1. Haematoma
} Phase 1 : inflammation
2. Inflammation
3. Formation of Soft Callus
} Phase 2 : reparation
4. Formation of Hard Callus
5. Remodeling } Phase 3
N Phase 1 / Inflammation consist of :
- Bleeding of fractureÆ haematoma form
e- Inflammation
- Next 2 – 3 days granulation tissue formation
- Osteogenic cells invade tissue and laydown osteoid
N Phase 2 / Reparation
- At 3 weeks soft callus form consist of osteoid
and cartilage
- In 6 – 12 weeks hard callus is formed
- In 12 – 16 weeks clinical union (+)

N Phase 3 / Remodeling of united fracture

From the stand point of biomechanics Æ
4 stages of fracture repair (White 1977)

St 1 : Bone stiffness similar to soft tissue stiffness;

fracture site has low stiffness & low strength
due to formation fibrous granulation tissue

St 2 : Bone stiffness more similar to mineralized tissue;

fracture site has normal bone stiffness but low
strength Æ due to formation of woven bone
From the stand point of biomechanics Æ
4 stages of fracture repair (White 1977)

St 3 : Fracture site has normal bone stiffness & medium

strength – due mixture of woven bone and
lamellar bone that increases over all strength

St 4 : Fracture site has normal bone stiffness & normal bone

strength due completely remodeled bone
(all lamellar)
Three form of bone repair bring about fracture union :
endochondral ossification, intramembrane ossification
& appositional bone formation Æ
- Closed to fracture site Æ production of cartilage tissue Æ
undergo endochondral ossification
- Peripheral site Æ direct intramembrane ossification &
areas of appositional bone formation to reinforce the
entire callus
- These mechanism primarily produce WOVEN bone which
is later remodeled into LAMELLAR bone
Role of Periosteum
Periosteum : 2 layers – outer fibrous layer & inner
cambial layer

Inner cambial layer contain cells responsible for

production of new bone – osteoprogenitor cells
Osteoprogenitor cells in fact can be found on
all free bone surfaces: endosteal & periosteal Æ
if periosteum is removed Æ osteogenic potential
of bone is NOT deprived
Source of Osteogenic Cells : 2 theory

1. Arise from specialised cell Æ osteoprogenitor cells

2. Arise from surrounding soft tissue (fibroblast)

if given the appropriate environmental stimulus
Æ known as osteogenic induction
N Cells with osteogenic potential in marrow my have
access to the circulation Æ
EXTRA Skeletal Bone Formation
N This NOT quite the same as METAPLASIA of cells of the
soft tissue

N Effect is the same

N Normal Skeleton : Continuous process of replacement
(osteoblastic activity) & repair
(osteoclastic activity)

N Fracture repair : same process

N Differences of process depend on type of bone
cancellous or compact bone

N Cancellous : whole process of bone apposition or

replacement take place in the surface Æ
“creeping substitution”
Compact bone : process take place in deeply placed
cells Æ which require the presence of
Haversian system which must be
replaced Æ “Primary Bone Union” Æ
since no intermediate / precursor
cells are involved
Fate of dead bone at the fracture site :
- Resorbed Æ not always; depend on
mechanical factors

Normal alignment preserved Æ dead bone will form

an important mechanical link in restoration of
continuity Æ will be preserved in accordance
of Wolff’s law Æ the whole dead bone may be
converted into living cancellous bone
Alternatively if the presence of compact bone is more
appropriate Æ then it will be revitalised by penetration
of new Haversian systems
If there is Malunion, when incorporation of the bones
ends would serve no useful purpose Æ completely
removed / resorbed
Union of fracture need a critical step Æ establishment
of intact bone contact/bony bridge between
the fragment Æ joining of hard tissue and the whole
system MUST become IMMOBILE at least momentarily
Union / Healing of fracture develop by 3 mechanism

1. Healing by external callus

2. Healing by medullary callus
3. Healing by primary bone union
Healing by External Callus
Explained by 3 hypotheses / theory

1. Cellular contact theory

2. Mechanical influences/bio electrical phenomena
3. Humoral theory
Cellular Contact Theory

If the two fragment remain connected by periosteum or

related material Æ callus bridge (Charnley)

If fragments are excessively separated either by

distraction or by interposition of soft tissue or held
apart by long segment of terminal dead bone Æ
contact can not occur Æ non union
Bioelectrical Phenomenon
In the process of fracture healing Æ role of fibroblast
of soft tissue which by induction mechanism become
osteogenic cells Æ possible through medium of bioelectrical
forces

Fukada (1957) Æ mechanical deformities of bone gave

rise to electric potentials Æ as a result of piezo electric
effect
Electro negativity favours bone formation and vice
versa Æ explained Wolff’t Law Æ self regulating
feed back mechanism Æ stresses & strain in the
bone modifies the electrical environment of the bone
Promising field, but electrical environment of bone
is extremely complex Æ piezo electric potential are
only a part of it
Clinical application :Treat human fracture by
applying electrical stimuli either with direct
current or non invasive use of electro magnetic
fields
Humoral theory :

Fracture bone end liberate Æ agent which influence

the healing process Æ “wound hormone” especially
in the fracture haematoma – present only for
limited period Æ search without success
Heterotopic bone formation can be induced by
dead tissue or by bone transplant Æ humoral
inducing agent must exist
Several hypothesis Æ none of these are mutually
exclusive Æ reasonable to join the together
Healing by Medullary Callus

- Distinguished for external callus only by its location

- Cartilage formation is much less prominent in
medullary callus
Obvious difference is the effect of mechanical stability
Æ Inhibitory effect in external callus while medullary
callus flourishes
In the process may be involved

- Electrical phenomenon
- Biochemical phenomenon
- Even neurological mechanism

Part of fracture healing process which is still

inadequately studied
Study by Olerud (1971) in more realistic mode :
in segmental fracture Æ

After ensuring the middle fragment was entirely

devoid of vascular connection & fixed the whole
with a compression plate as rigidly as possibile
Æ the dead bone did NOT disappear but was
invaded by new osteons for the neighboring live bone
Primary Bone Healing

Study of Willenegger (1967) – Apply rigid

compression plates to dog’s radius Æ dead ends
of cortical bone were not resorbed but were
recanalised by new Haversian systems
This process is different from the other two
that is NOT inhibited by stability as in external
callus (method 1) and indeed even small degrees
of movement is harmful to the process, unlike
medullary callus (second method)
However due to large amount of dead tissue Æ
the process was extremely slow Æ patient will
be dependent in the implant for a very long
time, and most of the revascularisation occurred
from vessels lyng in the medullary canal
The X-ray obliteration of the fracture gap
does NOT necessarily mean that the bone
has returned to its pre injury strength
In practice to achieve direct bone union use
the Swiss School (AO, Muller 1965) Æ
with compression method
Clinical implication :
Three main ways in which essential bridging
process of fracture healing can came about
and each of these is differently affected by
environmental circumstances
External Callus :
N The most rapid of all the process, normally predominates
in fx treated by External Fixation

N The quickest way to restore the strength of a fractured

diaphysis to its former level

N The process will not continue indefinitely / short lived

unless fracture is Bridged Æ
N Primary purpose is the arrest of movement between
fragment
This process is NOT incompatible with internal
Fixation; provided does NOT impose condition
of total rigidity
If consider ORIF Æ careful consideration must be
given to soft tissue from which much of the repair
tissue will come, in particular blood vessels which
pass from the muscle and fascia to the periosteum
N With extra periosteal dissection Æ formation
of callus may be inhibited (Trueta 1968)

N With subperiosteal dissection Æ these blood vessels

are preserved Æ facilitating production of cuff
of subperiosteal callus.
If rigid plating in considered Æ formation
of external callus is deliberately abandoned Æ
preservation of blood supply of the bone is VERY
important
If IM nailing as to be used Æ even more care is
required with the soft tissue, because medullary
circulation will be interrupted at least temporarily Æ
and depend solely on the supply from soft tissue
Medullary Callus :
N This method predominate when extra callus response
has failed
N It arises principally from the medullary cavity
N It has 2 special properties Æ relatively independent
of mechanical influences and can replace fibrous
tissue by new bone
N The factors that govern this uncertain process are
still unknown

N This process assisted by immobilization Æ need

SECURE internal fixation.
Primary Bone Union :
If RIGID fixation is applied Æ process of healing is
altered Æ ext. bridging callus is suppressed and
the healing is dependent in the activity of medullary
callus and direct osteonal penetration
N Disadvantage : great slowness especially if
there is a large amount of dead bone

N It is NOT really method of union at all but

a remodeling process which normally occurs
very late in the normal healing process Æ
artificial stability must be maintained for
many months and even years
In rigid / compressed fixation NOT logical
to supply bone graft external to bone
Bone graft is to facilitate formation of
Ext. Callus which is deliberately inhibited
Ideal Fixation Æ preserved security without
imposing total rigidity
Inhibition of Fracture Healing
Factors that playing in these occasion :

1. Age
2. Co Morbidities
3. Medication
N Age : Children faster rate of healing due to
thicker periosteum & larger subperiosteal
haematoma

N Age related change : delay in onset of periosteal

reaction cell differentiation and angiogenic
invasion ; decreased bone formation and impaired
remodeling of bone
N Parker (1994): Age was predictive of non union after
ORIF of intracap fx. Of neck of femur

N Over all – increasing age is a factor in the inhibition

of fx repair in the human
CO Morbidities
a/ Diabetes Mellitus (DM)
N Animal experiment fx callus 29% decrease
in tensile strength and 50% decrease is stiffness
N Between 4 – 11th day of healing : 50% decrease
in collagen content & 40% decrease of DNA content of
the callus
Clinical Studies :
N Significant higher incidence of delayed union,
non union and doubling time to heal

N Key treatment of fracture with DM : proper control

of blood sugar level, which will minimize the
complications of delayed fracture healing
CO Morbidities :
b/ Anemia

Animal studies : poor mineralization of callus due

to decrease in oxygen tension and deficiency of iron
which is required for function of electron transport
system within the cell & hydroxylation of proline
in collagen formation
N Secondary anemia due acute blood loss without
maintenance of blood VOLUME may affect
wound healing

N Normovolemic anemia had NO adverse affect Æ

following trauma fluid Rehydration very important
(not blood transfusion) to maintain fracture healing
c/ Mal nutrition

Animal study : deficiency vit B6 Æ delay maturation of

callus
- Vit C need in maintenance of function of osteoblast
& supplementary vit. C Æ accelerates fx healing

- Importance of dietary protein, Ca+, PO4, Vit D

in fx healing
N Human Study : Albumin level < 3,5 gr % was predictive
of increase length of stay and in hospital mortality
following a fracture

N Low albumin level : 4,6 times less likely to recover to

prefracture level of independence in basic activities
of daily living

N Post menopausal women with hip fracture had occult

vit D deficiency Æ easily treated with supplementation
 Hypothyroidism
N Animal Study : Inhibit endochondral ossifciation

N Inhibit secondary bone healing, although primary

bone healing appear to be unaffected
 Prescribed Medication :

N NSAID : MOA inhibit synthesis of prostaglandin

N Result : Animal study : conflicting evidence as

their affect on fracture repair
NSAID :
N Clinical terms : NSAID prevent heterotropic bone formation
following THR
N Balanced information : Suggest it is prudent to avoid
use of NSAID during fracture repair
N Corticosteroid, long term steroid therapy is detrimental
to fracture repair
Statins :
Animal Study : anabolic effect on bone – enhancement
of fracture healing Æ 63% greater strenght
than control at 14 days
Antibiotics :
Remain an important part of trauma care in
preventing infection but we should be aware of
studies which indicate it is prudent to avoid high doses
of ciprofloxacin, rifampicin and topical gentamicin
to minimize risk of non union
 Anticoagulant

LMWH used to prevent thromboembolism

Animal study : significant negative effect in
fracture healing both biomechanically
& histologically
 Fracture Treatment :

N Animal Studies : gap > 2 mm inhibit fracture healing

N Majority of fracture heal by secondary union Æ

a degree of motion at fracture site assist the process Æ
early w.b. is encourage
N However excess motion and instability leads to NON union Æ
hypertrophic union Æ gross callus formation but NO
bridging of bone ends

N Type of motion : - axial movement – beneficial

- shear; rotational movement inhibit
repair
Lifestyle
Smoking : Balance of evidence indicates a clear
inhibition of healing of fracture Æ
complicate fracture healing – develop
non union – infection – flap failure

Causes by nicotine or other component of cigarette

is not yet determined.
 Alcohol :

Dose dependent; toxic effect on activity of osteoblast

References
1. 1978; Mc Kibin: The Biology of Fracture healing in Long Bones;
JBJS 60B : 150 – 62
2. 2007; Little D et al : Review articles.The anabolic and catabolic
responses in bone repair; JBJS 89B: 425-33
3. 2007; Gaston MS et al: Inhibition of fracture healing; JBJS
89B: 1553 – 60
4. 2007; Biomechanics of Fracture Healing, diakses dari :
www.engin.unich.edu/class/bone456/.bonefracture:htm