1. PRESENTER : Dr ANKUR MITTAL

2. What is fracture?
Any break in continuty of bone is fracture
BUT
An injury that fractures bone not only damages its
cells , blood vessels and bone matrix but also
surrounding tissues, including periosteum and
muscles.

3. Components of Bone Formation
•Bone marrow
•Cortex
•Periosteum
•Soft tissue
Note: Periosteum has 2 layers:
•an outer fibrous layer
• inner more cellular and vascular cambium layer
It covers the external surface of bone and participates in healing of
many types of fractures.
The thicker more cellular periostium of infants and children has more
extensive vascular supply therefore more active in fracture healing
than adults.

4. Blood Supply
Long bones have three blood
supplies
Periosteal
vessels
1. Nutrient artery
(intramedullary)
Nutrient
2. Periosteal vessels artery
3. Metaphyseal vessels Metaphysea
vessels

5. Nutrient ARTERY
•Normally the major blood supply for the diaphyseal cortex (80 to 85%)
•Enters the long bone via a nutrient foramen
•Forms medullary arteries up and down the bone
PERIOSTEAL VESSELS
•Arise from the capillary-rich periosteum
•Supply outer 15 to 20% of cortex normally
•Capable of supplying a much greater proportion of the cortex in the
event of injury to the medullary blood supply

6. METAPHSEAL VESSELS
•Arise from periarticular vessels
•Penetrate the thin cortex in the metaphyseal region and
anastomose with the medullary blood supply
Vascular Response in Fracture Repair
•Initially decreased flow due to
disrupted vessels
•In several days the blood flow
greatly increases, peaking at 2
weeks
•Gradually returns to normal by 12
weeks

7. MECHANISM OF BONE FORMATION
1. Cutting Cones
2. Intramembranous Bone Formation
3. Endochondral Bone Formation
CUTTING CONES
Primarily a mechanism to remodel
bone
Osteoclasts at the front of the cutting
cone remove bone
Trailing osteoblasts lay down new
bone

8. Intramembranous (Periosteal) Bone Formation
Mechanism by which a long bone grows in width
Osteoblasts differentiate directly from preosteoblasts and lay down
seams of osteoid
Does NOT involve cartilage anlage
Endochondral Bone Formation
Mechanism by which a long bone grows in length
Osteoblasts line a cartilage precursor
The chondrocytes hypertrophy, degenerate and calcify (area of low
oxygen tension)
Vascular invasion of the cartilage occurs followed by ossification
(increasing oxygen tension)

10. Hematoma Formation (1st)
Last for less than 7 days
Tissue disruption results in hematoma at
the fracture site
Local vessels thrombose causing bony
necrosis at the edges of the fracture
Increased capillary permeability results in
a local inflammatory milieu
Osteoinductive growth factors stimulate
the proliferation and differentiation of
mesenchymal stem cells

11. Cellular Formation Phase(2nd)
• 2-3 weeks
• Acidic environment but turning neutral
• Influx of endosteal cells from
cambium layer produce a fibrous
callus (environment has high
oxygen tension) then cartilage (has
a low oxygen tension environment)

12. Callus Formation Phase (3rd)
4-12 weeks
Fibroblast deposit collagen in the
granulation tissue
Soft Callus is formed (Unorganized
network of woven bone);
Internal callus (grows quickly to create
rigid immobilization)
The hard callus lasts 3-4 months.
Hard callus – a gradual connection of
bone filament to the woven bone (Acts
like a temporary splint)
Bone is beginning to strengthen and
immobilize
If proper immobilization does not
occur; cartilage will form instead of
bone

13. Periosteal callus forms along the
periphery of the fracture site
Intramembranous ossification
initiated by preosteoblasts
Intramedullary callus forms in the
center of the fracture site
Endochondral ossification at
the site of the fracture
hematoma
Chemical and mechanical factors
stimulate callus formation and
mineralization

14. Schematic drawing of the callus healing process. Early
intramembranous bone formation (a), growing callus volume
and diameter mainly by enchondral ossification (b), and
bridging of the fragments (c).

15. A: Roentgenogram of a callus healing in a tibia with the
osteotomy line still visible (6 weeks p.o.).
B: Histological picture of a tibia osteotomy (fracture model)
after bone bridging by external and intramedullary callus
formation. A few areas of fibrocartilage remain at the level of
the former fracture line (dark areas).

16. Callus is the first sign of union visible on
x-ray after 3 weeks of #

17. Ossification Phase (4 th)
•1- 4 Years
•It will occur with adequate
immobilization
•Bone ends become crossed with a new
Haversian system that will eventually
lead to the laying down of primary
bone
Fracture is bridged and united

18. Remodeling Phase (5th)
•Remodeling hard callus to compact bone or woven bone is gradually
converted to lamellar bone.
•May take a few years
•Medullary cavity is reconstituted
•Bone is restructured in response to stress and strain (Wolff’s Law)

20. Differences in healing between cortical and cancellous
bone:
Healing in cancellous bone occurs without the formation of
significant external callus.
After the inflammatory stage bone formation is dominated by
intramembranous ossification
This is due to tremendous angiogenic potential of trabecular bone
as well as fixation used for metaphyseal fractures which is often
more stable.

21. Prerequisites for Bone Healing
•Adequate blood supply
•Adequate mechanical stability
Mechanisms for Bone Healing
•Direct (primary) bone healing
•Indirect (secondary) bone healing

22. DIRECT BONE HEALING
Mechanism of bone healing seen when there is no motion at the
fracture site (i.e. rigid internal fixation)
Does not involve formation of fracture callus
Osteoblasts originate from endothelial and perivascular cells
A cutting cone is formed that crosses the fracture site
Osteoblasts lay down lamellar bone behind the osteoclasts forming a
secondary osteon
Gradually the fracture is healed by the formation of numerous
secondary osteons
A slow process – months to years

23. Components of Direct Bone Healing
Contact Healing
Direct contact between the fracture
ends allows healing to be with
lamellar bone immediately
Gap Healing
Gaps less than 200-500 microns
are primarily filled with woven bone
that is subsequently remodeled into
lamellar bone
Larger gaps are healed by indirect
bone healing (partially filled with
fibrous tissue that undergoes
secondary ossification)

24. INDIRECT 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 subsequently undergoes
endochondral ossification
•Process fairly rapid - weeks

25. Local Regulators of Bone Healing
•Growth factors
•Cytokines
•Prostaglandins/Leukotrienes
•Hormones
•Growth factor antagonists

26. GROWTH FACTORS
•Transforming growth factor[TGF]
•Bone morphogenetic proteins[BMP]
•Fibroblast growth factors[FGF]
•Platelet-derived growth factors[PDGF]
•Insulin-like growth factors[IGF]

27. TRANSFORMING GROWTH FACTORS
•Superfamily of growth factors (~34 members)
•Act on serine/threonine kinase cell wall receptors
•Promotes proliferation and differentiation of mesenchymal
precursors for osteoblasts, osteoclasts and chondrocytes
•Stimulates both endochondral and intramembranous bone
formation
•Induces synthesis of cartilage-specific proteoglycans and type
II collagen
•Stimulates collagen synthesis by osteoblasts

28. BONE MORPHOGENETIC PROTIENS
Osteoinductive proteins initially isolated from demineralized
bone matrix
Proven by bone formation in heterotopic muscle pouch
Induce cell differentiation
BMP-3 (osteogenin) is an extremely potent inducer of
mesenchymal tissue differentiation into bone
Promote endochondral ossification
BMP-2 and BMP-7 induce endochondral bone formation in
segmental defects
Regulate extracellular matrix production
BMP-1 is an enzyme that cleaves the carboxy termini of
procollagens I, II and III

29. These are included in the TGF-β family
Except BMP-1
BMP2-7,9 are osteoinductive
BMP2,6, & 9 may be the most potent in osteoblastic differentiation
Work through the intracellular Smad pathway
Follow a dose/response ratio
BMP ANTAGONISTS
May have important role in bone formation
Noggin
Extra-cellular inhibitor
Competes with BMP-2 for receptors

30. BMP FUTURE DIRECTIONS
•BMP-2
•Increased fusion rate in spinal fusion
•Must be applied locally because of rapid systemic clearance
•
•? Effectiveness in acute fractures
•? Increased wound healing in open injuries
•Protein therapy vs. gene therapy

31. FIBROBLAST GROWTH FACTORS
•Both acidic (FGF-1) and basic (FGF-2) forms
•Increase proliferation of chondrocytes and osteoblasts
•Enhance callus formation
•FGF-2 stimulates angiogenesis

32. PLATELET DERIVED GROWTH FACTORS
•A dimer of the products of two genes, PDGF-A and PDGF-B
•PDGF-BB and PDGF-AB are the predominant forms found in
the circulation
•Stimulates bone cell growth
•PDGF-AB Increases type I collagen synthesis by increasing the
number of osteoblasts
•PDGF-BB stimulates bone resorption by increasing the number
of osteoclasts

33. INSULIN LIKE GROWTH FACTORS
Two types: IGF-I and IGF-II
Synthesized by multiple tissues
IGF-I production in the liver is stimulated by Growth Hormone
Stimulates bone collagen and matrix synthesis
Stimulates replication of osteoblasts
Inhibits bone collagen degradation

34. CYTOKINES
•Interleukin-1,-4,-6,-11, macrophage and
granulocyte/macrophage (GM) colony-stimulating factors (CSFs)
and Tumor Necrosis Factor Stimulate bone resorption
•IL-1 is the most potent
•IL-1 and IL-6 synthesis is decreased by estrogen
May be mechanism for post-menopausal bone resorption
Peak during 1st 24 hours then again during remodeling
•Regulate endochondral bone formation

35. PROSTAGLANDINS/LEUKOTRIENS
Effect on bone resorption is species dependent and their overall
effects in humans unknown
Prostaglandins of the E series
•Stimulate osteoblastic bone formation
•Inhibit activity of isolated osteoclasts
Leukotrienes
Stimulate osteoblastic bone formation
Enhance the capacity of isolated osteoclasts to form
resorption pits

36. HORMONES
•Estrogen
Stimulates fracture healing through receptor mediated
mechanism
Modulates release of a specific inhibitor of IL-1
•Thyroid hormones
Thyroxine and triiodothyronine stimulate osteoclastic bone
resorption
•Glucocorticoids
Inhibit calcium absorption from the gut causing increased
PTH and therefore increased osteoclastic bone resorption

37. Parathyroid Hormone
Intermittent exposure stimulates
•Osteoblasts
•Increased bone formation
Growth Hormone
•Mediated through IGF-1 (Somatomedin-C)
•Increases callus formation and fracture strength
•VASCULAR FACTORS
Metalloproteinases
Degrade cartilage and bones to allow invasion of vessels
Angiogenic factors
Vascular-endothelial growth factors
Mediate neo-angiogenesis & endothelial-cell specific
mitogens
Angiopoietin (1&2)
Regulate formation of larger vessels and branches

38. Bone Healing under Interfragmentary Movement
Fracture healing under interfragmentary movement occurs by
callus formation that mechanically unites the bony fragments.
•The flexural and torsional rigidity of a fracture depends on the
material properties and the second moment of inertia (rigidity
= EI) of the callus.
•Particularly the increase in callus diameter has a significant
effect on the stabilization of the fracture.
• Linear relation to the mechanical quality of the callus tissue
(E),
•The rigidity is proportional to the fourth power of the
diameter (IBending = πd4/64, ITorsion = π d4/32)

39. The interfragmentary movement under external loading
decreases with healing time in relation to the rigidity of the
callus.
Finally, the hard callus bridges the bony fragments and
reduces the interfragmentary movement to such a low level that
a healing of the fracture in the cortex can take place
When this has happened, the callus tissue is no longer required
and is resorbed by osteoclasts.
Finally, after a remodeling process, the shape and strength of
the normal bone are reconstituted

40. Healed osteotomy of a metatarsal with bony bridging of
the cortical osteotomy gap and only small remaining callus volume.

41. Fracture Healing under Interfragmentary Compression
•Implants and external loads  Compression forces
compression and close contact ( the external traction forces =>
the internal compression preload )
•compression preload +friction between the
fragmentsrelative movement between the fragments is
avoided.
•Under this absolutely stable fixation, bone healing can occur
by direct osteonal bridging of the fracture line with minimally
or no callus formation .
•In areas with direct contact, remodeling starts a few weeks
after fracture fixation, which leads to bridging of the fragments
by newly formed osteons .

42. Haversian osteons with osteoclasts in their cutter heads
resorb bone, create a tunnel that crosses the fracture line,
and fill the tunnel with new bone in a process of
osteoblastic activity.
In areas with a gap between the fragments, a filling of the
gap by woven bone occurs as a first step before the
Haversian osteons can cross the fracture area .
In reality a mixture of contact and gap healing will occur.

43. Osteon with bone-resorbing osteoclasts (left) that drill a tunnel into
the bone and osteoblasts that lay down new bone (osteoid) and fill
the tunnel with a new bone layer (original magnification 100×)
New
Osteoclast Osteoblast bone

44. Contact healing with osteons crossing the fracture line (left). Healing
of a fracture gap (right). Woven bone fills the gap before the osteons
can bridge the fracture area.

45. An advantage of absolute stability is that the blood vessels may
cross the fracture site more easily and lead to faster
revascularization .
In contrast to callus healing, there is no increased bone
diameter under direct osteonal healing.
This limits the load-bearing capacity of the healing bone, which
consequently requires a longer period of protection by the
implant.

46. Delayed Healing and Nonhealing under Unstable
Fixation
When the interfragmentary movement is too large, the bony bridging of
the fragments is delayed or even prevented.
Large interfragmentary movements cause large tissue strains and
hydrostatic pressures in the fracture that prevent the vascularization of
the fracture zone.
Without this vascularization bone cells cannot survive, bone cannot be
built, and only fibrocartilage can be formed .
Because the resisting fibrocartilage layer in between the two bony
fragments looks like the image of a joint, the nonunion is also called
pseudarthrosis (false joint).

47. Variables that influence fracture healing:
1. Injury variables :
• Open fractures
• Severity of injury : The more impact the injury has made
on bone and on the tissues surrounding it, the worse the
healing will become. Slight injury will only likely cause
mild contusions and will thus heal so easily. However,
comminuted injuries which also damaged the surrounding
tissues will not heal that quickly.
• Intra articular fractures : Collagenasses can break the
healing process of the bone as these fractures continue to
be in contact with synovial fluid. The more that
collegenasses partner with synovial fluid, the slower the
healing process will even become.

48. • Segmental fractures
• Soft tissues interposition
• Damage to the blood supply : Regulate blood supply well for
lack of it will drag down the healing process. This is one of the
factors affecting bone healing especially in parts such a scaphoid
bones, talus, and femoral head.
2. Patient variables
• Diseases/Disorders : Diseases which are discovered to slow
down the healing of fractures are diabetes, osteoporosis, and
others which result to immunocompromised state. Abnormal
healing is also caused by diseases such as Ehlers-Danlos
syndrome and Marfan’s syndrome.

49. • Age : The younger the patients and the bones are, the faster
the healing process works. Young patients have bones with the
ability to recover from deformities soon enough and remodel
them. However, the remodeling and recovering abilities of the
bones decrease as they reach maturity.
• Nutrition : For healing to occur, energy is necessary in the
form of protein and carbohydrates.
• Systemic hormones : These hormones that affect bone
healing include the growth hormone, thyroid hormone,
calcitonin, and corticosteroids. The last hormone mentioned
can slow down the healing process.
• Nicotine and other agents

50. 3. Tissue variables
• Form of bone (cancellous or cortical) : Two types of bones –
calcellous or spongy and cortical or compact bones – can be
compared with the differences in the rate of their healing
duration. The spongy bones have greater surface areas, more
stable, and have better foods when put side by side with
compact bones.
• Bone necrosis
• Bone disease : Any disease process that weakens the
musculoskeletal tissue, like osteoporosis or osteomalacia,
may impair union.
• Infection : Infections cause necrosis and edema, take energy
away from the healing process, and may increase the mobility
of the fracture site.

51. 4. Treatement variables
• Apposition of fracture fragments : Normal apposition of fracture
fragments is needed for union to occur. Inadequate reduction, excessive
traction, or interposition of soft tissue will prevent healing
• Loading and micromotion
Inter Fragmentary Movement-
Axial Movement
Small interfragmentary(IFM) movements stimulate callus
formation
Small fracture gaps
Cyclic axial movement  stimulated callus volume
to be advantageous

52. Large fracture gaps
Callus formation seems to be limited and bridging of the fracture
gap is delayed
Very stiff fixation of a fracture can suppress the callus formation
and delay healing. In such cases, an externally applied
interfragmentary movement can be used to stimulate callus healing.
However, when the fracture fixation itself allows axial movements to
a sufficient extent to stimulate callus formation, an additional
external application of interfragmentary movements does not lead
to further improvement of the healing process.

53. Shear Movement
Shear movement delays the fracture healing ?
Impede vascularization and promote fibrous tissue differentiation
Oblique tibial fracture (shear movements : 4 mm)
-- treated with functional bracing show rapid natural healing
Shear movement to induce delayed unions and nonunions ?
Control
Shear movement
Osteotomies of oblique or transverse type