A.Type of bone: Calcellous (spongy) bone V/S cortical bone. B. Degree of Trauma: Extensive soft tissue injury and comminuted #‘s V/S Mild contusions C.Vascular Injury: Inadequate blood supply impairs healing. Especially vulnerable areas are the femoral head, talus, and scaphoid bones.
D. Degree of Immobilization: Immobilized for vascular ingrowth and bone healing to occur.
Repeated disruptions of repair tissue, especially to areas with marginal blood supply or heavy soft tissue damage, will impair healing.
E. Type of Fractures: Intraarticular fractures communicate with synovial fluid, which contains collagenases that retard bone healing V/S Open fractures result in infections V/S Segmental fractures have disrupted blood supply.
F. others: Bone death caused by radiation, thermal or chemical burns or infection.
Estrogen Stimulates fracture healing through receptor mediated mechanism.
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. Parathyroid Hormone Accelerates callus formation (+osteoprogenitor cells) with enhanced remodeling & biomechanical properties of healing # Growth Hormone Mediated through IGF-1 (Somatomedin-C) Increases callus formation and fracture strength
Bone union and advances
FRACTURE UNION AND
Dr Dipendra Maharjan
First year resident
• Fracture is defined as a
– break in the continuity of bone
– results in loss of its mechanical stability
– partial destruction of blood supply.
• But following fracture a scar is not formed,
instead a bone has formed
• bone healing the appropriate nomenclature
would be BONE REGENERATION
What is Fracture?
What is a Fracture Healing?
• A complex process that requires the
recruitment of appropriate cells
• the subsequent expression of the
appropriate genes at the right time and
in the right anatomical location.
• A fracture initiates a sequence of
inflammation, repair, and remodeling
that can restore the injured bone to its
original state or near original state.
There are 3 major phases with sub divisions:
• Reactive Phase
– Fracture and inflammatory phase
– Stage of hematoma formation
– Granulation tissue formation.
• Reparative Phase:
– Cartilage Callus formation.
– Lamellar bone deposition.
• Remodeling Phase:
– Remodeling to original bone contour.
STAGES OF FRACTURE HEALING
• Union is incomplete repair and the ensheathing
callus is calcified.
• Clinically the fracture site is still a little tender,
the bone moves in one piece, attempted
angulation is painful.
• X-Rays show the fracture line still clearly visible,
with fluffy callus around it.
• Repair is incomplete and it is not safe to subject
the unprotected bone to stress.
• Clinical union
– occurs when progressively increasing stiffness and
strength provided by the mineralization process
makes the fracture site stable and pain free.
• Radiographic union
– present when plain radiographs show bone
trabeculae or cortical bone crossing the fracture
• Radioisotope studies have shown increased
activity in fracture sites long after painless
function has been restored and radiographic
union is present, indicating that the remodeling
process continues for years.
• MESSENGER SUBSTANCE:
IL-1,4,6,11, macrophage and granulocyte/macrophage
stimulate bone resorption.
IL-1 ,6 synthesis is decreased by estrogen
Stimulate osteoblastic bone formation and inhibit activity
of isolated osteoclasts.
Stimulate osteoblastic bone formation and enhance the
capacity of isolated osteoclasts to form resorption pits.
A.Transforming growth factor(TGF):
-Act on serine/threonine kinase cell wall receptors
- Promotes proliferation and differentiation of osteoblasts,
osteoclasts and chondrocytes
- Stimulates both endochondral and intramembranous
bone formation and collagen type 2 synthesis.
B.Fibroblast growth factors(FGF):
-Increase proliferation of chondrocytes and osteoblasts
-Enhance callus formation & stimulates angiogenesis.
C.Platelet derived growth
•Stimulates bone cell growth
•Increases type I collagen synthesis by
increasing the number of osteoblasts.
•PDGF-B stimulates bone resorption.
D.Insulin like growth factor(ILGF):
•Stimulates bone collagen & matrix synthesis and
replicates osteoblasts .
•It also inhibits collagen degradation.
• E.Bone Morphogenic Proteins (BMP):
BMP are Osteoinductive proteins initially isolated from
demineralized bone matrix.
–Induce cell differentiation : BMP 3(osteogenin).
–Promote endochondral ossification: BMP 2 & 7.
–Regulate extracellular matrix production :BMP1.
–Increase fusion rates in Spinal fusions (anterior lumbar
interbody fusion): BMP 2
–Non unions: BMP 7 as good as bone grafting .
• 3.PERMEABILITY FACTORS:
-Protease – Plasmin , Kalikrein, Globulin permeability
-Polypeptides –leucotaxime, Bradykinin, Kallidin
-Amines – Adrenalin, nor-adrenalin, Histamine.
These factors work in ways that :
– Increase capillary permeability
– Alteration in diffusion mechanism in intracellular
– Cellular migration
– Proliferation & differentiation
– New blood vessel formation
– Matrix synthesis
– Growth & development.
–Degrade cartilage and bones to allow invasion
•B Angiogenic factors:
-Vascular-endothelial growth factors mediate neo-
angiogenesis & endothelial-cell specific mitogens.
•C. Angiopoietin (І & ІІ)
–Regulate formation of larger vessels and branches.
Young patients heal rapidly and have a remarkable ability
to remodel V/S old .
An adequate metabolic stage with sufficient carbohydrates
and protein is necessary.
an immunocompromised state will likely delay healing.
Illnesses like Marfan’s syndrome and Ehlers-Danlos
syndrome cause abnormal musculoskeletal healing.
• Stimulates fracture healing through receptor mediated
– Thyroid hormones
• stimulate osteoclastic bone resorption.
• increased osteoclastic bone resorption.
– Parathyroid Hormone
• Accelerates callus formation (+osteoprogenitor cells) with
enhanced remodeling & biomechanical properties of healing #
– Growth Hormone
• Increases callus formation and fracture strength
• In vitro bone deformation produces
piezoelectric currents and streaming
• Electromagnetic (EM) devices are based on
Wolff’s Law that bone responds to
mechanical stress: Exogenous EM fields may
simulate mechanical loading and stimulate
bone growth and repair
• TYPES ARE :
– Direct electrical current.
– Pulsed electromagnetic fields (PEMF).
• Modulates signal transduction,
increases gene expression
(aggrecan ), increases blood flow,
enhances bone remodeling and
increases callus torsional strength
in animal models.
• Low-intensity ultrasound is
approved by the FDA for stimulating
healing of fresh fractures.
• Direct Electrical
– Electric stimulation of
bone has been taught
to be an effective and
non invasive method
for fracture healing
and treating fracture
non union. Studies
shows that electric
field generated helps
in proliferation of bone
C. Pulsed electromagnetic fields (PEMF).
• Approved for the
treatment of non-unions
• Efficacy of bone
stimulation appears to be
– are most effective (15 to 30 Hz
Autogenous (iliac crest, prox. tibia, distal femur)
Scaffold for osteoconduction
Has bone matrix proteins osteoinduction
Has progenitor stem cells osteogenesis
(free vascular fibular graft for absent radius/ long bone)
Allogenic (from cadaver)
Synthetic (demineralized bone matrix, collagen, ceramics,
cements, polymers- Si, PMMA)
2 emerging products
Tricalcium PO4 composite (VITROSS, CORTOSS)
Hydroxyapatite compound (pro osteon) – marine coral
•Bone Marrow Aspirate
•bone marrow contains mesenchymal stem cells and circulating
•Mesenchymal stem cells can differentiate into osteoblasts,
chondrocytes, and other connective tissue cells in vitro under appropriate
•circulating endothelial progenitors that can contribute to adult
•some of the effects of bone marrow aspirate on fracture healing could
be due to the local application of osteochondrogenic cells and/or
endothelial progenitor cells during bone healing.
• Use of Serological Bone Formation Markers
– Current serum markers of bone formation activity
• bone-specific alkaline phosphatase (ALP)
• procollagen type-I N-terminal propeptide (PINP)
• procollagen type-I C-terminal propeptide (PICP)
• osteocalcin (OC)
– to Monitor Callus Development and Fracture
– PINP is superior in reflecting bone formation
processes when compared with ALP, PICP, and OC.
PINP can also be characterized as an index of
collagen synthesis, a marker of the early stages of
bone formation, and a marker of callus formation.
• Laser Photobiomodulation on Bone
– Laser Phototherapy (LPT) is an effective tool to stimulate
– results show that the use of IR laser results on increased
– LPT effect depends not only on the total dose, but also on
both irradiation time and mode.
– Energy density and intensity are biologically independent
and accounts for the success and the failure of the
– Vertebroplasty is a minimally invasive, image-guided
therapy used to relieve pain from a vertebral body fracture.
– It has been used for osteoporotic or malignant fractures.
– Vertebroplasty can increase patient mobility, decrease
narcotic needs, and prevent further vertebral collapse.
– Percutaneous vertebroplasty (PVP) usually involves
percutaneous injection of a cement, polymethylmethacrylate
(PMMA), into the vertebral bodies.
– Occasionally, PMMA has been placed manually into vertebral
lesions during open surgical operations.
Percut. Inj. (Fibroblast GF-2 + hyaluronon) callus
formation & mechanical strength
• OTHER RECENT ADVANCES:
• GROWTH FACTOR THERAPY
Due to their ability to stimulate proliferation and
differentiation of mesenchymal and osteoprogenitor cells they
have shown great promise for their ability to promote fracture
• APPLICATION OF PLATELET RICH PLASMA
PRP improves cellular proliferation and chondrogenesis during early
fracture healing and increases the mechanical strength of callus during
late fracture healing
Injecting platelet rich plasma at fracture site helps in fracture healing .
• TISSUE ENGINEERING, STEM CELLS AND GENE
In past decade tissue culture and stem cells have
been implicated in enhancing fracture healing and articular
• Fracture healing is influenced by
many variables including mechanical
stability, electrical environment,
biochemical factors and blood flow
• Our ability to enhance fracture
healing will increase as we better
understand the interaction between
• CAMPBELL TEXTBOOK OF ORTHOPAEDICS 11TH EDITION..
• APLEYS PRINCIPLE OF ORTHOPAEDICS
• REVIEW OF ORTHOPAEDICS BY MILLER
• Orthopaedic Knowledge Update 10
• Recent Developments in the Biology of Fracture Repair
• Recent Advances in the Use of Serological Bone Formation
Markers to Monitor Callus Development and Fracture
Healing Marlon O. Coulibaly1, Debra L.
• Recent Advances on the Use of Laser Photobiomodulation
on Bone. A. Pinheiro
• Gene therapy for in vivo bone formation: recent advances
W. LATTANZI1*, E. POLA2*
• The evidence of low-intensity pulsed ultrasound for in
vitro, animal and human fracture healingPilar Martinez de
Albornoz†, Anil Khanna‡,