Fracture healing

Tony Olasinde
Dept of Surgery,
Faculty of Clinical Medicine and Dentistry
KIU( western Campus)
Ishaka
Learning objectives- student will be able to
• Define fracture healing
• Know modes of bone healing
• Know the process of bone healing
• Factors that aid and retard healing
• Apply this knowledge to clinical care
Definition
• Defined as the process of complex and sequential set of events to
restore injured bone to pre-injured or pre-fractured condition
• Stem cell are very crucial to # healing cum repair process
• Sources – endosteum and periosteum
What dictates type of fracture healing?
• The stability of fracture.
• Governed by mechanical strain across the # line
• When the mechanical strain is less than 2% Primary bone healing occurs
• i.e. no callus formation
• Strictly intramembranous ossification
• When the mech. Strain is between 2 and 10% Secondary bone healing occurs
• More callus formation
• Endochondral ossification
Modes of bone healing
• Primary bone healing
• Intramembranous ossification via the Harversian remodelling
• Found in rigid anatomical fixation that used compression plate device
• Absolute stability constructs
• Also called direct healing or cutting cone healing
• Secondary bone healing
• Endochondral ossification with more callus formation
• Found in all types of fractures immobilization and treatment-
• Casting, IMN, external fixation, all fracture pattern minus transverse # where rigid stability
wasn’t achieved
• Also called indirect healing
• No rigid anatomical reduction required
Peculiar Note
• Bone healing may occur as combination of Primary and Secondary
healing modes depending on the degree of stability of the construct
Stages of fracture healing
• Stage of hematoma formation
• Stage of inflammation
• Stage of Primary callus formation ( soft callus)
• Stage of secondary Callus formation ( hard Callus )
• Stage of remodeling
Stage of Hematoma and inflammation
• Hematoma form
• Brings hematopoietic cell which secretes growth cytokines
• Macrophages , Neutrophils, and platelets
• Integrated release of cytokines
• TNF- alpha, IL-1, 6, 11, & 18
• Lead to Osteogenic differentiation of MSC via TNFR1 & R2
• R1 normally expressed in bone, while R2 only injured n=bone
• Production rise and detectable with 24hrs and peaks\
• Clinical correlates…… HIV – deficient TNF-alpha lead reduced or
delayed intramembranous /endochondral ossification
Stage 1 and 2 continues
• Granulation forms around the fractures site from migration of MSC
and fibroblasts
• Proliferation of osteoblast and fibroblast
• Clinical correlates
• Inhibition of RUNX2/ osterix by NSAID critical to differentiation of
Osteoblastic cell
Stage of Primary or soft callus
• Form within 2 weeks
• Soft callus forms if bone ends aren’t touching
• Mech. Environment dictates differentiation of either osteoblastic in
Stable environment or chondrocytic ( unstable environment)
• Endochondral ossification converts soft callus to hard callus or woven
bone
• Medullary callus supplement soft callus
• Cytokine drives chondrocytic differentiation
Stage of hard callus formation
• Cartilage production initially provides provisional stability
• Type II collagen initially produced in early # later replaced with Type I

• Amount of callus inversely proportional to extent of immobilization

•
Stage of remodeling
• Begin in the middle of repair process and continue long after clinical
union
• Complex interplay of factors Osteoblast/osteoclast activities
• Chondrocyte undergo terminal differentiation
• At Molecular level:
• Indian Hedgehog( Ihh), Parathyroid related peptides (PTHrP)
• FGF and BMP
• Type X collagen expressed as extraarticular matrix undergo calcification vis proteases
activity
• As bone is formed the following cytokines are expressed; TNF-beta, IGFs Osteocalcin,
Collagen type I V and XI
Remodeling contd
• Wolff’s law helps in remodeling i.e woven are organized in response
to stress they are subjected to
• Also Piezoelectric Charges- compression – negative and tension –
positive charge stimulating osteoblastic and Osteoclastic activity
respectively
Stages of fracture healing
R

Process of fracture healing after fracture of the

femoral shaft in a 39-year-old patient (a). Anatomical
reduction and flexible fixation with locked plating (b).
Four weeks after fracture, advanced periosteal and
endosteal callus formation was observed (c) which
progressed by week fourteen (d). Almost complete
remodelling of the periosteal callus was observed
four years after trauma (e). Residuals of
intramedullary callus after metal removal six years
Factors that influence healing
• Internal factors
• Blood supply
• Unreamed nailing maintain endosteal blood supply compared reamed nailing
• Loose fitting nails allows more reperfusion of endosteal blood supply compared to canal
filling nails
• Head injury increase osteogenic response
• Mechanical factors
• Bony soft tissue attachment
• Mechanical stability
• Location of the injury
• Degree of bone loss
• Pattern of fracture- segmental with butterfly fragment increased chance of non union
External factors
• Low intensity Pulsed Ultrasound (LIPUS)
• Via increased vascularity, dev. Mech. Strain gradient
• Accelerated healing
• 30mW/square cm
• Clinical correlates Union rates closed to 80% when used in delayed/ non union
• Bone stimulators
• 4 modes of delivery
• Direct current
• Capacitively coupled electrical fields( AC)
• Pulsed electromagnetic fields
• Combined magnetic fields
• All lead to elevated concentration of TGF- beta and BMP
External factors cont.
• COX2
• Promotes # healing by causing MSC stem to differentiate into osteoblasts
• Radiation ( high dose)
• Reduced cellularity
Patient factors
• Diet
• Calcium and Vitamin D deficiency
• 66% reported in case of non union
• Gastric bypass patients
• Reduced Calcium absorption
• DM patients
• Affect repair and remodeling of bone
• Takes 1.6time longer in DM patient for fracture healing
• Nicotine use
• Smokers takes 70% longer to heal in open # vs non smokers
• >500 % pseudarthrosis in spinal fusion
• Decreased strength of callus
• Inhibits new blood vessel formation as bone is remodeled.
Patient factors continues
• HIV
• higher prevalence of fragility # with ass. Delayed healing
• Via reduce or lack of TNF- alpha production, ARV drug, poor intake, and poor
intraosseous circulation
• Medications that affects healing
• Bisphosphonates
• Systemic steroids
• NSAID
• Quinolones
References
• Fracture healing in www.orthobullet.org
• Augut P, Hollenstiener M, Von Ruden C. The role of mechanical
stimulation in the enhancement of Bone healing. Injury. 2021:
52(suppl.2): S75-S85.