Fracture Healing
Biology of Bone Repair
Healing Pathways
Critical Must-Knows
- Primary Healing: Requires absolute stability (less than 2% strain) + gap less than 0.1mm. Mechanism: Cutting Cones.
- Secondary Healing: Occurs with relative stability (2-10% strain). Mechanism: Enchondral Ossification (Callus).
- Phases: Inflammation → Soft → Hard → Remodeling
- Diamond Concept: The holy grail of union = Cells + Scaffold + Signals + Mechanical Stability.
- Perren's Strain Theory: Tissues can only exist if they can withstand the mechanical strain of the environment.
Examiner's Pearls
- "Soft Callus = Type II Collagen (Cartilage). Hard Callus = Type I Collagen (Bone).
- "Primary Healing has NO callus.
- "BMP-2 = Open Tibia (INFUSE). BMP-7 = Non-union (OP-1).
- "Nicotine is a potent vasoconstrictor and inhibitor of healing.
Clinical Imaging
Imaging Gallery



The Stability Rule
Absolute Stability
Primary Healing. Occurs when strain is less than 2%. Compression plating eliminates micromotion. The bone thinks it is intact and remodels via cutting cones.
Relative Stability
Secondary Healing. Occurs when strain is 2-10%. IM nails allow micromotion. The body responds by throwing down cartilage (callus) to stiffen the gap.
At a Glance
Primary vs Secondary Healing
| Feature | Primary (Direct) | Secondary (Indirect) |
|---|---|---|
| Stability Requirement | Absolute (No motion) | Relative (Micromotion) |
| Strain | Less than 2% | 2% - 10% |
| Mechanism | Haversian Remodeling | Enchondral Ossification |
| Callus? | NO Callus | YES Callus (Bridging) |
| Example | Lag Screw + Neutralization Plate | Intramedullary Nail |
Mnemonics
CSSMThe Diamond Concept
Memory Hook:What you need for a Union.
I-S-H-RPhases of Healing
Memory Hook:I Shall Heal Right.
N-I-C-O-T-I-N-ENon-Union Risk Factors
Memory Hook:Causes of Non-Union.
Overview and Epidemiology
Overview Fracture healing is the process of bone regeneration. Unlike other tissues which heal by scar formation, bone heals by regeneration of normal tissue structure. It is a complex cascade of cellular and biochemical events that restores the integrity of the bone.
Primary (Direct) Healing
- Definition: Bone healing without callus formation.
- Prerequisites: Absolute Stability (Strain less than 2%) + Anatomic Reduction.
- Mechanism (Gap less than 0.01 mm): Cutting Cones (Osteoclasts bore tunnels, Osteoblasts fill with osteoid).
- Gap Mechanism (Gap less than 1 mm): Gap healing (Woven bone to Refined by Cutting Cones).
Secondary (Indirect) Healing
- Definition: The natural form of healing involving callus.
- Prerequisites: Relative Stability (Strain 2-10%) + Vitality.
- Phases:
- Inflammation: Hematoma, MSC recruitment.
- Soft Callus: Cartilage formation (Enchondral ossification).
- Hard Callus: Mineralization (Woven bone).
- Remodeling: Wolff's Law (Lamellar bone).
Biology and Core Concepts
Biology of Bone Before understanding healing, one must understand the players.
Cellular Components
- Osteoblasts ("Build"):
- Secrete Osteoid (Type I Collagen) and regulate mineralization.
- Express RANK-L to control osteoclasts.
- Derived from Mesenchymal Stem Cells (MSCs).
- Osteocytes ("Sense"):
- Mechanosensors trapped in lacunae deep within the mineralized matrix.
- Communicate via canaliculi.
- Secrete Sclerostin (inhibits bone formation). Mechanical loading inhibits Sclerostin (allowing bone formation).
- Osteoclasts ("Chew"):
- Multinucleated giant cells derived from Monocyte/Macrophage lineage (Hematopoietic).
- Resorb bone via acid secretion (HCL) and proteases (Cathepsin K).
- Activated by RANK-L. Inhibited by OPG.
The Matrix
- Inorganic (65%): Hydroxyapatite (Calcium Phosphate crystals). Provides compressive strength.
- Organic (35%):
- Collagen Type I (90%): Provides tensile strength. Triple helix structure.
- Non-Collagenous Proteins: Osteocalcin (marker of turnover), Osteopontin (cell attachment), BMPs (growth factors).
Blood Supply
- Centrifugal Flow (Normal): Marrow → Cortex → Periosteum. (Inside to Outside).
- Centripetal Flow (Post-Fx): Periosteum → Cortex → Marrow. (Outside to Inside). The Periosteal blood supply becomes dominant after medullary disruption (e.g., reaming). This highlights the importance of preserving the soft tissue envelope (periosteum) during surgery.
Biophysics of Stimulation
- Piezoelectricity:
- Stress on collagen generates electric potentials.
- Compression side: Electronegative → Stimulates Osteoblasts (Bone Formation).
- Tension side: Electropositive → Stimulates Osteoclasts (Bone Resorption).
- Streaming Potentials: Fluid flow in canaliculi stimulates osteocytes.
Biomechanics (Strain Theory)
Perren's Strain Theory: Tissues can only exist if they can withstand the strain of the gap.
- Strain Formula: Change in Gap / Original Gap.
- Bone: Ruptures at 2% Strain.
- Cartilage/Granulation: Tolerates greater than 10% Strain.
- Conclusion: To form bone (Primary), strain must be less than 2%. To heal via callus (Secondary), granulation tissue first stiffens the gap, reducing strain to allow cartilage, then bone.
Classification Systems
Healing Pathways
- Primary (Direct) Healing:
- Contact Healing: Less than 0.01mm gap. Cutting cones cross directly. Haversian remodeling.
- Gap Healing: Less than 1mm gap. Woven bone fills gap first (scaffold), then cutting cones remodel it.
- Secondary (Indirect) Healing:
- Inflammation → Soft Callus → Hard Callus → Remodeling.
- Requires micromotion.
- Distraction Osteogenesis:
- Intramembranous ossification via tension stress (Ilizarov).
- Requires: Stability, Latency (7 days), Rate (1mm/day), Rhythm (4x 0.25mm).
These pathways exist on a spectrum.
Clinical Assessment
History
- Pain: Resolution of pain is the first sign of union.
- Function: Ability to weight bear. Return to activities of daily living.
- Risk Factors: Ask about smoking, diabetes, steroid use, NSAIDs.
Physical Exam
- Tenderness: No tenderness at fracture site (Clinical Union).
- Motion: No abnormal mobility (Clinical Union).
- Stress: Painless stressing of the fracture.
- Soft Tissue: Assess status of the envelope (healed wounds, skin grafts).
Investigations


Radiographic Assessment (RUST Score)
- Radiographic Union Scale for Tibial fractures (RUST).
- Methodology: Review AP and Lateral X-rays. Identify the 4 cortices (Anterior, Posterior, Medial, Lateral).
- Scoring Per Cortex:
- 1 Point: Fracture line visible, No callus. (Unhealed)
- 2 Points: Fracture line visible, Callus present. (Healing)
- 3 Points: Fracture line invisible, Bridging callus. (Healed)
- Interpretation:
- Minimum Score: 4 (Unhealed).
- Maximum Score: 12 (Fully United).
- clinical Definition of Union: Score of greater than 10 usually correlates with mechanical stability and ability to weight bear without pain.
- General Signs: Bridging bone on 3 of 4 cortices. Blurring of fracture line. Remember: X-rays lag behind clinical signs.
Assessment of Non-Union
- CT Scan: Gold standard to assess bridging. Can differentiate bony union from fibrous non-union.
- Labs: Vitamin D, PTH, Calcium, ESR/CRP (Infection).
- MRI: Assessing infection (osteomyelitis) vs sterile non-union.
Management Algorithm
Surgical Technique
Compression Plating (Absolute Stability)
- Mechanism: Primary Healing.
- Principles:
- Anatomic Reduction: Essential for articular surfaces.
- Compression: Achieved via Lag Screw (interfragmentary) or DCP Plate (axial).
- Indication:
- Articular fractures (must be perfect).
- Forearm fractures (length/rotation).
- Osteotomy sites.
- Disadvantage: Wide exposure (strips blood supply). High strain if gap remains.
Primary healing is intolerant of gaps.
Implant Materials and Stiffness
| Material | Modulus (GPa) | Biological Effect |
|---|---|---|
| Stainless Steel | 200 GPa | Very Rigid. Good for absolute stability. |
| Titanium Alloy | 110 GPa | Less Rigid (closer to bone). Better for load sharing. |
| Cortical Bone | 15-20 GPa | Target stiffness. |
| Cancellous Bone | 0.1-1 GPa | Spongy. |
Biomaterials and Healing The stiffness of the implant dictates the strain at the fracture site.
- Stress Shielding: If an implant is too stiff (e.g., thick steel plate), it takes all the load. The bone beneath it senses no load (strain less than 2%) but also no "need" for strength. This causes bone resorption (Wolff's Law in reverse) and porosis under the plate.
- Titanium: Being less stiff (closer to bone), it allows some load transfer, reducing stress shielding.
- Carbon Fiber: Even closer modulus to bone. Used in oncology (radiolucent).
Management: Conservative
Casting Principles
- Three-Point Molding: To maintain reduction, pressure must be applied at the apex of the curve and counter-pressure at the proximal/distal ends.
- Functional Bracing (Sarmiento):
- Allows joint motion.
- Hydrostatic containment of soft tissues stabilizes the fracture.
- Micro-motion stimulates callus (Secondary Healing).
- Common for: Humeral shaft, Tibial shaft.
Biologic Adjuvants
When biology is poor (Atrophic Non-union), we augment it.
Bone Grafts
- Autograft (Self):
- Source: Iliac Crest (Gold Standard), RIA (Reamer Irrigator Aspirator - Femur).
- Properties: Osteogenic (Cells) + Osteoinductive (Signals) + Osteoconductive (Scaffold).
- Cons: Donor site morbidity (pain, infection, nerve injury).
- Allograft (Cadaver):
- Source: Bone bank (structural struts or morcellized chips).
- Properties: Osteoconductive strictly. (No cells, minimal signals).
- Cons: Disease transmission (rare 1 in 1 million), slower incorporation, immune reaction (minor).
- Synthetics (Ceramics/TCP):
- Properties: Osteoconductive (Scaffold).
- Cons: Brittle, expensive, can cause seroma.
Growth Factors
- BMP-2 (Infuse):
- Potent Osteoinductor. Indicated for Acute Open Tibia fractures.
- Mechanism: Recruits MSCs to differentiate into osteoblasts.
- Risks: Swelling (C-spine airway compromise), Heterotopic ossification, Cost.
- BMP-7 (OP-1): Historic use for non-unions.
- PRP/BMAC: Bone Marrow Aspirate Concentrate. Rich in MSCs and growth factors (PDGF, TGF-beta).
Factors Affecting Healing
Patient Optimization
- Smoking:
- Nicotine is a vasoconstrictor of microvasculature.
- Carbon Monoxide binds Hemoglobin (hypoxia).
- Increases non-union risk significantly (e.g., Tibia, Fusion, Ankle).
- Diabetes:
- Microvascular disease (ischemia).
- AGEs (Advanced Glycation End-products) inhibit collagen cross-linking.
- Decreased cellular proliferation.
- Medications:
- NSAIDs: Inhibit COX-2, which is needed for Enchondral Ossification (Soft to Hard Callus conversion). Controversial, but generally avoided in high-risk fractures.
- Steroids: Inhibit osteoblasts and calcium absorption.
- Bisphosphonates: Inhibit osteoclasts (remodeling). Long half-life. Can cause atypical fractures.
- Quinolones: Toxic to chondrocytes? (Minor factor).
- Nutrition:
- Albumin less than 3.5 = Malnutrition.
- Vitamin D / Calcium essential for mineralization.
Optimizing the host is as important as the surgery.
Complications of Healing
Healing does not always go to plan.
1. Delayed Union
- Definition: Healing that takes longer than expected for the specific fracture and host (typically 3-6 months), but is still progressing.
- Management:
- Conservative: Functional bracing, LIPUS (Low Intensity Pulsed Ultrasound), Nutrition.
- Surgical: Dynamization (remove locking screws) to increase load/strain.
2. Non-Union
- Definition: Failure to heal by 6-9 months, or no progression on X-rays for 3 consecutive months (FDA definition).
- Types:
- Septic Non-Union: Infection until proven otherwise. Check CRP/ESR. MRI.
- Hypertrophic: Good Biology, Poor Stability. (Needs Stability). Elephant Foot appearance.
- Atrophic: Poor Biology. (Needs Biology + Stability). Pencil Tip appearance.
- Oligotrophic: Intermediate.
- Workup:
- History: Smoking, Diabetes, NSAIDs.
- Exam: Mobility at fracture site? Sinus?
- Imaging: CT Scan (Gold Standard for union).
- Labs: Infection markers, Vitamin D, Ca/PO4, PTH.
3. Malunion
- Definition: Healed but in a non-anatomic position.
- Parameters: Shortening, Rotation, Angulation.
- Tolerance:
- Humeral Shaft: Tolerates huge deformity (20 deg angulation, 3cm shortening).
- Forearm: Zero tolerance (loss of pronation/supination).
- Tibia: Tolerates minimal varus/valgus (less than 5 deg).
4. Synostosis
- Definition: Fusion between two adjacent bones (e.g., Radius/Ulna, Tibia/Fibula).
- Cause: Disruption of Interosseous Membrane (IOM) + High Energy + Same approach (single incision).
- Consequence: Loss of rotation (Forearm).
Preoperative Planning
Planning for Union
- Patient: Stop smoking, Optimize diabetes, Nutrition.
- Implant: Choose load-sharing (Nail) vs load-bearing (Plate) based on fracture pattern and soft tissue.
- Biology: Preserve soft tissue (Open reduction vs Closed).
Postoperative Care
Early Phase (0-2 weeks)
- Elevation: Reduce edema.
- Motion: Early ROM (if fixation allows) to prevent stiffness and stimulate blood flow.
- Review: Wound check.
Middle Phase (2-6 weeks)
- Loading: Proprioceptive weight bearing. Wolff's law stimulation.
- X-rays: Check alignment and maintenance of reduction.
Late Phase (6-12 weeks)
- Strengthening: Restore muscle mass.
- Full Weight Bearing: When hard callus visible (3/4 cortices).
Rehabilitation Goals by Phase
| Phase | Goal | Restrictions | Biology |
|---|---|---|---|
| Inflammatory (0-2w) | Protect Soft Tissue | NWB / Elevation | Hematoma Formation |
| Reparative (2-6w) | Prevent Stiffness | Touch WB / ROM | Soft Callus (Cartilage) |
| Consolidation (6-12w) | Load the Bone | Progressive WB | Hard Callus (Bone) |
| Remodeling (greater than 12w) | Return to Sport | Full Activity | Haversian Remodeling |
Outcomes and Prognosis
Time to Union (Average)
- Upper Limb: 6-8 weeks.
- Lower Limb: 12-16 weeks.
- Tibia: Slowest bone to heal (poor blood supply). 16-20 weeks common for open fractures.
Non-Union Rates
- Tibia: 10-15% (especially open). The most common long bone non-union.
- Femur: 1-2% (with IM nail). Success story of modern orthopaedics.
- Clavicle: 5-10% (conservative).
- Scaphoid: High rate due to retrograde blood supply.
Factors Predicting Poor Outcome
- Smoking (Odds ratio greater than 3).
- Open fracture (Gustilo III).
- Infection.
- NSAID use (Prolonged).
Pediatric Healing
Key Differences
- Speed: Heals twice as fast. High osteogenic potential of thick, vascular periosteum.
- Remodeling Potential:
- Can correct Angulation (in plane of motion).
- Cannot correct Rotation.
- Overgrowth: Femur fractures stimulate growth (1-2cm leg length discrepancy common) due to hyperemia.
- Physeal Injuries:
- Growth arrest (Physeal bar) → Deformity.
- Salter-Harris Classification.
Children are not just small adults.
History of Fracture Treatment
Historical Evolution
- Ancient Era: Splinting and casting (Egyptians).
- 1950s (AO Foundation):
- Founded by Mueller, Allgower, et al.
- Emphasis on Anatomic Reduction and Rigid Fixation.
- Result: Primary healing, but high non-union rate due to biological stripping.
- 1990s (Biological Fixation):
- Shift to MIPO (Minimally Invasive Plate Osteosynthesis) and IM Nails.
- Emphasis on Biology (Blood supply) over Anatomy.
- Acceptance of secondary healing (Callus).
- Future: Gene therapy (BMP), 3D printed scaffolds, Stem Cells.
- Gene Therapy: Viral vectors delivering BMP-2 genes to local cells.
- 3D Printing: Custom scaffolds matching the defect, seeded with MSCs.
- Biophysical Stimulation:
- LIPUS: Low Intensity Pulsed Ultrasound. Mechanical vibration stimulates integrins.
- PEMF: Pulsed Electromagnetic Fields. Induces electrical currents (streaming potentials) to stimulate calcification. NOTE: Contraindicated in patients with pacemakers.
Evidence Base
BMP-2 (INFUSE)
- RCT of BMP-2 in Open Tibial Shaft Fractures.
- Reduced time to union.
- Reduced need for secondary intervention (bone graft).
- FDA Approved for Acute Open Tibial Shaft Fractures (with IM nail).
NSAIDs and Healing
- Review of evidence regarding NSAIDs.
- Animal data strongly suggests inhibition of healing.
- Human data is mixed/inconsistent.
- Recommendation: Avoid in high-risk non-union cases; short course for simple fractures likely safe.
Sprint Trial
- Reamed vs Unreamed Nails for Tibial Fractures.
- Reamed nailing reduced time to union and reoperation rates in closed fractures.
- No difference in open fractures (but trend favored reaming).
- Conclusion: Ream the canal (harvests bone graft, increases stability).
The Diamond Concept
- Introduced the concept of 4 pillars for union.
- Osteogenic Cells, Osteoconductive Scaffolds, Osteoinductive Signals, Mechanical Stability.
- Later added Vascularity (The 5th Diamond).
- Framework for assessing and treating non-unions.
TRUST Trial (LIPUS)
- Multi-center RCT of Low Intensity Pulsed Ultrasound (Exogen) for Tibial Fractures.
- Result: NO difference in time to union or functional recovery compared to sham device.
- Conclusion: LIPUS provides no benefit in fresh tibial fractures.
Exam Viva Scenarios
Practice these scenarios to excel in your viva examination
The Smoker
"Patient with a tibial shaft fracture asks why they need to stop smoking. Convince them."
Non-Union Classification
"Show me an X-ray of a non-union. How do you classify it and treat it?"
MCQ Practice Points
Collagen Types
Q: What type of collagen is found in soft callus? A: Type II Collagen. (Think "Two" for "Tissue" / Cartilage). Hard callus replaces it with Type I (Bone).
Osteoclasts
Q: How do Osteoclasts attach to bone? A: Via the Sealing Zone (Integrins, specifically alpha-v beta-3). They create a "Howship's Lacuna" and secrete H+ ions (acid) to dissolve mineral.
Strain Theory
Q: A simple fracture is plated with a bridging plate (long span). Why might it fail? A: Strain Concentration. In a simple gap, all motion is concentrated. Strain = Motion / Gap. Small gap = High Strain. Bridging plates work best in comminuted fractures (Strain = Motion / Long Gap).
Smoking Risk
Q: What is the odds ratio for non-union in smokers? A: Greater than 3. Smoking is the most significant modifiable risk factor.
Diamond Concept
Q: What are the 4 pillars of the Diamond Concept for fracture healing? A: C-S-S-M: Cells (osteogenic), Scaffold (osteoconductive), Signals (osteoinductive BMPs), and Mechanical stability.
Specific Fracture Scenarios
The Tibial Shaft (The "Unforgiving Bone")
- Anatomy: One third is subcutaneous (anteromedial surface). Poor blood supply.
- Healing: Slow (16-20 weeks).
- Management: IM Nail (standard) vs Plate (distal/proximal).
- Pearl: Reamed nailing creates a "bonfire" of growth factors and autograft.
The Scaphoid (Retrograde Flow)
- Anatomy: Blood enters distal pole. Proximal pole depends on intraosseous flow.
- Risk: Proximal pole fracture → Avascular Necrosis (AVN).
- Healing: Compression screw (Herbert screw) buried in bone.
The Clavicle (S-Shaped Strut)
-
Anatomy: Membranous bone formation (unique).
-
Malunion: Shortening greater than 2cm affects shoulder biomechanics (scapular dyskinesis).
-
Non-Union: Atrophic common in smokers.
-
Non-Union: Atrophic common in smokers.
The Femoral Neck (Intracapsular)
- Anatomy: Synovial fluid washes away hematoma (no clot = no callus).
- Result: Must heal by Primary Healing (Compression).
- Risk: AVN due to medial circumflex artery damage.
The Humeral Shaft (Holing Time)
- Healing: Typically 8-12 weeks.
- Acceptance: Accepts up to 20 degrees anterior angulation and 30 degrees varus/valgus due to shoulder range of motion compensation.
- Nerve: Radial nerve palsy (Holstein-Lewis fracture in distal third). 90% resolve spontaneously. Watch and wait for 3 months if closed injury.
The Distal Radius (Colles)
- Healing: 6 weeks for bony union.
- Remodeling: Limited in adults. Malunion (shortening) leads to ulnar impaction syndrome.
- Management: Volar locking plate allows early motion.
The Ankle (Weber B)
- Mortise: 1mm shift = 42% decrease in contact area.
- Healing: 6 weeks NWB (Syndesmosis) or 2 weeks NWB then boot (stable).
- Risk: Post-traumatic arthritis if articular step greater than 2mm.
The Pelvis (Ring)
- Healing: Cancellous bone heals fast (6-8 weeks).
- Weight Bearing: Depends on posterior ring stability (Sacrum/SIJ).
- Complication: Venous Thromboembolism (highest risk in orthopaedics).
The Fifth Metatarsal (Jones Fracture)
- Zone 2: Metaphyseal-Diaphyseal junction.
- Physics: Adductor longus traction creates tension side failure.
- Healing: Poor blood supply. High non-union rate.
- Management: Screw fixation often required for athletes.
Australian Context
- Bone Stimulators (LIPUS): Not subsidized by PBS/Medicare generally, but available privately (approx $4000). Evidence is weak (TRUST Trial showed no benefit).
- BMPs: Indication specific (Open Tibia) via PBS Authority. Requires specialist approval.
- Smoking Cessation:
- Quitline (13 7848): Referral service for counseling.
- PBS Pharmacotherapy:
- Nicotine Replacement Therapy (NRT).
- Varenicline (Champix) - currently unavailable/restricted.
- Bupropion (Zyban).
- Pre-Operative: Elective osteotomies/fusions should be delayed until 6 weeks of cessation confirmed (COTININE urine test).
Exam Day Cheat Sheet
Healing Summary
High-Yield Exam Summary
Primary (Direct)
- •Absolute Stability
- •less than 2% Strain
- •Cutting Cones
- •No Callus
Secondary (Indirect)
- •Relative Stability
- •2-10% Strain
- •Callus (Enchondral)
- •IM Nail
PHASES
- •Inflammation 0-1wk
- •Soft callus 1-3wk
- •Hard callus 3-12wk
- •Remodeling months-years
Diamond Concept
- •Cells
- •Scaffold
- •Signals
- •Stability
Future Directions
The Next Frontier The future of fracture healing lies in targeted biological intervention.
- Personalized Medicine: Genetic profiling for non-union risk.
- Smart Implants: Sensors embedded in plates to measure strain and notify patients when to weight bear.
- Bio-printing: 3D printed vascularized bone grafts.