Bone Structure and Healing: Cortical vs Cancellous, Fracture Healing, Callus, and Influencing Factors

Definition / Overview

Bone is a specialised connective tissue that provides structural support, mineral homeostasis (primarily calcium and phosphate), and haematopoietic function. Unlike most connective tissues, bone has a remarkable capacity for true regenerative repair, restoring original architecture rather than producing scar tissue. Understanding bone structure and the biology of fracture healing underpins safe perioperative fracture management and the selection of fixation strategies.

Bone Structure

Cortical (Compact) Bone

• Forms the outer shell of all bones and the diaphysis of long bones
• Accounts for approximately 80% of total skeletal mass
• Organised into osteons (Haversian systems): concentric lamellae of mineralised matrix surrounding a central Haversian canal containing neurovascular structures
• Haversian canals communicate transversely via Volkmann's canals
• Osteocytes occupy lacunae within the lamellae and communicate via canalicular networks, sensing mechanical strain
• High density, low porosity (~5-10%), confers rigidity and resistance to torsional and bending loads
• Periosteum (outer) and endosteum (inner) contain osteoprogenitor cells critical to healing

Cancellous (Trabecular) Bone

• Found at epiphyses, metaphyses, vertebral bodies, and flat bones
• Accounts for approximately 20% of skeletal mass but ~80% of bone surface area
• Arranged as an interconnected lattice of trabeculae oriented along lines of mechanical stress (Wolff's law)
• High porosity (~50-90%), high surface-area-to-volume ratio, metabolically much more active than cortical bone
• Richly vascularised marrow spaces allow rapid cellular response to injury
• Heals faster than cortical bone because of greater vascularity and osteoprogenitor cell density

Cellular Composition

Fracture Healing: Mechanisms and Stages

Two fundamentally different healing processes exist depending on the mechanical environment at the fracture site.

Secondary (Indirect) Bone Healing, Healing with Callus

This is the predominant biological pathway and occurs whenever some movement (strain) persists at the fracture site, i.e. under relative stability. It mirrors endochondral ossification and proceeds through overlapping stages.

Stage 1, Haematoma and Inflammation (Days 0-3)

• Fracture disrupts intraosseous and periosteal vessels → haematoma fills the fracture gap
• Platelet degranulation releases PDGF, TGF-β, FGF, initiating the inflammatory cascade
• Neutrophils then macrophages debride necrotic tissue and dead bone
• Fibrin scaffold forms the structural template for cellular ingrowth
• Clinical correlate: local swelling, warmth, pain, normal and necessary

Stage 2, Soft Callus (Days 3 to ~2-3 Weeks)

• Mesenchymal stem cells from periosteum, endosteum, and surrounding soft tissue proliferate and migrate into the fracture gap
• In the mechanically active (higher-strain) regions, these cells differentiate into chondrocytes, producing fibrocartilage and hyaline cartilage, a compliant bridging tissue that resists the residual movement
• In lower-strain regions closer to intact bone, cells differentiate directly into osteoblasts producing woven bone trabeculae perpendicular to the cortical axis (subperiosteal new bone)
• The soft callus acts as an internal biological splint, stabilising the fracture and protecting the reparative vasculature
• Maximal callus girth is typically reached at the end of the second to third week

Stage 3, Hard (Bony) Callus (Weeks 2-3 to ~3 Months)

• Endochondral ossification converts the cartilaginous template to woven bone, avascular cartilage is invaded by capillaries and osteoblasts deposit mineralised matrix
• Fracture ends are progressively bridged; stiffness and load-bearing capacity increase
• Radiographically visible callus, fracture line becomes less distinct
• Local strain at the fracture site falls progressively: once strain drops below approximately 2%, mineralised bone can form

Stage 4, Remodelling (Months to Years)

• Coupled osteoclast-osteoblast activity (basic multicellular units, BMUs) replaces woven bone with organised lamellar bone
• Callus bulk is progressively resorbed; medullary cavity is re-established
• Bone architecture adapts to mechanical load (Wolff's law): trabeculae form along stress lines, excess bone is removed
• In children and adolescents, angular deformity can remodel substantially with growth; this capacity is greatly diminished in adults

Primary (Direct) Bone Healing, Healing without Callus

• Occurs only when absolute stability is achieved (strain < 2% from outset), typically through rigid internal fixation with direct interfragmentary compression (e.g. lag screw + plate)
• Two sub-types:
  • Contact healing: where cortical surfaces are in direct apposition, osteons bridge the fracture directly by cutting cones of osteoclasts followed immediately by osteoblasts
  • Gap healing: small gaps (< 1 mm) first fill with woven bone (lamellar organisation follows later)
• No visible callus on imaging, fracture line gradually disappears
• Clinically important: absence of callus on X-ray after rigid fixation does not indicate non-union

Zones of the Fracture and Healing Environment

The spatial relationship between mechanical strain and tissue type at different zones of the fracture determines what tissue forms:

Fracture Healing: Growth Factors and Molecular Mediators

Factors Influencing Fracture Healing

Factors Promoting Healing

• Youth / skeletal immaturity: abundant osteoprogenitor cells, greater periosteal vascularity, higher growth factor expression; children achieve union rapidly and remodel substantially
• Adequate immobilisation / appropriate stability: allows progressive stiffening; reduces pathological strain
• Good soft tissue envelope: preserved periosteum and muscle provide vascularity and progenitor cells
• Physiological loading: compressive stress across healing bone stimulates osteoblast activity (Wolff's law); rationale for early weight bearing in certain fractures
• Adequate nutrition: particularly protein, calcium, phosphate, and vitamins C and D

Factors Impairing Healing

Patient-Related

Fracture-Related

• Degree of comminution: more fragments = greater soft tissue stripping and devascularisation
• High-energy injury: extensive periosteal and muscle damage; reduced osteoprogenitor supply
• Open fracture: contamination risk; periosteal stripping
• Intra-articular location: synovial fluid bathing the fracture inhibits callus; predisposes to non-union (e.g. scaphoid waist, femoral neck)
• Infection: biofilm and bacterial proteases destroy repair tissue; osteoclast activation
• Pathological bone: tumour, metabolic disease, Paget's disease disrupt normal healing scaffolding

Treatment-Related

• Excessive instability: persistent high strain prevents mineralisation; fibrous non-union
• Excessive rigidity without compression: gap healing may fail if gap too large
• NSAIDs: inhibit COX-mediated prostaglandin synthesis, which is required for early inflammatory phase; animal data suggest prolonged use impairs healing, clinical evidence is less definitive but caution is warranted perioperatively
• Corticosteroids: suppress inflammation; inhibit osteoblast differentiation; impair angiogenesis
• Bisphosphonates: inhibit osteoclast resorption, theoretical concern for remodelling; associated with atypical subtrochanteric fractures with chronic use

Complications of Fracture Healing

Delayed Union

• Healing slower than expected for the fracture type and site
• Not an absolute failure, may still proceed to union with continued management or adjunctive intervention (e.g. bone stimulators, bone grafting)

Non-Union

• Failure of healing, typically diagnosed after 6 months without radiographic progression
• Clinically: persistent pain on loading, mobility at fracture site
• Types:
  • Hypertrophic: adequate biology, insufficient stability → "elephant foot" callus; treat by improving fixation
  • Atrophic: inadequate biology (poor vascularity, infection, bone loss) → no callus; requires biological augmentation (bone graft, BMP) plus stable fixation
  • Oligotrophic: intermediate, some callus, malaligned or distracted; address alignment and fixation

Malunion

• Healing in an unacceptable position (angulation, rotation, shortening)
• May require corrective osteotomy if functionally or cosmetically significant

Avascular Necrosis (AVN)

• Disruption of blood supply to a bone segment → necrosis
• The overlying articular cartilage remains viable initially (nourished by synovial fluid) but subchondral collapse follows
• High-risk anatomical sites: femoral head (posterior retinacular vessels), scaphoid (distal-to-proximal blood supply), talus, humeral head
• Microscopy: empty osteocyte lacunae, necrotic adipocytes, calcium soap formation

Infection / Osteomyelitis

• Haematogenous or direct inoculation (open fractures, surgical contamination)
• Creates avascular sequestra, foci of dead bone that maintain infection
• Management: debridement (including dead bone), stable fixation, prolonged culture-directed antibiotics, healthy soft tissue cover

Perioperative and Surgical Considerations

Stability Principle and Implant Selection

• Relative stability (some fracture motion under load) → healing by callus; appropriate for diaphyseal fractures (e.g. intramedullary nail, cast)
• Absolute stability (no motion, direct compression) → primary bone healing; required for articular fractures to restore congruent joint surface

Bone Grafting

• Gold standard: autogenous cancellous graft (iliac crest), all three properties
• Recombinant BMP-2 and BMP-7 are licensed adjuncts for specific indications (open tibial fractures, spinal fusion)

Scaphoid Fractures, Surgical Relevance

• Retrograde blood supply means proximal pole fractures have high AVN and non-union risk
• Clinical snuffbox tenderness warrants splinting even with normal initial X-ray
• CT or MRI confirms occult fracture; early fixation is favoured for displaced or proximal pole fractures

Monitoring Healing

• Radiographic: callus bridging ≥3 cortices on orthogonal views; loss of fracture line
• Clinical: painless on loading; no tenderness at fracture site
• CT scan: gold standard for confirming union in complex or non-union cases

High-Yield Summary Table

Viva pearl: The key determinant of whether a fracture heals by callus or primary bone healing is the local mechanical strain environment, not the fracture type alone. Callus forms when strain exceeds ~2%; primary bone healing occurs only when strain is below ~2% from outset, achievable only with anatomical reduction and rigid compression fixation. The absence of callus after plating is expected and does not indicate pathology.

Sources

• RACS position statements & curriculum (Royal Australasian College of Surgeons)
• ATLS (Advanced Trauma Life Support)