Healing of Fractures

Slide 1 · Healing of Fractures

Hematoma → callus → woven bone → remodeling

Pathology of skeletal repair

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Explain the orderly transitions from hematoma to soft callus, bony callus, and lamellar bone.

Identify the contributions of vessels, osteoprogenitors, osteoblasts, osteoclasts, and chondrocytes.

Relate the mechanical environment to callus maturation and remodeling.

Predict how displacement, instability, infection, neoplasia, and comorbidities disrupt union.

Slide 3 · The repair sequence

Vascular injury

Organizing hematoma

Soft callus

Bony callus

Remodeling

Repair begins with a fibrin-rich provisional scaffold.

Callus bridges the fracture before it can provide full rigidity.

Woven bone is ultimately reshaped into lamellar bone.

Slide 4 · Bone can restore its original architecture

Fracture repair is a regenerative sequence with production and removal of bone matrix.

Adequate immobilization supports progression from a weak bridge to weight-bearing strength.

In uncomplicated simple fractures without major comorbidity, near-perfect union is usual.

Restoration of the medullary cavity marks completion of the process.

Slide 5 · Repair occurs across cortex and marrow

Simplified long-bone cross-section at a fracture site

Schematic

Peripheral cortex surrounds the central medullary compartment.

The periosteal and medullary regions both contribute repair cells.

Slide 6 · Core cellular functions in skeletal repair

Osteoblast

Produce osteoid matrix

Promote matrix mineralization

Osteoclast

Resorb bone matrix

Remove excess callus

Chondrocyte

Produce cartilage

Enable endochondral bone formation

Cells are coordinated—not interchangeable—during repair.

Slide 7 · Woven bone and lamellar bone

Woven bone

Lamellar bone

Deposited rapidly during fracture repair

Haphazard collagen arrangement

Lower structural integrity

Ordered, parallel collagen fibers

Forms during maturation/remodeling

Restores organized mechanical architecture

The conversion from woven to lamellar bone is a defining maturation step.

Slide 8 · Fracture descriptors affect the healing context

Descriptor

Definition

Healing relevance

Simple

Overlying skin intact

Favorable if aligned and immobilized

Compound (open)

Communicates with skin

Greater concern for infection

Displaced

Ends are misaligned

May heal with deformity

Comminuted

Multiple bone fragments

Often complicates restoration

Pathologic

Bone weakened by disease

Abnormal substrate may inhibit healing

Slide 9 · Displacement means loss of fragment alignment

A fracture with misaligned ends changes the geometry of the repair bridge.

Schematic

Displaced fractures frequently leave residual deformity.

Fracture alignment and callus maturation are related but distinct issues.

Slide 10 · Comminution increases the geometric challenge

Comminuted fractures comprise multiple fragments rather than a single break.

The eventual repair must consolidate fragmented segments into one load-bearing structure.

Displaced and comminuted fractures as frequent causes of residual deformity.

Slide 11 · Closed and open fractures

Simple (closed)

Compound (open)

Skin remains intact

No fracture–skin communication by definition

Usual healing requires adequate stability

Fracture communicates with the skin

Fracture-site infection is a major complication

Infection is a serious obstacle to union

Slide 12 · Stress and greenstick fractures: Different patterns

A stress fracture develops gradually after repetitive loading associated with increased activity.

A greenstick fracture extends only partway through bone.

Greenstick fractures are frequent in young children because their bones are relatively soft.

These descriptors concern fracture configuration—not a separate molecular repair program.

Slide 13 · A pathologic fracture begins in diseased bone

The fracture occurs in bone weakened by an underlying disorder, including neoplasm.

Primary and metastatic bone tumors can inhibit otherwise normal repair.

Defining the bone substrate matters in addition to recognizing the fracture line.

Slide 14 · Fracture classification is multidimensional

Skin status

Fragment pattern

Alignment

Bone quality

Simple and compound describe skin communication.

Comminuted and greenstick describe the break pattern.

Displaced describes alignment; Pathologic describes diseased substrate.

Slide 15 · Immediate response: Vascular rupture

Injury tears local vessels and causes bleeding into and around the break.

Schematic

Blood accumulates within and around the fracture site.

A hematoma becomes the earliest visible repair environment.

Slide 16 · Blood becomes a provisional repair matrix

Vascular rupture

Blood accumulation

Clot formation

Fibrin scaffold

The clot helps seal the injury site.

Fibrin forms a substrate for incoming cells and neovessels.

The earliest repair matrix is not mineralized bone.

Slide 17 · Organizing hematoma is a cellular scaffold

Fibrin links the two sides of the injury while cells enter the clot.

Schematic

Fibrin supports cellular and capillary ingrowth.

The clot is progressively reorganized—not the final structural bridge.

Slide 18 · Three major ingrowth components

Inflammatory cells

Migrate into clot

Release activating signals

Fibroblasts

Grow into fibrin

Contribute to provisional tissue

New capillaries

Grow into injury

Support organizing repair tissue

Slide 19 · Inflammation drives reparative recruitment

Clot

Inflammatory influx

Local growth factors

Progenitor activation

Platelets degranulate while inflammatory cells migrate.

Mediators help recruit and activate bone-forming precursors.

Early inflammatory signals are part of normal healing.

Slide 20 · The source highlights three growth factors

PDGF

Platelet-derived growth factor

Released locally

TGF-β

Transforming growth factor β

Released locally

FGF

Fibroblast growth factor

Released locally

These factors contribute to osteoprogenitor activation in the healing milieu.

Slide 21 · Growth factors couple injury to cell activity

Platelet degranulation

PDGF · TGF-β · FGF

Osteoprogenitor activation

Bone cell activity

Signals from platelets and migrating inflammatory cells.

The downstream response includes osteoblastic and osteoclastic activity.

Slide 22 · Where osteoprogenitor cells originate

Periosteum

Outer bone envelope

Subperiosteal repair

Medullary cavity

Internal bone compartment

Internal repair matrix

Soft tissues

Adjacent mesenchymal cells

May adopt chondrocytic fate

Slide 23 · Periosteal and internal repair are coordinated

The repair response surrounds the fracture and extends within bone.

Schematic

Progenitor populations are not confined to a single surface.

The eventual callus can span periosteal and medullary spaces.

Slide 24 · Formation and resorption are simultaneous activities

Bone formation arm

Bone resorption arm

Osteoprogenitors are activated

Osteoblasts synthesize osteoid

Woven bone is deposited

Osteoclasts are activated

Bone matrix can be removed

Later remodeling eliminates excess tissue

Slide 25 · Early repair is a transition—not an isolated stage

Hematoma formation, inflammatory-cell influx, and fibrovascular ingrowth overlap.

Osteoprogenitor activation begins before the callus becomes mechanically strong.

The source describes a continuous sequence rather than mutually exclusive compartments.

Slide 26 · By the first week: Soft callus bridges the ends

Predominantly uncalcified procallus begins anchoring the fragments.

Schematic

The bridge increases local continuity across the injury.

The bridge is not yet sufficiently rigid for weight bearing.

Slide 27 · Soft callus is a provisional bridge

Soft callus is also called procallus.

It consists predominantly of uncalcified reparative tissue.

It joins fracture ends enough to provide some anchorage.

It lacks the structural rigidity needed to withstand substantial loading.

Anatomical bridging and mechanical competence do not emerge simultaneously.

Slide 28 · Anchorage is not equivalent to strength

What soft callus provides

What it does not yet provide

Continuity between bone ends

Some provisional anchorage

Substrate for further ossification

Mature lamellar architecture

Sufficient load-bearing rigidity

Restored medullary cavity

Slide 29 · A stable environment permits callus maturation

Fracture immobilization

Protected soft callus

Woven-bone deposition

Increasing rigidity

Movement within the callus disrupts normal maturation.

Inadequate immobilization may cause delayed union or nonunion.

Slide 30 · Around two weeks: Bony callus begins to form

Woven bone is deposited within the previous procallus.

Schematic

Osteoblast-derived bone begins mineralizing the repair bridge.

The healing tissue is becoming stronger, but not yet fully remodeled.

Slide 31 · Woven bone is the first bony framework

Conversion of procallus into bony callus at approximately two weeks.

Activated osteoprogenitors deposit new trabeculae of woven bone.

The relatively disordered woven architecture is suited to rapid deposition rather than final structural organization.

Slide 32 · Subperiosteal trabeculae bridge the fracture

Woven-bone trabeculae form within the periosteal repair zone.

Schematic

The described trabeculae are oriented perpendicular to the cortical axis.

External callus formation reinforces continuity around the cortical break.

Slide 33 · The medullary cavity also participates

Activated osteoprogenitors can deposit trabeculae in the medullary compartment.

New woven bone is not restricted to an external callus.

The medullary space is ultimately reconstituted during late remodeling.

Slide 34 · A second route uses cartilage as a precursor

Soft-tissue mesenchyme

Chondrocyte differentiation

Cartilage matrix

Endochondral ossification

Some activated mesenchymal cells differentiate into chondrocytes.

Fibrocartilage and hyaline cartilage may occur in the callus.

Cartilage is eventually replaced by new bone.

Slide 35 · Cartilage may coexist with early bone deposition

Simplified cartilaginous portion of the bridging callus.

Schematic

Chondrocytes produce fibrocartilage or hyaline cartilage.

This component can undergo endochondral ossification.

Slide 36 · Two pathways make the new bony bridge

Direct woven-bone deposition

Cartilage-mediated deposition

Activated osteoprogenitors form osteoblasts

Osteoblasts deposit woven trabeculae

Subperiosteal and medullary sites

Mesenchymal cells differentiate to chondrocytes

Fibrocartilage / hyaline cartilage forms

Endochondral ossification yields bone

Slide 37 · Endochondral ossification links cartilage to bone

Cartilaginous callus

Chondrocyte activity

Replacement by bone

Stronger bridge

The mechanism reprises a developmental pathway used by the skeleton.

The fracture source identifies cartilage as a temporary component in some cases.

Slide 38 · Early callus is compositionally heterogeneous

Fibrous tissue, cartilage, and woven bone may coexist.

Schematic

The reparative mass initially exceeds final structural requirements.

Maturation depends on mineralization and subsequent remodeling.

Slide 39 · Progressive mineralization increases strength

Mineral deposition makes the bony callus stiffer.

As stiffness and strength increase, the bridge becomes better able to transmit mechanical load.

Mineralization is necessary but is not itself the final remodeling step.

Woven-bone formation produces a functional bridge; Remodeling refines it.

Slide 40 · Compare the early and bony callus

Feature

Soft callus / procallus

Bony callus

Typical period

By end of first week

Around 2 weeks onward

Dominant matrix

Predominantly uncalcified

Deposited woven bone

Mechanical role

Anchorage without rigidity

Increasing stiffness and strength

Cell processes

Fibrovascular and progenitor activity

Osteoblastic deposition; Cartilage replacement

Slide 41 · Early callus is deliberately exuberant

The early repair mass contains excess fibrous tissue, cartilage, and woven bone.

The initial goal is to bridge the defect, not immediately recreate original contours.

Excess material can later be removed as loading clarifies mechanical requirements.

Slide 42 · Mechanical loading guides late remodeling

Callus experiences load

Less-stressed zones resorbed

Excess mass reduced

Functional architecture restored

Robbins specifies resorption of regions not subjected to physiological stress.

Mechanical input is a determinant of callus shape.

Slide 43 · Formation and removal reshape the callus

Early repair

Mature repair

Produce fibrous tissue, cartilage, and woven bone

Create a broad provisional bridge

Prioritize union across the fracture

Resorb mechanically unnecessary tissue

Replace irregular matrix with lamellar bone

Restore cortical outline and medullary space

Slide 44 · The mature callus regains a narrower profile

Excess callus is resorbed as the original bone contours return.

Schematic

Lamellar matrix progressively replaces woven bone.

The medullary cavity is restored as repair completes.

Slide 45 · Lamellar bone provides mature architecture

The disordered collagen arrangement of woven bone is replaced by parallel lamellar organization.

Maturation restores the shape and outline of the fractured bone.

The late process is architectural as well as cellular.

Slide 46 · Restoration of the medullary cavity completes repair

Early bony callus can occupy medullary regions of the injury.

Remodeling removes unneeded tissue and restores the central cavity.

The healed bone more closely approximates the prefracture cortex and marrow arrangement.

Slide 47 · Repair stages: Predominant process and consequence

Stage

Principal substrate / process

Functional implication

Immediate

Hematoma + fibrin scaffold

Sealed injury; Cell recruitment

First week

Soft callus / procallus

Anchorage, not load-bearing rigidity

Around 2 weeks

Woven-bone callus

Increasing stiffness as bone mineralizes

Late

Resorption and lamellar remodeling

Restored contour and medullary cavity

Slide 48 · What allows nearly complete union?

Simple fracture

Immobilization

Callus maturation

Bone remodeling

The absence of interfering comorbidities.

Near-perfect union is the expected outcome when conditions are favorable.

Slide 49 · Complications arise when a necessary step fails

Unstable callus cannot mature normally.

Malaligned fragments can be united but remain deformed.

Infection, neoplastic bone disease, and systemic comorbidity hinder the repair response.

Delayed union, nonunion, and pseudoarthrosis are distinct possible outcomes.

Slide 50 · Instability can progress to nonunion

Inadequate immobilization

Callus movement

Impaired maturation

Delayed union / nonunion

Persistent movement disrupts conversion of the provisional bridge.

The mechanical environment influences biological progression.

Slide 51 · Delayed union versus nonunion

Delayed union

Nonunion

Healing proceeds more slowly than expected

Insufficient immobilization as a possible cause

Progress may remain incomplete

The fractured ends fail to unite

A malformed callus may persist

Long-standing cases may form pseudoarthrosis

Slide 52 · Pseudoarthrosis: A false joint in persistent nonunion

Persistent nonunion may form a cavity with a synovial-like lining.

Schematic

Malformed callus can undergo cystic degeneration.

The luminal surface may acquire synovial-like cells.

This is a pathologic false joint, not a normal articular joint.

Slide 53 · The false-joint sequence

Persistent nonunion

Malformed callus

Cystic degeneration

Synovial-like lining

The final structure is called pseudoarthrosis.

It reflects failed fracture bridging and maturation.

Slide 54 · Displacement and comminution can leave deformity

Fragment alignment is central to the final shape of the repaired bone.

Displaced fractures present nonaligned ends.

Comminuted fractures contain fragmented bone.

Both categories frequently result in some deformity.

Slide 55 · Pathologic bone changes the repair substrate

Underlying bone disease

Weakened bone

Pathologic fracture

Healing may be inhibited

Primary or metastatic bone neoplasms are highlighted inhibitors.

Union problems may reflect both the break and the underlying lesion.

Slide 56 · Open fractures expose the repair site to infection

Skin communication

Contamination risk

Fracture-site infection

Healing impeded

Compound/open fractures are particularly associated with infection.

Infection is described as a serious obstacle to healing.

Slide 57 · Systemic modifiers of the repair response

Malnutrition

Insufficient nutritional support

Impedes effective healing

Diabetes

Comorbid metabolic disorder

Hinders fracture repair

Skeletal dysplasia

Abnormal skeletal substrate

May compromise repair

Robbins specifically includes osteoporosis as an example in this context.

Slide 58 · Osteoporosis affects fracture vulnerability and healing

The source lists osteoporosis among skeletal disorders that can hinder healing.

Abnormal bone substrate complicates the biological and mechanical context of repair.

Do not equate osteoporosis with a neoplastic pathologic fracture; The mechanisms differ.

Slide 59 · Barriers to union: A mechanism-based comparison

Barrier

Main disturbance

Potential consequence

Instability

Repetitive callus movement

Delayed union / nonunion

Malalignment

Fragment position abnormal

Residual deformity

Infection

Infected fracture site

Impaired healing

Bone neoplasm

Diseased osseous substrate

Inhibited normal repair

Systemic comorbidity

Malnutrition, diabetes, skeletal disease

Impaired healing capacity

Slide 60 · Applied case: Favorable repair

A simple, aligned fracture is adequately immobilized; There is no major accompanying illness.

What sequence should follow?

Organized hematoma → soft callus during the first week → woven-bone callus around two weeks → mineralization and remodeling toward lamellar bone.

Slide 61 · Applied case: Persistent movement

A fracture remains mobile within its callus, and bridging fails to mature normally.

What mechanism best explains delayed union?

Inadequate immobilization permits repeated callus movement, interfering with maturation. Persistent nonunion may eventually form a pseudoarthrosis.

Slide 62 · Applied case: Infected open fracture

An open fracture develops local infection during the repair period.

Why is union at risk?

Infection of the fracture site is a major impediment to repair and is particularly associated with compound fractures.

Slide 63 · Applied case: Fracture through tumor

A break occurs through bone involved by a primary or metastatic neoplasm.

What makes this more than an ordinary fracture?

The underlying neoplastic lesion weakens bone and may inhibit the normal repair response. The bone substrate must be considered alongside the fracture.

Slide 64 · Applied case: Weak callus at one week

A fractured bone has developed a soft, predominantly uncalcified bridge by the end of week one.

Can bridging be equated with safe weight bearing?

No. Soft callus provides some anchorage but lacks load-bearing rigidity. Woven bone deposition and mineralization increase stiffness later.

Slide 65 · Recognize structures by the process they indicate

Hematoma + fibrin

Vascular injury and scaffold

Early organization

Cartilage + woven bone

Temporary callus matrices

Active osseous repair

Lamellar architecture

Remodeled organized bone

Later maturation

Slide 66 · Integrating biology with mechanics

Scaffold

Cell recruitment

Matrix deposition

Load-guided remodeling

Cells and signals construct a provisional bridge.

Adequate immobilization permits maturation of that bridge.

Mechanical forces help select the final architecture.

Slide 67 · Essential clinicopathologic synthesis

Clot and fibrin initiate organization; They are not the final bone repair product.

Soft callus anchors before bony callus can bear load.

Woven bone and optional cartilage-mediated ossification build the bridge.

Lamellar remodeling restores contours and the medullary space.

Stability, alignment, infection, bone disease, and nutrition modify the outcome.

Slide 68 · Primary source and scope

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th edition (2026).

Chapter 26: Bones, Joints, and Soft Tissue Tumors — “Healing of Fractures,” pp. 1075–1076.

Relevant parent context: “Basic Structure and Function of Bone,” pp. 1064–1065; “Fractures,” p. 1075.

All fracture-stage and complication claims in this lecture are based on those supplied excerpts.