1 2009-Principles of Fracture Healing and Disorders of Bone Union

OrthOpaedics i: general principles

Principles of fracture healing and disorders of bone unionrajeev Jahagirdar

Brigitte e scammell

Abstractthis article describes the mechanisms of fracture healing (direct and

indirect), general fracture management, the influence of the surgeon

on the biology and biomechanical environment of bone healing, and

disorders of bone union.

Keywords delayed union; fracture callus; fracture healing; non-union

A fracture is defined as the structural failure of bone. Several fac-tors, such as the load, rate of loading, direction of load and bone properties, affect how a bone fractures.

Extrinsic factors: bone fails under applied compression, ten-sion, rotation, shear or a combination of these forces. Depending on the mechanical characteristics of the bone, loads applied in a specific direction and rate will produce predictable patterns of failure. For example, a bone that fractures as it is pulled apart in tension will have a transverse fracture pattern, whereas one sub-jected to a twisting force will result in a spiral fracture pattern.

Intrinsic factors: these are factors related to the biomechani-cal characteristics and shape of the bone. Bone is a composite tissue made up of inorganic mineral and cells surrounded by a large volume of extracellular matrix, which is mainly type I col-lagen. Bones consist of an outer cortical layer, where the osteons are organized into compact Haversian systems and the bone is strong but brittle, and inner cancellous bone, where the Haver-sian systems are much less compact and are separated by large areas of marrow or fat. The relative amounts of cortical and can-cellous bone can determine how bones fracture; for example the calcaneum, which is mainly cancellous bone with very little cor-tex, often sustains a crush or compression fracture.

Bone is anisotropic, which means that it has different mechan-ical properties when loaded in different axes. Bone absorbs more energy before failure if a compressive load is applied along its longitudinal axis compared to the same load applied in the trans-verse axis. Bone is also viscoelastic, which is a time-dependent property and means that the rate of loading affects the amount of

Rajeev Jahagirdar MBBS MRCS is a Registrar in Orthopaedics at New

Cross Hospital, Wolverhampton, UK. Conflicts of interest: none

declared.

Brigitte E Scammell DM FRCS(Orth) is a Reader and Honorary Orthopaedic

Consultant at Nottingham University Hospitals, Nottingham, UK.

Conflicts of interest: none declared.

sUrgerY 27:2 63

energy the bone can absorb. With higher loading speeds, as in a road traffic accident, more energy is absorbed, resulting in greater damage to the bone and surrounding soft tissues (Figure 1).

Healing of a fracture depends on the blood supply to the bone, the amount of force producing the fracture and the condition of the soft tissues.

Fracture classification

Fractures can be classified based on: • cause (traumatic, stress, pathological) • fracture pattern (transverse, spiral, compression, oblique)

a

b

Figure 1 a at a low rate of loading, little energy is dissipated to the

surrounding soft tissues. b at a high loading rate much surrounding

soft tissue damage occurs.

© 2008 published by elsevier ltd.


• displacement (displaced or undisplaced) • which section of the bone is fractured (intra-articular, meta-

physis, diaphysis) • whether the skin is intact (closed fracture) or damaged (open

fracture).

Open vs closedA closed fracture is one where the overlying skin is intact. An open fracture is one in which a break in the skin and underlying soft tissues leads directly to, or communicates with, the fracture and its haematoma.

A fracture with a skin wound in the same limb segment must be considered to be open until proven otherwise. Special chal-lenges faced in open fractures result from: • bacterial contamination • crushing/stripping and devascularization of surrounding soft

tissues leading to increased susceptibility to infection • difficulty with immobilization • loss of function due to damage to muscles, tendons, nerves

and vessels.

Fracture healing

Bone differs from other tissues owing to its remarkable ability to repair itself and heal without leaving a scar. The processes involved depend on the biomechanical stability of the fracture

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and this is directly influenced by what method of fixation the surgeon chooses.

Direct bony union or primary fracture healing occurs when there is absolute stability (no motion between fracture surfaces under functional load), as found with anatomical reduction and rigid internal fixation.

If left alone, a broken bone will heal by callus formation. Callus is nature’s response of living bone to interfragmentary movement where there is relative stability (some controlled motion between the fracture fragments under functional load). When a bone is shown to have healed by visible callus formation on radiography, it is said to have united by secondary or indirect bone healing.

Secondary or indirect bone healingFracture healing may be considered as a series of phases that overlap and occur sequentially (Figure 2).

Initial haematoma: bone has an excellent blood supply. The medullary cavity and inner two-thirds of the cortex are supplied centrifugally by nutrient arteries within the bone, whereas the outer third of the cortex is supplied by the periosteal arteries. Bleeding from the bone and surrounding soft tissues results in a fracture haematoma.

There is disruption of the Haversian systems and necrosis of osteocytes at the fracture surfaces. The extent of bone cell death depends on:

Secondary fracture healing: bridging of a fracture by external callus

Haematoma forms at the fracture site and the periosteum is torn. The bone ends die and are resorbed by osteoclasts

Granulation tissue replaces the haematoma and woven bone or hard callus starts to form the abutments of the bridge from the cambium layer of the periosteum by intramembranous ossification

The fracture gap is bridged by soft callus or cartilage. This is replaced with bone by the process of endochondral ossification. The gap is also bridged by hard external callus arching over the soft cartilaginous callus as shown in the lower half of the diagram. Internal or medullary callus forms more slowly and finally cortical continuity is restored

a Haematoma

Haematoma

Dead bone atfracture site

Granulation tissue

Cartilage/soft callus

New woven bone/external hard callus

Fracture sitePeriosteum

Medullary canal Cortex

b Inflammation

c Repair

Figure 2

4 © 2008 published by elsevier ltd.


• the degree of fracture comminution and displacement, and thus disruption of the local blood supply

• the amount of periosteal stripping, which affects the cortical blood supply and removes the cambial layer of periosteal stem cells from the surface of the bone.In general, the greater the bone and surrounding soft tissue

damage, the slower the bone is to heal.Within the haematoma, histamine is released from mast cells,

and platelets and other blood cells release cytokines. These result in increased capillary permeability, chemotaxis and small vessel dilatation. Along with these changes a clot of insoluble fibrin is formed at the fracture site.

Stage of inflammation: the clot provides a framework of fibrin fibres for the influx of various migrating cells (e.g. neutrophils, lym-phocytes, monocytes, macrophages, mast cells, platelets). These release various cytokines, including transforming growth factor-β, platelet-derived growth factor, fibroblast growth factor, and inter-leukin-1 and -6. Endothelial cells undergo mitosis to form capillar-ies and, together with fibroblasts, granulation tissue is formed.

Granulation tissue is able to form under conditions of high strain, such as are found initially when the fracture surfaces are very mobile. (Strain is the change in length of a given material when a given force is applied.) Osteoblasts are able to tolerate only very low strain (<1%), whereas immediately after a frac-ture the area between the bone fragments has a strain of more than 100%, so bone cannot form. Initial healing is thus via gran-ulation tissue, which tolerates very high strains.

Osteoclasts start to resorb the dead bone ends and phagocytes remove other necrotic tissue. This phase lasts about a week.

Stage of repair: as the granulation tissue matures, it reduces strain at the fracture site as it forms in between the bone ends. Cartilage forms when the strain is below 10% and then bone formation eventually replaces the cartilaginous phase when the strain is less than 1%. Callus formation requires angiogenesis and an intact periosteum. The term ‘hard callus’ refers to new woven bone that is mineralized and therefore visible on radiographs. ‘Soft callus’ refers to the cartilaginous phase that occurs at the fracture gap which then differentiates into hard callus. The process whereby soft callus is replaced by hard callus is called endochondral ossi-fication. The chondrocytes become hypertrophic, calcify and die, allowing angiogenesis to occur, and osteoblasts lay down woven bone on the collagen framework left by the chondrocytes.

External callus forms on the outside of the fractured bone to bridge the gap. Internal callus forms more slowly from the med-ullary canal and, finally, cortical continuity is restored. Exter-nal callus initially forms by intramedullary ossification from the periosteum. If the periosteum is intact, a bridge of callus readily forms from the cambium (inner) layer, arching over the dead bone. If, however, the periosteum is ruptured, cuffs of callus grow outwards from the living bone, eventually joining together like the abutments to a bridge. Between the abutments of hard callus, soft callus forms, which is seen as a gap on radiographs and only becomes visible when it is replaced by endochondral ossification into mineralized woven bone.

Cyclical micro-movements stimulate the growth of cartilage and then bone. The optimal size of these movements is about 1 mm. As the callus grows in size, it becomes stiffer, thus facilitating

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osteogenesis. Bone union by callus formation is the predominant form of healing when simple fractures are treated by traction, sling or plaster-cast immobilization, or external fixation or intramedul-lary nailing. The stage of repair lasts several weeks (Figure 3).

Stage of remodelling: once the fracture has been satisfactorily bridged by callus the newly formed bone is remodelled. Any excess callus is removed and the woven ‘osteoid’ bone is remodelled into lamellar bone. The medullary canal and bone shape are restored. Bone is laid down in areas of excess stress and removed from areas where there is too little (‘Wolff’s law’). Remodelling, which is really just an extension of normal bone turnover, can continue long after the fracture has healed clinically (up to 7 years).

In children remodelling is usually very effective at restor-ing shape; even completely displaced fractures may heal and remodel without trace. The younger the child, the greater is the propensity for remodelling, and the physis of a bent bone grows eccentrically to help restore alignment and growth in bone length and width to conceal deformity. There is some ability to correct angulation but this decreases in adolescents, and axial malrota-tion must never be accepted as it will not remodel.

In adults there is very little correction of angulation or axial rotation so both must be corrected before the bone unites, or malunion will occur.

Primary or direct bone healingPrimary bone repair or direct healing is the term given to fracture repair when the fracture ends have been rigidly immobilized and there is absolute stability under functional load. Healing of the fracture occurs without radiographic evidence of callus. Under these conditions strain is very low and bone can form directly. With a fracture gap between the bone ends of less than 200 μm and absolute stability, osteoclasts can tunnel across the fracture line, and establish a ‘cutting cone’ across the fracture (Figure 4). Osteoblasts follow, and lay down bone matrix and re-establish continuity between the Haversian systems. Vessel ingrowth is absent and the bone filling the interfragmentary gap appears with-out the intermediate formation of cartilage or connective tissue.

Figure 3 radiographs of a mid-shaft femoral fracture treated with a

locked intramedullary nail, showing union progressing by indirect

healing with external callus (from left to right). the third image shows

both ‘hard’ external callus which is mineralized and therefore easily

visible, with central ‘soft’ callus that is cartilaginous.



Fracture healing with the formation of new cortical bone between the bone ends occurs slowly, and is essentially the same biological process as occurs in normal bone turnover and late remodelling.

Healing with different methods of stabilization

The pattern of bone healing can be modified by the mechanical environment of the fracture and this can in turn be manipulated by surgical intervention. The purpose of fracture stabilization is to maximize the biology of fracture healing to aid early union and restore function while minimizing complications. Generally, the amount of callous formed is inversely proportional to the sta-bility of the fracture. Extremely unstable fractures will, however, not unite as the strain remains high, ossification fails and only fibrous union occurs.

Relative stability techniquesExamples of relative stability techniques are shown in Figures 3 and 5.

Plaster casts prevent angulation and malrotation but provide only relative stability. Secondary fracture healing takes place with callus visible on radiographs. However, only transverse fractures have axial stability in a cast, and oblique fractures may displace and shorten.

Traction is considered old-fashioned, but is an effective and safe way of maintaining reduction in some clinical situations. Here again healing is by abundant callus formation.

Intramedullary nails prevent angulation and provide axial sta-bility. They also provide rotational stability if locking screws are

Primary bone healing

This schematic diagram shows a cutting cone tunnelling the bone from left to right. The cutter head is at the right with multinucleated osteoclasts to resorb the dead bone. The tail, with its conical surface, is lined with osteoblasts (as seen on the left) laying down new bone. This is a slow process which is also seen in normal turnover of bone. Direct bone healing occurs without an intermediary cartilaginous phase

Closing cone with osteoblasts laying down new bone

Fracture line

Cutting conewith osteoclastsresorbing bone

Figure 4

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used. There is always some movement at the fracture site so external bridging callus is seen on the radiograph.

Unilateral external fixation is particularly useful if there is an overlying soft tissue injury. All external fixators allow movement at the fracture site, so promote healing with callus formation.

radiographs of fixation techniques with relative stability.

a comminuted intra-articular fracture of the distal radius with an

associated fracture of the ulna styloid stabilized by external fixation.

b Fracture of the distal third of the shaft of the femur stabilized

with a bridging plate. Both of these techniques will result in indirect

healing of the fracture with external callus formation.

Figure 5

© 2008 published by elsevier ltd.


Circular frames provide stability in three planes and allow axial micro-movement to encourage callus formation. They are useful if the fracture is very close to a joint and associated soft tissue injuries preclude safe internal fixation.

Internal fixation with relative stability permits some controlled movement at the fracture site and encourages callus formation. Examples are: • a buttress plate resists axial load by applying a force at 90° to

the potential deformity • a plate on the tensile surface of the bone resists tensile force

and dynamically compresses the far cortex • a bridging plate secures the two main fragments, leaving the

fracture zone undisturbed (so called ‘biological plating’).

Absolute stabilityInternal fixation with absolute stability: an anatomical reduc-tion allows maximal friction at the fracture site. If this is com-bined with interfragmentary compression to prevent motion, absolute stability is achieved. Absolute stability is when there is no motion between the fracture surfaces under functional load; there is very low strain across the fracture and primary bone healing occurs without formation of external callus. This is a slow process that relies on internal remodelling of the bone. Interfragmentary compression can be achieved with a lag screw across the fracture or a dynamic compression plate that causes compression as the screws are tightened (Figure 6). Simple frac-tures, osteotomies and non-unions are best treated using a tech-nique of absolute stability.

Anatomical reduction is required in two special situations: • the forearm: when the radius and ulna are fractured and dis-

placed pronation and supination will be reduced unless an-atomical reduction is achieved; the bones are held reduced with a lag screw and plate

• displaced intra-articular fractures to reconstruct the joint surface.

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There are different fixation methods for treating the same frac-ture, but an understanding of the type of healing one wishes to achieve avoids adverse outcomes. An example of poor treat-ment is rigid internal fixation of a diaphyseal fracture with dam-age to surrounding soft tissues, and periosteal stripping without achieving compression and leaving fracture ends separated. This prevents primary bone healing because of a gap at the fracture site and inhibits external bridging callus because of the absolute stability, resulting in non-union and possible implant failure.

Management

This includes initial assessment of the patient, then the injured limb, followed by definitive fracture treatment.

Initial assessment and managementThe Advanced Trauma Life Support™ protocol of airway, breath-ing and circulation must be applied to all patients. The history should determine the situation, direction and magnitude of the force. Antibiotics must be given as soon as an open fracture is suspected, and the wound covered with a sterile dressing until for-mal exploration and debridement can take place in the operating theatre. Antibiotics must cover Gram-positive and Gram-negative organisms and anaerobes, depending on the local hospital proto-col. Examples include intravenous cephalosporin or flucloxacillin, plus an aminoglycoside. High-dose penicillin is added where clos-tridial infection (e.g. farmyard injuries) is a possibility. The status of tetanus vaccination must be considered for open fractures.

Clinical examination must include assessment of the distal neurovascular status of the limb. Radiological assessment should include the whole of the fractured bone and the joint above and below the fracture.

The principles of debridement include wound extension to determine the extent of the injury, removal of all devitalized tissues including bone, followed by irrigation of the wound with at least 6 litres of warmed Hartmann’s solution to reduce the

Figure 6 radiographs of a galeazzi fracture.

absolute stability is provided by the lag screw

across the fracture protected by a plate. the

fracture united without external callus.



bacterial load. Patients with highly contaminated wounds and severely damaged soft tissues should return to theatre every 48 hours until the wound is clean and only healthy tissues remain. If possible, a plastic surgeon should be present at the initial debridement as exposed bone must be covered as soon as possible (usually within 5 days).

The state of the soft tissue surrounding the fracture dictates management, even in closed fractures. One must not operate through bruised and highly swollen tissues where the wound may be impossible to close or break down later.

Definitive fracture treatmentThis involves reduction, stabilization and rehabilitation. Reduc-tion can be achieved by closed methods (traction and manipula-tion) or open reduction (surgical). Stabilization can be achieved by conservative techniques (plaster cast) in stable fractures, and by surgery using either internal or external fixation in unstable or potentially unstable fractures.

Factors affecting fracture healing

GeneralAge: children’s bones unite more rapidly; the speed decreases as skeletal maturity approaches. Children’s bones also have great capacity for remodelling (except for axial rotation).

Nutrition and drug therapy: poor nutrition and general health reduce rates of healing. Smoking, and use of corticosteroids and non-steroidal anti-inflammatory drugs impair the inflammatory response and delay bone healing.

Bone pathology: pre-existing bone disease such as malignancy inhibits bone healing and screws in osteoporotic bone often fail.

Type of bone: cancellous bone tends to heal faster than corti-cal bone. This is due to a large area of bony contact (e.g. in the metaphysis) and the greater number of active bone cells present.

LocalMobility at fracture site: excess mobility at the fracture site will interfere with vascularization of the fracture haematoma, cause high strain and disrupt the bridging callus, thus interfering with union.

Separation of the bone ends: bony union may be delayed or pre-vented if the bone ends are separated by interposed soft tissue, or held apart with the fixation device or traction.

Disturbance of blood supply: a fundamental factor affecting healing is the blood flow to the bone. Fractures compromising blood flow to the fracture site or one of the fragments at the fracture are slow to unite if they unite at all. Examples include intracapsular fractures of the neck of femur and scaphoid fractures where the blood supply to the bone is via an end artery.

High-energy injuries resulting in comminution, loss of soft tissue attachments and periosteal stripping heal slowly. In these injuries the soft tissues dictate the definitive fracture

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management and the biology of the compromised fracture site must be respected when considering surgical intervention.

Property of bone involved: there is a variation in the speed at which bones heal in the same individual. Fractures of the upper limb generally heal more quickly than fractures in the lower limb. Clavicle fractures heal remarkably well; on the other hand, tibial shaft fractures heal slowly.

Type of fracture: displaced and comminuted fractures frequently result in delayed healing. The avascular fragments of splintered bone require resorption, a more extensive inflammatory and cal-lus phase, and more time to remodel. Transverse fractures take longer to heal than spiral fractures because they usually have more displacement of the periosteum and a smaller surface area of contact.

Infection in a fracture will delay or prevent healing. This is a common cause of delayed or non-union. There is a prolonged inflammatory phase and cellular activity is directed towards fighting the infection rather than bone healing. A further prob-lem is, in the presence of metalwork, that bacteria readily pro-duce biofilms which render normal antibiotic dosage regimens useless, as toxic concentrations of antimicrobials are required to inhibit bacterial growth.

Biomechanical environment: there is an optimal balance between stability and micro-motion to encourage callus forma-tion. Small, cyclical movement of about 1 mm increase the rate of healing by 25% and are a feature of many external fixation devices.

Electromagnetic environment: direct current helps stimulate an inflammatory-type response and pulsed electromagnetic fields initiate calcification of fibrocartilage. Their therapeutic use is controversial.

Ultrasound: low-intensity pulsed ultrasound accelerates fracture healing, and improves mechanical strength by increasing the stiffness and torque of fracture callus. Its use is controversial.

High-dose irradiation is associated with a decrease in cellularity, long-term changes within the Haversian system and an increased risk of non-union.

Disorders of bone union

Some fractures are slow to unite despite optimal treatment.

Delayed unionHealing fails to occur within the expected time for the fracture. The fracture proceeds through the normal stages of healing clinically and radiologically but at a slower rate. This can be due to intrin-sic factors (tibial diaphyseal fractures are often slow to unite), a reduced blood supply or infection at the fracture site. Choosing a technique of absolute stability and leaving a fracture gap of more than 1 mm will also delay union as the rigid fixation will inhibit healing by callus formation and the gap will delay or even inhibit direct bone healing.



Non-unionThe healing process ceases to be active and this is usually thought to be the case if by 6 months there is no progression to union. Non-union occurs if there is wide separation of the bone ends, soft tissue interposition, and lack of blood supply, infection or an adverse biomechanical environment. There are two types of non-union.

Hypertrophic: inadequate stability of the fracture leads to hypertrophic non-union, with normally viable bone ends that

Figure 7 established atrophic non-union at 8 months after

intramedullary nailing. treated with a lag screw across the fracture

gap and blade plate fixation. the fracture united with minimal callus

4 months later.

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appear sclerotic and flared owing to excess callus formation; this gives a typical appearance on radiographs of an ‘elephant’s foot’. Here the biomechanical environment is faulty, and the gap between bone ends is filled by cartilage and fibrous tissue. The blood supply at the bone ends is good and immobilizing the fracture (e.g. with an intramedullary nail) usually results in union.

Atrophic: in atrophic non-union, there is no attempt at healing, the bone ends are resorbed and rounded; the bone biology is faulty. The gap between the bone ends is filled by fibrous tis-sue (Figure 7). Rigid fixation with interfragmentary compression and elimination of the fracture gap is required, and supplemen-tary bone grafting may be required. Recombinant human bone morphogenetic proteins are now commercially available and are licensed for use in difficult non-union surgery. ◆

FuRtHeR ReADING

Mcrae r, esser M, eds. practical fracture management, 4th edn.

edinburgh: churchill livingstone, 2002.

rüedi tp, Buckley re, Moran cg, eds. practical fracture management,

2nd edn. new York: thieme, 2007.

standing s, ed. gray’s anatomy, the anatomical basis of clinical

practice, 40th edn. edinburgh: churchill livingstone, 2008.

Wraighte pJ, scammell Be. principles of fracture healing. The

Foundation Years 2007; 3(6): 243–51.

Acknowledgements

thanks to professor christopher Moran and Mr nitin Badhe for

their assistance with the images used in this article.


1 2009-Principles of Fracture Healing and Disorders of Bone Union

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