Fracture healing in a broken bone is quite a complex process that begins by hematoma formation, a collection of inflammatory agents which render the bone forming cells to form bone tissue to bridge the defect created by fracture.
How Does Fracture Healing Occur – An Overview
Bone is surrounded by a thin membranous layer of tissue called periosteum. Periosteum plays a vital role in fracture healing. The periosteum is the primary source of precursor cells which develop into chondroblasts( cartilage cells) and osteoblasts ( bone cells) that are essential to the healing of bone.
When a bone breaks, it bleeds from its torn ends due to injury to its vessels which supply the blood.
Injury to the vessels leads to the collection of the blood at the fracture site. The blood is collected at the fracture site. The collected blood is called fracture hematoma. [If a fracture is of open nature, then the blood comes out through the wound that communicates with fracture and hematoma is not formed. This is contemplated to be a major cause of poor bone fracture healing in open fractures.]
With a fracture, the periosteum may be completely torn or partially damaged depending upon the force of injury.
Due to loss of vascularity or blood supply adjacent portions of broken ends die. Inflammatory changes occur in the hematoma over next few hours. An inflammatory reaction by the body occurs whenever there is an insult to a part or structure. The basic purpose of the inflammation is to contain the damage and facilitate the healing and regeneration. Inflammation is responsible for redness, pain, warmth, and tenderness of the wounds and abscesses).
This inflammation brings in many cells that would help in regeneration of the broken bone.
As the time progresses, the fibroblasts ( A kind of cells which produce fibrous tissue in the body) get interspersed with small vessels and form a loose mesh-like structure uniting the broken ends of the bone and on which the future layers of bone tissue would be added.
This structure is called granulation tissue.
Over the next few days, the cells of the periosteum replicate and transform. The periosteal cells proximal to the fracture gap develop into chondroblasts and form hyaline cartilage. The periosteal cells distal to the fracture gap develop into osteoblasts and form woven bone a kind of bone which is structurally different from the lamellar bone found in the body.
These two new tissues grow until they unite with their counterparts from other pieces of the fracture. This process forms the fracture callus. The callus is the first sign of union visible in x-ray and generally appears around 2-3 weeks after fracture. Eventually, the fracture gap is bridged by the cartilage and woven bone, restoring some of its original strength.
A picture like this is produced.
From here on slowly and steadily bone is restructured by a process called remodeling.
Detailed Description of Fracture Healing
This whole process can be divided into three phases. These phases are
- Inflammatory phase
- Repair phase
- Remodeling phase
It must be understood that actual fracture healing is a continuous process and the events of different phases may overlap with respect to their occurrence.
That means events of the preceding phase may continue into next phase and events of subsequent phases may begin in an earlier phase
As a result of the fracture, the soft tissue envelope [periosteum and surrounding muscles] is also torn along with the break in the bone, leading to rupture of blood vessels crossing the fracture line. A hematoma is formed within the medullary canal, between the fracture ends, and beneath any elevated periosteum. Due to loss of blood supply, immediate ends of fracture fragments undergo necrosis
Necrotic material leads to an immediate and intense acute inflammatory response which leads to dilation of vessels and exudation of plasma.
This brings acute inflammatory cells – macrophages, neutrophils, and platelets which release several factors such as plasma-derived growth factor [PDGF], tumor necrosis factor –alpha, transforming growth factor-beta, IL-1,6, 10,12 etc. These factors are detected as early as 24 hours after injury.
Lack of TNF-Alpha has been found to be associated with delay of both ossification [e.g. in HIV infection]
NSAIDs are known to repress runx-2/osterix which is critical for the differentiation of osteoblastic cells.
The repair cells are of mesenchymal origin and are pluripotent cells [stem cells] probably of the common origin of bone, cartilage, and collagen.
The tissue formed eventually is determined by the microenvironment. High oxygen concentration and mechanical stability favor bone formation whereas low oxygen and instability lead to the formation of cartilage.
The repair cells produce the tissue known as callus, which is made up of fibrous tissue, cartilage, and young, immature bone. This quickly envelopes the bone ends and leads to a gradual increase in stability of the fracture fragments.
Primary callus forms within two weeks. If the bone ends are not touching, then bridging soft callus forms.
Enchondral ossification converts soft callus to hard callus, a type of woven bone. Medullary callus also supplements the bridging soft callus
Amount of callus is dependent on the extent of immobilization.
As this phase of repair takes place, the bone ends gradually become enveloped in a fusiform mass of callus as noted in the picture above. Immobilization of the fragments occurs due to callus and is considered as on of the clinical signs of union.
Remodeling about a fracture takes place for a prolonged period of time. In remodeling, osteoclasts resorb the woven bone trabeculae and new struts of bone are laid down that correspond to lines of force. Remodeling is thought to be modulated by electrical signals. When a bone is subjected to stress, electro-positivity occurs on the convex surface and electro-negativity on the concave, a current produced by a piezoelectric effect. Regions of electropositivity are thought to be associated with osteoclastic activity and regions of electronegativity with osteoblastic activity.
The cellular module that controls remodeling is the resorption unit, consisting of osteoclasts, which first resorb bone, followed by osteoblasts, which lay down new Haversian systems.
The requirement for Normal Fracture Healing
- The viability of fragments (i.e. intact blood supply)
- Mechanical rest – Immobilization by cast or fixation
- Absence of infection
Duration of Healing of Fracture in Different Bones
Depending on the fracture site, normal healing may take from 3-12 weeks.
- Phalanges: 3 weeks
- Metacarpals: 4-6 weeks
- Distal radius: 4-6 weeks
- Distal Humerus: 8-10 weeks
- Humerus: 6-8 weeks
- Femoral neck: 12 weeks
- Femoral shaft: 12 weeks
- Tibia: 10 weeks
What is Primary and Secondary Fracture Healing
Primary bone fracture healing and secondary bone healing are two different types of healing in fractures depending on the rigidity of fixation of the fracture. The one described in the initial part of the article is a type of secondary fracture healing. But when the fragments are fixed rigidly by a plate or other gadget, the type of healing that occurs is primary.
Fracture stability dictates the type of healing that will occur.
When mechanical strain is less than 2%, primary bone healing will occur. When the strain is between 2% and 10%, secondary bone healing will occur.
Thus when fracture fragments are more stable, as fixed by plate and screws primary fracture healing would occur. If the immobilization is not rigid as in plaster cast or external fixator, secondary healing would follow.
Primary Bone Healing
In this kind of fracture, healing callus is not formed at all and it occurs with rigid stabilization with or without compression of the bone ends. For example, in a fracture fixed by plating, primary bone fracture healing occurs. It occurs when the mechanical strain on the fracture is < 2%. It is also called intramembranous healing and occurs via Haversian remodeling.
Rigid stabilization suppresses the formation of a callus in either cancellous or cortical bone.
Primary healing per se is rare and most of the fractures heal by secondary healing. This is so because management of most of the fractures allows some degree of movement.
Primary bone fracture healing can be divided into gap healing and contact healing. Union occurs in both types.
Rigid stabilization suppresses the formation of a callus in either cancellous or cortical bone.
Because most fractures are managed in a way that results in some degree of motion, primary healing per se is rare.
Primary bone fracture healing can be divided into gap healing and contact healing. Union occurs in both types.
If internal fixation leaves a gap between fragments, the fracture heals by gap healing.
Gap healing occurs in two stages.
Firstly, the width of the gap is filled by direct bone formation. An initial scaffold of woven bone is laid down, followed by formation of lamellar bone as support. The orientation of the new bone formed in this first stage is transverse to that of the original lamellar bone orientation.
In the second stage, which happens after several weeks, longitudinal Haversian remodeling reconstructs the necrotic fracture ends and the newly formed bone to replace the woven bone with osteons of the original orientation. In the end, the normal bone structure results.
Contact healing occurs where fragments are in direct apposition with [< 0.1 mm distance] and neutralization of interfragmentary strain so that osteons can grow across the fracture site, parallel to the long axis of the bone.
The process is initiated by osteoclasts forming cutting cones, that traverse the fracture line at 50-100 µm/d. This tunneling allows the penetration of capillaries and eventually the formation of new Haversian systems. These blood vessels are then accompanied by endothelial cells and osteoprogenitor cells for osteoblasts leading to the production of osteons across the fracture line eventually leading to regeneration of the normal bone architecture.
Secondary Fracture Healing
Secondary bone fracture healing occurs when there is no rigid fixation of the fractured bone ends, which leads to the development of a fracture callus. It includes an inflammatory phase, a reparative phase, and a remodeling phase as described above at the beginning of this article.
Bone healing can occur as a combination of the above two processes depending on the stability throughout the construct
Factors Affecting Fracture Healing
Both local and systemic variables influence the rate and degree of fracture healing.
Systemic Factors Affecting Fracture Healing
Young patients heal rapidly and have a remarkable ability to remodel and correct angulation deformities. These abilities decrease once skeletal maturity is reached.
A substantial amount of energy is needed for fracture healing to occur. An adequate metabolic stage with sufficient carbohydrates and protein is necessary. Studies have shown as high as 84% of patients with nonunion to have metabolic issues. More than 66% of these patients had vitamin D deficiencies.
Diseases like osteoporosis, diabetes, and those causing an immunocompromised state will likely delay healing. Illnesses like Marfan’s syndrome and Ehlers-Danlos syndrome cause abnormal musculoskeletal healing.
Calcium absorption is affected in gastric bypass patients leading to decreased Ca/Vit D levels, hyperparathyroidism (secondary) & increased calcium resorption from bone.
Diabetes mellitus affects the repair and remodeling of bone by decreasing cellularity of the callus and delayed enchondral ossification.
HIV infection has a higher prevalence of fragility fractures with associated delayed healing. Contributing factors are anti-retroviral medication, poor intraosseous circulation, TNF-Alpha deficiency, and poor nutritional intake.
Bisphosphonates and systemic corticosteroids are associated with osteoporotic fractures in long-term use.
Use of NSAIDs is known to cause a 6.5% higher rate of intertrochanteric fracture nonunions NSAIDs and prolong healing time because of COX enzyme inhibition.
ling nails head injury may increase osteogenic response
Local Factors Affecting Fracture Healing
Type of Bone
Cancellous (spongy) bone fractures are usually more stable, involve greater surface areas, and have a better blood supply than do cortical (compact) bone fractures. Cancellous bone heals faster than cortical bone.
Degree of Trauma
The more extensive the injury to bone and surrounding soft tissue, the poorer the outcome. Mild contusions with local bone trauma will heal easily, whereas severely comminuted injuries with extensive soft tissue damage heal poorly. This is due to a decrease both in the rapidity of differentiation of the mesenchymal cells and in their total number. The soft tissue envelope around the fracture in this situation has to heal themselves as well as provide mesenchymal cells for fracture healing. In addition, the hematoma escapes into the soft tissues, leading to a diffusion of mesenchymal cell effort.
Inadequate blood supply impairs healing. Especially vulnerable areas are the femoral head, talus, and scaphoid bones.
In long bones also, studies have shown that un-reamed nails maintain the endosteal blood supply and reaming compromises of the inner 50-80% of the cortex
It is postulated that loose fitting nails would allow quick recovery of endosteal blood supply than canal filling nails.
Degree of Immobilization
The fracture site must be immobilized for vascular ingrowth and bone healing to occur. Repeated disruptions of repair tissue, especially to areas with marginal blood supply or heavy soft tissue damage, will impair healing.
These fractures communicate with synovial fluid, which contains collagenases that retard bone healing. The joint movement will cause the fracture fragments to more, further impairing union. When intraarticular fractures are comminuted, the fragments tend to float apart owing to loss of soft tissue support.
Separation of Bone Ends
Normal apposition of fracture fragments is needed for the union to occur. Inadequate reduction, excessive traction, or interposition of soft tissue will prevent healing.
Infections cause necrosis and edema, take energy away from the healing process, and may increase the mobility of the fracture site. Local defenses, which should concentrate on fracture healing would have to wall off infection, thus affecting healing.
Fractures through bone involved with primary or secondary malignancies usually do not heal unless malignancy is also treated.
In nonmalignant conditions, fractures may heal but in conditions likes Paget’s disease or fibrous dysplasia, fractures heal slowly or not at all due to the failure of normal differentiation of mesenchymal cells and of ingrowth of capillaries.
The bone that has been irradiated heals at a much slower rate due to the patchy death of cells in the local region, to thrombosis of vessels, and to the fibrosis of the marrow.
Sometimes, one fracture fragment becomes avascular because fracture affects the blood supply of the fragment. Fractures associated with avascular necrosis of one fragment will heal, but the rate is slower. If both fragments are avascular, the chances for a union are very poor.
Exercise and Stress
Use of a fractured extremity promotes repair, and the recent development of weight-bearing techniques has confirmed this conviction.
Other Factors Affecting Fracture Treatment Decisions
The pathoanatomy of the fracture is defined by the location, morphology, and degree of displacement of the fracture and has a marked influence on the outcome of the fracture treatment. As important as the pathoanatomy of the fracture itself is the state of the soft tissues.
A careful analysis of the pathoanatomy of the fracture and the state of the soft tissues enables us to predict the expected outcome.
Pathoanatomy of the Fracture
The natural history of the fracture is influenced by the location of the fracture, whether it is in the diaphysis, the transition zone extending into the metaphysis, or the epiphysis, with or without joint involvement.
An intraarticular fracture assumes significance and overriding importance over other injuries as the result will depend upon obtaining a stable anatomical reduction and early motion of the joint.
Metaphysis and Transition Zone
Fractures in the metaphysis or in the transition zone between the metaphysis and the diaphysis may be caused by compressive or tensile forces. If caused by compressive forces, the fractures are often crushed and axially malaligned.
Transition zone fractures caused by shear forces may be due to direct or indirect trauma.
A shearing injury through the metaphysis or the transition zone between the metaphysis and diaphysis is, therefore, a high-energy one and may be associated with considerable instability and displacement.
Cancellous metaphyseal bone heals quickly if compressed and slowly if displaced. Therefore in case of displacement and compression, open reduction and compression of some fractures in the metaphysis or the transition zone may be desirable.
Unstable, displaced diaphyseal fractures often require surgery in most of the long bones as the maintenance of an acceptable reduction may be difficult and union may be delayed by non-operative means.
Morphology of Fracture
The morphology of the fracture will suggest the type of injury that caused it, whether transverse, short oblique, or spiral, displaced or undisplaced, comminuted or not.
Transverse and short oblique fractures are indicative of a greater force than are spiral fractures. Marked comminution and gross displacement, suggesting complete disruption of the soft tissue, emphasize the violent nature of the injury.
Soft Tissue Injury
The state of the soft tissues is at least as important as the morphological appearance of the fracture.
Greater the trauma, the more likely the presence of major soft tissue damage.
The soft tissue damage may be overt, with an open wound, or could be in form of massive swelling, ecchymoses, and instability of the fracture.
Other Injuries to the Limb
The presence or absence of other injuries in the same limb will greatly affect the natural history of a fracture.
The presence or absence of an arterial or nerve injury or an early compartment syndrome will greatly influence the decision-making in the management of a fracture.
Patient Factors Affecting Fracture Healing
Age is important at the two extremes.
In skeletally immature patients, open reduction of the is almost never indicated.
In older individuals, on the other hand, though open reduction and internal fixation are strongly indicated an important, an extremely osteoporotic bone in which it is impossible to achieve stable internal fixation or medical conditions which could affect patient’s outcome may force the treating physician to choose non-operative treatment.
The patient’s occupation and recreational habits should be known so that there can be no major disparity between the expectation of the patient and the treatment offered. For example, the expectations of an athlete are different from that of the one who leads a sedentary life.
Patients with injuries to many body systems have a high risk of developing respiratory complications. If these patients are rapidly mobilized, especially in the upright position, many of these complications may be prevented or reversed.
How to Enhance Fracture Healing – Use of Stimulators
Enhancement of fracture healing is desirable where the healing is not up to mark. Though the exact mechanism and efficacy is not known, following methods of stimulation are feasible
Bone stimulators enhance fracture healing by electrical stimulation. There are four main delivery modes of electrical stimulation
Decrease osteoclast activity and increase osteoblast activity by reducing oxygen concentration and increasing local tissue pH.
Capacitively Coupled Electrical Fields
This supplies alternating current. These affect synthesis of cAMP, collagen, and calcification of cartilage.
Pulsed Electromagnetic Fields
cause calcification of fibrocartilage
Combined Magnetic Fields
They lead to elevated concentrations of TGF-Beta and BMP.
The exact mechanism for enhancement of fracture healing is not clear but the alteration of protein expression, increase in vascularity and development of mechanical strain gradient are thought to be the reasons to accelerate fracture healing. LIPUS is also known to increase the mechanical strength of callus (including torque and stiffness)
Healing rates for delayed unions/nonunions have been reported to be close to 80%
Impaired Fracture Healing
Normal fracture healing can be disrupted in numerous ways:
Fracture healing takes about twice as long as expected for a specific location
Fracture healing does not occur within 6-9 months. Sites with known predilection are scaphoid bone, femoral neck, tibial shaft
It means healing of the fractures in the wrong position. It may or may not be compensated to a certain degree by remodeling of the bone.
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