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Rubin's Pathology : Clinicopathologic

Foundations of Medicine, 5th Edition

Editors: Rubin, Raphael; Strayer, David S.
Copyright 2008 Lippincott Williams & Wilkins

The most common bone lesion is a fracture, which is defined as a
discontinuity of the bone. A force perpendicular to the long axis of the
bone results in a transverse fracture. A force along the long axis of the
bone yields a compression fracture. Torsional force results in spiral
fractures, and combined tension and compression shear forces cause
angulation and displacement of the fractured ends.
A force powerful enough to fracture a bone also injures adjacent soft
tissues. In this situation, there is often (1) extensive muscle necrosis;
(2) hemorrhage because of shearing of capillary beds and larger
vessels of the soft tissues; (3) tearing of tendinous insertions and
ligamentous attachments; and (4) even nerve damage, caused by
stretching or direct tearing of the nerve.
Fracture Healing is Divided into Inflammatory, Reparative, and
Remodeling Phases
The duration of each phase (Fig. 26-15) depends on the patient's age,
the site of fracture, the patient's overall health and nutritional status,
and the extent of soft tissue injury. Local factors, such as vascular
supply and mechanical forces at the site, also play a role in healing. In
the repair of a bone fracture, anything other than the formation of
bone tissue at the fracture site represents incomplete healing.

The Inflammatory Phase
In the first 1 to 2 days after a fracture, rupture of blood vessels in the
periosteum and adjacent muscle and soft tissue leads to extensive
hemorrhage. Extensive bone necrosis at the fracture site also occurs
because of disruption of large vessels in the bone and interruption of
cortical vessels (i.e., Volkmann and haversian canals). Dead bone is
characterized by the absence of osteocytes and empty osteocyte

In 2 to 5 days, the hemorrhage forms a large clot, which must be

resorbed so that the fracture can heal. Neovascularization begins to
occur peripheral to this blood clot. By the end of the first week, most of
the clot is organized by invasion of blood vessels and early fibrosis.
The earliest bone, which is invariably woven bone, is formed after 7
days. This corresponds to the scar of bone. Because bone
formation requires a good blood supply, the woven bone spicules begin
to appear at the periphery of the clot. Pluripotential mesenchymal cells
from the soft tissue and within the bone marrow give rise to the
osteoblasts that synthesize the woven bone. In most fractures,
cartilage also is formed and is eventually resorbed by endochondral
ossification. Granulation tissue containing bone or cartilage is termed a
callus. Woven bone also forms inside the marrow cavity at the
periphery of the blood clot because vascular tissue is also present in
this location.
The Reparative Phase
The reparative phase follows the first week after a fracture and
extends for months, depending on the degree of movement and the
fixation of the fracture. By this time, acute inflammation has
dissipated. Pluripotential cells differentiate into fibroblasts and
osteoblasts. Repair proceeds from the periphery towards the center of
the fracture site and accomplishes two objectives: (1) it organizes and
resorbs the blood clot; and, (2) more importantly, it furnishes
neovascularization for construction of the callus, which will eventually
bridge the fracture site. The events leading to repair are as follows:
Armies of osteoclasts within the haversian canals form cutting
cones that bore into the cortex toward the fracture site. A new
vessel accompanies the cutting cone, supplying nutrients to
these cells and providing more pluripotential cells for cell
At the same time, the external callus, which is found on the
surface of the bone and is formed from the periosteum and the
soft tissue mesenchymal cells, continues to grow toward the
fracture site.
Simultaneously, an endosteal, or internal, callus forms within the
medullary cavity and grows outward toward the fracture site.
The cortical cutting cones reach the fracture site and the ends of
the fractured bone begin to appear beveled and smooth, as the
site is remodeled by osteoclasts.
The same is true of the endosteal surface of the cortex, as the
internal callus works its way to the fracture site.
Where there are large areas of cartilage, new blood vessels
invade the calcified cartilage, after which the endochondral

sequence duplicates the normal formation of bone at the growth

The Remodeling Phase
Several weeks after a fracture, the ingrowth of callus has sealed the
bone ends and remodeling begins. In this phase, the bone is
reorganized so that the original cortex is restored. Occasionally, the
bone is strong enough to qualify as a clinically healed fracture, but
biologically, the fracture may not be truly healed and may continue to
undergo remodeling for years. For instance, the callus of rib fractures
may remain throughout life because the continual respiratory
movement of the ribs shears blood vessels and preserves extensive
cartilage callus. In a child, in whom the growth plates are still open,
normal modeling of growing bone overtakes the callus, so that a
fracture may not be recognizable in later life. Similarly, normal
modeling in a child may correct the angulation of a bone at a fracture
site. If a fracture is near the growth plate, differential growth rates of
the growth plate also correct the angulation. In an adult, however,
because the plates are closed, angulation often requires correction
with external or internal devices.
Special Considerations
There are unusual nuances to fracture healing that deserve mention.
PRIMARY HEALING: A fracture does not necessarily result in bone
displacement and soft tissue injury. For example, a drill hole in the
bone cortex or a controlled fracture, such as an osteotomy created
with a fine saw during orthopedic surgery, does not displace bone. In
this situation, there is almost no soft tissue reaction and callus
formation because the bone is rigidly fixed. The fracture callus grows
directly into the fracture site by a process called primary healing. This
results in rapid reconstitution of the cortex, including restoration of the
haversian systems. Similarly, if a fracture site is held in rigid alignment
by metal screws and plates, there is also little external callus. The
cortical cutting cones will then be prominent and will heal the fracture
site quickly.

FIGURE 26-15. Healing of a fracture. A. Soon after a fracture is

sustained, an extensive blood clot forms in the subperiosteal and soft
tissue, as well as in the marrow cavity. The bone at the fracture site is
jagged. B. The inflammatory phase of fracture healing is characterized
by neovascularization and beginning organization of the blood clot.
Because the osteocytes in the fracture site are dead, the lacunae are
empty. The osteocytes of the cortex are necrotic well beyond the
fracture site, owing to the traumatic interruption of the perforating
arteries from the periosteum. C. The reparative phase of fracture
healing is characterized by the formation of a callus of cartilage and
woven bone near the fracture site. The jagged edges of the original
cortex have been remodeled and eroded by osteoclasts. The marrow
space has been revascularized and contains reactive woven bone, as
does the periosteal area. D. In the remodeling phase, during which the
cortex is revitalized, the reactive bone may be lamellar or woven. The
new bone is organized along stress lines and mechanical forces.
Extensive osteoclastic and osteoblastic cellular activity is maintained.
NONUNION: If a fracture site does not heal, the condition is termed
nonunion. Causes of nonunion include interposition of soft tissues at
the fracture site, excessive motion, infection, poor blood supply, and
other factors mentioned above. Continued movement at the unhealed
fracture site may also lead to pseudoarthrosis, a condition in which
jointlike tissue is formed. Pluripotential tissue cells become
histologically indistinguishable from synovial cells, secrete synovial

fluid, and form a jointlike structure. In such cases, the fracture never
heals and the jointlike material must be removed surgically for the
fracture to heal properly.

Robbins and Cotrans Pathologic Basis of

Seventh edition
Kumar, Abbas, Fausto

Traumatic and nontraumatic fractures are some of the most common
pathologic conditions affecting bone. Fractures are classified as
complete or incomplete; closed (simple), when the overlying tissue is
intact; compound, when the fracture site communicates with the skin
surface; comminuted, when the bone is splintered; or displaced, when
the ends of the bone at the fracture site are not aligned. If the break
occurs in bone already altered by a disease process, it is described as a
pathologic fracture. A stress fracture is a slowly developing fracture
that follows a period of increased physical activity in which the bone is
subjected to new repetitive loadsas in sports training or marching in
military boot camp.
Bone is unique in its ability to repair itself; it can completely
reconstitute itself by reactivating processes that normally occur during
embryogenesis. Bone repair is a highly regulated process that can be
separated into overlapping histologic, biochemical, and biomechanical
stages. The completion of each stage initiates the next stage, and this
is accomplished by a series of interactions and communications among
the various cells and proteins located in the healing zone.
Immediately after fracture, rupture of blood vessels results in a
hematoma, which fills the fracture gap and surrounds the area of bone
injury. The clotted blood provides a fibrin mesh, which helps seal off
the fracture site and at the same time creates a framework for the
influx of inflammatory cells and ingrowth of fibroblasts and new
capillary vessels. Simultaneously, degranulated platelets and migrating
inflammatory cells release PDGF, TGF-, FGF, and other cytokines,
which activate the osteoprogenitor cells in the periosteum, medullary
cavity, and surrounding soft tissues and stimulate the production of
osteoclastic and osteoblastic activity.[28] Thus, by the end of the first
week, the hematoma is organizing, the adjacent tissue is being
modulated for future matrix production, and the fractured ends of the

bones are being remodeled. This fusiform and predominantly

uncalcified tissuecalled soft tissue callus or procallusprovides some
anchorage between the ends of the fractured bones but offers no
structural rigidity for weight bearing.
Subsequently, the activated osteoprogenitor cells deposit
subperiosteal trabeculae of woven bone that are oriented
perpendicular to the cortical axis and within the medullary cavity. In
some cases the activated mesenchymal cells in the soft tissues and
bone surrounding the fracture line also differentiate into chondroblasts
that make fibrocartilage and hyaline cartilage. In an uncomplicated
fracture, the repair tissue reaches its maximal girth at the end of the
second or third week, which helps stabilize the fracture site, but it is
not yet strong enough for weight bearing. The newly formed cartilage
along the fracture line undergoes enchondral ossification, such as
normally occurs at the growth plate, forming a network of bone that
connects to the reactive trabeculae deposited elsewhere in the
medullary cavity and beneath the periosteum. In this fashion, the
fractured ends are bridged by a bony callus, and as it mineralizes, the
stiffness and strength of the callus increase to the point that controlled
weight bearing can be tolerated ( Fig. 26-18 ).
In the early stages of callus formation, an excess of fibrous tissue,
cartilage, and bone is produced. If the bones are not perfectly aligned,
the volume of callus is greatest in the concave portion of the fracture
site. As the callus matures and transmits weight-bearing forces, the
portions that are not physically stressed are resorbed, and in this
manner the callus is reduced in size until the shape and outline of the
fractured bone has been reestablished. The medullary cavity is also
restored, and after this has been completed it may be impossible to
demonstrate the site of previous injury.

Figure 26-18 A, Recent fracture of the fibula. B, Marked callus

formation 6 weeks later. (Courtesy of Dr. Barbara Weissman, Brigham
and Women's Hospital, Boston, MA.)
The sequence of events in the healing of a fracture can be easily
impeded or even blocked. Displaced and comminuted fractures
frequently result in some deformity. The devitalized fragments of
splintered bone require resorption, and this delays healing, enlarges
the callus, and requires extremely long periods of remodeling so that in
essence there is a permanent abnormality. Inadequate immobilization
permits constant movement at the fracture site so that the normal
constituents of callus do not form. Consequently the callus may be
composed mainly of fibrous tissue and cartilage, perpetuating the
instability and resulting in delayed union and nonunion. If a nonunion
allows for too much motion along the fracture gap, the central portion
of the callus undergoes cystic degeneration, and the luminal surface
can actually become lined by synovial-like cells, creating a false joint,
or pseudoarthrosis. In the setting of a nonunion or pseudoarthrosis, the
normal healing process can be re-instituted if the interposed soft
tissues are removed and the fracture site stabilized. A serious obstacle
to healing is infection of the fracture site, which is a risk in comminuted
and open fractures. The infection must be eradicated before bony
union can be achieved. Bone repair can also be derailed by inadequate
levels of calcium or phosphorus, vitamin deficiencies, systemic
infection, diabetes, and vascular insufficiency.
Generally, with children and young adults, in whom most fractures are
uncomplicated, practically perfect reconstitution can be anticipated. In
older age groups, in whom fractures tend to occur on a background of
some other disease (e.g., osteoporosis and osteomalacia), repair is less

optimal and often requires mechanical methods of immobilization to

facilitate healing.