Residents Section Pat tern of the Month

Rana et al.
Periosteal Reaction

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Residents Section
Pattern of the Month

Residents

inRadiology
Rich S. Rana1
Jim S. Wu
Ronald L. Eisenberg
Rana RS, Wu JS, Eisenberg RL

Periosteal Reaction
Periosteal reaction results when cortical bone reacts to one of many possible insults. Tumor, infection, trauma, certain drugs, and some arthritic conditions can elevate the periosteum from the cortex and form various patterns of periosteal reaction (Fig. 1). The appearance
of periosteal reaction is determined by the intensity, aggressiveness, and duration of the underlying insult. Moreover, the periosteum in children is more active and less adherent to the
cortex than in adults. Thus, periosteal reaction can occur earlier and appear more aggressive
in children than in adults.
TABLE 1: Types of Periosteal Reaction
Nonaggressive
Thin
Solid
Thick irregular
Septated
Aggressive
Laminated (onionskin)
Spiculated

TABLE 2: Differential Diagnosis of

Periosteal Reaction
Arthritis
Psoriatic arthritis
Reactive arthritis
Metabolic
Hypertrophic pulmonary osteoarthropathy
Thyroid acropathy
Congenital

Perpendicular/hair-on-end

Pachydermoperiostosis

Sunburst

Periosteal reaction of newborn

Disorganized
Codman triangle

Trauma
Stress fracture
Fracture
Drugs
Fluorosis

Keywords: bone, periosteal reaction, periosteum

Hypervitaminosis A

DOI:10.2214/AJR.09.3300

Prostaglandins

Received July 8, 2009; accepted after revision

July 30, 2009.
1

All authors: Department of Radiology, Beth Israel

Deaconess Medical Center, 330 Brookline Ave., Boston,
MA 02215. Address correspondence to R. L. Eisenberg
(rleisenb@bidmc.harvard.edu).

WEB
This is a Web exclusive article.
AJR 2009; 193:W259W272
0361803X/09/1934W259
American Roentgen Ray Society

AJR:193, October 2009

Tumors
Osteosarcoma
Ewings sarcoma
Chondroblastoma
Eosinophilic granuloma
Osteoid osteoma
Leukemia and lymphoma
Infection
Genetic
Caffey disease
Vascular
Venous stasis
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Rana et al.

Fig. 1Various subtypes of nonaggressive and aggressive periosteal reaction.

AI, Diagrams show thin (A), solid (B), thick irregular (C), septated (D), laminated (onionskin) (E), perpendicular/
hair-on-end (F), sunburst (G), disorganized (H), and Codman triangle (I) periosteal reactions. (Courtesy of
Larson ME, Boston, MA)

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Periosteal Reaction

Fig. 2Solid periosteal reaction (osteoid osteoma).

A, Lateral radiograph reveals thick, smooth periosteal reaction in anterior cortex of distal femur (arrow).
B, Axial CT image shows lucent central nidus (arrow) of osteoid osteoma and thick reactive periosteal reaction
(arrowhead).

Types of Periosteal Reaction

There is confusing overlap in the literature regarding the terminology used to describe
periosteal reaction. It has been classified in terms of continuous versus interrupted forms,
single versus multiple layers, and aggressive versus nonaggressive subtypes. In evaluating
periosteal reaction, the major goal is to recognize its presence rather than the specific subtype
because there is significant overlap in the disease entities that result in the two major forms of
periosteal reaction: aggressive and nonaggressive. In many cases, it is not possible to radiographically determine whether the underlying process is benign or malignant. Processes that
cause rapid deposition of woven bone over a short time can produce aggressive periosteal
reaction, whereas processes that are less intense and progress more slowly produce a nonaggressive appearance (Table 1 and Figs. 1A1I).
Although there is considerable overlap, at times the subtype of periosteal reaction can be suggestive of a certain disease. For example, solid periosteal reaction is a nonaggressive form that
is primarily seen with benign, slow processes. A healed fracture, osteoid osteoma, and osteomyelitis can all exhibit solid periosteal reaction that appears as either thin or thick sheets (Fig. 2).
In the laminated subtype of periosteal reaction, multiple layers of new bone are formed
concentrically around the cortex, producing a laminated or onionskin appearance (Fig. 3).
Originally, it was believed that alternating cycles of rapid and slow injury to bone led to the

Fig. 3Onionskin periosteal reaction (osteomyelitis).

Frontal radiograph shows localized laminated
periosteal reaction (arrow) along lateral cortex of
distal femur.

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Fig. 4Hair-on-end periosteal reaction (Ewings

sarcoma). Lateral radiograph of lower leg shows bony
spicules emanating perpendicular to cortex (arrows).

Fig. 5Hair-on-end periosteal reaction (chronic

osteomyelitis). Axial CT image of shoulder shows
spiculations (arrows) arising along posterior cortex of
scapula. (Courtesy of Katz L, New Haven, CT)

formation of concentric layers. However, more recent studies suggest that the multiple layers
form because of modulation of sheets of fibroblasts in the adjacent soft tissue, which develop
osteoblastic potential and give rise to sheets of new bone. Another suggested mechanism is
that as the new layer of bone is lifted off the cortex, the inner cambium layer is stimulated to
form a new bone layer below. The laminated appearance is seen in a variety of lesions, including sarcomas, osteomyelitis, and chondroblastomas.
The spiculated pattern is an aggressive form of periosteal reaction that includes both hairon-end and sunburst subtypes. Spicules of bone form perpendicular to the periosteal surface
in the hair-on-end subtype (Figs. 4 and 5), which is highly suggestive of Ewings sarcoma.
The linear spicules of new bone form along newly formed vascular channels and fibrous
bands (Sharpey fibers). In the sunburst subtype of periosteal reaction, the spicules of new
bone radiate in a divergent pattern instead of perpendicular to the cortex (Fig. 6), an appearance often associated with conventional osteosarcomas.
A Codman triangle develops when a portion of periosteum is lifted off of the cortex by
tumor, pus, or hemorrhage at a leading edge (Fig. 7). This aggressive form of periosteal reaction is commonly seen in osteosarcomas and occasionally with infection and metastases.
Differential Diagnosis of Periosteal Reaction
An outline of the differential diagnosis of periosteal reaction is presented in Table 2.
Psoriatic Arthritis
Psoriatic arthritis is a seronegative spondyloarthropathy with inflammatory changes involving the skin and joints. Bone proliferation is an important feature of psoriatic arthritis,
and periostitis can occur along the phalangeal shafts. The periosteal reaction initially is exu-

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Periosteal Reaction

Fig. 6Sunburst periosteal reaction (osteogenic sarcoma complicating long-standing Pagets disease).
A, Frogleg radiograph of femur shows sunburst and disorganized aggressive periosteal reaction (arrows).
B and C, Axial T2-weighted MR (B) and axial CT (C) images show extensive cortical thickening (arrowheads)
and large soft-tissue mass (arrows) surrounding diaphysis of femur.

berant and fluffy. Later it matures into solid new bone, causing a widened appearance to the
shafts (Fig. 8). Additional radiographic findings include juxtaarticular osteopenia, soft-tissue
swelling, loss of cartilage, and marginal erosions.
Reactive Arthritis
Reactive arthritis is another seronegative spondyloarthropathy, which can occur after a
genital infection (Chlamydia trachomatis, Neisseria gonorrheae) or gastrointestinal infection (Salmonella, Shigella, or Campylobacter species). Localized periosteal reaction develops that is indistinguishable from psoriatic arthritis but more commonly affects the lower
extremities (such as the calcaneus and metatarsals). The periosteal reaction may result in
fluffy bone formation along the shaft and metaphyses.
Pachydermoperiostosis
Pachydermoperiostosis is an autosomal-dominant inherited disorder characterized by
marked thickening of the skin of the extremities, face, and scalp. It is also known as primary
hypertrophic osteoarthropathy because it is not due to a secondary cause such as lung disease.
Pachydermoperiostosis is a self-limited disease that most commonly affects adolescent boys
and progresses for several years before stabilizing. The generalized and symmetric periosteal
reaction in pachydermoperiostosis tends to blend with the cortex and primarily involves the
distal ends of the radius, ulna, tibia, and fibula.
Physiologic Periosteal Reaction of the Newborn
Physiologic periosteal reaction of the newborn is typically symmetric and occurs in infants
up to 6 months old, most commonly between 1 and 4 months old. The rapid growth of the
infant and loosely adherent periosteum may account for this finding. The usual appearance is

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Rana et al.

Fig. 7Codman triangle (prostate cancer). Frontal

radiograph of distal femur shows edge of periosteum
(thin arrow) lifted off cortex (arrowhead) at site of
sclerotic metastasis (thick arrow). (Courtesy of Katz
L, New Haven, CT)

Fig. 8Psoriatic arthritis. Frontal radiograph of hand

shows thick solid periosteal reaction along proximal
phalanx of long finger (arrows). Marginal erosions
are seen at heads of middle and proximal phalanges
(arrowheads).

a single-layered, thin periosteal reaction (< 2 mm) involving one aspect of the long bones,
especially in the femurs and tibias (Fig. 9).
Fluorosis
Fluorosis is known to stimulate osteoblasts and can cause a solid periosteal reaction, most
often in tubular bones in a symmetric distribution, especially at sites of muscle and ligament
attachment. Associated findings are calcified tendons and ligaments (posterior longitudinal,
iliolumbar, sacrotuberous, and sacrospinous) and dense skeletal sclerosis (most prominent in
vertebrae and the pelvis).

Fig. 9Physiologic periostitis. Frontal radiograph of both femurs show smooth, single-layer periosteal reaction
on lateral aspects of both femoral shafts (arrows). (Courtesy of Kotecha M, Philadelphia, PA)

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Periosteal Reaction
Hypervitaminosis A
Retinoids are commonly used to treat children and teens with severe acne, psoriasis, and
burn injuries. Overuse can lead to hypervitaminosis A, which results in solid periosteal reaction along the long bones, growth retardation, and premature closure of growth plates. The
periosteal reaction occurs greatest near the center of the shaft and tapers toward the ends of
the bone. Unlike Caffey disease, the periosteal reaction rarely involves the mandible. The
ulna, lower leg, metatarsals, and clavicle are the most common locations.
Prostaglandins
Prostaglandins can be used to maintain the patency of the ductus arteriosus in infants with
congenital heart disease and ductal-dependent physiology. They are believed to decrease osteoclast bone resorption, which can result in periosteal reaction associated with limb pain and
considerable swelling of the extremities, all of which improve after cessation of the drug.
Infection
Osteomyelitis can cause localized periosteal reaction anywhere but primarily causes this
appearance in the long bones. Subperiosteal spread of inflammation elevates the periosteum
and stimulates the laying down of layers of new bone parallel to the shaft. Eventually, a large
amount of new bone surrounds the cortex in a thick irregular bony sleeve (involucrum) (Fig.

Fig. 10Chronic osteomyelitis. Lateral radiograph

of distal femur shows dense thick periosteal reaction
(involucrum, straight arrows) surrounding dead
bone (sequestrum, arrowheads). (Reprinted with
permission from Eisenberg RL. Clinical imaging: an
atlas of differential diagnosis, 4th ed. Philadelphia,
PA: Lippincott Williams & Wilkins, 2003)

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Fig. 11Caffey disease. Lateral radiograph of lower

leg of 2-month-old girl with left lower extremity pain
shows extensive thick periosteal reaction along tibia
and fibula (arrows).

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10). Disruption of the cortical blood supply leads to bone necrosis with dense segments of
avascular dead bone (sequestra) remaining. Among the many subtypes of periosteal reaction
that can occur with infection are disorganized, thin, lamellated, or spiculated forms. A Codman triangle can also develop, often with lytic destruction of bone in the acute phase.
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Caffey Disease
Caffey disease, also known as infantile cortical hyperostosis, is a rare self-limiting inflammatory disease of infancy that is characterized by hyperirritability, soft-tissue swelling, and
cortical hyperostosis and particularly involves the mandible and facial bones. The disease is
believed to be an autosomal-dominant disease related to type 1 collagen mutation. Caffey disease almost always occurs before 6 months and is characterized by a laminated periosteal reaction affecting the mandible, scapula, clavicle, and ulna and, less frequently, the ribs (Fig. 11).
Hypertrophic Pulmonary Osteoarthropathy
Hypertrophic pulmonary osteoarthropathy is a common cause of periosteal reaction in
adults that is associated with many underlying malignancies or chronic diseases. It most frequently arises in patients with primary intrathoracic neoplasms, especially nonsmall cell
lung cancer. Other common causes include tumors of the pleura and mediastinum, chronic

C
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Fig. 12Secondary hypertrophic osteoarthropathy.

A and B, Bilateral frontal views of distal femur show
thin and thick single layer periosteal reaction (arrows)
along femoral shafts bilaterally.
C, Frontal chest radiograph shows right upper lobe
masses from nonsmall cell lung cancer (arrows).

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Periosteal Reaction
suppurative lung lesions (lung abscess, bronchiectasis, and empyema), cystic fibrosis, and
pulmonary metastases in infants and children. It occasionally occurs in association with extrathoracic neoplasms and gastrointestinal diseases (biliary cirrhosis, ulcerative colitis, and
Crohns disease).
Because hypertrophic osteoarthropathy is systemically mediated, although through an unknown mechanism, it typically produces periosteal reaction that is symmetric and widely
distributed (Figs. 12 and 13). It typically involves the diaphyses of tubular bones, sparing the
ends. There can be associated clubbing of the fingers and toes and often enlargement of the
extremities and swollen joints.
Thyroid Acropachy
Thyroid acropachy is a rare complication of autoimmune thyroid disease that is characterized by progressive exophthalmus, relatively symmetric swelling of the hands and feet, clubbing of the digits, and pretibial myxedema. It can develop after thyroidectomy or radioactive
iodine treatment of primary hyperthyroidism, with most patients being euthyroid or hypothyroid when symptoms develop. Thyroid acropachy produces generalized and symmetric spiculated periosteal reaction that primarily involves the midportions of the diaphyses of tubular
bones of the hands and feet.
Stress Fracture
Stress fractures can show subtle solid periosteal reaction in the region of pain or trauma.
Abnormalities are seen earlier on MR images than on radiographs, with bone marrow edema
and increased signal in the muscles and periosteum on T2-weighted images. Common sites of
stress fracture include the tibias, metatarsals, long bones, pelvis, and calcaneus.

Fig. 13Hypertrophic pulmonary osteoarthropathy.

A and B, Frontal radiographs of both hands show
thick, fluffy, symmetric periosteal reaction along
shafts of several metacarpals and phalanges (arrows).
C, Radionuclide bone scan shows increased
radiotracer uptake bilaterally at sites of periosteal
reaction.

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Fracture
Periosteal reaction related to fractures can show a solid, nonaggressive appearance or a
more disorganized, aggressive appearance (Fig. 14). A fracture occurring at a site involved in
a greater degree of motion may produce a more disorganized pattern of periosteal reaction.
Periosteal reaction from traumatic and pathologic fractures can have a similar appearance. In
addition, there may be a related soft-tissue mass on radiographs, which should be followed up
to confirm resolving hematoma.
Osteosarcoma
Conventional osteosarcomas are common high-grade intramedullary neoplasms that produce an osteoid matrix. The majority of lesions occur in patients under 25 years old , with the
femur, tibia, and fibula the most common sites. The sunburst, hair-on-end, or Codman triangle subtypes of periosteal reaction are most frequently seen (Fig. 15). However, laminated,
solid, thin, or disorganized forms of periosteal reaction can also be present. A wide zone of
transition, cortical breakthrough, and soft-tissue mass are all concerning features that warrant further evaluation.
Ewings Sarcoma
Ewings sarcoma is derived from undifferentiated mesenchymal cells of bone marrow or
primitive neuroectodermal cells and accounts for 68% of primary malignant bone tumors.
Although characteristically intramedullary in location, on radiographs, only the cortical
changes may be apparent with a permeative or moth-eaten osteolytic component. A large softtissue mass can be seen. The periosteal reaction pattern is typically aggressive, with the hairon-end subtype highly characteristic for Ewings sarcoma.
Chondroblastoma
Chondroblastomas are benign cartilage-producing lesions that typically occur in the epiphyses of skeletally immature patients. The lesions are typically lytic and may have a sclerotic

Fig. 14Fracture.
A, Frontal radiograph obtained 7 days after injury shows disorganized aggressive periosteal reaction at site of
fracture (arrow) involving neck of third metatarsal.
B, Repeat radiograph obtained 4 weeks after injury shows smooth, thin, nonaggressive periosteal reaction at
same site (arrow), consistent with healing.

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Periosteal Reaction

Fig. 15Osteogenic sarcoma. Lateral radiograph

of mid femur shows sunburst periosteal reaction
with bone formation in divergent pattern (arrow).
(Courtesy of Haims A, New Haven, CT)

Fig. 16Chondroblastoma. Radiograph shows

laminated (arrow) and disorganized periosteal
reaction along proximal humerus.

margin. Periosteal reaction due to chondroblastoma most commonly occurs in large lesions in
flat or small tubular bones. The periosteal reaction can be thick, solid, or laminated (Fig. 16).
Eosinophilic Granuloma
Eosinophilic granuloma is the benign form of the three clinical variants of Langerhans cell
histiocytosis (the others are Letterer-Siwe and Hand-Schller-Christian diseases). Neoplastic
proliferation of Langerhans cells present predominantly as lytic lesions. However, there may
be sclerotic areas with a thick or laminated pattern of periosteal reaction, especially during
the healing phase. This appearance can be mistaken for osteomyelitis.
Osteoid Osteoma
Osteoid osteoma is a benign bone-forming tumor affecting children and adolescents, most
commonly occurring in the femur, tibia, fibula, or humerus. A thick and dense periosteal reaction develops as a response to the tumor. The central lucent nidus may be difficult to visualize on radiographs, and CT can be helpful in these instances (Fig. 17). Subperiosteal osteoid
osteomas can produce extensive aggressive periosteal reaction, whereas intraarticular lesions
typically cause relatively little periosteal new bone formation.
Leukemia and Lymphoma
Both leukemia and lymphoma can be associated with an aggressive-appearing periosteal
reaction. In children, leukemia is more likely to affect long bones, whereas in adults, the axial
skeleton is more commonly affected. A thin or laminated pattern of periosteal reaction is common (Fig. 18), with a hair-on-end appearance less frequent. Lymphoma may produce an aggressive and disorganized periosteal reaction, and there may be an associated soft-tissue mass that
is larger than the area of bone destruction.
Venous Stasis
Venous stasis, especially in the lower extremities, can result in generalized solid undulating periosteal reaction that initially can be separate from the cortex (Fig. 19). The increase in

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Rana et al.

B
Fig. 17Osteoid osteoma.
A, Frontal radiograph of proximal tibia shows smooth,
thick periosteal reaction along medial tibia cortex
(arrow).
B and C, Coronal reformatted (B) and axial CT
(C) images show lucent central nidus (arrows)
surrounded by reactive periosteal reaction
(arrowheads).

C
mean interstitial fluid pressure in venous stasis may exert pressure on the periosteum, leading
to periosteal new bone formation. Although not always present, clues to this diagnosis include
widespread subcutaneous edema and phleboliths in varicose veins.
Unilateral Versus Bilateral Periosteal Reaction
Unilateral periosteal reaction is caused by a localized process, such as trauma, tumor, or
infection. Bilateral periosteal reaction is typically due to systemic processes, and the differential diagnosis can often be narrowed by patient age and clinical presentation. Before 6
months, the most common causes are physiologic periostitis of the newborn, Caffey disease,
and periostitis related to prostaglandin use. Bilateral periosteal reaction that appears after 6
months should suggest hypertrophic osteoarthropathy, juvenile idiopathic arthritis, hypervitaminosis A, and venous stasis. In the appropriate clinical situation, it is essential to consider
nonaccidental trauma resulting in multiple healing fractures as the underlying cause.
Conclusion
Periosteal reaction results from the response of cortical bone to a variety of insults. Recognition of the presence of periosteal reaction is the most important step. Occasionally, the pattern
of periosteal reaction is highly suggestive of a particular process, but in general there is signifi-

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Periosteal Reaction

Fig. 18Leukemia. Frontal radiograph of femurs

shows dense thick periosteal reaction along femoral
shafts bilaterally. (Reprinted with permission from
Eisenberg RL. Clinical imaging: an atlas of differential
diagnosis, 4th ed. Philadelphia, PA: Lippincott
Williams & Wilkins, 2003)

Fig. 19Venous stasis. Periosteal new bone

formation cloaks tibia and fibula. (Reprinted with
permission from Eisenberg RL. Clinical imaging: an
atlas of differential diagnosis, 4th ed. Philadelphia,
PA: Lippincott Williams & Wilkins, 2003)

cant overlap in the disease entities that result in aggressive and nonaggressive forms. Intense,
rapid-acting processes usually result in aggressive periosteal reaction; slower, indolent processes result in a nonaggressive form. The causes of periosteal reaction are broad, including trauma,
infection, arthritis, tumors, and drug-induced and vascular entities. When periosteal reaction
occurs in a bilateral distribution, a systemic disease process should be considered.

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