AJR:193, October 2009 W259

Periosteal Reaction

Res idents ’ Sect ion • Pat tern of the Month

WEB This is a Web exclusive article.

AJR 2009; 193:W259–W272

0361–803X/09/1934–W259

© American Roentgen Ray Society

Rich S. Rana1

Jim S. Wu Ronald L. Eisenberg

Rana RS, Wu JS, Eisenberg RL

1All 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).

Keywords: bone, periosteal reaction, periosteum

DOI:10.2214/AJR.09.3300

Received July 8, 2009; accepted after revision July 30, 2009.

Residents

inRadiology

Rana et al.Periosteal Reaction

Residents’ SectionPattern of the Month

Periosteal reaction results when cortical bone reacts to one of many possible insults. Tu-mor, infection, trauma, certain drugs, and some arthritic conditions can elevate the perioste-um 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 un-derlying 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

Perpendicular/hair-on-end

Sunburst

Disorganized

Codman triangle

TABLE 2: Differential Diagnosis of Periosteal Reaction

Arthritis

Psoriatic arthritis

Reactive arthritis

Metabolic

Hypertrophic pulmonary osteoarthropathy

Thyroid acropathy

Congenital

Pachydermoperiostosis

Periosteal reaction of newborn

Trauma

Stress fracture

Fracture

Drugs

Fluorosis

Hypervitaminosis A

Prostaglandins

Tumors

Osteosarcoma

Ewing’s sarcoma

Chondroblastoma

Eosinophilic granuloma

Osteoid osteoma

Leukemia and lymphoma

Infection

Genetic

Caffey disease

Vascular

Venous stasis

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A

D

G

B

E

H

C

F

I

Fig. 1—Various subtypes of nonaggressive and aggressive periosteal reaction.A–I, 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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Types of Periosteal ReactionThere 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 radio-graphically 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 nonag-gressive appearance (Table 1 and Figs. 1A–1I).

Although there is considerable overlap, at times the subtype of periosteal reaction can be sug-gestive 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 osteomy-elitis 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

A

Fig. 2—Solid 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).

B

Fig. 3—Onionskin periosteal reaction (osteomyelitis). Frontal radiograph shows localized laminated periosteal reaction (arrow) along lateral cortex of distal femur.

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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, includ-ing sarcomas, osteomyelitis, and chondroblastomas.

The spiculated pattern is an aggressive form of periosteal reaction that includes both hair-on-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 Ewing’s 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 appear-ance 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 reac-tion is commonly seen in osteosarcomas and occasionally with infection and metastases.

Differential Diagnosis of Periosteal ReactionAn outline of the differential diagnosis of periosteal reaction is presented in Table 2.

Psoriatic ArthritisPsoriatic arthritis is a seronegative spondyloarthropathy with inflammatory changes in-

volving 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-

Fig. 4—Hair-on-end periosteal reaction (Ewing’s sarcoma). Lateral radiograph of lower leg shows bony spicules emanating perpendicular to cortex (arrows).

Fig. 5—Hair-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)

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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 ArthritisReactive arthritis is another seronegative spondyloarthropathy, which can occur after a

genital infection (Chlamydia trachomatis, Neisseria gonorrheae) or gastrointestinal infec-tion (Salmonella, Shigella, or Campylobacter species). Localized periosteal reaction devel-ops 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.

PachydermoperiostosisPachydermoperiostosis 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 NewbornPhysiologic 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

A

Fig. 6—Sunburst periosteal reaction (osteogenic sarcoma complicating long-standing Paget’s 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.

C

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a single-layered, thin periosteal reaction (< 2 mm) involving one aspect of the long bones, especially in the femurs and tibias (Fig. 9).

FluorosisFluorosis 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. 7—Codman 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. 8—Psoriatic 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).

Fig. 9—Physiologic 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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Hypervitaminosis ARetinoids 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 reac-tion 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.

ProstaglandinsProstaglandins 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 os-teoclast 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.

InfectionOsteomyelitis 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. 10—Chronic 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)

Fig. 11—Caffey 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 Cod-man triangle can also develop, often with lytic destruction of bone in the acute phase.

Caffey DiseaseCaffey disease, also known as infantile cortical hyperostosis, is a rare self-limiting inflam-

matory 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 dis-ease almost always occurs before 6 months and is characterized by a laminated periosteal reac-tion affecting the mandible, scapula, clavicle, and ulna and, less frequently, the ribs (Fig. 11).

Hypertrophic Pulmonary OsteoarthropathyHypertrophic pulmonary osteoarthropathy is a common cause of periosteal reaction in

adults that is associated with many underlying malignancies or chronic diseases. It most fre-quently arises in patients with primary intrathoracic neoplasms, especially non–small cell lung cancer. Other common causes include tumors of the pleura and mediastinum, chronic

A

Fig. 12—Secondary 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 non–small cell lung cancer (arrows).

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suppurative lung lesions (lung abscess, bronchiectasis, and empyema), cystic fibrosis, and pulmonary metastases in infants and children. It occasionally occurs in association with ex-trathoracic neoplasms and gastrointestinal diseases (biliary cirrhosis, ulcerative colitis, and Crohn’s disease).

Because hypertrophic osteoarthropathy is systemically mediated, although through an un-known 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 AcropachyThyroid acropachy is a rare complication of autoimmune thyroid disease that is character-

ized by progressive exophthalmus, relatively symmetric swelling of the hands and feet, club-bing of the digits, and pretibial myxedema. It can develop after thyroidectomy or radioactive iodine treatment of primary hyperthyroidism, with most patients being euthyroid or hypothy-roid when symptoms develop. Thyroid acropachy produces generalized and symmetric spicu-lated periosteal reaction that primarily involves the midportions of the diaphyses of tubular bones of the hands and feet.

Stress FractureStress 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.

A

Fig. 13—Hypertrophic 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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FracturePeriosteal 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.

OsteosarcomaConventional osteosarcomas are common high-grade intramedullary neoplasms that pro-

duce 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 trian-gle 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 war-rant further evaluation.

Ewing’s SarcomaEwing’s sarcoma is derived from undifferentiated mesenchymal cells of bone marrow or

primitive neuroectodermal cells and accounts for 6–8% 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 soft-tissue mass can be seen. The periosteal reaction pattern is typically aggressive, with the hair-on-end subtype highly characteristic for Ewing’s sarcoma.

ChondroblastomaChondroblastomas are benign cartilage-producing lesions that typically occur in the epiphy-

ses of skeletally immature patients. The lesions are typically lytic and may have a sclerotic

A

Fig. 14—Fracture.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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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 GranulomaEosinophilic granuloma is the benign form of the three clinical variants of Langerhans cell

histiocytosis (the others are Letterer-Siwe and Hand-Schüller-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 OsteomaOsteoid 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 re-action develops as a response to the tumor. The central lucent nidus may be difficult to visual-ize 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 LymphomaBoth 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 com-mon (Fig. 18), with a hair-on-end appearance less frequent. Lymphoma may produce an aggres-sive and disorganized periosteal reaction, and there may be an associated soft-tissue mass that is larger than the area of bone destruction.

Venous StasisVenous stasis, especially in the lower extremities, can result in generalized solid undulat-

ing periosteal reaction that initially can be separate from the cortex (Fig. 19). The increase in

Fig. 15—Osteogenic 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. 16—Chondroblastoma. Radiograph shows laminated (arrow) and disorganized periosteal reaction along proximal humerus.

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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 ReactionUnilateral 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 differ-ential 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, hypervi-taminosis 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.

ConclusionPeriosteal reaction results from the response of cortical bone to a variety of insults. Recogni-

tion 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-

A

Fig. 17—Osteoid 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).

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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 process-es 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.

Fig. 18—Leukemia. 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. 19—Venous 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)

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