Three-phase bone scan in osteomyelitis and other musculoskeletal disorders

Three-phase bone scan in osteomyelitis and other musculoskeletal disorders

Charles W. Sutter

The clinical suspicion of occult osteomyelitis may be clarified with radiologic imaging. Plain radiographs should be performed initially and will guide the selection of subsequent radionuclide imaging. Other studies might include three-phase bone scans, indium-111- or technetium99m-labeled leukocyte scans, gallium scans or, in selected cases, magnetic resonance imaging (MRI). Medical indications and clinical rationale for these diagnostic studies offer a cost-effective work-up of benign bone conditions such as osteomyelitis, athletic and occupational injuries such as shin splints, stress and occult fractures, enthesiopathies and reflex sympathetic dystrophy.

Bone is a mineralized connective tissue that is highly vascular and in a constant state of flux.[1] Bone largely consists of an inorganic mineral, hydroxyapatite [[Ca.sub.3] [([P[O.sub.4]).sub.2]).sub.3]*[Ca(OH).sub.2]], which is composed of calcium, phosphate and hydroxyl ions, and a bone matrix of collagen and polysaccharides.[2] Bone growth or repair occurs in the endosteum, periosteum and epiphyseal plates and depends on three cellular elements: osteoblasts, osteocytes and osteoclasts. The inner layer of the periosteum and the endosteum produce osteoclasts to remove dying bone while creating osteoblasts to provide new bone.

Radiopharmaceutical Uptake in Bone

The most common radiopharmaceutical agents used in bone imaging are the diphosphonates, which are taken up by bone and rapidly cleared from the blood. Technetium-99m-labeled methylene diphosphonate (MDP) is the most commonly used bone agent and binds to bone primarily by chemisorption to the surface of hydroxyapatite crystals.[2,3] The skeletal uptake of these tracers largely depends on bone blood flow, sympathetic tone[3] and osteoblastic activity. Of the three, osteoblastic activity is the most important factor for localized uptake.[3,4]

Increased osteoblastic activity in reactive bone lesions such as osteomyelitis, fractures and tumors may be seen as areas of increased uptake (“hot spots”) on bone scans. While the bone scan is very sensitive to bone pathology, its specificity is lower because many insults to bone, including tumor, trauma, infection and vascular or metabolic injury, result in increased bone formation and increased uptake on the scan.[5]

In normal three-phase bone scan imaging, 25 mCi (925 MB q) of technetium-99m MDP is administered intravenously as a bolus injection, with the area of interest positioned directly under the gamma camera. The first phase (radionuclide angiogram) includes a series of sequential images taken every two seconds for 40 to 60 seconds. The second phase (blood pool) is acquired as a static image for one to three minutes immediately after the angiogram phase. The third phase (delayed bone phase) is obtained at least three hours later. A fourth phase (24-hour delayed image) is occasionally useful to improve the specificity of the bone scan for osteomyelitis or when soft tissue elimination is unusually slow.[3,5] The incidence of side effects is extremely low.[4]

Table 1 summarizes the characteristic bone scan findings in various disorders.



Osteomyelitis is an infection of bone and marrow. There are three principal ways to contract osteomyelitis: (1) hematogenous, (2) contiguous spread of infection, such as from a skin infection or puncture wound, and (3) as a result of ulcers that are due to peripheral vascular disease.[6,7]

Radiographs are relatively inexpensive and should be the initial study done in patients with suspected osteomyelitis.[2-5, 8-10] If the radiographs reveal swelling of the soft tissue, periosteal new bone formation and bony demineralization, this triad is virtually pathognomonic of osteomyelitis.[8,11] However, it usually takes 10 to 14 days for characteristic bone changes to appear on radiographs.[9,11]


If the radiographs are normal, the three-phase bone scan is the next imaging study of choice because it is cost-effective, sensitive and, in the case of suspected osteomyelitis, specific.[5,9,10] The bone scan is usually abnormal within 24 hours of the onset of symptoms.[12]

The classic finding of osteomyelitis on three-phase bone scan is the “triple-phase abnormality”: increased blood flow on the first phase (angiogram), focal hyperemia on the second phase (blood pool) and abnormally increased focal bony uptake on the third or delayed phase (bone activity). Figures 1a, 1b and 1c illustrate the findings on three-phase bone scan in a patient with osteomyelitis. The bone scan may show abnormal uptake of the radiopharmaceutical agent 10 to 14 days before abnormalities are apparent on plain films.[9,12]

In a review of six studies of three-phase bone scans, an overall sensitivity of 94 percent and a specificity of 95 percent were found for the detection of osteomyelitis in adults and children with normal radiographs.[10] In its typical presentation, simple cellulitis demonstrates increased activity of the radiopharmaceutical agent on the first two phases of the bone scan, but no intense focal abnormal activity is apparent in the bone during the third phase, thus distinguishing cellulitis from osteomyelitis.[10,13]

The fourth-phase image shows increased tracer activity in an osteomyelitic bony lesion and better differentiates osteomyelitis from soft tissue inflammation. The fourth phase may better show focal localization on delayed (24-hour) imaging, which increases the diagnostic accuracy of osteomyelitis, especially in patients with diabetes and atherosclerotic peripheral vascular disease.[13-15]

Osteomyelitis in children is usually caused by the hematogenous spread of bacteria and occurs most commonly in the metaphyseal-epiphyseal region of the long bones. Plain films are usually normal in children with osteomyelitis.[5] In this setting, a positive three-phase bone scan is strongly suggestive of osteomyelitis. A negative three-phase bone scan in patients over three years of age essentially excludes the diagnosis of osteomyelitis.[9,16] However, in neonates the bone scan is even less sensitive for osteomyelitis. In infants, gallium scans may be considered as the first imaging study.[5,17] If the three-phase bone scan is not diagnostic, a gallium scan may demonstrate the presence of osteomyelitis in children (Figure 2). The results of gallium scans, however, generally require one to two days.


If the radiograph shows degenerative disease, healing fracture, tumor or postinflammatory or postsurgical changes, an indium-111- or technetium-99m-labeled leukocyte scan may be the study of choice.[9,18] Reinjected labeled leukocytes accumulate in areas of infection and osteomyelitis and are generally far more specific for osteomyelitis than bone scan in these patients. Correlation with a three-phase bone scan is recommended and usually required for accurate localization[9,10] (Figures 3a and 3b).

A review of the literature showed that indium-labeled leukocyte scans have a sensitivity of 88 percent with a specificity of 85 percent in the diagnosis of osteomyelitis.[10] If the patient has had a recent fracture and osteomyelitis is suspected, an indium-labeled leukocyte scan should be the first test since the bone scan will be “hot” as a result of the recent trauma[10,11] (Figures 4a and 4b).

Diagnostic algorithms for suspected osteomyelitis in neonates, children and adults are shown in Figures 5, 6 and 7.


Indium-111-labeled leukocyte scans are very sensitive and specific in the detection of osteomyelitis of the foot in patients with diabetes.[18,19] In several large clinical studies, indium-labeled leukocyte imaging was more specific than three-phase bone scans, especially in patients with diabetes, postsurgical patients and patients with underlying foot pathology.[15]

Occupational and Sports Injuries

The emphasis on fitness and exercise in our society has resulted in an increasing number of repetitive motion injuries and stress-related musculoskeletal injuries. The bone scan is more sensitive than radiographs for the detection of stress injuries[12] and is usually positive at least 10 to 14 days sooner than radiographs.[9] In cases where prompt diagnosis is required or follow-up films are nondiagnostic, use of the three-phase bone scan proves to be both cost-effective[9] and diagnostic.[1]


Stress fracture can result from repetitive and prolonged muscular exercise without proper conditioning.[20] Continued excessive stress on the bone may result in complete fracture. The three-phase bone scan has become a common cost-effective imaging study in the detection of stress fractures.[9]

Patients usually present with the complaint of focal bone pain, with or without localized tenderness on examination. Stress fractures of the tibia are the most frequently reported stress fractures in athletes, followed by stress fractures of the fibula, metatarsals and the femur.[21] An acute stress fracture shows focal intense activity on all three phases of the bone scan (Figures 8a and 8b).


The term “shin splints” has been used to describe intermittent pain in the lower extremities associated with exercise.[1,21] It is believed to result from periostitis of the tibia at the origin of the soleus muscle.[21] Shin splints usually occur in young, healthy, active people, especially runners and joggers, and may be confused with stress fracture. As in cases of stress fracture, plain films are usually normal but in patients with shin splints the bone scan reveals vertical elongated uptake in the tibia that is due to periostitis.[21]


Occult fractures are fractures not easily detected on radiographs (Figures 9a and 9b). The bones most commonly involved are the scaphoid,[1,20,22] hamate,[23] pelvis,[13] talar dome,[13,23] ribs[23] and proximal femur. Occult fractures show positive results on all three phases of the bone scan within 24 hours of injury in at least 95 percent of patients under 65 years of age.


The term “enthesiopathy” refers to disease processes that occur at the sites of tendon and ligament attachment to bone. These processes may be inflammatory, degenerative, metabolic or traumatic in etiology.[1] Examples include trochanteric bursitis, osteitis pubis (Figure 10), planter fasciitis (Figure 11)[24] and Achilles tendinitis[1,13] (Figure 12). Plain films usually are not helpful, but the three-phase bone scan is focally positive on all three phases.


Reflex sympathetic dystrophy is a syndrome characterized by pain, tenderness, vasomotor instability, swelling and trophic skin changes, usually affecting the extremities.[12] The diagnosis of reflex sympathetic dystrophy should be suspected, for example, when pain is persistent after recent trauma or stroke. A three-phase bone scan of the extremity is the most sensitive and specific diagnostic test, particularly in the early phase (less than 20 weeks) of the syndrome[23,25,26] (Figures 13 and 14).


The authors thank Marija Ivanovic for her technical assistance.


[1.] Matin R Basic principles of nuclear medicine techniques for detection and evaluation of trauma and sports medicine injuries. Semin Nucl Med 1988; 18:90-112. [2.] Mettler FA, Guiberteau MJ. Essentials of nuclear medicine imaging. 3d ed. Philadelphia: Saunders, 1991:209-36. [3.] Alazraki N. Musculoskeletal imaging. In: Taylor A, Datz FL, eds. Clinical practice of nuclear medicine. New York: Churchill Livingstone, 1991:379-431. [4.] Palmer EL, Scott JA, Straus HW. Practical nuclear medicine. Philadelphia: Saunders, 1992:121-83. [5.] Alazraki NP. Radionuclide imaging in the evaluation of infections and inflammatory disease. Radiol Clin North Am 1993;31:783-94. [6.] Swartz MN, O’Hanley PO. Osteomyelitis. In: Rubenstein E, Federman DD, eds. Scientific American medicine. New York: Scientific American, 1995:1-9. [7.] Resnick D, Niwayara G. Osteomyelitis, septic arthritis, and soft tissue infection: mechanisms and situations. In: Resnick D, ed. Bone and joint imaging. 3d ed. Philadelphia: Saunders, 1989:728-55. [8.] Palestro CJ. Musculoskeletal infection. In: Freeman LM, ed. Nuclear medicine annual 1994. New York: Raven Press, 1994:91-119. [9.] Grossman ZD, Katz DS, Santelli ED, Math KR, Wasenko JJ, eds. Cost-effective diagnostic imaging–the clinician’s guide. 3d ed. St. Louis: Mosby, 1995:247-68. [10.] Schauwecker DS. The scintigraphic diagnosis of osteomyelitis. Am J Roentgenol 1992;158:9-18. [11.] Thrall JH, Ziessman HA. Nuclear medicine: the requisites. St. Louis: Mosby, 1995:149-70. [12.] Datz FL, Patch GG, Arias JM, Morton KA. Nuclear medicine: a teaching file. St. Louis: Mosby, 1992:21-57,206. [13.] Ryan PJ, Fogelman I. The role of nuclear medicine in orthopaedics. Nucl Med Commun 1994;15.341-60. [14.] Alazraki N, Dries D, Datz F, Lawrence P, Greenberg E, Taylor A Jr. Value of a 24-hour image (four-phase bone scan) in assessing osteomyelitis in patients with peripheral vascular disease. J Nucl Med 1985;26:711-7. [15.] Gupta NC, Prezio JA. Radionuclide imaging in osteomyelitis. Semin Nucl Med 1988;18:287-99. [16.] Ryan PJ, Fogelman I. The bone scan: where are we now? Semin Nucl Med 1995;25:76-91. [17.] Treves ST, Connolly LP, Kirkpatrick JA, Packard AB, Roach P, Jaramillo D. Bone. In: Treves ST, ed. Pediatric nuclear medicine. 2d ed. New York: Springer-Verlag, 1995:233-301. [18.] Keenan AM, Tindel NL, Alavi A. Diagnosis of pedal osteomyelitis in diabetic patients using current scintigraphic techniques. Arch Intern Med 1989;149: 2262-6. [19.] Larcos G, Brown ML, Sutton RT. Diagnosis of osteomyelitis of the foot m diabetic patients: value of 111In-leukocyte scintigraphy. Am J Roentgenol 1991;157:527-31. [20.] Collier BD Jr, Fogelman I, Brown ML. Bone scmtigraphy: part 2. Orthopedic bone scanning. J Nucl Med 1993;34:2241-6. [21.] Martire JR, Levinsohn EM. Imaging of athletic injuries: a multimodality approach. New York: McGraw-Hill, 1992:45-131. [22.] Tiel-van Buul MMC, Broekhuizen TH, van Beek EJ, Bossuyt PM. Choosing a strategy for the diagnostic management of suspected scaphoid fracture: a cost-effectiveness analysis. J Nucl Med 1995;36:45-8. [23.] Martire JR. The role of nuclear medicine bone scans in evaluating pain in athletic injuries. Clin Sports Med 1987;6:713-37. [24.] Intenzo CM, Wapner KL, Park CH, Kim SM. Evaluation of planter fasciitis by three-phase bone scintigraphy. Clin Nucl Med 1991;16:325-8. [25.] Dzwierzynski WW, Sanger JR. Reflex sympathetic dystrophy. Hand Clin 1994;10:29-44. [26.] Demangeat JL, Constantinesco A, Brunot B, Foucher G, Farcot JM. Three-phase bone scanning in reflex sympathetic dystrophy of the hand. J Nucl Med 1988;29:26-32.

The Authors CHARLES W. SUTTER, M.D. is an assistant clinical professor of nuclear medicine in the Department of Radiology at the University of California-Davis Medical Center, Sacramento. He received his medical degree from the University of Southern California, Los Angeles, and completed a residency in family medicine and a residency in nuclear medicine at the University of California-Davis Medical Center.

DAVID K. SHELTON, M.D. is an associate professor of nuclear medicine in the Department of Radiology at the University of California-Davis Medical Center. He is vice chairman of clinical affairs for radiology and chief of nuclear medicine. Dr. Shelton received his medical degree from Bowman Gray Medical School, Winston-Salem, N.C.

Address correspondence to Charles W. Sutter, M.D., Division of Nuclear Medicine, G-202, University of California-Davis Medical Center, 2315 Stockton Blvd., Sacramento, CA 95S17.

COPYRIGHT 1996 American Academy of Family Physicians

COPYRIGHT 2008 Gale, Cengage Learning