Orthopedics

Review Article 

Bone Scintigraphy: A Review of Technical Aspects and Applications in Orthopedic Surgery

John W. Krumme, MD; Madelyn F. Lauer, MD; Justin T. Stowell, MD; Nebiyu M. Beteselassie, MD; Suhel Y. Kotwal, MD

Abstract

Due to its high sensitivity, low cost, accessibility, and ease of use, bone scintigraphy is used in orthopedic surgery for the diagnosis and management of varied pathology. It is commonly used for insufficiency fractures, metastatic neoplasia, staging and surveillance of sarcoma, and nonaccidental trauma. It augments diagnoses, including stress or occult fractures, musculoskeletal neoplasia or infection, and chronic regional pain syndrome, in patients presenting with normal results on radiographs. Bone scan images are resistant to metal-based implant artifact, allowing effective evaluation of failed total joint prostheses. Bone scintigraphy remains an underused tool in the evaluation and management of orthopedic patients. [Orthopedics. 2019; 42(1):e14–e24.]

Abstract

Due to its high sensitivity, low cost, accessibility, and ease of use, bone scintigraphy is used in orthopedic surgery for the diagnosis and management of varied pathology. It is commonly used for insufficiency fractures, metastatic neoplasia, staging and surveillance of sarcoma, and nonaccidental trauma. It augments diagnoses, including stress or occult fractures, musculoskeletal neoplasia or infection, and chronic regional pain syndrome, in patients presenting with normal results on radiographs. Bone scan images are resistant to metal-based implant artifact, allowing effective evaluation of failed total joint prostheses. Bone scintigraphy remains an underused tool in the evaluation and management of orthopedic patients. [Orthopedics. 2019; 42(1):e14–e24.]

Bone scintigraphy, commonly referred to as bone scan, is a radionuclide imaging modality with diverse applications.1–3 Although low cost, accessible, and highly sensitive, it is potentially underused, with modern modalities gaining popularity and preference. Its effectiveness and importance cannot be overstated. This comprehensive review discusses the technical aspects and clinical applications of bone scintigraphy.

Technical Aspects

Bone is composed of calcium hydroxyapatite and organic compounds, mainly collagen. With the use of radiopharmaceutical analogs of calcium, hydroxyl groups, or phosphates, selective honing of compounds to areas of interest can be achieved.2,4,5 Bone-seeking compounds, most commonly technetium-labeled diphosphonate (99mTc-MDP), have been used for orthopedic imaging.2,4,5 The stable decay activity, long half-life (6 hours), principle photon energy of 140 keV, and minimal particulate emission of 99mTc-MDP permit its widespread use in medical imaging.4 It quickly leaves the vascular system and accumulates in extracellular compartments. Locoregional factors such as blood flow, pH, capillary permeability, hydrostatic pressure within the medullary canal, bone turnover, and quantity of mineralized bone contribute to uptake.4Table 1 lists causes of increased radiotracer accumulation.

Causes of Abnormal Increased Technetium-Labeled Diphosphonate Uptake on Bone Scan

Table 1:

Causes of Abnormal Increased Technetium-Labeled Diphosphonate Uptake on Bone Scan

After the radiotracer is taken up by the bone, it undergoes a decay process that a detector can visualize. Isotopes of elements used as tracers have subatomic structures that are unstable. Stability is achieved through nuclear decay where energy is released. Radiation particles, synonymous with radionuclides, including alpha and beta particles, gamma rays, and positrons, are emitted, detected, and recorded.4

Bone scintigraphy may be performed as either single phase or multiphase. Single phase (Figure 1) takes a single image and acts as a screening examination for hypermetabolic regions.4 In a triple phase bone scan (TPBS), 3 images are taken at set time intervals. First, an angiogram is obtained immediately after the injection. Next, a blood pool phase is obtained within 5 minutes detecting radiotracer in the vasculature and extracellular space. Last, bone uptake is imaged 2 to 3 hours after injection.4 Triple phase bone scan allows for differentiation between bony and soft tissue pathology (Figure 2).

Normal adult single-phase technetium-labeled diphosphonate bone scan. There is symmetric radiotracer distribution throughout the skeletal system. Note normal uptake within the renal collecting systems and bladder as well as faint activity within the soft tissues.

Figure 1:

Normal adult single-phase technetium-labeled diphosphonate bone scan. There is symmetric radiotracer distribution throughout the skeletal system. Note normal uptake within the renal collecting systems and bladder as well as faint activity within the soft tissues.

Cellulitis on technetium-labeled diphosphonate bone scan. Angiographic images showing hyperemia of the right foot (A). Delayed images showing persistent soft tissue uptake diffusely throughout the right foot, without focal increased activity to suggest osteomyelitis (B).

Figure 2:

Cellulitis on technetium-labeled diphosphonate bone scan. Angiographic images showing hyperemia of the right foot (A). Delayed images showing persistent soft tissue uptake diffusely throughout the right foot, without focal increased activity to suggest osteomyelitis (B).

Differentiating normal from pathologic radiotracer accumulation requires knowledge of typical patterns of distribution. Patients with active physeal growth plates will show intense symmetric uptake, which can obscure areas of interest (Figure 3).4 In adults, physiologic radiotracer uptake occurs in common locations, including the acromion, coracoid processes, sternoclavicular joints, sternomanubrial joint, and sacral alae5 (Figure 1). Spurious uptake of 99mTc-MDP may occur from technical errors in preparation. Oxidation may occur if air is introduced into the syringe and if there is a delay in administration of 99mTc-MDP, both of which increase formation of free pertechnetate. Imaging should occur within 4 hours of preparation.4,5 Arterial injection of the radiopharmaceutical can cause the “glove” or “sock” phenomenon, which resembles uptake seen in complex regional pain syndrome.4,6

Ewing sarcoma. Anteroposterior pelvic radiograph of a 13-year-old girl who presented to the emergency department with left hip pain and fevers showing subtle mixed sclerosis and mottled lysis of the proximal left femur (arrow). There is also right hip periarticular soft tissue swelling (A). Magnetic resonance imaging of the left femur showing osseous and surrounding soft tissue enhancement on T1 post contrast fat-suppressed image (B) and edema on short tau recovery sequence (C) (arrowheads). Posterior technetium-labeled diphosphonate bone scan showing confined uptake in the proximal left femur (arrow) (D). Whole body bone scan is used in the initial staging of Ewing sarcoma as well as monitoring of response to therapy.

Figure 3:

Ewing sarcoma. Anteroposterior pelvic radiograph of a 13-year-old girl who presented to the emergency department with left hip pain and fevers showing subtle mixed sclerosis and mottled lysis of the proximal left femur (arrow). There is also right hip periarticular soft tissue swelling (A). Magnetic resonance imaging of the left femur showing osseous and surrounding soft tissue enhancement on T1 post contrast fat-suppressed image (B) and edema on short tau recovery sequence (C) (arrowheads). Posterior technetium-labeled diphosphonate bone scan showing confined uptake in the proximal left femur (arrow) (D). Whole body bone scan is used in the initial staging of Ewing sarcoma as well as monitoring of response to therapy.

Diphosphate radiopharmaceuticals accumulate within the bladder. This can either obscure pelvic lesions or be misinterpreted as pathologic lesions. Frequent voiding can help circumvent this problem.4,5 In patients with impaired renal function, diffuse soft tissue uptake can occur and delay osseous uptake, making evaluation of the osseous structures suboptimal. Patients with decreased cardiac output can have insufficient delivery of radiopharmaceutical. Metallic devices and articles of clothing can produce a photopenic defect that obscures a pathologic lesion.4,5 There is a risk of allergic reaction to the radiopharmaceutical and exposure to ionizing radiation, but complications rarely occur.4

Other Nuclear Imaging Modalities

Single Photon Emission Computed Tomography

The major difference between bone scintigraphy and single photon emission computed tomography (CT) is that the latter employs 360° tomographic images, allowing 3-dimensional localization of lesions. A standard gamma detector acquires data as a series of several planar images detected at sequential angles. Images are overlaid digitally with CT images for 3-dimensional localization.

Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography

Fluorine-18 fluorodeoxyglucose is a glucose analog that undergoes positron emission. It selects for metabolically active cells, becomes trapped by phosphorylation, and releases positrons that are detected.4 Positron emission tomography imaging can then be performed. Positron emission tomography can be integrated with CT, resulting in 3-dimensional localization and characterization of hypermetabolic lesions.7,8 The positron collides with electrons in an annihilation reaction, producing 2 gamma photons that are emitted in opposite directions at identical energies (511 keV). Cameras detect emitted gamma photons and then localize them to a single source and distance called an annihilation event. An image is reconstructed from annihilation events.4

Common Applications in Musculoskeletal Trauma

Computed tomography, magnetic resonance imaging (MRI), and bone scintigraphy are useful for detecting occult fractures. Hsu and Hearty1 and Lee and Worsley3 reported a 95% sensitivity and a 99% negative predictive value of bone scintigraphy for occult fractures. The scintigraphic appearance of fractures varies from the acute phase (up to 4 weeks) to the subacute phase (2 to 3 months) to the progressive healing phase (>3 months). The time frame to scintigraphic normalization ranges from 6 months to 2 years.3–5 In fracture nonunion, 99mTc-MDP uptake may persist.3

Acute Fractures

Bone scintigraphy can detect acute scaphoid fractures 3 days after injury. A recent Cochrane review by Mallee et al9 suggested that bone scan was superior to CT and MRI for sensitivity in detecting scaphoid fractures. A summation of studies in which 4 involved CT, 5 involved MRI, and 6 involved bone scintigraphy reported sensitivities and specificities of 0.72 and 0.99, 0.88 and 1.00, and 0.99 and 0.86, respectively. However, the most cost-effective strategies are immediate MRI, immediate CT, and MRI in 3 days as opposed to bone scintigraphy in 3 days.10 A 3-day postinjury bone scan strategy has shown decreased immobilization time (from an average of 12 days to an average of 6 days) for patients with no fracture when compared with follow-up radiographs.11

Occult hip fractures also require advanced imaging.1 Fairclough et al12 reviewed 693 charts of patients with acute hip pain. Forty-three patients had equivocal radiographs and underwent bone scan. Of these, 30 had negative results and were allowed to mobilize. Thirteen were found to have some variant of femoral neck or intertrochanteric fracture, indicating the utility of bone scintigraphy for occult hip fractures 3 days postinjury.12 Although bone scans have high sensitivity and specificity, MRI is superior.1,13 Other, nontraumatic pathologic processes, such as osteoarthritis and fractures of the acetabulum or pubic ramus, may lead to false-positive results.14 Although bone scintigraphy can predict avascular necrosis (AVN) in operative femoral neck fractures, it changed the treatment plan in only 1 of 83 reported cases.15

Insufficiency Fractures and Stress Fractures

When the balance between osteoblastic and osteoclastic activity tips in favor of osseous resorption, microfractures may occur. In the setting of overuse, these are called stress fractures. In the setting of osteoporosis, these are called insufficiency fractures.

Spinal compression fractures (Figure 4) are a significant cause of back pain in osteoporotic patients. Magnetic resonance images, CT scans, and radiographs can be equivocal in reaching the diagnosis. Bone scintigraphy can aid in the diagnosis and the determination of the age of the fracture. Cook et al16 examined 60 patients presenting with back pain. The results of bone scintigraphy changed the management of 18 (30%) patients and eliminated compression fracture as the diagnosis for 30 (50%) patients. The retrospective study was not designed to compare radiologic methods.16 Bone scintigraphy is not as useful in the evaluation of multilevel spine trauma, with 1 study reporting that it was able to diagnose the correct fracture levels in only 36% of patients.17

Acute compression fracture. Posterior image from a technetium-labeled diphosphonate bone scan of the thoracic spine in a patient with acute pain after a fall showing focal radiotracer up-take (arrow) in the T5 vertebral body (A), consistent with acute compression fracture (arrow) (B). Other areas of abnormal uptake on the same image relate to degenerative changes.

Figure 4:

Acute compression fracture. Posterior image from a technetium-labeled diphosphonate bone scan of the thoracic spine in a patient with acute pain after a fall showing focal radiotracer up-take (arrow) in the T5 vertebral body (A), consistent with acute compression fracture (arrow) (B). Other areas of abnormal uptake on the same image relate to degenerative changes.

The sacrum is a common location of insufficiency fracture following low-impact trauma in elderly patients. Other causes of insufficiency fracture include spinal constructs that extend into the sacrum. Although CT and MRI are commonly used, bone scintigraphy can be a valuable addition. It can determine the location of other potential osteoporotic fractures. Hatzl-Griesenhofer et al18 reported that, in 85% of patients with sacral insufficiency fractures, another insufficiency fracture was diagnosed on bone scintigraphy.3

Stress fractures are another cause of pain in weight-bearing structures that are not evident on radiographs.19,20 Bone scintigraphy has high sensitivity in this setting and can detect comorbid injuries elsewhere in the body.20 Stress fractures are particularly a problem in running athletes, especially females.21–24 Common locations of stress fractures include the tibia, the metatarsals, the calcaneus, and other tarsal bones. The sensitivities of MRI, CT, and bone scintigraphy for tibial stress fractures are 88%, 42%, and 74%, respectively.25,26

Triple phase bone scan is useful in differentiating tibial stress fractures from shin splints. Shin splints represent a reactive periostitis of the tibia that manifests scintigraphically as increased longitudinal linear signal at the posteromedial third of the tibia during phase 3. Angiographic and blood pool images have normal findings. In acute stress fracture, all 3 phases are positive.27

Fracture Nonunion

Differentiation of the morphologic type of fracture nonunion (hypertrophic, oligotrophic, comminuted, bone defect, or atrophic) is important for the future direction of treatment. A common indicator is the quality of bone callus noted on radiographs. Niikura et al28 compared bone scans and radiographs in 48 nonunions. All nonunions had uptake, and they were graded as 1, 2A, 2B, and 3 based on photon-deficient regions. Grade 1 had no deficient regions, 2A had a cleft between 2 high up-take regions, 2B had a cleft other than 2A, and 3 had uneven uptake throughout. This particular study also examined synovial pseudoarthroses where a pseudocapsule of synovial fluid separates fracture ends and can be confused with nonunion. It was found that hypertrophic nonunions tended toward grade 1 (7 of 7). Atrophic, defect, and comminuted were not graded as 1 in any cases. Five synovial pseudoarthroses were diagnosed, with 4 being grade 1 and 1 being grade 2A. These results indicate that bone scintigraphy can help determine the type of nonunion and assist with surgical decision making, including determining the utility of bone stimulation.28 Others have confirmed these findings, although synovial pseudoarthrosis presented as grade 2A.29–31

Avascular Necrosis

Bone scintigraphy has utility in monitoring patients for development of AVN of the femoral head. Using the femoral head ratio, the natural progression of bone scintigraphy findings in nondisplaced femoral neck fractures can be examined by comparing the density of radiotracer uptake in the postoperative hip with that in the nonsurgical side. Yoon et al32 evaluated 54 patients, with 1 of 54 developing AVN. The findings of bone scintigraphy were reviewed retrospectively at 2 weeks, 1 to 6 months, 12 to 18 months, and 18 to 24 months, showing average femoral head ratios of 0.99, 1.69, 1.29, and 1.05, respectively. These findings can be used to determine routine healing of nondisplaced femoral neck fractures.32

Idiopathic AVN of the hip in pediatric patients, called Legg–Calvé–Perthes disease, may be evaluated with bone scintigraphy early in the disease. It reveals decreased tracer uptake in the femoral head. This may occur before any discernible signs are present on plain radiographs. Unfortunately, many patients are not referred for bone scintigraphy until later in the course of the disease, after epiphysis fragmentation or femoral head collapse.33 Because of this radiographic lag, a scintigraphic classification was proposed by Conway34 that splits patients into 2 pathways based on the pattern of revascularization: recanalization (A) and neovascularization (B). The difference is the persistence of the lateral column in the A pathway but its absence in the B pathway in stages II and III. Stages I and IV are identical with no uptake in the epiphysis and then full uptake in the epiphysis, respectively. Conway's system was later validated by Comte et al,35 who found that 23 of 27 patients in pathway A had a good outcome vs 1 of 32 patients in pathway B. Bone scintigraphy can confirm healing of the lateral column, and this finding predicts a good outcome.36

Additionally, bone scintigraphy is sensitive for diagnosing AVN in the hand, wrist, and foot. Examples including Kienbock's disease, osteonecrosis of the lunate, and Freiberg's disease, osteonecrosis of the lesser toes. Early Kienbock's disease, stage I, is characterized by normal findings on radiographs and requires more advanced imaging, such as MRI or bone scintigraphy, for diagnosis.37,38 Freiberg's disease is similar.39,40

Arthroplasty

Whereas total joint arthroplasty prostheses often interfere with modern imaging because of metal artifact, nuclear scans are not distorted. However, uptake remains increased within 2 years of the procedure. Duus et al41 reported that 20% of patients with cemented total knee arthroplasties had increased uptake at 1 year postoperatively, and half of these had increased uptake at 2 years postoperatively. For cementless hydroxyapatite-coated hips, uptake ratios decreased between 1 and 3 months postoperatively and stabilized after 3 months.42 The results of bone scintigraphy may be affected by acetabular cup placement and geometry, with increased uptake in the superior and inferior acetabulum from remodeling.43

Periprosthetic Joint Infection Versus Aseptic Loosening

A common dilemma in the evaluation of painful arthroplasty is distinguishing infection from nonseptic loosening. Nagoya et al44 evaluated TPBS in patients who were scheduled to undergo revision surgery who had periprosthetic joint infection in the differential diagnosis. Forty-six patients with total hip arthroplasty or bipolar hemiarthroplasty were evaluated. Imaging with positive results for infection shows increased radiotracer uptake in all 3 phases. Bone scintigraphy had 88% sensitivity, 90% specificity, a positive predictive value of 83%, and a negative predictive value of 93% for periprosthetic joint infection.44 Reinartz45 found white blood cell imaging and positron emission tomography to be more accurate than bone scintigraphy. The accuracies, in the hip and knee, respectively, were as follows: white blood cell imaging, 91% and 84%; positron emission tomography, 89% and 83%; and TPBS, 80% and 81%. However, TPBS is more cost-effective and available. Because the difference in accuracy between the modalities is small, TPBS is acceptable.45 Smith et al46 attempted to differentiate infection from loosening based on blood pool images, although the differences were not significant. A 95% negative predictive value led them to recommend TPBS to rule out infection or loosening in patients with normal findings on radiographs.46

In the case of treatment of septic failure, the decision to proceed with reim-plantation is often unclear despite multiple sources of information, including clinical examination, radiology, microbiology, and intraoperative histopathology. Triple phase bone scan can play a supportive role. When TPBS was compared with histopathology and cultures, Ikeuchi et al47 found sensitivity of 94%, specificity of 69%, a positive predictive value of 80%, and a negative predictive value of 90%. In patients with cancer or rheumatologic diseases, inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein are not reliable and TPBS is highly sensitive.

In the case of aseptic loosening (Figure 5), Claassen et al48 found that bone scan had 76% sensitivity and 83% specificity for detecting aseptic loosening in patients with prosthetic knees. Geerdink et al,49 however, found that bone scan had only 34% and 38% sensitivity for detecting progressive acetabular osteolysis and component loosening, respectively.

Arthroplasty loosening and fracture. Coronal computed tomography scan showing serpiginous lucency (arrow) along the medial tibial plateau component–cement interface, consistent with loosening. Also note subacute fracture of the medial femoral condyle (arrowhead) (A). Technetium-labeled diphosphonate bone scan blood pool (B) and delayed (C) images showing increased radiotracer uptake at the site of loosening (arrows) as well as in the healing medial femoral condyle fracture (arrowheads). The clinical history must be considered in the differentiation of abnormal periprosthetic radiotracer uptake to exclude periprosthetic fracture, loosening, infection, or expected physiologic changes.

Figure 5:

Arthroplasty loosening and fracture. Coronal computed tomography scan showing serpiginous lucency (arrow) along the medial tibial plateau component–cement interface, consistent with loosening. Also note subacute fracture of the medial femoral condyle (arrowhead) (A). Technetium-labeled diphosphonate bone scan blood pool (B) and delayed (C) images showing increased radiotracer uptake at the site of loosening (arrows) as well as in the healing medial femoral condyle fracture (arrowheads). The clinical history must be considered in the differentiation of abnormal periprosthetic radiotracer uptake to exclude periprosthetic fracture, loosening, infection, or expected physiologic changes.

Anterior Knee Pain Evaluation After Arthroplasty

Anterior knee pain is a complaint following total knee arthroplasty. Bone scintigraphy can play a significant role in its management, specifically in cases of patellar ischemia. Gelfer et al50 examined patients who received total knee replacement without patellar replacement or lateral release through either a midvastus or a parapatellar approach. They found that more than 10% had transient patellar ischemia. These findings correlated with clinical symptoms and resolved within 4 to 6 weeks.50 Ahmad et al51 found that 51% of patients with symptomatic total knee replacements with primary patellar components had increased patellar uptake in the delayed uptake phase. Of the patients with anterior knee pain, 95% had positive results on imaging. All patients with positive results on imaging and pain who underwent revision experienced relief of symptoms.

Musculoskeletal Oncology

In musculoskeletal oncology, bone scintigraphy is used to identify disease distant from the primary tumor.2 Neoplasia to bone will tend to show increased uptake, given their increased metabolism. However, some tumors, including multiple myeloma, may not.

Metastatic Bone Disease

In the United States alone, 350,000 individuals develop bone metastasis annually, and scintigraphy has a 95% sensitivity for detecting bone lesions.2 Although other imaging modalities are more sensitive and specific, bone scintigraphy is an efficient way to monitor for skeletal metastasis because it evaluates the entire body.52 In patients older than 40 years, bone scintigraphy should be performed to evaluate for other metastasis, as only 8% to 15%4,53 have a single lesion.2,54 Findings on bone scintigraphy consistent with metastasis include new lesions compared with prior studies, increasing size or uptake over time, random scattering of lesions, extension into the medullary cavity, increase in soft tissue, target lesions, and reduced renal uptake or activity “superscan.”52

Primary Bone Neoplasia

Table 2 lists common benign bone lesions causing uptake on bone scintigraphy.55 Bone scintigraphy is especially useful in identifying osteoid osteoma in an area of complex anatomy; bone tumors that can be multifocal, including fibrous dysplasia and multiple hereditary exostosis; and Langerhans cell histiocytosis. However, lesions in Langerhans cell histiocytosis may not have uptake on bone scintigraphy, and skeletal survey may be a more accurate test.55 Bone scintigraphy is part of the workup in the differentiation between low-grade chondrosarcoma and enchondroma because of the increased uptake in the former.56,57 In evaluating osteoid osteoma, bone scintigraphy has high uptake at the nidus. It had positive results in all 16 cases in which it was used when 4 of 18 cases had no findings on radiographs.58 However, CT has more utility due to increased specificity and when performing guided ablation.2,58

Benign Osseous Lesions That May Show Radiotracer Uptake

Table 2:

Benign Osseous Lesions That May Show Radiotracer Uptake

Bone scintigraphy has a role in evaluating osseous and soft tissue sarcoma to determine the presence of metastasis, “skip lesions,” and to monitor for recurrence of disease.59–61 In the most common pediatric bone tumors, osteosarcoma and Ewing's sarcoma (Figure 3), bone scintigraphy is used to evaluate skip lesions, lung metastasis, and staging.59,62 In cases of bone sarcomas where reconstruction is performed using autografts, bone scintigraphy can be a sensitive modality in diagnosing mechanical complications. Van Laere et al60 identified 22 of 22 patients with mechanical failure or infection. Triple phase bone scan was also sensitive in identifying 20 of 20 recurrences of bone and soft tissue sarcoma.61 However, Powers et al63 and Meyer et al64 have recommended against its use in routine surveillance in Ewing's sarcoma and osteosarcoma.

Musculoskeletal Infection

Although clinical evaluation and laboratory values provide clues to etiology, imaging must confirm what is suspected. Radiographs and CT scans are commonly used as first-line evaluative tools, but they cannot quantify inflammation. Magnetic resonance imaging and nuclear medicine tests can identify sources of inflammation, although MRI can be affected by artifact. Triple phase bone scan (Figure 2), tagged white cell scan, and positron emission tomography studies allow examination of the bones and soft tissue without interference from orthopedic implants. With its high sensitivity, low cost, ease of performance, and resolution, bone scintigraphy functions as a screening tool for infection.65,66 However, its low specificity requires additional supportive workup.65 This is particularly true in the acute phase, in which case tagged white cell scans are preferred. When TPBS is used, the first 2 phases may be unremarkable. Thus, the third phase is important.

Posttraumatic Chronic Osteomyelitis

Following orthopedic trauma, diagnosis of infection can be difficult for multiple reasons: bone remodeling is normal, inflammation occurs due to the fracture healing process, and metal implants may interfere with imaging. As normal fracture healing changes may persist on bone scan 2 years after injury, tagged white cell scans offer increased specificity by targeting areas of increased leukocyte uptake.67 These scans are 89% accurate,68 becoming 97% to 100% accurate with the addition of single photon emission CT.67,69 Unfortunately, tagged white cell studies require much preparatory work and have potential for complication, including re-injecting the labeled cells back into the already presumably infected patient. Additionally, 2 separate scans must be obtained, one at 3 to 4 hours and one at 20 to 24 hours after reinjection. Although time consuming, this does allow close scrutiny of the differences in images. If the uptake is stable, no infection is suggested. In the case of persistent uncertainty, comparison with the contralateral side is appropriate.67

Diabetic Foot

Because they present similarly clinically, difficulty exists in differentiating osteomyelitis from Charcot arthropathy in diabetic patients. Thus, advanced imaging is needed for accurate diagnosis. A systematic review compared imaging modalities, using bone biopsy as a reference. This indicated similar sensitivities of fluorine-18 fluorodeoxyglucose positron emission tomography, white blood cell scintigraphy (with either 111In-oxine or 99mTc-hexamethylpropyleneamineoxime), and MRI: 89%, 92%, 91%, and 93%, respectively. However, positron emission tomography and 99mTc-white blood cell scintigraphy provided the greatest specificities at 92% each, as compared with MRI (75%).70 Adding quantitative values to TPBS images may provide an adjunct to clinical examination. Quantitative values can monitor progression of disease and diagnose contralateral disease by comparing uptake between the foot and the body and using blood flow velocity.71 Another group showed increased intraob-server reliability when diagnosing Char-cot arthropathy with quantitative data, but no change in sensitivity, specificity, and interobserver reliability.72

Complex Regional Pain Syndrome

Complex regional pain syndrome is often related to trauma and immobilization, with symptoms of pain and heightened sympathetic activation near the site of injury. Although the diagnosis is clinical, imaging assists with confirming the diagnosis.73,74 Increased sympathetic activity leads to vasodilation, which in turn leads to increased signal in early phases of TPBS.74 In patients with complex regional pain syndrome, signal in blood flow and pool phases could be elevated or diminished; however, the 2 phases correlate. The most common presenting pattern is increased uptake in all 3 phases (Figure 6). The most characteristic finding for diagnosing complex regional pain syndrome is increased periarticular uptake in the affected limb in the delayed uptake phase in multiple joints.75 Additionally, when a validated scoring system comparing the contralateral limb with the affected limb called the asymmetry score was used, a score of 1.06 or greater in the delayed phase had 100% specificity for the diagnosis of complex regional pain syndrome.73 Bone scintigraphy can be used to monitor the response to treatment, as resolving signal corresponds with improvement.74

Complex regional pain syndrome. A patient presented with pain, hyperesthesia, and swelling in the right hand and wrist several months after injury. Blood flow images from technetium-labeled diphosphonate bone scan showing increased radiotracer perfusion to the right hand (A). Blood pool and delayed images revealing increased radionuclide activity, particularly involving the periarticular regions of the right wrist (B). Normal results were seen on radiographs.

Figure 6:

Complex regional pain syndrome. A patient presented with pain, hyperesthesia, and swelling in the right hand and wrist several months after injury. Blood flow images from technetium-labeled diphosphonate bone scan showing increased radiotracer perfusion to the right hand (A). Blood pool and delayed images revealing increased radionuclide activity, particularly involving the periarticular regions of the right wrist (B). Normal results were seen on radiographs.

Metabolic Bone Disease

A combination of tetracycline administration and iliac crest biopsy is the most accurate method for managing metabolic bone conditions and assessing bone turnover and remodeling. This and other methods are invasive and cumbersome. Bone scintigraphy can be used to assess turnover based on the kinetics of bone turnover and tracer uptake76 and to assess metabolic activity by measuring whole body retention of tracer.77 These methods can be used to evaluate metabolic defects.

Osteoporosis Response to Therapy

Bone scintigraphy can be used to evaluate the response to therapy in patients with osteoporosis and osteoporotic fractures.16,78,79 Moore et al79 evaluated the effects of teriparatide in osteoporotic women. They found that uptake increased throughout therapy, with a median total skeletal increase of 22% and 34% at 3 and 18 months, respectively. These increases in total body uptake disappeared once treatment was stopped, with values returning to baseline; however, the spine and upper extremities continued to have statistically significant increases (16.9% and 62.8%, respectively).79

Osteomalacia

Evidence of osteomalacia can be seen on bone scintigraphy. Fogelman et al80 evaluated patients with vitamin D deficiency, Crohn's disease, celiac disease, and anticonvulsant-induced osteomalacia and after gastrectomy. They found that an increased bone-to-soft tissue ratio of tracer was indicative of osteomalacia. They also found other nonspecific markers, including increased uptake of the long bones and wrists and pseudofractures. They also suggested markers, including costochondral junction beading and the presence of a tie sternum. However, the primary use of bone scan in osteomalacia is for identifying pseudofractures,78 which are found typically in the ribs, lateral scapula, pubic rami, and medial femoral cortices.81

Paget's Disease

The typical pattern of Paget's disease involves significantly increased tracer up-take that spreads proximally or distally. In certain areas, the entire bone may be involved. This pattern most frequently appears in vertebrae, the scapula, and the pelvis. Tracer uptake may decrease in response to bisphosphonate therapy.81

Osteopetrosis

Bone scintigraphy can identify increased uptake in the metaphysis of long bones in patients with osteopetrosis.82,83 The diagnosis of infantile or pediatric osteopetrosis must be made early because of the implications of clinical manifestation. Serial bone scans may be used to monitor fractures and to evaluate for new, asymptomatic fractures.33

Pediatric Bone Pathology

Diagnostic applications for bone scintigraphy in children are similar to those in adults.33 The imaging can often be completed without sedation. Dosing of radiotracer is based on weight and is safe.4 For nonverbal children, bone scintigraphy can be especially useful as a screening examination when the location of pain cannot be accurately detemined.84

Slipped Capital Femoral Epiphysis

Plain radiographs are often sufficient for the diagnosis of slipped capital femoral epiphysis, although bone scintigraphy can identify resultant AVN postoperatively. These are ideally obtained within the first week postoperatively, but are sensitive for up to 2 weeks.85 Bone scintigraphy has a 100% negative predictive value for AVN in the setting of slipped capital femoral epiphysis and shows evidence of change long before radiographs.86

Nonaccidental Trauma

When patients present with suspected nonaccidental trauma, a comprehensive skeletal survey is performed. Bone scintigraphy also has utility in the evaluation. Tracer uptake may be elevated as early as 24 to 48 hours after the trauma.33 Twenty-five percent to 50% more areas of involvement may be detected by bone scintigraphy, and it allows for better recognition of periosteal trauma compared with radiographs.2,87 In a 10-year review, Bainbridge et al88 found that bone scintigraphy supported skeletal survey in 74% of cases and identified occult fractures in 12%. They proposed using bone scintigraphy as follow-up 10 to 14 days after skeletal survey. Bone scintigraphy is sensitive for rib fractures, which are suggestive of nonaccidental trauma.2,89,90

Growth Arrest

In pediatric orthopedic patients, trauma has the potential complication of growth arrest when the injury involves the physis, and 15% of all pediatric fractures involve the physis.91 Growth arrest is difficult to diagnose early, and bone scintigraphy can reveal changes in the uptake at the physis compared with the contralateral extremity.91,92 Abnormalities in the physeal signal can determine the location of the physeal bar.

Conclusion

Bone scintigraphy is a highly sensitivity, easy to use, accessible, and economical tool that can be synergistic with additional and advanced modern imaging. It is useful when imaging of the entire body, in osteoporosis, osteomalacia, metastatic bone cancers, sarcoma staging, and non-accidental trauma, is indicated. Bone scintigraphy can lead to and supplement diagnoses, including stress fractures, insufficiency fractures, occult fractures, bone tumors, infection, and complex regional pain syndrome, in patients with normal findings on radiographs. Unaffected by metal artifacts, bone scintigraphy permits unbiased evaluation of bone around implants. The many advantages of bone scintigraphy make it useful in orthopedic surgery, even when compared with CT and MRI.

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Causes of Abnormal Increased Technetium-Labeled Diphosphonate Uptake on Bone Scan

Localized
  Osseous tumors (primary or metastases)
  Osteomyelitis
  Trauma (fractures, stress injury, contusion, postsurgical)
  Loose prostheses
  Arthritis (eg, osteoarthritis, inflammatory)
  Paget's disease
  Melorheostosis
  Fibrous dysplasia
  Hyperemia
  Decreased sympathetic control
Generalized
  Hyperparathyroidism (primary or secondary)
  Renal osteodystrophy
  Diffuse metastases (breast, lung, prostate)
  Hematologic conditions

Benign Osseous Lesions That May Show Radiotracer Uptake

Aneurysmal bone cyst (may also be photopenic)
Bone island (bone hamartoma)
Chondroblastoma
Cortical desmoid
Enchondroma
Fibrous dysplasia
Fibroxanthoma
Giant cell tumor
Hemangioma
Osteochondroma
Osteoblastoma
Osteoid osteoma (intense uptake)
Authors

The authors are from the Department of Orthopaedic Surgery (JWK, MFL, SYK) and the Department of Radiology (JTS), Truman Medical Center, University of Missouri–Kansas City, Kansas City, Missouri; and the Department of Radiology (NMB), University of Kansas Medical Center, University of Kansas, Kansas City, Kansas.

The authors have no relevant financial relationships to disclose.

Correspondence should be addressed to: John W. Krumme, MD, Department of Orthopaedic Surgery, Truman Medical Center, University of Missouri–Kansas City, 2301 Holmes St, Kansas City, MO 64108 ( jwkgy5@gmail.com).

Received: September 28, 2017
Accepted: April 23, 2018
Posted Online: November 28, 2018

10.3928/01477447-20181120-05

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