Radiol Oncol 2001; 35(1):21-30.
review
Bone scintigraphy in clinical routine
Vika Müller1, Jörn Steinhagen2, Maike de Wit3, Karl H. Bohuslavizki1
Departments of 1Nuclear Medicine, 2Orthopedic Surgery and 3Hematology and Oncology, University Hospital Eppendorf, 20246 Hamburg, Germany
Background. In 1971, bone scintigraphy was performed the first time using 99mTc-labeled polyphospho-nates. Since that time, bone scintigraphy has become one of the most frequent diagnostic procedures in nuclear medicine departments. However, in the last decade, indications for this skeletal imaging procedure have been changing continuously. This paper, therefore gives a concise review of the current spectrum of indications for bone scintigraphy and its realization.
Conclusions. Just as many other nuclear medicine procedures, the bone scintigraphy has a high sensitivity, and the changes of the bone metabolism are seen often earlier than the changes in bone structure developing after x-ray. Therefore, occult lesions in the whole skeleton might be detected early by bone scintigra-phy. On the other hand, bone turnover is increased in various bone diseases. Consequently, bone scintigraphy usually has a low specificity, and differential diagnosis of the underlying etiology is often not feasible. However, three-phase bone scintigraphy and SPECT can significantly increase the specificity in some skeletal areas.
Key words: Bone diseases-radionuclide imaging; technetium; diphosphonates; bone neoplasms; bone scintigraphy, 99mTc-diphosphonates, indications
Introduction
Since 1961 bone turnover has been examined using various radio-labeled substances. In 1971 bone scintigraphy was performed the first time using modern 99mTc-labeled polyphosphonates, e.g. 99mTc-hydroxyethyl-Received: 28 September 2000 Accepted: 16 October 2000
Correspondence to: Karl H. Bohuslavizki, MD, PhD, Department of Nuclear Medicine, University Hospital Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany. Phone: +49 40 42803 4047; Fax: +49 40 42803 6775; E-mail: bohu@uke.uni-hamburg.de
enephosphonate(HDP) or 99mTc-methoxyeth-ylenephosphonate (MDP). After intravenous injection, these radiopharmaceuticals are adsorbed at the bone surface within some hours. The amount of adsorption depends both on the perfusion of the bones and the intensity of bone metabolism. Moreover, bone-seeking radiopharmaceuticals are excreted by the kidneys, and the kidneys and bladder can be seen routinely on a bone scan. Thus, total bone uptake depends not only on the perfusion and metabolic turnover, but also on renal function. In regions with a high bone metabolism, e.g. epiphyseal plates of children or mechanically stressed regions, e.g. ileosacral
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joints, the radiopharmaceutical uptake is increased physiologically. Additionally, in several pathophysiological conditions, even ex-traskeletal accumulation of tracer can be seen, e.g. in scars, myositis ossificans, liver metastases or tumors.1-3 On the other hand, fat patients (high absorption of radiation) and patients with renal failure show a reduced bone-to-background contrast resulting in degraded images.
Since the first bone scans using 99mTc-la-beled polyphosphonates by Subramanian and Mc Affee4 in 1971, the radioactive load has decreased continuously for the patient due to radiopharmaceutical and technological advantages, and bone scintigraphy has become a routine method in clinical nuclear medicine. However, in the last decade, the indications for bone scanning have changed dramatically. Therefore, the current spectrum of indications for bone scintigraphy and its realization are reviewed concisely in this paper.
Indications in benign bone diseases
In inflammatory joint diseases, both soft tissue and bone metabolism can be affected. The three-phase bone scintigraphy can image the activity of both processes. Increased perfusion, higher blood pool and raised activity of osteoblasts may be demonstrated by bone scan. Moreover, bone scan may contribute to the differential diagnosis of rheumatical joint diseases due to specific distribution patterns of several joint affections.
Fractures are seen primarily in radiographic images. Nevertheless, fractures in radi-ographically unclear regions can be excluded sufficiently by bone scintigraphy, and bone scanning also allows establishing the vitality of bone grafts or the loosening and infections of prostheses.
Current clinical indications for bone scintigraphy in benign bone diseases are listed in Table 1.




















Radiol Oncol 2001; 35(1): 21-30.
Degenerative joint diseases - osteoarthroses
Bone scintigraphy is uncommon
Avascular necrosis Perthe's disease Osteonecrosis
3-phase bone scintigraphy may help, if MRI is not predicative.1'2'21 MRI is the method of choice for avascular necrosis of the hip.22
Bone fractures and stress fractures
Reflex sympathetic dystrophy
Child abuse
Frostbite and ischemic injuries
Normal bone scan can exclude bone fractures after distinct time intervals,1'2'23 especially in carpal bones24'25 and
tarsal bones, in scapula, vertebrae, proximal femur, sternum, pelvic bones,26 sacrum.27
3-phase bone scan is of major importance for establishing the diagnosis, in staging and to control results of
therapy.28
Bone scan provides an overview over the whole skeleton, and periostal lesions can be seen.1'2'29 Metaphyseal
lesions in younger children, multiple fractures in different stages of healing, posterior rib fractures, long-bone
fractures in younger children are typical signs.
Bone scan may help to specify the need and the line of amputation.2'30
Paget's disease
Plantar fasciitis, archilles tendinitis, osteitis pubis
Normal 3-phase bone scintigraphy excludes dedifferentiation, helps to screen both regions and extent of bone
involvement.2'11
Normal 3-phase bone scan excludes inflammation in patients with clinical symptoms and
negative x-ray.2
Heterotopic ossification
Bone scan is abnormal before radiographic lesions show up.-
Osteoporosis
Bone scan is usually used to exclude stress and compression fractures.
Osteomalacia
Bone scan excludes pseudofractures earlier than x-ray.:
Benign bone tumors (enchondroma, chondroblastoma, giant cell tumors, eosinophilic granuloma, fibrous dysplasia, brown tumors of hyperparathyroidism, osteoid osteoma, aneurysmal bone cyst, vertebral hemangioma)
Normal 3-phase bone scintigraphy excludes any bone involvement if radiographically no lesion is shown.
However, bone scan has low specifity since most lesions will accumulate radioactive tracer. Characteristic
findings are rare, e.g. in osteoid osteoma.11 Usually, vertebral hemangioma show normal uptake in planar
scintigraphy.32
Malignancy cannot be excluded by bone scintigraphy.2
Bone infarction
Bone scan has a high sensitivity but is less specific.
Erdheim-Chester disease
Scintigraphic patterns of involved skeletal sites may lead to the diagnosis.-
"Bone" pain of unknown origin
Bone scan allows the differential diagnosis between soft tissue and bone lesion.2 In patients older than 50 years a bone scan is useful to exclude occult malignancy or metastases.34
Myositis ossificans                                 3-phase bone scan may demonstrate the activity of the process.
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Indications in malignant bone diseases
In primary bone tumors, the three-phase bone scintigraphy is often used to evaluate the primary lesion and to search for other occult bone lesions. In oncology, bone scintigra-phy is used to exclude bone metastases of various malignancies. Current recommendations for bone scanning in daily clinical nuclear medicine are given in Table 2.
Bone scanning
The injected activity of 99mTc-polyphospho-nates varies from 700 to 800 MBq. In children, the activity is adapted to body weight, with a minimum of 80 MBq. Younger children should get a sedative during image acquisition in order to reduce movement arti-
Figure 1. Recurrent osteosarcoma in the right femur in a 17-year-old boy and metastatic disease in the right tibia (arrows).



























Radiol Oncol 2001; 35(1): 21-30.
Lung cancer                                           Bone scan in primary staging only in resectable tumors47'48 or in clinical evidence.46'49
About 10% of metastases are missed due to pure osteolyses.1 Renal cell or bladder carcinoma           Bone scan should be done in patients with clinical evidence of bone metastases only.2'50
Differentiated thyroid cancer               In advanced follicular thyroid tumors or increasing Tg-levels without any correlates in 1311-scan or in bone pain.
About 30-50% of metastases may be missed due to pure osteolyses.1
Patients with elevated serum calcitonin and patients with medullary thyroid carcinoma should undergo bone
scintigraphy.2 Gastrointestinal cancer                         Only in patients with advanced regional tumors and clinical evidence of bone metastases or in patients in
whom an infiltration of sacrum is possible. Malignant Melanoma                            In patients with clinical evidence of bone metastases or in patients with advanced regional tumors or
histological positive lymph nodes. Bone scan cannot exclude bone metastases.2 Squamous-cell carcinoma of the           Only in patients with an advanced-stage disease, local and regional recurrences, and in second primaries
upper aerodigestive tract                     located below the clavicle.51
Cervical carcinoma, endometrial          Only in patients with clinical evidence of bone metastases or with advanced regional or histologically poorly
carcinoma, ovarian carcinoma              differentiated tumors.2
Testicular carcinoma                             Only in patients with stage IV seminoma with bone pain.2
Neuroblastoma                                      123I-MIBG-scintigraphy is more sensitive.2 Bone scan can show MIBG-negative metastases.52
Lymphoma                                             Useful in primary lymphoma of the bone and in reticulum cell sarcoma.3
Multiple Myeloma                                 Not useful since metastases are missed in 60-80% due to pure osteolyses.1
Systemic Mastocytosis                          Bone marrow scintigraphy is more sensitive.2 The degree of uptake and progress in serial scans marks more
aggressive bone marrow disease.53 Langerhans cell histiocytosis                Bone scan may detect additional regions of bone involvement.54
Palliative pain-therapy with                  Bone scan is a prerequisite for palliative pain-treatment with 186Re-HEDP or 153Sm-HDTMP
osteotrope radiopharmaceuticals. Soft tissue tumors                                  Bone scintigraphy can establish the activity and perfusion of soft tissue processes. Screening for bone
metastases or postoperative recurrences is also possible.
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Bloodpool
Mineralization
Anterior
Posterior
Anterior
Posterior
Figure 2. Bloodpool and late whole body images in a 75-year-old women with diabetes. Images show active osteomyelitis of the talus (arrows) and degenerative disease in the lumbar spine due to scoliosis. Artificial photope-nia in the left thorax is caused by a pacemaker.
facts. In standard bone scintigraphy, images are acquired approximately 3 hours after injection. In the interim period, the patients should drink at least 1 liter of fluid. Immediately before image acquisition, the patients are asked to empty their bladder. In order to reduce the radiation burden of physicians and nurses, bone scintigraphy should be performed directly after dialysis of the patients with renal failure.
In several focused problems, the three-phase bone scintigrams may give an overview of perfusion, blood pool, and bone mineralization. Dynamic image acquisition is started directly after intravenous injection of 99mTc-polyphosphonates (perfusion phase). After the first minute, a static image is acquired for 5 minutes (blood pool phase). Late static images (mineralization phase) are performed at least after three hours. Usually, whole-body
images are acquired at a double-headed gamma camera with large field-of-view.
The quantification of images may help to establish specific diagnoses, e.g. in sacro-ileitis, or may help to monitor treatment regimen, e.g. during chemotherapy of primary bone tumors. Additional images may be acquired from unusual angles optimized for best views of distinct bone areas. The images with a pinhole collimator permit clear identifications of small lesions, e.g. of bone infarction in the femoral head of children. Additionally, tomographic image acquisition using single photon emission computed tomography (SPECT) allows to separate overlapping bone structures, e.g. in pelvic, vertebrae, or in hip joints in transaxial, coronal and sagittal projections.
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Figure 3. 61-year-old women with radiological obscure findings in the sacrum. Bone scintigraphy performed 6 days after trauma revealed sacrum fracture (arrows). Additionally, hip prosthesis on the right side without any signs of loosening or infection and degenerative changes of bone metabolism in the left hip, both shoulders and in the left big toe can be seen.
Contraindications
Bone scintigraphy will usually not be performed during pregnancy, and only life-threatening indications will lead to bone scanning in breast-feeding women. In these patients, breast-feeding should be discontinued for 48 hours after injection. In children, repeated imaging need rigorous indication, particularly because of the higher radioactive load in their epiphyseal plates.
Radiation load
The effective dose in normal bone metabolism and regular renal function amounts to
Q	Ô
/>'	5.    \
	jr
	•
Anterior	Posterior
Figure 4. Multilocalar bone metastases in a 73-year-old woman with breast cancer.
0.008 mSv/MBq, which is equivalent to 6 mSv
per study.5
Conclusion
Just as many other nuclear medicine procedures, the bone scintigraphy has a high sensitivity, and changes of the bone metabolism are often seen earlier than the subsequent changes in bone structure in x-ray. Therefore, occult lesions in the whole skeleton might be detected early by bone scintigraphy.6 On the other hand, bone turnover is increased in various bone diseases. Consequently, bone scintigraphy usually has a low specificity, and the differential diagnosis of the underlying etiology is often not feasible. However, three-phase bone scintigraphy and SPECT7,8 can significantly increase the specificity in some skeletal areas.
Radiol Oncol 2001; 35(1): 21-30.
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Müller V et al. / Bone scintigraphy
Bloodpool
Mineralization
-vi'*.
f       Ï


Anterior
Anterior                               Posterior                                  Anterior                            Posterior
Figure 5. Bloodpool and late whole body images of 67-years-old man with Paget's disease in the pelvis (arrows).
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