2. INTRODUCTION
• Bone is the third most common organ affected by metastases, after the lung
and liver
• Bone metastases represent a prominent source of morbidity
• Skeletal-related events (SREs) that are due to bone metastases can include
pain, pathologic fracture, hypercalcemia, and spinal cord compression
3. MECHANISMS
• Bone undergoes constant remodeling, maintaining a dynamic balance
between osteoclastic and osteoblastic activity
• Activated osteoblasts stimulate production of the receptor activator of
nuclear factor kappa B (RANK) ligand (RANKL), which interacts with
RANK receptors to activate osteoclasts
• These activated osteoclasts then resorb bone, which results in osteolysis with
concomitant release of growth factors to induce tumor growth
4.
5. • The osteoblastic component of a lytic metastasis represents the reaction of
normal bone to the metastatic process
• The mechanism underlying predominantly osteoblastic metastasis is not well
understood, but tumor factors, such as tumor-derived peptide endothelin-1
(ET-1), may be implicated in some solid tumors, such as prostate cancer
7. CLINICAL PRESENTATION
• There is usually no reason to scan for bone metastases in the absence of
symptoms
• Unless routine laboratory studies indicate an elevated alkaline phosphatase or
an elevated calcium level
• In those cases, further evaluation with a fractionated alkaline phosphatase
test (liver versus bone) would be indicated and could lead to further
diagnostic imaging
• Hypercalcemia might prompt further diagnostic evaluation as well
8. • For symptomatic patients, pain is the most common symptom
• The character of the pain may be somatic (ie, achy, sharp, well-localized),
neuropathic (ie, burning, shooting, radiating), or both
• It may be constant or exacerbated by movement of the joint or involved bone (so-
called "incident" pain)
• Incident pain is particularly hard to treat in these patients because it comes on and
remits suddenly and may be very severe
• Neuropathic pain is often worse at night
9. • If the epidural space is invaded by the tumor, producing compression of the
spinal cord, the pain is likely to be worse at night and very intense
• Sudden severe pain may be caused by a pathologic fracture, and prompt
evaluation is necessary
• Symptoms of cord compression range from pain to neurologic deficits,
including motor weakness and paralysis, sensory deficits, bowel and bladder
dysfunction, and ataxia.
10. • Typically, the deficits result from soft tissue tumor compressing the spinal
cord or cauda equina, rather than the pathologic fracture itself
• Soft tissue expansion of bone metastasis and compression fracture may also
cause nerve root impingement, leading to radiculopathy and pain
11. Distribution
• The most common locations for metastatic disease are the vertebral column, sacrum, pelvis,
and proximal femurs
• Within the spine, the lumbar segment is most frequently involved, followed by the thoracic
and cervical segments
• The distribution of bone metastases may also be influenced by the specific type of primary
malignancy
• As an example, metastatic disease is distinctly unusual in anatomic sites distal to the elbow in
the upper extremity and distal to the knee in the lower extremity (termed acrometastasis).
• When bone lesions in these locations are found to be due to metastatic carcinoma, lung and
renal cell cancers are the most common primary sites
12. Overview of the diagnostic approach
• For extremity lesions, radiographs of the affected area are recommended for
initial evaluation
• If there is no apparent lesion on radiograph, but the clinical suspicion is high
then computed tomography (CT) or magnetic resonance imaging (MRI)
should be done
• Intravenous contrast is not required with either modality but could be helpful
in MRI to evaluate for extraosseous soft tissue extension
13. • For cancer patients presenting with significant back pain, spinal MRI contrast
is indicated, even in the absence of any neurologic signs (ie, changes in
sensation, weakness, or bowel or bladder dysfunction), to evaluate bone
metastasis as well as to rule out epidural extension of tumor and spinal cord
compression
14.
15. • Biopsy- For patients with no history of cancer, biopsy of skeletal abnormality may
be necessary for pathologic diagnosis
• For patients whose cancer is in remission, documentation of a pathologic diagnosis
may be necessary if this is the first evidence of recurrence or disease progression
• For patients with known history of stage IV malignancy or who were found to have
other visceral metastasis on staging or restaging evaluation, clinical diagnosis with
one or more imaging modalities may be sufficient to make a presumptive diagnosis
of bone metastasis.
17. Radiographs
• Used as an initial screen to evaluate symptomatic areas
• Poor sensitivity (44 to 50 percent)
• The typical radiographic appearance of a lytic metastasis is a permeative lesion of
the diaphysis or metadiaphysis of a proximal long bone or bone of the axial
skeleton
• Osteoblastic lesions are usually sclerotic in appearance, sometimes admixed with
lytic elements
• Radiographs may also be useful to assess the extent of cortical compromise and the
risk of pathologic fracture in a tubular bone.
18.
19. Computed tomography
• To assess the integrity of the bone cortex at a site with a known bone metastasis,
CT is preferred
• CT demonstrates superior bony detail compared with radiographs and can detect
osteolytic and osteoblastic metastases within the bone marrow before there is
destruction sufficient to become evident on radiography
• When compared with bone scan, CT demonstrates similar sensitivity
• CT involves faster image acquisition than MRI and may be more readily available
• However, the soft tissue contrast of CT is inferior to MRI
20. Magnetic resonance imaging
• MRI demonstrates greater accuracy than CT or bone scan and comparable
accuracy to FDG-PET/CT
• MRI with and without contrast should be used when spinal cord
compression and/or epidural disease/nerve root impingement is suspected
because of the excellent soft tissue resolution
• MRI can be used to help distinguish a pathologic fracture from an
insufficiency fracture
21. • Limitations
1. MRI is sensitive to movement and artifact due to metallic objects, which
may obscure evaluation
2. In addition, patients with implantable devices may not be able to undergo
MRI
3. Patients with severe claustrophobia also may not tolerate this study
23. Bone scan
• Most widely used method to detect bone metastases
• 99m-Tc-methylene diphosphonate (99mTc-MDP) is the most commonly used
tracer
• It accumulates in areas of increased osteoblastic activity, provides a total
skeletal examination, and is reliable for detecting metastases in diseases like
prostate and breast cancers
• Bone scan is less sensitive for detecting tumors with little to no osteoblastic
activity
24. Positron emission tomography (PET) scanning
• Metabolic imaging with FDG-PET, without or with integrated CT, has high
sensitivity and specificity for diagnosis of distant metastases, including the
bone
• There is growing evidence that integrated PET/CT scanning using 18-
fluorine sodium fluoride (NaF PET/CT) may offer increased sensitivity and
specificity in evaluating metastatic bone disease compared with Tc-99m-
based bone scan
25. Low-dose, whole-body computed tomography
• As a screening test for bone metastases in patients with solid tumors, CT has
lower sensitivity than bone scan, whole-body MRI, and FDG-PET
• However, one setting in which whole-body, low-dose CT may have utility is
in patients with multiple myeloma as an alternative to skeletal survey
26. Whole-body magnetic resonance imaging
• Whole-body MRI is less sensitive and less specific than FDG-PET/CT and
less sensitive than bone scan
• However,Whole-body MRI techniques are rapidly advancing with the
potential for faster acquisition times and may replace other means of
imaging bones, such as bone scan, in the future
27. Differential diagnosis
• The differential diagnosis of a lytic bone abnormality includes
1. Primary malignant bone tumors
2. Bone metastases from distant primary sites
3. Benign bone lesions such as hemangioma, various types of cysts, lipomas
28. Modified Lodwick-Madewell Grading System
• Grade I lesions represent lesions with low risk of malignancy, and include
well-defined geographic lesions with a sclerotic rim (IA) and geographic
lesions with a sharp margin without a sclerotic rim (IB)
• Grade II lesions are geographic lesions with ill-defined margins
• Grade III lesions include those with a moth-eaten or permeative appearance,
indicating a high risk of malignancy
29. • The differential diagnosis of a sclerotic or blastic bone lesion is narrower
A bone island, also known as an enostosis, is a focus of compact bone
located in cancellous bone
30. Enchondroma
Osteoid osteoma
Bone infarct
Fibrous dysplasia
Paget disease of bone
Vertebral venous congestion in patients with thrombosis of the superior
vena cava
