**8.1 Osteoporosis**

108 12 Chapters on Nuclear Medicine

in the affected area (cold area surrounded by a hyperfixation rim) enables early diagnosis, before the appearance of anatomical changes, which only show up later with radiography (Jones, 2011; as cited in Feggi et al., 1987 and Maillefert et al., 1997). The presence of this tipical pattern may increase the diagnostic accuracy to distinguish between osteonecrosis and transient osteoporosis, which usually has a diffuse pattern of tracer uptake, with no cold area. The accuracy of scintigraphy can be improved by using SPECT in patients with suspected avascular necrosis of the femoral head but have concomitant changes that may show up as false positives, such as severe acetabular osteoarthritis (Jones, 2011; as cited in Collier et al.,

Transient osteoporosis of the hip, also called transient marrow edema syndrome, is characterized by the presence of intense radionuclide uptake in the femoral head, which may extend to the femoral neck, to the intertrochanteric region, or to proximal femoral diaphyseal region. It is also typical to find hyperactivity at the images of flow phase and blood pool phase. Ischemia of the femoral head, that has not caused necrosis, has been suggested as a possible cause of this process. The reactive hyperemic response to this ischemic phenomenon, with a repair process, would explain scintigraphic changes. Insufficiency fractures in this

Reflex sympathetic dystrophy (RSD) is a complex physiologic response of the body to an external stimulus resulting in pain sympathetically mediated, usually nonanatomic pattern, which is out of proportion to the inciting event or expected healing response (Fournier & Holder 1998). It is a syndrome affecting an extremity after a minor trauma or surgery, but the particular mechanism remains uncertain. The diagnosis of RSD relies on clinical evaluation, scintigraphy or MR imaging, and routine radiographs. In the spontaneous course of this syndrome three phases can be distinguished: Stage I is the warm or hypertrophic phase, stage II is called the cold or atrophic phase and the third stage corresponds to stabilization or, in rare

Fig. 4. Bone scanning: Diffusely increased uptake in the distal right upper extremity in reflex

Three-phase scintigraphy has been widely utilized in both the diagnosis and monitoring of treatment (Murray, 1998). Scintigraphy imaging (**Fig. 4**) shows increased perfusion during the angiographic and vascular pool phases and widespread increases in radiophosphonate bone uptake in the late stage (Colamussi et al., 2004). The highest diagnostic accuracy is

1985). It also may help us to avoid overlooking a subchondral fracture.

location can provide similar scintigraphic imaging (Schneider, 2006).

instances, to healing (Driessens et al., 1999; Ornetti & Maillefert, 2004).

**6.1 Transient osteoporosis** 

**7. Reflex sympathetic dystrophy** 

sympathetic dystrophy.

Osteoporosis is defined as a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue, with an increase in bone fragility and susceptibility to fractures. Despite an increase in bone turnover that is usually present in osteoporosis, the bone scan has no role in the diagnosis of uncomplicated osteoporosis, but the Tc-99m-MDP bone scan is most often used in established osteoporosis to diagnose fractures, particularly at sites that are difficult to image with plain film radiography (eg, sacrum, ribs), and may be particularly useful in the diagnosis and timing of vertebral fractures. It also has an important role in assessing suspected fractures where radiography is unhelpful, either because of poor sensitivity related to the anatomical site of the fracture (eg, sacrum **Fig. 5**) or because adequate views are not obtainable because of the patient's discomfort (Fogelman & Cook, 2003). The characteristic appearance of these fractures is discussed elsewhere in this chapter. If a patient complains of back pain with multiple previous vertebral fractures noted on

Fig. 5. Posterior and anterior Tc-99m-MDP bone scan showing a typical "H-shaped" pattern in the sacrum, indicating a sacral insufficiency fracture.

Nuclear Medicine in Musculoskeletal Disorders: Clinical Approach 111

**6**) of Paget's disease like fractures (shown as a linear area of increased activity perpendicular to the cortex) or sarcomatous degeneration. The latter should be suspected in patients with persistent pain. The most common scintigraphic sign in the setting of sarcomatous degeneration is a cold area inside an area of increased uptake. The scan may also show heterogeneous and irregular uptake in the study area or adjacent soft-tissue uptake. The evaluation of the lesion should always be completed with x-ray and, even if doubts persist,

with an MRI, which could allow a more precise diagnosis (Fransen et al., 1998).

Fig. 6. A Tc-99m-MDP bone scan showing Paget's disease affecting the left humerus, midthoracic and lower lumbar spine, sacrum, right 11th rib, left pelvis, left femur and tibia, and the right tibia. Focal linear activity in the right tibia indicates an incremental fracture

Most cases of primary hyperparathyroidism are asymptomatic and are unlikely to be associated with changes on bone scintigraphy. The diagnosis is made biochemically and the use of bone scintigraphy does not make sense with this goal. But bone scan may be useful to differentiate the causes of hypercalcemia, in particular, hyperparathyroidism vs malignancy, so that typical features of metabolic bone disorders may be recognized. There is increased skeletal turnover in hyperparathyroidism, commonly seen as part of renal osteodystrophy, and in the more severe cases, this will be evident scintigraphically. A bone scan may show several features in hyperparathyroidism, but the most important is the generalized increased uptake throughout the skeleton that may be identified because of increased contrast between bone and soft tissues. This is commonly termed the metabolic superscan to differentiate from superscans caused by widespread bone metastases. Other typical features that have been described in this context include a prominent calvarium and mandible, beading of the costochondral junctions, and a "tie" sternum (Fogelman & Carr, 1980). Severe forms of hyperparathyroidism may be associated with uptake of bone radiopharmaceuticals

**8.3 Hyperparathyroidism** 

radiographs, and the bone scan is normal, then this essentially excludes recent fracture as the cause of symptoms and other causes of pain should then be considered.

#### **8.2 Paget**

Paget's disease is a localized disease of bone remodeling characterized by an increased bone resorption mediated by osteoclasts and a compensatory increase in bone formation. The result is a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This structural change produces bone that is expanded in size, less compact, more vascular and more susceptible to deformity and fracture than in normal bone. It can affect any bone, but is more common in skull, hip, pelvis, legs and back. Paget's disease may be monostotic, but the majority of patients have a polyostotic disease (80-90%). Most patients are asymptomatic, but they can experience a variety of symptoms such as bone pain, bone deformity, secondary arthritic problems, excessive warmth over bone area and different neurological complications caused by compression of adjacent neural tissues.

Bone scintigraphy, combined with radiology, is the technique of choice for assessing the location and extent of the pagetic bone lesions. It allows of evaluating the entire skeleton and is more sensitive than radiography in identifying metabolically active lesions (Fogelman & Carr, 1980): there is no radiological correspondence over 10% of scintigraphic hot spots (Devogelaer & De Deuxchaisnes, 2003). Symptomatic lesions are usually characterized by an increased uptake. Characteristically, affected bones show a striking increase in metabolic activity that starts at one edge of the bone and extends distally or proximally, often showing a "V" or "flame – shaped" leading edge. Both osteolytic and osteoblastic lesions are associated with and increase in radiotracer uptake on bone scan (**Fig. 6**). Scintigraphic pagetic bone features are usually characteristic, presenting as "hot spots". Whole bone may be affected, especially at pelvis, scapula and vertebrae. Abnormal tracer accumulation throughout the vertebra, affecting the body and posterior elements, is the characteristic finding in this localization. The skull may show a different pattern with a ring of increased activity only in the margins of the lesion (Fogelman & Cook, 2003). The intensity of radiactive tracer uptake, usually Tc-99m-MDP, depends on the metabolic activity of Paget's disease. In later stages, the disease may go into a period of inactivity and bone scan shows little or no uptake. Therefore, bone scintigraphy is complementary to the use of biochemical markers (e.g. serum alkaline phosphatase, urine hydroxyproline) for the assessment of bone turnover and may be useful in assessing therapeutic efficacy, since a good correlation between bone scintigraphy uptake and clinical and biochemical markers has been found (Cook et al., 2010). Cases of scintigraphic evidence of pagetic activity in the setting of normal serum alkaline phosphatase have been reported. In these cases, bone scintigraphy is the main technique in the evaluation of the effectiveness of the treatment. Bone scan can be performed 3-6 months after treatment with bisphosphonates, although scintigraphic images may respond in a heterogeneous way (after intravenous bisphosphonate therapy, some bones may become normal, most bones show some improvement, and a small proportion remain unchanged), and even lead to infrequent images that sometimes mimic those of bone metastases. In these cases, knowing the medical history of the patient is essential (Fogelman & Cook, 2003). The superior quantitative accuracy of PET using 18F-fluoride ion has been described in the evaluation of pagetic bone (Cook et al., 2002), and this method has also been described to measure response to bisphosphonate treatment. An increase in 18F-FDG uptake has also been reported in pagetic bone (Cook et al., 2010; as cited in Cook et al., 1997), correlating also with disease activity. Bone scintigraphy can also identify complications (**Fig.** 

radiographs, and the bone scan is normal, then this essentially excludes recent fracture as the

Paget's disease is a localized disease of bone remodeling characterized by an increased bone resorption mediated by osteoclasts and a compensatory increase in bone formation. The result is a disorganized mosaic of woven and lamellar bone at affected skeletal sites. This structural change produces bone that is expanded in size, less compact, more vascular and more susceptible to deformity and fracture than in normal bone. It can affect any bone, but is more common in skull, hip, pelvis, legs and back. Paget's disease may be monostotic, but the majority of patients have a polyostotic disease (80-90%). Most patients are asymptomatic, but they can experience a variety of symptoms such as bone pain, bone deformity, secondary arthritic problems, excessive warmth over bone area and different

Bone scintigraphy, combined with radiology, is the technique of choice for assessing the location and extent of the pagetic bone lesions. It allows of evaluating the entire skeleton and is more sensitive than radiography in identifying metabolically active lesions (Fogelman & Carr, 1980): there is no radiological correspondence over 10% of scintigraphic hot spots (Devogelaer & De Deuxchaisnes, 2003). Symptomatic lesions are usually characterized by an increased uptake. Characteristically, affected bones show a striking increase in metabolic activity that starts at one edge of the bone and extends distally or proximally, often showing a "V" or "flame – shaped" leading edge. Both osteolytic and osteoblastic lesions are associated with and increase in radiotracer uptake on bone scan (**Fig. 6**). Scintigraphic pagetic bone features are usually characteristic, presenting as "hot spots". Whole bone may be affected, especially at pelvis, scapula and vertebrae. Abnormal tracer accumulation throughout the vertebra, affecting the body and posterior elements, is the characteristic finding in this localization. The skull may show a different pattern with a ring of increased activity only in the margins of the lesion (Fogelman & Cook, 2003). The intensity of radiactive tracer uptake, usually Tc-99m-MDP, depends on the metabolic activity of Paget's disease. In later stages, the disease may go into a period of inactivity and bone scan shows little or no uptake. Therefore, bone scintigraphy is complementary to the use of biochemical markers (e.g. serum alkaline phosphatase, urine hydroxyproline) for the assessment of bone turnover and may be useful in assessing therapeutic efficacy, since a good correlation between bone scintigraphy uptake and clinical and biochemical markers has been found (Cook et al., 2010). Cases of scintigraphic evidence of pagetic activity in the setting of normal serum alkaline phosphatase have been reported. In these cases, bone scintigraphy is the main technique in the evaluation of the effectiveness of the treatment. Bone scan can be performed 3-6 months after treatment with bisphosphonates, although scintigraphic images may respond in a heterogeneous way (after intravenous bisphosphonate therapy, some bones may become normal, most bones show some improvement, and a small proportion remain unchanged), and even lead to infrequent images that sometimes mimic those of bone metastases. In these cases, knowing the medical history of the patient is essential (Fogelman & Cook, 2003). The superior quantitative accuracy of PET using 18F-fluoride ion has been described in the evaluation of pagetic bone (Cook et al., 2002), and this method has also been described to measure response to bisphosphonate treatment. An increase in 18F-FDG uptake has also been reported in pagetic bone (Cook et al., 2010; as cited in Cook et al., 1997), correlating also with disease activity. Bone scintigraphy can also identify complications (**Fig.** 

cause of symptoms and other causes of pain should then be considered.

neurological complications caused by compression of adjacent neural tissues.

**8.2 Paget** 

**6**) of Paget's disease like fractures (shown as a linear area of increased activity perpendicular to the cortex) or sarcomatous degeneration. The latter should be suspected in patients with persistent pain. The most common scintigraphic sign in the setting of sarcomatous degeneration is a cold area inside an area of increased uptake. The scan may also show heterogeneous and irregular uptake in the study area or adjacent soft-tissue uptake. The evaluation of the lesion should always be completed with x-ray and, even if doubts persist, with an MRI, which could allow a more precise diagnosis (Fransen et al., 1998).

Fig. 6. A Tc-99m-MDP bone scan showing Paget's disease affecting the left humerus, midthoracic and lower lumbar spine, sacrum, right 11th rib, left pelvis, left femur and tibia, and the right tibia. Focal linear activity in the right tibia indicates an incremental fracture
