Skeletal System
Report template: Bone scintigraphy
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Solve questions (26) →Contents
- 15.1 Bone Scintigraphy (Tc-99m MDP/HDP)
- 15.2 Three-Phase Bone Scintigraphy
- 15.3 Bone Imaging with SPECT/CT
- 15.4 NaF PET/CT
- 15.5 Metabolic Bone Diseases
- 15.6 Avascular Necrosis (AVN)
- 15.7 Evaluation of Prostheses
- 15.8 Stress Fracture and Trauma
- 15.9 Superscan and Other Patterns
- Key Points for the Board
- Current guidelines on this chapter's topics
Learning objectives and modules3 modules · about 2 h 55 min
Learning objectives
After this chapter you will be able to:
- Explain the uptake mechanism and normal distribution of bone-seeking agents.
- Interpret the phases of three-phase bone scintigraphy and the patterns that differentiate osteomyelitis, cellulitis and fracture.
- Explain what SPECT/CT and NaF PET/CT add to bone scintigraphy.
- Recognise the patterns of metastatic and metabolic bone disease (superscan, flare, cold lesion).
- Interpret findings in avascular necrosis, prosthetic loosening and infection, stress fracture and trauma.
Modules
The chapter is divided into study modules without changing the order of the text: read, watch the animations, then answer the questions linked to those headings.
- Module 115.1–15.4 Bone Scintigraphy (Tc-99m MDP/HDP) · Three-Phase Bone Scintigraphy · Bone Imaging with SPECT/CT · NaF PET/CT55 min · 2 animations · 18 questionsAnswer the questions →
- Module 215.5–15.7 Metabolic Bone Diseases · Avascular Necrosis (AVN) · Evaluation of Prostheses55 min · 24 questionsAnswer the questions →
- Module 315.8–15.9 Stress Fracture and Trauma · Superscan and Other Patterns · Key Points for the Board1 h 5 min · 28 questionsAnswer the questions →
Times are estimates: 130 words per minute, 3 min per animation, 1.5 min per question.
MOST FREQUENTLY ASKED IN THIS CHAPTER
✓
Agent: Tc-99m MDP/HDP → chemisorption to hydroxyapatite
✓
Most important determinant of uptake: Osteoblastic activity
✓
Dose: 20-25 mCi, imaging 2-4 hours later
✓
High sensitivity (~95%), low specificity
✓
Critical organ: Bladder (renal excretion)
✓
Commonest indication: Screening for bone metastases
✓
Phase 1: Perfusion (flow) → arterial blood flow
15.1 Bone Scintigraphy (Tc-99m MDP/HDP)9 questions
Radiopharmaceuticals:
•
Tc-99m MDP (Methylene Diphosphonate): The most widely used bone scintigraphy agent
•
Tc-99m HDP (Hydroxymethylene Diphosphonate): Alternative to MDP, similar biodistribution
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Both have a diphosphonate (bisphosphonate) structure
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Agents listed by EANM: Tc-99m HMDP/HDP and Tc-99m DPD (DPD and HMDP are also used in cardiac ATTR amyloidosis → see 14.5)
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Diphosphonates contain a P-C-P bond (pyrophosphate has P-O-P); they are therefore more stable in vivo, clear from the blood faster and give a higher bone/background ratio. During preparation pertechnetate is reduced by stannous ion (Sn²⁺) and binds to the diphosphonate
•
If air or oxygen enters the vial, free pertechnetate (thyroid, stomach, salivary gland) and reduced-hydrolysed Tc colloid (liver, spleen) form; this appearance should suggest a quality control failure
Uptake mechanism:
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Chemisorption (adsorption) to hydroxyapatite crystals on the bone surface
•
Determinants of uptake:
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Osteoblastic activity (the most important factor) → increased uptake in areas of new bone formation
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Regional blood flow → uptake increases as perfusion increases
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Sympathetic tone: When lost (stroke/hemiplegia, sympathectomy), capillaries dilate and blood flow increases, raising uptake on the same side. The agent binds more to amorphous calcium phosphate in newly formed bone than to mature hydroxyapatite
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Osteoblastic lesions → increased uptake (hot lesion)
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Purely osteolytic lesions → uptake may not increase or may be reduced (cold lesion) → example: multiple myeloma
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Kinetics (EANM): Plasma clearance is biphasic; at 4 hours ~60% of the activity is fixed in the skeleton, ~34% has been excreted in the urine and ~6% remains in the circulation. Gastrointestinal excretion is negligible
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Bone accumulation peaks at 1 hour and remains practically unchanged up to 72 hours; the best bone/soft tissue ratio is at 2-3 hours
BOARD TIP
▸
"Most important factor determining uptake on bone scintigraphy?"
→ Osteoblastic activity.
▸
"Which malignancy shows cold lesions on bone scintigraphy?"
→ Multiple myeloma (purely osteolytic, minimal osteoblastic response). Renal cell carcinoma, anaplastic thyroid cancer and some aggressive metastases may also show cold lesions.
First, Tc-99m MDP molecules bind to the bone surface by chemisorption (more often where new bone is forming) and fluoride exchanges with OH⁻ for F-18 NaF. In the second step a whole-body image changes over 4 hours while the fractions in skeleton, urine and circulation build up on the chart.
Continuous stream · no seeking
Key idea: diphosphonate is retained by chemisorption driven by osteoblastic activity, NaF by forming fluorapatite; imaging waits for soft-tissue background to clear (MDP 2-4 h, NaF 45-60 min).
Source: book (15.1: chemisorption, osteoblastic activity, ~60/34/6% at 4 h (EANM), peak bone accumulation at 1 h, best ratio at 2-3 h; 15.4: NaF fluorapatite, first-pass 100%, ~50% in bone, 45-60 min). Time curves are a representative model fitted to these values; the NaF curve is representative.
How to use: a single click on the drawing pauses and resumes; in the second step ↑ ↓ or the buttons below switch the tracer (MDP / NaF); ← → change steps.
Did this animation help you understand the topic?
Figure 15.1: Mechanisms of uptake of Tc-99m diphosphonate and F-18 NaF on the bone surface, and the distribution of MDP at 4 hours (schematic).
Dose and Protocol:
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Dose: 20-25 mCi (740-925 MBq) IV
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Imaging time: 2-4 hours after injection (delayed phase / bone phase)
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Plenty of fluids + frequent voiding during the waiting time → reduces bladder dose, increases soft tissue clearance
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Imaging: Whole-body (anterior + posterior) planar imaging
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SPECT or SPECT/CT is added if needed
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Collimator: LEHR or general-purpose collimator for routine imaging; pinhole or converging collimator for small structures (femoral head, hands and feet, paediatric hip). On spot images the detector is closer to the patient, so resolution is better than on the whole-body sweep
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If a full bladder obscures the symphysis pubis: The image is repeated after voiding, a caudal view is acquired ("tail-on-detector"; the patient sits on the detector) or SPECT/CT is performed
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EANM: 300-740 MBq in adults (8-10 MBq/kg), at least 40 MBq in children; 4.9 µSv/MBq, i.e. 3-4 mSv (~2.5 mSv in children)
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No preparation is needed; at least 0.5 L of water should be drunk and the bladder emptied frequently between injection and delayed imaging
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Pregnancy is a relative contraindication; breastfeeding is not stopped (for safety, 4 hours or one feed may be skipped)
Normal biodistribution:
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Symmetric, homogeneous uptake throughout the skeleton
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Kidneys and bladder are seen (renal excretion)
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Growth plates (in children): Intense symmetric uptake → normal
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Axial skeleton > appendicular skeleton (higher bone turnover)
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Sternomanubrial joint: Mildly increased uptake → normal variant
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Other normal variants: Heterogeneous skull uptake, hyperostosis frontalis interna, uptake in the sphenoid bone and between the orbits; sacroiliac joints; mild asymmetry of the joints of the dominant hand; lower neck lordosis or thyroid cartilage activity
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Diffusely increased calvarial uptake ("hot skull") is not specific for metastasis: it may be seen in metabolic bone diseases (renal osteodystrophy, hyperparathyroidism), in old age/hyperostosis and after chemotherapy (especially in breast cancer)
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Vertical linear activity in the posterior ribs (~7%; insertion of the iliocostalis muscle) may be seen; bilateral "hot patellae" are mostly degenerative or non-specific. Renal activity is considered increased if it is more intense than the lumbar vertebrae (e.g. chemotherapy, hypercalcaemia, obstruction)
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A sharply defined, round photopenic defect in the lower sternum is a sternal foramen (normal variant); in Tietze syndrome focally increased uptake is seen at the upper costochondral junction
Indications:
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Screening for bone metastases (the commonest indication) → breast, prostate, lung cancer
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Evaluation of osteomyelitis
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Stress fracture
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Avascular necrosis (AVN)
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Metabolic bone diseases (Paget, hyperparathyroidism)
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Prosthesis complications (loosening, infection)
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Primary bone tumours
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Condylar hyperplasia (mandible)
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Trauma (occult fracture)
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Suspected child abuse
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Complex regional pain syndrome (CRPS / RSD)
Sensitivity and Specificity:
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High sensitivity for bone metastases (~95%) but low specificity
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Increased uptake → may be metastasis, fracture, infection, degenerative change, Paget, etc.
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Specificity is improved by clinical correlation and SPECT/CT
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Metastatic pattern: Multiple randomly distributed focal lesions in the axial skeleton (red marrow). The commonest sources are prostate, breast, lung, kidney and thyroid; appendicular (distal) skeletal involvement is more common in lung cancer
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A metastasis requires 30-50% loss of bone mineral to be visible on radiography, so scintigraphy becomes positive earlier. However, marrow-based or purely lytic lesions may be negative on scintigraphy; MRI or FDG PET/CT is then performed
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Whole-body MRI shows more lesions in the spine, pelvis and femur; bone scintigraphy shows more in the ribs and skull. In a cancer patient with new back pain or neurological signs, whole-spine MRI is performed for cord compression
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Clues in differential diagnosis: Aligned focal lesions in consecutive ribs suggest trauma; in osteoarthritis uptake is on both sides of the joint. Osteomalacia (Looser zones) and Cushing syndrome/steroid use may mimic metastases with multiple rib foci
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Inflammatory arthritis: Bone scintigraphy shows active synovitis with high sensitivity (periarticular uptake in the blood pool and delayed phases). In RA a normal scan largely excludes active arthritis and predicts a low risk of erosion and a good prognosis
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Bone metastases are uncommon in early breast and prostate cancer (~3-5%), so routine screening is not needed. In prostate cancer a low PSA largely excludes metastasis, but not in patients on hormonal therapy
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In breast cancer, sternal uptake on the same side as the primary tumour suggests local spread via internal mammary lymph nodes. On the side of mastectomy the ribs may appear asymmetrically more intense because of reduced soft tissue attenuation
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Hypertrophic (pulmonary) osteoarthropathy: Bilateral, symmetric, linear periosteal uptake along the diaphyseal-metaphyseal cortices of long bones ("tram-track" appearance); most commonly associated with bronchogenic carcinoma
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HPO: Most common in the tibia-fibula, femur and radius-ulna (hands and feet, clavicle and scapula may also be involved; the axial skeleton is usually spared). It is more sensitive than radiography and regresses with treatment. Other causes: mesothelioma, bronchiectasis, cystic fibrosis, cyanotic heart disease, cirrhosis and inflammatory bowel disease
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Other indications (EANM): Before radionuclide palliative therapy (Ra-223, Sr-89, Sm-153, Re-186); distinguishing benign from malignant compression fractures before vertebroplasty/kyphoplasty; assessing activity in Paget disease before bisphosphonates; osteoid osteoma; Legg-Calvé-Perthes disease; transient synovitis of the hip; Tietze syndrome; periostitis (shin splints); enthesopathies; pseudarthrosis; bone graft viability; hypertrophic pulmonary osteoarthropathy
Interpretation pitfalls (EANM):
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Diffusely increased soft tissue uptake: Drug interaction, failed Tc-99m labelling, severe osteoporosis, renal failure, dehydration or too short an interval between injection and imaging
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Markedly reduced bone uptake with increased soft tissue and renal activity: bisphosphonate therapy such as etidronate (EHDP) (occupies binding sites) and aluminium-related osteomalacia (dialysis patients)
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Reduced or absent soft tissue uptake: Superscan or a very long interval between injection and imaging
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Commonest artefact: Urinary contamination (dilatation/stasis after urological surgery, urine soiling); others include paravenous injection, metal attenuation and motion
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Wholly or predominantly lytic lesions (myeloma, infarction, haemangioma, lytic metastasis), especially if <2 cm, are hard to see on planar images; SPECT/CT is then performed
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Because bone healing takes months, repeating a follow-up scan within 4-6 months is rarely useful; an increase in foci at an interval of less than 6 months may represent either progression or flare
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Symmetrically increased uptake may also be pathological (e.g. sacroiliitis)
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Report content (EANM 2016): in addition to the common items (see 27), radiopharmaceutical (MDP/HDP), interval between injection and delayed images, acquisition mode (whole body, spot views, SPECT/CT); in three-phase studies the flow and blood pool phases. Findings: overall distribution (diffusely increased uptake, superscan, absent kidneys), site, number and pattern of foci in the axial and appendicular skeleton, extraosseous uptake (kidneys, bladder, soft tissue), correlation with SPECT/CT or radiographs and change from prior studies; possibility of post-treatment flare
BOARD TIP
▸
"Why does bone scintigraphy have high sensitivity but low specificity?"
→ Increased osteoblastic activity occurs in many conditions (metastasis, fracture, infection, degeneration, Paget).
▸
"Commonest indication for bone scintigraphy?"
→ Screening for bone metastases.
▸
"Critical organ?"
→ Bladder (because of renal excretion).
15.2 Three-Phase Bone Scintigraphy3 questions
Principle:
Three-phase bone scintigraphy adds a perfusion (angiographic) phase and a blood pool phase to standard bone scintigraphy. It is used especially to distinguish osteomyelitis from cellulitis and to assess avascular necrosis.
The Three Phases:
Phase 1 – Perfusion (Angiographic/Flow) Phase:
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Dynamic imaging at injection → 2-5 s/frame for 60 seconds
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Assesses arterial perfusion of the region of interest
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Increased perfusion → hyperaemia (infection, inflammation, fracture)
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Reduced perfusion → AVN, vascular insufficiency
Phase 2 – Blood Pool (Soft Tissue) Phase:
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Static image 5-10 minutes after injection
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Soft tissue hyperaemia and vascular permeability are assessed
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Increased → infection, inflammation, soft tissue pathology
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Increased in cellulitis (diffuse), increased in osteomyelitis (focal)
Phase 3 – Delayed (Bone) Phase:
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2-4 hours after injection
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Reflects osteoblastic activity
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Focally increased uptake in bone pathology
Osteomyelitis vs Cellulitis:
| Phase | Osteomyelitis | Cellulitis |
|---|---|---|
| Phase 1 (Perfusion) | Increased (focal) | Increased (diffuse) |
| Phase 2 (Blood pool) | Increased (focal) | Increased (diffuse) |
| Phase 3 (Bone) | Increased (focal) | Normal |
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Osteomyelitis: Focally increased uptake in all three phases → bone involvement present
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In acute osteomyelitis, bone scintigraphy becomes positive within 24-72 hours of symptom onset; plain radiographic findings appear only after 10-14 days, once 30-50% of bone has been lost
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Cellulitis: Diffusely increased in phases 1 and 2, normal in phase 3 → no bone involvement, soft tissue only
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In cellulitis, mild, diffuse, non-focal soft tissue activity may persist in the delayed phase (there is no focal bone uptake). Normal phases 1-2 with a positive phase 3 usually suggest a chronic, non-hypervascular bone lesion
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Septic arthritis: Diffuse periarticular hyperaemia on both sides of the joint in phases 1-2; phase 3 is normal or shows mildly increased periarticular uptake
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False negative / cold osteomyelitis: In peripheral vascular disease the agent cannot reach the region; in early osteomyelitis ischaemia, or in advanced cases a central necrotic abscess, appears as a photopenic area
BOARD TIP
▸
"Key phase in distinguishing osteomyelitis from cellulitis?"
→ Phase 3 (delayed/bone phase). In osteomyelitis there is focally increased uptake in phase 3; in cellulitis phase 3 is normal.
▸
"Focally increased in all three phases?"
→ Osteomyelitis.
▸
"Phases 1-2 diffusely increased + phase 3 normal?"
→ Cellulitis.
On an anterior image of both legs between knee and ankle, phase 1 frames, phase 2 and phase 3 are shown in turn; osteomyelitis, cellulitis, stress fracture, CRPS and septic arthritis can be chosen, and the phase 1 time–activity curve is drawn for the lesion and the contralateral side. The second step compares 4 h and 24 h images and the lesion/contralateral ratio.
Continuous stream · no seeking
Key idea: phases 1-2 show hyperaemia, phase 3 shows bone formation; osteomyelitis and cellulitis separate on phase 3, and a ratio that rises at 24 h supports a bone lesion.
Source: book (15.2: phase 1 2-5 s/frame for 60 s, phase 2 5-10 min, phase 3 2-4 h; osteomyelitis, cellulitis, stress fracture (fusiform), CRPS (periarticular), septic arthritis; fourth phase). Images and curves are a schematic model; intensities are representative.
How to use: a single click on the drawing pauses and resumes; ↑ ↓ or the buttons below change the disease in the first step and the fourth-phase example in the second; ← → change steps.
Did this animation help you understand the topic?
Figure 15.2: Main disease patterns on three-phase bone scintigraphy (schematic).
Fourth Phase (24-Hour Delayed Imaging):
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Some centres acquire additional images 24 hours later
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More soft tissue activity has cleared → bone/soft tissue contrast increases
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Particularly useful in evaluating the diabetic foot and neuropathic (Charcot) joint
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Fourth-phase criterion: In osteomyelitis the lesion/normal bone ratio continues to rise from 4 hours to 24 hours (new bone keeps taking up the agent); uptake that disappears by 24 hours favours soft tissue (cellulitis)
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However, the specificity of three-phase bone scintigraphy in the diabetic foot is low → labelled leucocyte scintigraphy is preferred (→ see Chapter 24)
15.3 Bone Imaging with SPECT/CT1 questions
Advantages:
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Much better anatomical localisation than planar imaging
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Increases specificity → distinguishes whether a lesion is in bone or soft tissue
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Superior in anatomically complex regions (vertebrae, pelvis, skull base)
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CT component → morphological information (osteolytic, osteoblastic, mixed lesion)
Indications:
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Characterisation of equivocal lesions on planar imaging
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Vertebral lesions → metastasis vs degenerative change
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Vertebral body involvement → suggests metastasis
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Facet joint / posterior element involvement → suggests degenerative change
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EANM/ESNR/EUROSPINE 2025 (facet joint arthropathy and non-infectious postoperative spine): for bone SPECT/CT, 8-10 MBq/kg in adults (11-13 MBq/kg in the markedly obese), acquisition 2-5 hours after injection. Marked uptake in a facet joint improves the success of targeted injection (facet or medial branch block); it is particularly useful after a failed previous injection. After surgery, with inconclusive MRI, it is highly sensitive for complications such as pseudarthrosis, implant loosening and adjacent segment degeneration. Per treatment guidelines, active rehabilitation comes first in axial pain; a SPECT/CT finding alone does not decide an intervention
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Extension of body uptake into the pedicle supports metastasis; uptake at the anterolateral margin of the body (osteophyte) or adjacent to the end-plate is degenerative; an isolated focus in the spinous process is usually benign
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Mandibular / maxillary lesions
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Assessment of the pelvis and sacroiliac joints
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Localisation of stress fractures (spondylolysis → pars interarticularis)
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Periprosthetic assessment
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Specific indications for SPECT/CT according to EANM: Trauma of the small tarsal and carpal bones, osteoid osteoma, spine and sacroiliac joints, osteonecrosis/bone infarction, osteomyelitis/spondylodiscitis (with infection imaging), painful prosthesis, residual pain after orthopaedic surgery and extraskeletal uptake
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Also used to increase sensitivity when planar scintigraphy is normal despite strong suspicion of pathology
BOARD TIP
▸
"Increased vertebral uptake → metastasis or degeneration?"
→ Distinguish with SPECT/CT. Vertebral body uptake → metastasis more likely. Facet joint/posterior element uptake → degenerative change more likely.
▸
"Most important method for increasing specificity in bone scintigraphy?"
→ SPECT/CT.
Figure 15.3: Differential diagnosis by location of vertebral uptake on SPECT/CT (schematic).
Did this figure help you understand the topic?
15.4 NaF PET/CT5 questions
Radiopharmaceutical:
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F-18 Sodium Fluoride (NaF)
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PET agent → the PET version of bone scintigraphy
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Production: Cyclotron
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T½: 110 minutes (F-18)
Uptake mechanism:
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Fluoride ion → exchanges with OH⁻ in hydroxyapatite crystals on the bone surface → forms fluorapatite
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2-fold higher bone uptake and faster blood clearance than Tc-99m MDP
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First-pass extraction: 100% (very high)
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~50% of injected NaF is retained in bone. ~30% is in red cells, but because it diffuses freely this does not affect bone uptake; excretion is renal
Advantages (compared with Tc-99m MDP):
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Higher sensitivity → detects small lesions better
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Better spatial resolution (PET > SPECT)
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Faster imaging → 45-60 minutes after injection (vs 2-4 hours)
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Better image quality → high target-to-background ratio
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Anatomical correlation with CT (PET/CT)
Disadvantages:
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High cost (cyclotron, PET/CT scanner needed)
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Limited access
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Specificity similar to Tc-99m MDP (still low)
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Radiation dose may be slightly higher
Indications:
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Screening for bone metastases (especially prostate, breast cancer)
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Alternative to Tc-99m MDP bone scintigraphy
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Evaluation of benign bone lesions
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Situations where it is particularly valuable: End-stage renal disease and morbid obesity (where imaging with bisphosphonates is difficult)
Protocol and dosimetry (EANM):
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1.5-3.7 MBq/kg (185-370 MBq) in adults; in children at least 14 MBq and at most 185 MBq
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Effective dose 17 µSv/MBq, i.e. 3.1-6.3 mSv; the bladder wall receives the highest organ dose (150 µGy/MBq)
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No fasting needed; good hydration should be ensured (at least 2 glasses of water before and after injection)
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Imaging: 30-45 min after injection for the axial skeleton, 90-120 min for the extremities; 1-2 min per bed position in 3D mode
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False negatives: Osteomedullary lesions that do not form new bone and show no osteolysis on CT
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Flare: Seen within the first 2-3 months after treatment and usually regresses within 6 months; SUV is not used in routine interpretation
•
Normal distribution (SNM 2010; EANM 2015): fluoride is distributed throughout the skeleton; in adults uptake is generally uniform and symmetrical left to right (periarticular sites may vary). In children and adolescents growth causes increased uptake in the metaphyses. Excretion is urinary, so the kidneys, ureters and bladder are seen: urinary tract activity falls in renal insufficiency and rises proximal to an obstruction. Soft-tissue activity is minimal; regional hyperaemia makes soft tissue and bone more prominent
–
Because PET has higher resolution, physiological variability is more prominent than on planar bone scintigraphy: subclinical joint disease (especially the spine and the small bones of the hands and feet; may be asymmetrical), periodontal disease and subclinical injury of the ribs and costochondral junctions increase uptake. The degree of uptake does not separate benign from malignant processes; correlation with CT is needed
•
Report content (SNM 2010; EANM 2015): in addition to the common items (see 27), significant findings are grouped by region or significance; for each focus the name of the bone and, where relevant, its subdivision, whether it is focal or diffuse, its CT appearance (normal, sclerotic, lytic, mixed) and, if clinically important, at least one axial dimension on CT. The level of uptake may be described but has no standard nomenclature; SUV is descriptive only and not diagnostic. Urinary tract and soft-tissue uptake, significant non-skeletal CT findings and factors limiting sensitivity or specificity are reported; a lesion at risk of pathological fracture is also communicated directly
BOARD TIP
▸
"Mechanism of bone uptake of NaF?"
→ Exchange with OH⁻ in hydroxyapatite → fluorapatite.
▸
"NaF vs Tc-99m MDP?"
→ NaF: higher sensitivity, better resolution, faster imaging.
▸
"First-pass extraction of NaF?"
→ 100%.
▸
"Disadvantage of NaF?"
→ Cost and access.
15.5 Metabolic Bone Diseases12 questions
Paget Disease (Osteitis Deformans)
Pathophysiology:
•
Increased and disorganised bone turnover → osteolytic and osteoblastic activity together
•
Three phases: Osteolytic (early) → Mixed (active) → Osteosclerotic (late/inactive)
•
Monostotic (10-35%) or polyostotic (65-90%)
Bone scintigraphy findings:
•
Intense uptake in an expanded bone → involving all or most of the affected bone
•
Characteristic pattern: The bone is expanded and shows intense uptake
•
Most frequently involved bones: Pelvis, vertebrae, skull, femur, tibia
•
Skull: "Osteoporosis circumscripta" (osteolytic phase) → then diffusely increased uptake
•
Assessment of activity: Bone scintigraphy shows disease activity and extent
•
Treatment response: Reduced uptake after bisphosphonate therapy
•
Pagetic involvement usually starts at the end of the bone and extends towards the diaphysis, sharply demarcated from normal bone; the whole hemipelvis or vertebra may be involved. Mandibular involvement gives the "Lincoln (black beard) sign"
•
Uptake is usually increased even in Pagetic lesions that look lytic on radiography (photopenia is rare); sarcoma arising in Paget disease usually appears as a photopenic area
•
Paget: In the early lytic stage radiography is subtle or normal while scintigraphy is clearly positive and shows more lesions. In a long bone the advancing lytic front has a 'flame/blade of grass' shape; lesions may vary in intensity, and burnt-out sclerotic lesions show reduced uptake
•
Pagetic lesions usually take up no or very little FDG; intense FDG uptake in Paget disease therefore suggests sarcomatous transformation or metastasis
•
Fibrous dysplasia: May be monostotic (most commonly rib, proximal femur and craniofacial bones; vertebra rare) or polyostotic (McCune-Albright syndrome: café-au-lait spots, precocious puberty/GH excess). Often unilateral, markedly increased uptake; craniofacial lesions are sclerotic
•
Sclerosing dysplasias: Bone scintigraphy is normal in osteopoikilosis and osteopathia striata (distinguishes them from metastases); melorheostosis shows unilateral cortical ('flowing candle wax') increased uptake that may cross joints; Camurati-Engelmann disease shows symmetric diaphyseal increase
•
Vertebral Paget: Combined involvement of the body and posterior elements gives a 'Mickey Mouse' appearance and may mimic metastasis. After bisphosphonate (e.g. pamidronate) therapy, homogeneous uptake may become patchy or focal and also mimic metastasis
•
Erdheim-Chester disease: Bilateral, symmetric, intense uptake in the diaphyses and metaphyses of the lower limb long bones (epiphyses relatively spared); an almost pathognomonic pattern
BOARD TIP
▸
"Expanded bone + intense uptake on bone scintigraphy?"
→ Think of Paget disease.
▸
"Most frequently involved bone in Paget?"
→ Pelvis.
▸
"Complication of Paget?"
→ Osteosarcoma (less than 1% → but often asked on boards) → sudden increase in pain + new lesion in Paget disease → think of malignant transformation.
Hyperparathyroidism
Primary Hyperparathyroidism:
•
Raised PTH → increased osteoblastic and osteoclastic activity
•
Bone scintigraphy findings:
–
Diffusely increased bone uptake (resembling a metabolic superscan)
–
Reduced renal visualisation (increased bone uptake → less agent reaches the kidneys)
–
Increased calvarial uptake
–
Focal increase at sites of subperiosteal resorption (radial side of the phalanges)
•
Brown tumour: Focally increased uptake → giant cell reparative granuloma
Renal Osteodystrophy (Secondary Hyperparathyroidism):
•
Chronic renal failure → secondary HPT
•
Bone scintigraphy: "Metabolic superscan" pattern (→ see 15.9)
•
Additional findings: Uptake in extraosseous calcifications (lung, stomach, kidney)
•
Radiography in renal osteodystrophy: Band-like sclerosis of the vertebral end-plates ('rugger-jersey' spine), subperiosteal resorption and osteopenia
Osteoporosis
•
Bone scintigraphy is not used to diagnose osteoporosis (DEXA is the gold standard)
•
However, osteoporotic insufficiency fractures are seen on bone scintigraphy
–
Sacral insufficiency fracture → "H" or "Honda" sign (characteristic H-shaped uptake in the sacrum)
–
Vertebral compression fractures → focally increased uptake
BOARD TIP
▸
"H-shaped uptake in the sacrum?"
→ Sacral insufficiency fracture (osteoporotic).
▸
"Diffusely increased bone uptake + kidneys not seen on bone scintigraphy?"
→ Metabolic superscan → think of hyperparathyroidism or renal osteodystrophy.
▸
"Brown tumour?"
→ Focally increased uptake in hyperparathyroidism → giant cell reparative granuloma.
Bone Densitometry (DXA / DEXA)
•
Principle: Based on the different absorption of X-rays of two energies by bone and soft tissue (the energy difference is obtained by switching the tube voltage or by filtering the beam). Older SPA/DPA methods used a radioactive source
•
Pencil beam: Low dose, long acquisition; fan beam: fast acquisition, better image quality, higher dose
•
The patient's effective dose is 1-10 µSv; staff dose can be kept at <1 mSv per year
•
Before DXA: The longest wait is needed after a recent barium gastrointestinal study (until the barium is fully excreted, ~10-14 days); a few days' wait is also needed after iodinated contrast and radionuclide studies
•
Who is tested: Women aged 65 and older and men aged 70 and older; younger postmenopausal women and men under 70 with a risk factor for low bone mass (low body weight, prior fracture, high-risk medication, a disease associated with bone loss)
•
BMD is given in g/cm² (an areal density, not a volumetric measurement); bone mineral content (BMC) is in grams
•
Quantitative CT (QCT): Gives volumetric density (g/cm³) and can measure trabecular bone separately, but the patient dose is much higher than with DXA. DXA measures bone mass; it does not show bone quality or structure
•
Quantitative US (calcaneus): Speed of sound (SOS) and broadband US attenuation (BUA) fall in osteoporosis; it involves no ionising radiation, but is not used for diagnosis based on the WHO T score
WHO diagnostic criteria (postmenopausal women, men ≥50 years):
•
T score ≥ −1.0 normal; between −1.1 and −2.4 low bone mass (osteopenia); ≤ −2.5 osteoporosis
•
T score = (patient's BMD − young adult mean) / young adult SD. The Z score is the same calculation using a reference matched for age, sex and ethnicity. T ≤ −2.5 together with a fragility fracture indicates established osteoporosis
•
Each 1 SD fall in BMD increases fracture risk about 1.5-2.5-fold; bone loss of 1-2% per year after menopause is an expected, physiological finding
•
Sites used for diagnosis: Lumbar spine (L1-L4), total hip and femoral neck; the lowest T score is used. If these cannot be assessed, the radius 33% (1/3) ROI of the non-dominant arm is used
•
The radius 33% measurement is also used in hyperparathyroidism and in obese patients exceeding the table weight limit; in children the preferred sites are the lumbar spine and total body less head
•
Ward's area and the trochanter are not used for diagnosis; a single diagnosis is reported for each patient
•
In the lumbar spine, the diagnosis should be based on at least 2 evaluable vertebrae; fractured or artefactual vertebrae and vertebrae whose T score differs by >1.0 from the adjacent one are excluded
•
In premenopausal women, men under 50, children and adolescents the Z score is used: ≤ −2.0 is reported as "below the expected range for age" (in this group osteoporosis is not diagnosed on BMD alone)
•
If VFA reveals a previously unknown vertebral fracture, osteoporosis is diagnosed even if DXA is normal
•
The reference database for the hip T score is NHANES III
Quality control and follow-up:
•
Each centre should calculate its own precision error and least significant change (LSC)
•
Minimum acceptable precision (per technologist): Lumbar spine 1.9% (LSC 5.3%), total hip 1.8% (LSC 5.0%), femoral neck 2.5% (LSC 6.9%); retraining is required if precision is worse
•
When both hips are scanned, diagnosis uses the lowest T-score of either femoral neck or total hip, not the mean; monitoring uses the mean bilateral total hip BMD
•
Daily phantom measurement: The phantom is scanned 10 times and the mean is taken as the baseline; the limit on the Shewhart chart is ±1.5% of the mean (about ±3 SD). A value outside the limit is followed by a rescan; if the rescan is also outside, patient scanning is postponed until service (ISCD 2016). On a multi-rule Shewhart chart a single measurement beyond ±2 SD is a warning; a single measurement beyond ±3 SD, or two consecutive measurements beyond ±2 SD, requires evaluation of the instrument (ANZBMS 2025). ISCD 2023 asks each facility to establish and enforce corrective action thresholds that trigger a call for service. Cross-calibration is performed when the scanner is replaced
•
The 2025 EANM DXA guideline recommends scanning a spine phantom daily before use, or at least three times a week (ISCD: at least once a week unless the manufacturer recommends otherwise). When a scanner is replaced by one of the same manufacturer and model, cross-calibration is done by scanning the phantom 10 times on each scanner; the difference should be within 1% (preferably 0.5%)
•
For follow-up at the hip the total hip ROI is preferred; follow-up measurement is performed only if it will change treatment management
•
TBS (trabecular bone score): Reflects bone quality and predicts fracture risk independently of BMD and FRAX (its use in monitoring antiresorptive therapy has not been validated)
•
VFA: Recommended if T score < −1.0 or height loss >4 cm (Genant method)
BOARD TIP
▸
"Osteoporosis according to WHO?" T score ≤ −2.5.
▸
"Which score is used in a premenopausal woman?" Z score (≤ −2.0 → below the expected range for age).
▸
"Which forearm site is used for diagnosis?" Radius 33% of the non-dominant arm.
▸
"When is a lumbar vertebra excluded from evaluation?" If there is a fracture or artefact, or its T score differs by more than 1.0 from the adjacent one.
Figure 15.4: WHO T score diagnostic criteria on DXA, diagnostic sites and use of the Z score.
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15.6 Avascular Necrosis (AVN)6 questions
Pathophysiology:
•
Interruption of bone blood flow → osteonecrosis
•
Commonest site: Femoral head (hip)
•
Risk factors: Corticosteroid use, alcohol, sickle cell anaemia, trauma (femoral neck fracture), radiotherapy, Gaucher disease, decompression sickness (Caisson)
•
Gaucher bone crisis (pseudo-osteomyelitis): In the acute phase uptake on bone scintigraphy is reduced (infarction); this distinguishes it from osteomyelitis, in which uptake is increased
Bone scintigraphy findings:
Early (acute) phase:
•
Reduced/cold uptake in the femoral head (photopenic area) → blood flow interrupted → the agent cannot reach it
•
Three-phase bone scintigraphy: Reduced perfusion in phases 1 and 2, cold lesion in phase 3
Late (reparative) phase:
•
Increased uptake in the femoral head → reactive hyperaemia and osteoblastic repair activity
•
Or a "doughnut" pattern → central cold area (necrotic) + surrounding increased uptake (reactive)
Pinhole collimator:
•
Provides high-resolution imaging of small structures such as the femoral head
•
Useful for detecting the early cold lesion in AVN
BOARD TIP
▸
"Early bone scintigraphy finding in AVN?"
→ Cold (photopenic) lesion → blood flow interrupted.
▸
"Late phase?"
→ Increased uptake or doughnut pattern.
▸
"Most sensitive imaging in AVN?"
→ MRI (gold standard). Bone scintigraphy is less sensitive than MRI but has the advantage of bilateral assessment and whole-body screening.
Figure 15.5: Bone scintigraphy patterns of Paget disease, the Honda sign, avascular necrosis and cold lesions (schematic).
Did this figure help you understand the topic?
MRI vs Bone Scintigraphy (AVN):
•
MRI → gold standard for diagnosing AVN → high sensitivity even in the early phase
•
Bone scintigraphy → less sensitive than MRI but useful for screening bilateral/multifocal AVN
•
A cold lesion on bone scintigraphy → should be confirmed by MRI
•
In AVN myeloid cells die before osteocytes; bone marrow (colloid) scintigraphy therefore shows the defect early. Bone scintigraphy may be normal or cold in the first days; increased uptake develops as revascularisation and repair begin
•
Spontaneous osteonecrosis of the knee (SONK; now regarded as a subchondral insufficiency fracture): presents with sudden severe pain in the elderly, most often in the medial femoral condyle; radiography is normal while all three phases show intense focal increased uptake
•
Transient osteoporosis of the hip: Seen in middle-aged men or in pregnant women in the third trimester, without a history of trauma. Diffuse, homogeneous increased uptake in the femoral head and neck (the photopenic/focal pattern of AVN is absent); resolves spontaneously within months
•
Osteochondritis dissecans: Common in adolescent males; most often in the knee (lateral aspect of the medial femoral condyle), then the talus and capitellum. Bone scintigraphy shows focal increased uptake at the site of the subchondral fragment
•
Osteochondroses and apophysitides: Köhler (tarsal navicular), Freiberg (2nd metatarsal head), Kienböck (lunate), Preiser (scaphoid), Panner (capitellum), Sinding-Larsen-Johansson (lower pole of patella), Osgood-Schlatter (tibial tubercle), Sever (calcaneus)
•
Bone marrow scintigraphy (Tc-99m colloid): A colloid defect at a site of increased uptake on bone scintigraphy suggests infarction (e.g. distinguishing bone infarction from osteomyelitis in sickle cell anaemia)
•
Acute pain in a sickle cell patient: A bone marrow defect with normal or reduced bone scintigraphy suggests acute infarction (ischaemic crisis); bone uptake increases with repair over days-weeks. Normal marrow with increased bone uptake suggests osteomyelitis (usually Salmonella, diaphyseal location)
•
Sickle cell anaemia: Increased uptake in the calvarium and at the ends of long bones, high bone/background ratio, large kidneys and splenic uptake (calcification due to autoinfarction); acute infarction appears as a cold lesion
15.7 Evaluation of Prostheses6 questions
Normal Prosthesis Bone Scintigraphy:
•
Mildly increased uptake around the prosthesis → normal postoperative healing response
•
This increased uptake:
•
Uncemented prosthesis: normal for up to 2 years
•
Cemented prosthesis: May be normal for up to 6-12 months
•
Uptake decreases and normalises over time
•
The overall accuracy of bone scintigraphy in the painful prosthesis is ~50-70%. In knee prostheses periprosthetic uptake may persist for more than 1 year (more often at the tibial than the femoral component), so the time criterion is less useful than in the hip
Prosthetic Loosening (Aseptic Loosening):
•
Focally increased uptake at the prosthesis-bone interface → mechanical stress
•
Typical pattern: Focal increase at the prosthesis tip and/or the bone-cement interface
•
Three-phase bone scintigraphy: Phases 1 and 2 usually normal or mildly increased, focal increase in phase 3
Prosthetic Infection:
•
Three-phase bone scintigraphy: Increased uptake in all three phases (perfusion + blood pool + bone)
•
However, bone scintigraphy alone is inadequate for distinguishing loosening from infection
•
Combination of labelled leucocyte scintigraphy (In-111 oxine or Tc-99m HMPAO) + bone marrow scintigraphy (Tc-99m sulphur colloid) → gold standard (→ see Chapter 24)
Loosening vs Infection:
| Feature | Aseptic Loosening | Prosthetic Infection |
|---|---|---|
| Phase 1 (Perfusion) | Normal/mildly ↑ | Increased |
| Phase 2 (Blood pool) | Normal/mildly ↑ | Increased |
| Phase 3 (Bone) | Focal ↑ (prosthesis tip) | Diffuse ↑ |
| Labelled leucocytes | Negative | Positive |
| Bone marrow scintigraphy | Congruent | Incongruent |
BOARD TIP
▸
"Increased uptake around a prosthesis → infection or loosening?"
→ Bone scintigraphy alone cannot distinguish them → combined labelled leucocyte + bone marrow scintigraphy is needed.
▸
"How long does normal increased uptake last around an uncemented prosthesis?"
→ Up to 2 years.
▸
"Labelled leucocytes positive + incongruent with bone marrow?"
→ Infection.
Combined Labelled Leucocyte + Bone Marrow Scintigraphy:
•
Labelled leucocytes normally accumulate in bone marrow → bone marrow distribution around a prosthesis may be altered → false positives
•
Bone marrow scintigraphy (Tc-99m sulphur colloid) → shows bone marrow distribution
•
Congruent: Labelled leucocyte uptake = bone marrow uptake → no infection (normal marrow activity)
•
Incongruent: Labelled leucocyte uptake present but no bone marrow uptake → infection (leucocyte accumulation due to infection)
Figure 15.6: Normal postoperative, aseptic loosening and infection patterns in a hip prosthesis, with leucocyte-marrow congruence (schematic).
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15.8 Stress Fracture and Trauma8 questions
Definition:
•
Repeated abnormal stress applied to normal bone → fatigue fracture
•
Normal stress applied to abnormal bone → insufficiency fracture
Bone scintigraphy:
•
Very high sensitivity for diagnosing stress fractures (close to 100%)
•
Becomes positive 2-4 weeks before radiography
•
Typical appearance: Focal, fusiform (spindle-shaped) increased uptake → in the region corresponding to the fracture line
•
Three-phase bone scintigraphy: Increased uptake in all three phases (in the acute phase)
•
Shin splints (medial tibial stress syndrome): Longitudinal, superficial uptake along the posteromedial cortex of the tibia, covering more than 1/3 of the bone length; only the delayed phase is positive and there is no focal lesion
•
Grading of stress fractures (Zwas): I: small, faint cortical; II: larger, well-defined cortical; III: wide, fusiform corticomedullary; IV: intense, transcortical uptake. During healing perfusion normalises first, then blood pool; the delayed phase remains positive for months
•
If stress continues, a stress fracture may progress to a complete fracture; shin splints do not predict further injury
Common locations:
•
Tibia (most common → in runners)
•
Metatarsals (2nd and 3rd → "march fracture")
•
Femoral neck
•
Pelvis (pubic ramus)
•
Pars interarticularis → spondylolysis (in young athletes)
•
High-risk stress fractures (prone to non-union or progression to complete fracture): superolateral (tension) side of the femoral neck, anterior cortex of the tibia, tarsal navicular, proximal diaphysis of the 5th metatarsal (Jones fracture) and sesamoids
Spondylolysis:
•
Stress fracture of the pars interarticularis
•
Common in young athletes (gymnastics, football)
•
SPECT/CT → localises the pars interarticularis lesion → far superior to planar imaging
•
Active spondylolysis → increased uptake on SPECT → may respond to treatment
•
Inactive spondylolysis → normal SPECT → chronic, healed
BOARD TIP
▸
"Most sensitive method for diagnosing stress fracture?"
→ Bone scintigraphy (positive 2-4 weeks before radiography) or MRI (both very sensitive).
▸
"In evaluating spondylolysis?"
→ SPECT/CT → pars interarticularis uptake.
▸
"Pattern of sacral insufficiency fracture?"
→ H (Honda) sign.
Trauma and Occult Fracture
•
Fractures not seen on radiography → may be detected by bone scintigraphy
•
Suspected hip fracture in the elderly → negative radiography → bone scintigraphy or MRI
•
Bone scintigraphy: becomes positive 24-72 hours after trauma (in patients under 65 ~95% of fractures are positive at 72 hours; in those over 65 maximal sensitivity is reached at ~1 week)
•
MRI → positive immediately after trauma → preferred for urgent evaluation
•
Scaphoid fracture: Radiography may remain negative for 2-3 weeks, and MRI is preferred. Bone scintigraphy at 72 hours has a sensitivity of ~100% (a negative scan excludes fracture), but lower specificity
•
Scintigraphic course of a fracture: May be cold in the first hours; 80% are positive at 24 hours. 60-80% of non-displaced, uncomplicated fractures normalise at 1 year and ~95% at 3 years
•
Stages of a fracture (Matin): In the acute stage (2-4 weeks) diffuse increase around the fracture; in the subacute stage (8-12 weeks) a distinct linear increase along the fracture line; in the healing stage uptake gradually decreases
•
Displaced or complicated fractures may remain positive indefinitely. Persistent intense uptake in an old fracture suggests non-union or refracture; in pseudarthrosis irregular, focal, intense uptake is seen along the fracture line
•
Non-union (most common in the tibia): Intense uptake at the fracture ends (reactive/hypertrophic) indicates healing potential and a good response to stimulation or grafting. A photopenic gap along the fracture line (atrophic non-union, soft tissue interposition or synovial pseudarthrosis) indicates a poor prognosis
•
After surgery: Ring-shaped uptake at the craniotomy margin lasting months; uptake due to periosteal reaction adjacent to a rib resected at thoracotomy
•
Frostbite: On three-phase bone scintigraphy in the first days, bone without perfusion or delayed-phase uptake is non-viable; this helps determine the amputation level early
•
Bone graft: A vascularised (pedicled) graft shows diffuse uptake early; in a non-vascularised intercalary graft uptake begins at the ends and progresses along the graft with revascularisation
Child Abuse (Non-Accidental Trauma)
•
Bone scintigraphy → whole-body screening → detects multiple fractures of different ages
•
Complementary to the radiographic skeletal survey (not a substitute)
•
Advantage of bone scintigraphy: More sensitive for rib (especially posterior rib) fractures and early fractures; classic metaphyseal lesions and skull fractures are better seen on radiography
•
Disadvantage of bone scintigraphy: Skull fractures → low sensitivity (high calvarial uptake → fracture may be masked) → radiography is better
BOARD TIP
▸
"Bone scintigraphy vs radiography in child abuse?"
→ Complementary → should be used together. Bone scintigraphy → better for rib fractures; classic metaphyseal lesions and skull fractures are better on radiography. Radiography → better for skull fractures.
▸
"When does bone scintigraphy become positive after trauma?"
→ 24-72 hours (may be delayed in the elderly).
15.9 Superscan and Other Patterns20 questions
Superscan
Definition:
Diffuse, intense, homogeneous increased uptake throughout the skeleton on bone scintigraphy + kidneys and soft tissue not visualised (all of the agent has gone to bone → none is left for the kidneys).
Two types of superscan:
A) Metastatic Superscan:
•
Widespread osteoblastic bone metastases → increased uptake throughout the skeleton
•
Most common: Prostate cancer, breast cancer
•
Features:
–
Irregular/heterogeneous uptake mainly in the axial skeleton (distal appendicular skeleton relatively spared)
–
Kidneys not visualised
–
Individual lesions may not be distinguishable
–
Uptake may be asymmetric
B) Metabolic Superscan:
•
Metabolic bone disease → increased turnover throughout the skeleton
•
Causes: Hyperparathyroidism, renal osteodystrophy, osteomalacia
•
Other causes of diffusely increased skeletal uptake: Myelofibrosis, systemic mastocytosis, hyperthyroidism, hypervitaminosis D, acromegaly and fluorosis
•
Features:
–
Symmetric, homogeneous increased uptake in the axial and appendicular skeleton (long bones)
–
Kidneys not visualised
–
Increased calvarial uptake
–
Increased periarticular uptake
–
Increased uptake at the costochondral junctions ("rosary bead" pattern → osteomalacia)
–
More symmetric and homogeneous than a metastatic superscan
–
Other metabolic findings: 'Tie' sign in the sternum, increased uptake in the maxilla and mandible ('Lone Ranger' mask), increased uptake at the acromioclavicular joints and around large joints. 'Hot patella' is non-specific and of little value in the differential diagnosis
Metastatic vs Metabolic Superscan:
| Feature | Metastatic Superscan | Metabolic Superscan |
|---|---|---|
| Cause | Widespread bone metastases | HPT, renal osteodystrophy, osteomalacia |
| Distribution | Asymmetric, heterogeneous | Symmetric, homogeneous |
| Appendicular skeleton | Relatively spared | Prominent (long bones) |
| Calvarium | Variable | Markedly increased |
| Periarticular uptake | Variable | Increased |
| Mandible | Usually normal | Increased |
| Kidneys | Not visualised | Not visualised |
| Commonest cause | Prostate, breast cancer | Renal osteodystrophy |
BOARD TIP
▸
"Metastatic vs metabolic superscan?"
→ Metastatic → asymmetric, heterogeneous, mainly axial. Metabolic → symmetric, homogeneous, prominent uptake in long bones + calvarium, periarticular increase.
▸
"Why are the kidneys not seen in a superscan?"
→ All of the agent has gone to bone → not enough reaches the kidneys.
▸
A study that looks like a "beautiful bone scan" → may be a superscan → check whether the kidneys are visualised!
Figure 15.7: Normal bone scintigraphy and metastatic and metabolic superscan patterns (schematic).
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Flare Phenomenon (Flare Response)
•
Paradoxical worsening on bone scintigraphy in the first 2-3 months of treatment in patients responding favourably to chemotherapy or hormonal therapy
•
Increased uptake in existing lesions and/or appearance of new lesions
•
Mechanism: Increased osteoblastic healing activity in response to treatment → uptake increases
•
It is important to distinguish it from true progression
•
Flare vs progression:
–
Flare: 2-3 months after treatment → improvement on follow-up scintigraphy at 6 months
–
Progression: Lesions continue to increase, accompanied by clinical deterioration
–
In flare, PSA and tumour markers fall and the clinical picture improves; a rising PSA with new lesions indicates progression. PCWG3 "2+2" rule: if ≥2 new lesions are seen at the first follow-up, they must be confirmed by ≥2 further new lesions on a scan ≥6 weeks later
•
Flare phenomenon → a sign of good prognosis (response to treatment)
BOARD TIP
▸
"Worsening on bone scintigraphy after chemotherapy?"
→ May be the flare phenomenon → favourable response to treatment.
▸
"Flare vs progression?"
→ Flare: appears at 2-3 months, resolves by 6 months. Progression: continued worsening + clinical deterioration.
▸
"What does the flare phenomenon mean?"
→ Good prognosis (the treatment is working).
Figure 15.8: Time course of the post-treatment flare phenomenon compared with progression (schematic).
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Solitary Lesion (Single Focus of Increased Uptake)
•
A single focus of increased uptake on bone scintigraphy in a patient with known cancer
•
Probability of metastasis: 50-60% (varies by location)
–
Vertebral body → higher probability of metastasis
–
Rib → higher probability of benign cause (fracture, degeneration)
–
Sternum: uptake at the sternomanubrial joint may be a normal variant; however, a solitary sternal lesion in breast cancer is metastasis with ~75% probability
•
Evaluation: SPECT/CT → anatomical correlation → increases specificity
•
If needed: Confirmation by radiography, CT, MRI or biopsy
•
Osteochondroma: The commonest benign bone tumour. Increased uptake in the cartilage cap is normal during growth; increased uptake in adults is not specific for malignant transformation (absence of uptake supports benignity). Cartilage cap thickness is measured by MRI
•
Osteoid osteoma: More common in adolescents and young adults (10-30 years) and in males; most often in the femur and tibia. The "double density" sign is typical (intense nidus with milder surrounding reactive uptake); SPECT/CT is used for localisation
•
Ring ("doughnut") pattern (increased peripheral, reduced central uptake): aneurysmal bone cyst, giant cell tumour, chondromyxoid fibroma, telangiectatic osteosarcoma and chondrosarcoma. Not seen in osteoid osteoma (there is an intense central nidus)
•
Most benign bone tumours show mild uptake; uptake is markedly increased in osteoid osteoma and osteoblastoma. Enchondroma shows marked uptake only if there is a fracture (or malignant transformation)
•
Marked uptake: Fibrous dysplasia, chondroblastoma (epiphysis), osteoblastoma, osteoma (skull, sinuses, mandible). Mild or normal uptake: Non-ossifying fibroma/fibrous cortical defect and bone island. A simple bone cyst appears normal or photopenic unless fractured
BOARD TIP
▸
"Single focus on bone scintigraphy in a cancer patient?"
→ Probability of metastasis 50-60% → evaluate with SPECT/CT.
▸
"Single rib focus?"
→ High probability of benign cause (fracture).
▸
"Single vertebral body focus?"
→ High probability of metastasis.
Cold (Photopenic) Lesions
Lesions showing reduced uptake on bone scintigraphy:
•
Multiple myeloma (the most classic → purely osteolytic, minimal osteoblastic response)
•
In myeloma (IMWG): Initial skeletal assessment is by whole-body low-dose CT. MRI is the most sensitive method for marrow involvement (>1 focal lesion ≥5 mm indicates myeloma requiring treatment); FDG PET/CT is used for staging and response assessment
•
Renal cell carcinoma metastasis (aggressively osteolytic)
•
Anaplastic thyroid cancer metastasis
•
Early AVN (blood flow interrupted)
•
After radiotherapy (reduced osteoblastic activity and vascularity)
•
Metal prosthesis (photon attenuation)
•
Early aggressive metastases (before an osteoblastic response develops)
•
Radiation osteitis: Mild increase in the first weeks; after 6-12 months, sharply defined, geometric reduced uptake corresponding to the radiotherapy field
•
Other causes of photopenia: Ring pattern in a large lytic tumour (uptake is in surrounding reactive bone), lytic lung cancer metastasis, bone cyst, early osteomyelitis, bone infarction and the first hours after a fracture
•
In myeloma, bone scintigraphy is usually normal or photopenic; hot foci usually correspond to pathological fractures. For differentiated thyroid cancer metastases, radioiodine scanning is more sensitive than bone scintigraphy
•
Langerhans cell histiocytosis: Most common in the skull; lesions may appear hot, cold, ring-shaped or normal. Because scintigraphy may miss lytic lesions, especially in the skull, it is used together with a radiographic skeletal survey; FDG PET/CT is useful for assessing activity and response
BOARD TIP
▸
"Malignancy showing cold lesions on bone scintigraphy?"
→ Multiple myeloma (a board classic).
▸
"What should be used for skeletal imaging in multiple myeloma?"
→ FDG PET/CT or low-dose whole-body CT (bone scintigraphy is inadequate).
▸
"Cold area after radiotherapy?"
→ An expected finding → reduced osteoblastic activity and vascularity.
Extraosseous Uptake
Uptake of Tc-99m MDP/HDP in non-bone structures on bone scintigraphy:
Physiological:
•
Kidneys and bladder (renal excretion)
•
Growth plates (in children)
Pathological:
•
Soft tissue calcification:
–
Metastatic calcification (hypercalcaemia → lung, stomach, kidney)
–
Dystrophic calcification (damaged tissue → myositis ossificans, dermatomyositis)
–
Heterotopic ossification
–
Heterotopic ossification / myositis ossificans: Uptake decreases as it matures; on serial scans, a fall and stabilisation of uptake indicates maturation and guides the timing of surgical resection
•
Tumoral uptake:
–
Osteosarcoma (soft tissue component)
–
Breast cancer (microcalcification)
–
Neuroblastoma
–
Meningioma (calcified)
•
Other:
–
Myocardial infarction (acute → dystrophic calcification)
–
Pleural effusion
–
Hepatic necrosis
–
Rhabdomyolysis
–
Amyloidosis
–
Free pertechnetate (thyroid, stomach, salivary glands → labelling failure)
–
Liver: Metastasis (especially mucinous colon cancer), hepatic necrosis, technical causes (colloid formation, excess Al³⁺) and recent colloid scintigraphy; spleen: sickle cell anaemia
–
Heart: Acute MI, amyloidosis, pericarditis/effusion, cardiac or renal failure; breast: normal variant, gynaecomastia, mastitis, cancer; brain: infarction, metastasis, abscess
–
Lung: Hypercalcaemia, alveolar microlithiasis, sarcoidosis, radiation and diffuse metastases. Uptake may also be seen at the site of IM iron dextran injection; the commonest cause of skin activity is urine contamination
–
Diffuse "hot kidney": Chemotherapy (cyclophosphamide, doxorubicin, vincristine, etc.), amphotericin B, aminoglycosides, radiation nephritis (corresponding to the radiotherapy field), myoglobinuria/rhabdomyolysis, hypercalcaemia/nephrocalcinosis, thalassaemia/iron overload and obstruction
–
Mechanisms of extraosseous uptake: Hyperaemia (more agent reaching the region), binding to calcification or ossification, and necrosis (calcium entering cells)
BOARD TIP
▸
"Uptake in the thyroid, stomach and salivary glands on bone scintigraphy?"
→ Free pertechnetate → labelling failure (Tc-99m pertechnetate not bound to MDP).
▸
"Diffuse uptake in the lungs, stomach and kidneys on bone scintigraphy?"
→ Metastatic calcification → hypercalcaemia (hyperparathyroidism, renal osteodystrophy).
▸
"Cardiac uptake on bone scintigraphy after myocardial infarction?"
→ Dystrophic calcification → calcium deposition in necrotic myocardium.
Figure 15.9: Patterns of extraosseous uptake on bone scintigraphy (schematic).
Did this figure help you understand the topic?
Complex Regional Pain Syndrome (CRPS / RSD)
•
Former name: Reflex Sympathetic Dystrophy (RSD)
•
Post-traumatic pain, swelling, vasomotor changes
•
Three-phase bone scintigraphy findings (classic):
–
Phase 1: Increased perfusion
–
Phase 2: Increased blood pool
–
Phase 3: Periarticular increased uptake (the most characteristic finding)
•
High sensitivity (60-80%), moderate specificity
•
Useful for diagnosis in the early phase
•
Blood flow may be reduced in a hemiplegic limb, but the periarticular increase persists. The differential diagnosis of diffuse increase in a single limb includes CRPS, loss of sympathetic tone (paralysis) and inadvertent intra-arterial injection
•
The pattern in CRPS varies with stage: In the early stage (up to ~20 weeks) increase in all three phases; in the intermediate stage phases 1-2 normal with periarticular increase in the delayed phase; in the late/atrophic stage phases 1-2 reduced and the delayed phase normal or reduced. In children uptake is often reduced
BOARD TIP
▸
"Post-traumatic pain + periarticular increased uptake on bone scintigraphy?"
→ Think of CRPS (RSD).
▸
"Most characteristic bone scintigraphy finding in CRPS?"
→ Periarticular increased uptake in phase 3.
Key Points for the Board
Bone Scintigraphy Basics:
•
Agent: Tc-99m MDP/HDP → chemisorption to hydroxyapatite
•
Most important determinant of uptake: Osteoblastic activity
•
Dose: 20-25 mCi, imaging 2-4 hours later
•
High sensitivity (~95%), low specificity
•
Critical organ: Bladder (renal excretion)
•
Commonest indication: Screening for bone metastases
Three-Phase Bone Scintigraphy:
•
Phase 1: Perfusion (flow) → arterial blood flow
•
Phase 2: Blood pool → soft tissue hyperaemia
•
Phase 3: Delayed (bone) → osteoblastic activity
•
Osteomyelitis: Focally increased in all three phases
•
Cellulitis: Phases 1-2 diffusely increased, phase 3 normal
•
Low specificity in the diabetic foot → labelled leucocytes + bone marrow preferred
•
Acute osteomyelitis: Bone scintigraphy positive at 24-72 hours, radiography only at 10-14 days; a continued rise in the lesion/bone ratio at 24 hours favours osteomyelitis
NaF PET/CT:
•
Mechanism: Exchange with OH⁻ → fluorapatite
•
First-pass extraction: 100%
•
Compared with Tc-99m MDP: Higher sensitivity, better resolution, faster (45-60 min)
•
Disadvantage: Cost, access
Superscan:
•
Metastatic: Asymmetric, heterogeneous → prostate, breast cancer
•
Metabolic: Symmetric, homogeneous → HPT, renal osteodystrophy, osteomalacia
•
Common feature: Kidneys not visualised
•
"Beautiful bone scan" → may be a superscan → check the kidneys!
Causes of Cold Lesions:
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Multiple myeloma (board classic → purely osteolytic)
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Renal cell carcinoma, anaplastic thyroid cancer
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Early AVN, after radiotherapy, metal prosthesis
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In myeloma → use FDG PET/CT or low-dose whole-body CT
Extraosseous Uptake:
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Free pertechnetate → thyroid, stomach, salivary glands (labelling failure)
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Metastatic calcification → lung, stomach, kidney (hypercalcaemia)
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Dystrophic calcification → MI, rhabdomyolysis, myositis ossificans
Specific Patterns:
•
H (Honda) sign: Sacral insufficiency fracture
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Doughnut pattern: AVN (late phase)
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Expanded bone + intense uptake: Paget disease
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Periarticular increased uptake: CRPS (RSD)
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Rosary bead: Osteomalacia (costochondral junctions)
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Double density sign: Osteoid osteoma (intense nidus + surrounding reactive uptake)
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Bilateral symmetric linear periosteal uptake along long bone cortices ("tram-track"): hypertrophic pulmonary osteoarthropathy (bronchogenic carcinoma)
AVN:
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Early phase: Cold lesion (blood flow interrupted)
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Late phase: Increased uptake or doughnut pattern (reparative)
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Gold standard: MRI
•
Commonest location: Femoral head
Evaluation of Prostheses:
•
Normal postoperative uptake: Uncemented → 2 years, cemented → 6-12 months
•
Loosening vs infection → bone scintigraphy alone cannot distinguish them
•
Gold standard: Labelled leucocyte + bone marrow scintigraphy
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Incongruent pattern → infection; congruent → no infection
Flare Phenomenon:
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Paradoxical worsening 2-3 months after treatment
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Sign of good prognosis (response to treatment)
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Improvement at 6 months → flare; continued worsening → progression
Stress Fracture:
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Positive 2-4 weeks before radiography
•
Spondylolysis → evaluate with SPECT/CT
•
Bone scintigraphy after trauma: positive 24-72 hours later (may be delayed in the elderly)
•
MRI → positive immediately → preferred for urgent evaluation
•
Shin splints: Longitudinal superficial uptake along the posteromedial tibial cortex, only the delayed phase positive (in stress fracture: focal fusiform, all three phases positive)
Child Abuse:
•
Bone scintigraphy + radiography → complementary
•
Bone scintigraphy → better for rib fractures; classic metaphyseal lesion and skull fracture → radiography better
•
Radiography → better for skull fractures
Paget Disease:
•
Most frequently involved bone: Pelvis
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Complication: Osteosarcoma (less than 1%)
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Bone scintigraphy → assessment of disease extent and activity
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Treatment response: Reduced uptake after bisphosphonates
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A photopenic area or intense FDG uptake in Paget disease → think of sarcomatous transformation
Vertebral Lesion Differentiation (SPECT/CT):
•
Vertebral body → high probability of metastasis
•
Facet joint / posterior elements → high probability of degenerative change
•
Disc space + both adjacent vertebrae → discitis-osteomyelitis
Additional Notes (EANM guidelines):
•
Bisphosphonate kinetics: at 4 hours ~60% skeleton, ~34% urine, ~6% circulation; maximal bone accumulation at 1 hour; adult 300-740 MBq, 4.9 µSv/MBq (3-4 mSv)
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Soft tissue ↑: Renal failure, dehydration, failed labelling, short wait; ↓: superscan, very long wait; commonest artefact: urinary contamination
•
NaF: 50% in bone, ~30% in red cells; 185-370 MBq, 17 µSv/MBq, critical organ bladder; axial 30-45 min, extremities 90-120 min; valuable in ESRD and morbid obesity
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DXA: T ≤ −2.5 osteoporosis, −1.1/−2.4 low bone mass; premenopausal/men <50 → Z score (≤ −2.0); forearm → non-dominant radius 33%; patient dose 1-10 µSv
Current guidelines on this chapter's topics
The latest guidelines and consensus documents on the procedures covered in this chapter (official EANM index and primary sources, November 2026). Comparison of the text with these versions is in progress; consult the guideline itself for details.
- 2025Bone SPECT/CT in suspected facet joint arthropathy and non-infectious postoperative spine conditions. Part 2: Joint EANM/ESNR/EUROSPINE clinical practice consensus guideline (opens in a new tab)
- 2016The EANM practice guidelines for bone scintigraphy (opens in a new tab)
- 201518F-NaF PET/CT: EANM procedure guidelines for bone imaging (opens in a new tab)
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