Functional Imaging for Bone, Infection & Tumour Assessment
Bone Scintigraphy (Tc-99m MDP): Whole-body skeletal survey — sensitive for metastases, infection, occult fracture
Three-Phase Bone Scan: Adds flow and blood pool phases — helps differentiate infection from other causes
SPECT-CT: Combines SPECT (3D nuclear) with CT — better anatomical localisation
PET-CT (F-18 FDG): Detects metabolic activity — superior for tumour staging and infection localisation
Labelled WBC Scan: Gold standard for prosthetic joint infection — labels patient's own white cells
Key: Nuclear medicine provides FUNCTIONAL information about biological processes, complementing the ANATOMICAL information from radiography, CT, and MRI
- Bone scintigraphy with Tc-99m MDP detects areas of increased osteoblastic activity — it reflects bone TURNOVER, not a specific diagnosis.
- The three-phase bone scan adds vascular (flow and blood pool) phases to the standard bone phase, improving differentiation of infection from other causes of increased uptake.
- Bone scans are highly SENSITIVE (95%) but poorly SPECIFIC — virtually any process that increases bone turnover will cause uptake.
- PET-CT with F-18 FDG detects metabolically active tissue (infection, tumour) with better specificity and resolution than bone scintigraphy.
- Labelled white cell scans (In-111 or Tc-99m HMPAO) are the gold standard nuclear medicine test for prosthetic joint infection.
- “A 'cold' lesion on bone scan (photopenic/absent uptake) suggests: aggressive tumour outpacing bone response, myeloma, avascular necrosis, or early infection before osteoblastic response.
- “The three-phase bone scan: Phase 1 (flow) = arterial vascularity, Phase 2 (blood pool) = soft tissue hyperaemia, Phase 3 (delayed) = bone turnover. All three positive in infection.
- “PET-CT is increasingly replacing bone scan for metastatic workup due to superior sensitivity, specificity, and anatomical localisation.
- “Bone scan remains positive for 1-2 YEARS after joint replacement — normal postoperative uptake. A WBC scan helps differentiate infection from normal healing.
- “The 'superscan' pattern (diffuse intense skeletal uptake with faint/absent kidneys) indicates widespread metastatic disease or metabolic bone disease.
Nuclear medicine is commonly examined in the context of: (1) investigation of suspected bone metastases, (2) workup of prosthetic joint infection, (3) differentiation of stress fractures from other lesions, and (4) evaluation of avascular necrosis. You must understand the three-phase bone scan phases, the concept of sensitivity vs specificity, the indications for PET-CT vs bone scan, and the role of labelled WBC scans. A classic trap is not knowing that bone scans can be FALSELY NEGATIVE in myeloma (lytic lesions without osteoblastic response).
FBDThree-Phase Bone Scan Phases
Hook:FBD: Flow first (seconds), Blood pool next (minutes), Delayed last (hours) — the three-phase bone scan progresses from seconds to hours.
FITMAPCauses of Increased Uptake (Hot Spots)
Hook:FITMAP: virtually any process causing increased bone turnover produces a hot spot. Bone scan is sensitive but NOT specific.
MARLCauses of Decreased Uptake (Cold Spots)
Hook:MARL cold spots: Myeloma, AVN, Rapidly destructive tumour, and irradiated Lesions — these are potential false negatives on bone scan.
Overview
Nuclear medicine imaging in orthopaedics provides unique functional information about biological processes within bone and soft tissue that cannot be obtained from anatomical imaging modalities (radiography, CT, MRI). Unlike anatomical imaging which shows structural changes, nuclear medicine detects PHYSIOLOGICAL changes — increased bone turnover, metabolic activity, white cell accumulation, and blood flow — often before structural abnormalities are visible.
The fundamental principle is that a radioactive tracer (radiopharmaceutical) is administered to the patient, typically intravenously. The tracer is designed to accumulate at sites of specific biological activity. A gamma camera detects the emitted radiation and creates images showing the distribution of the tracer throughout the body. Areas of increased accumulation ('hot spots') indicate increased biological activity, while areas of decreased accumulation ('cold spots') may indicate avascularity, bone destruction, or tissue death.
Nuclear medicine shows FUNCTION (how active the bone is), while radiography/CT/MRI show STRUCTURE (what the bone looks like). This is critical because: (1) Functional changes often precede structural changes (e.g., stress fracture on bone scan 1-2 weeks before visible on X-ray). (2) Functional imaging can assess the ENTIRE skeleton in one study (whole-body bone scan for metastatic survey). (3) Functional information helps characterise lesions that look similar on anatomical imaging (differentiating infection from tumour). The trade-off: nuclear medicine has lower spatial resolution and lower specificity than anatomical modalities.
Tc-99m MDP (methylene diphosphonate): binds to hydroxyapatite at sites of osteoblastic activity. The workhorse of skeletal nuclear medicine. F-18 FDG (fluorodeoxyglucose): glucose analogue taken up by metabolically active cells. Used in PET-CT for tumour and infection. In-111 oxine-labelled WBC: labels the patient's own white cells, which then migrate to infection sites. Used for prosthetic joint infection. Ga-67 citrate: accumulates in infection and some tumours. Largely replaced by FDG-PET and WBC scans.
Clinical Imaging
Imaging Atlas
Systematic Approach
Systematic Bone Scan Interpretation
| Step | Assessment | Key Considerations |
|---|---|---|
| 1. Technical adequacy | Assess overall image quality, symmetry, and artefacts | Check for injection site extravasation, urinary contamination, and patient motion artefacts |
| 2. Three-phase correlation | Match findings across flow, blood pool, and delayed phases | All 3 positive = infection/inflammation. Delayed-only positive = stress reaction, metastasis, degeneration |
| 3. Focal hot spots | Identify areas of focally increased uptake | Correlate with clinical history: single vs multiple, location (metaphysis = infection, vertebral body = metastasis), intensity |
| 4. Photopenic areas | Identify areas of decreased or absent uptake (cold spots) | Consider: myeloma, AVN, aggressive tumour, irradiated bone — these are false-negative patterns |
| 5. Pattern recognition | Assess the overall distribution pattern | Superscan = diffuse uptake. Linear = fracture. Juxta-articular = arthritis. Random = metastases. Single = infection/tumour |
| 6. Correlate with anatomy | Relate findings to anatomical imaging (radiographs, CT, MRI) | Always correlate nuclear medicine findings with anatomical imaging for definitive diagnosis |
Key Studies
Tc-99m MDP Bone Scintigraphy
Mechanism: Tc-99m MDP (methylene diphosphonate) is administered intravenously and distributes via the bloodstream to the skeleton. MDP binds to calcium hydroxyapatite in bone through chemisorption. Uptake is proportional to: (1) local blood flow (delivery of tracer), and (2) osteoblastic activity (binding of tracer). Therefore, any process that increases blood flow OR osteoblastic activity will produce increased uptake.
Standard three-phase protocol:
- Phase 1 (Flow): Dynamic images acquired immediately after injection (30-60 seconds). Assesses arterial blood flow to the region of interest.
- Phase 2 (Blood Pool): Static image at 5-10 minutes. Shows soft tissue distribution and venous pooling.
- Phase 3 (Delayed Bone): Static images at 2-4 hours. By this time, approximately 50% of the tracer has been taken up by bone, and background soft tissue activity has cleared.
Interpretation of three-phase patterns:
- All three phases positive: Osteomyelitis, acute fracture, active tumour, CRPS/RSD
- Phase 3 positive only: Stress fracture (subacute), metastasis (established), degenerative change
- Phase 1 and 2 positive, Phase 3 negative: Cellulitis (soft tissue infection without bone involvement)
Clinical applications in orthopaedics:
- Metastatic skeletal survey (sensitivity approximately 95% for blastic metastases)
- Occult fracture detection (visible on bone scan 1-2 weeks before radiographic changes)
- Stress fracture diagnosis
- Paget disease assessment (extent and activity)
- Complex regional pain syndrome (CRPS) — diffuse periarticular uptake
Differential Diagnosis of a Focal Hot Spot
A single area of increased uptake is the commonest diagnostic dilemma in skeletal nuclear medicine. The bone scan itself rarely gives the answer — the discriminators are clinical context, the three-phase pattern, the anatomical location, and correlative imaging. The table below frames the reasoning a candidate should articulate at the viva.
| Diagnosis | Typical Location / Pattern | Discriminating Feature |
|---|---|---|
| Metastasis | Axial skeleton, vertebral body/pedicle, random | Known primary; often multiple foci; lytic primaries (renal, myeloma) may be photopenic — confirm on CT/MRI |
| Osteomyelitis | Metaphysis (children), any bone | All three phases positive; focal flow and blood-pool uptake; correlate with CRP/ESR and MRI |
| Stress fracture | Tibia, metatarsal, femoral neck, pars | Fusiform or linear delayed uptake; positive 1-2 weeks before radiographic change; sport/load history |
| Degenerative / OA | Juxta-articular, facet joints, first CMC | Delayed-phase only; bilateral and symmetric; matches osteophytes on radiograph |
| Paget disease | Pelvis, femur, skull, vertebra | Intense uptake of an entire bone with expansion; classic bone deformity; raised ALP |
| Osteoid osteoma | Femur, tibia, posterior elements | Focal intense uptake with central 'double-density'; night pain relieved by NSAIDs; lucent nidus on CT |
| Avascular necrosis | Femoral / humeral head, scaphoid | Early photopenia, later 'doughnut' of surrounding uptake; correlate with MRI |
Evidence Base
FDG-PET-CT vs Bone Scintigraphy for Skeletal Metastases (Lung Cancer)
- Pooled analysis of 17 studies (2940 patients) comparing FDG-PET-CT, FDG-PET, MRI and bone scintigraphy for bone metastases in lung cancer.
- FDG-PET-CT had pooled sensitivity 0.92 and specificity 0.98 — the highest diagnostic odds ratio of all modalities.
- Bone scintigraphy had sensitivity 0.86 and specificity 0.88, inferior to PET-CT on every metric.
Bone Scan False Negatives in Myeloma
- Radionuclide images and radiographs compared in 51 myeloma patients across 562 skeletal sites.
- Scintigraphy failed to show radiographically evident disease, or underestimated its extent, at 27% of sites — confirming relative insensitivity.
- The shortfall reflects the purely lytic nature of myeloma lesions: no osteoblastic response means little or no MDP uptake.
Bone SPECT/CT vs Planar Bone Scintigraphy for Metastases
- 131 breast and prostate cancer patients at high risk of bone metastases underwent Tc-99m HMDP planar scintigraphy plus whole-body SPECT/CT, with NaF/PSMA PET-CT and whole-body MRI as reference.
- Every metastatic patient detected by planar scintigraphy was also detected by SPECT/CT, and SPECT/CT additionally identified three patients missed on planar imaging.
- Patient-level sensitivity rose from 75% (planar) to 87% (SPECT/CT-derived images).
Bone scan sensitivity depends on the osteoblastic response of the underlying lesion, and SPECT/CT meaningfully augments planar imaging where anatomical localisation is needed.
Controversies & Areas of Uncertainty
For prostate cancer, planar Tc-99m MDP bone scan is being displaced by PSMA-PET and F-18 NaF PET in centres where these are reimbursed, with higher sensitivity for early marrow disease. However, the bone scan remains the cheapest whole-body skeletal survey and underpins validated response criteria (PCWG3 "2+2" rule). The optimal first-line modality therefore depends as much on access and cost as on raw accuracy.
Combined leukocyte/marrow scintigraphy is the most specific nuclear study, but it is labour-intensive and increasingly challenged by FDG-PET, which is faster and comparably accurate (Verberne meta-analysis). No nuclear test is a stand-alone diagnostic — all major consensus definitions (MSIS/ICM) rank imaging below aspiration, serology and histology.
Paradoxical increase in bone-scan uptake 2-3 months after effective systemic therapy reflects osteoblastic healing, NOT progression. Misinterpreting flare as treatment failure is a classic trap; reassessment at 6 months or cross-sectional/biochemical correlation resolves it.
Hybrid SPECT/CT improves specificity and localisation and is becoming routine in high-resource settings, but adds dose and cost. Whether it should replace planar imaging universally — versus being reserved for equivocal foci — remains a pragmatic, resource-dependent question rather than a settled one.
Guidelines, Registries & Global Practice
Nuclear medicine in orthopaedics is governed by overlapping radiation-protection law and professional society guidance that converge on the same clinical principles worldwide. The unifying framework is the ICRP/IAEA "justification and optimisation" doctrine (ALARA): every study must be clinically justified and delivered at the lowest dose consistent with diagnostic quality. A standard Tc-99m MDP bone scan delivers an effective dose of roughly 3-6 mSv, and an FDG-PET-CT roughly 7-25 mSv (PET plus the CT component), figures that are broadly consistent across national reference-dose schemes.
Global Epidemiology and Utilisation
- Skeletal metastases are the dominant indication: bone is the third most common metastatic site, and prostate, breast and lung cancers account for the majority of bone-scan referrals globally.
- Periprosthetic joint infection complicates approximately 1-2% of primary hip and knee arthroplasties — a rising absolute burden as arthroplasty volumes grow in every major joint registry.
- Access is highly uneven: PET-CT scanner density ranges from many per million population in high-income settings to near-zero in much of sub-Saharan Africa and South Asia, where planar bone scintigraphy (or radiography/MRI alone) remains the practical mainstay.
Side-by-Side Society Guidance
| Body | Region/Scope | Position Relevant to Orthopaedics |
|---|---|---|
| EANM | Europe | Publishes procedure guidelines for bone scintigraphy, SPECT/CT and FDG-PET; endorses leukocyte/marrow imaging and the EANM/SNMMI joint criteria for prosthetic-joint and bone infection |
| SNMMI | North America | Co-authors the joint EANM/SNMMI infection-imaging guidance; supports FDG-PET and labelled-leukocyte imaging for osteomyelitis and PJI |
| ACR Appropriateness Criteria | USA | Rates MRI highly for osteomyelitis/PJI workup; positions bone scan and labelled-WBC studies as adjuncts when MRI is contraindicated or equivocal (e.g. metal artefact) |
| NICE / BOA (UK) | UK | Prioritise MRI and aspiration for PJI; reserve nuclear imaging for problem-solving. NICE supports skeletal staging by the most accurate available modality (often PET in lytic disease) |
| EORTC / RECIST framework | Oncology, global | Bone-only metastatic disease is not RECIST-measurable; functional response on bone scan/PET informs treatment decisions in prostate and breast cancer |
| MSIS / ICM consensus | PJI, global | Defines PJI diagnostically; nuclear studies are a minor (adjunct) criterion behind aspiration, serology and histology |
Registry and Resource-Setting Notes
- Arthroplasty registries (NJR for England/Wales, AJRR in the US, AOANJRR in Australia, the Swedish and Norwegian registries) track revision for infection rather than imaging modality, but they quantify the PJI burden that drives demand for leukocyte/marrow and FDG-PET studies.
- High-resource practice: hybrid SPECT/CT and FDG-PET-CT are increasingly first-line for problem-solving; F-18 NaF PET and PSMA-PET are displacing planar bone scans for prostate-cancer staging where reimbursed.
- Limited-resource practice: a single gamma camera may serve a large region; planar Tc-99m MDP remains the affordable workhorse, FDG/cyclotron access is the rate-limiting step, and MRI plus radiography often substitutes for advanced nuclear studies.
Clinical Decision Scenarios
Practise clinical reasoning and management decisions out loud
“A 65-year-old man with prostate cancer presents with back pain. His PSA has risen. You request a bone scan which shows multiple focal areas of increased uptake in the thoracic and lumbar spine, ribs, and pelvis.”
“You are investigating a 60-year-old woman with a painful total knee replacement at 3 years post-operatively. A bone scan shows increased periarticular uptake. The three-phase study is positive in all three phases.”
“An examiner asks: 'A 45-year-old patient presents with widespread bone pain. You notice a bone scan showing diffusely increased skeletal uptake with virtually no renal or soft tissue activity. What is the diagnosis?'”
Three-Phase Bone Scan (FBD)
- Phase 1 (Flow): arterial vascularity — first 30-60 seconds
- Phase 2 (Blood pool): soft tissue — 5-10 minutes
- Phase 3 (Delayed bone): osteoblastic activity — 2-4 hours
- All three positive: infection, acute fracture, active tumour
- Phase 3 only positive: stress fracture, degenerative, metastasis
Hot Spots (FITMAP)
- Fracture, Infection, Tumour, Metabolic, Arthritis, Post-surgical
- Sensitive (95%) but NOT specific — virtually any bone turnover shows up
Cold Spots (MARL — False Negatives)
- Myeloma (no osteoblastic response — bone scan NEGATIVE)
- AVN (early avascular phase before revascularisation)
- Rapidly destructive tumour (outpaces osteoblastic response)
- Lesion previously irradiated
Prosthetic Joint Infection
- Bone scan: sensitive but NOT specific for PJI (specificity 33%)
- Combined WBC/marrow scan: gold standard for PJI (sensitivity 83%, specificity 94%)
- Discordant WBC uptake (WBC+/marrow-) = infection
- Normal bone scan uptake after arthroplasty persists 1-2 years
PET-CT vs Bone Scan
- PET-CT: better specificity, detects lytic lesions, soft tissue disease
- Bone scan: better sensitivity for blastic metastases, cheaper, more available
- PET-CT increasingly preferred for comprehensive tumour staging
- Bone scan remains valid for prostate and breast cancer screening