Residency · Residency · Nuclear Medicine

Three-Phase Bone Scintigraphy

Overview

Three-phase bone scintigraphy evaluates blood flow, blood pool, and osteoblastic activity in a single study, providing both vascular and skeletal information. The standard agents are Tc-99m MDP (methylene diphosphonate) or Tc-99m HDP (hydroxymethylene diphosphonate). Adding the vascular phases to a standard bone scan improves specificity for conditions such as osteomyelitis, acute fractures, and complex regional pain syndrome.

Radiopharmaceutical

Tc-99m MDP and HDP adsorb onto hydroxyapatite crystals at sites of active bone formation. The adult dose is 20 to 25 mCi (740 to 925 MBq), with weight-based dosing in children. Uptake depends on osteoblastic activity, local blood flow, and bone surface area. Approximately 50 to 60% of the injected dose localizes in bone, with the remainder excreted renally. The delayed phase is imaged at 2 to 4 hours to allow blood pool clearance and bone uptake.

Three Phases

Phase 1: Flow (Angiographic) Phase

The flow phase consists of rapid sequential images at 2 to 5 second frames for 60 seconds during the intravenous bolus injection. It evaluates arterial blood flow to the region of interest. Increased flow is seen with infection, fracture, tumor, and inflammation. Decreased flow suggests avascular necrosis or vascular compromise.

Phase 2: Blood Pool (Tissue) Phase

The blood pool phase is obtained as immediate static images at 5 to 10 minutes post-injection. It reflects soft tissue vascularity and capillary permeability. Increased blood pool activity is seen with cellulitis, soft tissue infection, inflammation, and tumor. This phase is important for distinguishing soft tissue from bone pathology.

Phase 3: Delayed (Skeletal) Phase

The delayed phase consists of static images at 2 to 4 hours post-injection and reflects osteoblastic activity and bone turnover. Increased delayed uptake occurs with fracture, infection, tumor, Paget disease, and arthropathy. This is the standard "bone scan" phase.

<image>Three-phase bone scintigraphy of the foot showing increased flow, blood pool, and delayed uptake in the distal first metatarsal consistent with osteomyelitis, compared with the contralateral normal foot</image>

Osteomyelitis

Three-Phase Pattern

Positivity in all three phases, meaning increased flow, blood pool, and delayed uptake, carries high specificity for osteomyelitis. Focally increased delayed uptake with normal flow and blood pool is more likely a non-infectious process such as degenerative change or an old fracture.

Acute Osteomyelitis

The sensitivity of three-phase bone scintigraphy for acute osteomyelitis is 90 to 95%, which is very high. Specificity is more limited at 70 to 80% because other conditions can also produce three-phase positivity. "Cold" osteomyelitis, in which the affected area appears as a photopenic defect rather than increased uptake, occurs in neonates, patients with sickle cell disease, or when bone infarction interrupts the blood supply.

Chronic Osteomyelitis

Chronic osteomyelitis may show only delayed-phase positivity without increased flow or blood pool activity. Specificity is further limited when prior surgery, hardware, or fracture is present. In these complex situations, WBC-labeled scans or FDG PET/CT may be needed for confirmation.

Diabetic Foot

In the diabetic foot, three-phase bone scintigraphy alone has poor specificity because Charcot neuroarthropathy also produces three-phase positivity. The solution is to combine the bone scan with a WBC-labeled scan using In-111 or Tc-99m HMPAO labeled leukocytes. Osteomyelitis produces concordant positive results on both the bone scan and the WBC scan. Charcot neuroarthropathy produces a positive bone scan with a negative WBC scan, or spatially incongruent uptake between the two studies.

Fracture Evaluation

Stress Fractures

Acute stress fractures are three-phase positive, with increased activity in all phases. The delayed phase may show a linear or fusiform pattern along the cortex. Common sites include the tibial shaft in runners, the metatarsals (march fracture), the femoral neck, and the sacrum. Sensitivity approaches 95% within 72 hours of symptom onset, which is earlier than conventional radiographs typically show abnormality.

Occult Fractures

Bone scintigraphy detects fractures that are not visible on radiographs. For hip fractures in elderly patients, sensitivity exceeds 95% within 72 hours. In elderly or osteoporotic patients, the scan may take 24 to 72 hours to become positive. MRI has replaced bone scanning for acute hip fracture evaluation at many centers because MRI is positive immediately.

Insufficiency Fractures

Sacral insufficiency fractures produce the characteristic "H-sign" or "Honda sign" on the delayed posterior view, showing bilateral vertical uptake in the sacral alae connected by a horizontal bar of uptake. Pelvic insufficiency fractures may also be seen at the parasymphyseal region and pubic rami. These fractures are common in osteoporotic patients, those who have received pelvic radiation, and patients with rheumatoid arthritis.

<image>Delayed phase bone scan showing the characteristic "Honda sign" (H-shaped uptake pattern) in the sacrum from bilateral sacral insufficiency fractures in an osteoporotic patient</image>

Complex Regional Pain Syndrome (CRPS/RSD)

Scintigraphic Findings

In the flow phase, there is increased blood flow to the affected extremity. The blood pool phase shows diffusely increased activity. The delayed phase demonstrates diffusely increased periarticular uptake throughout the affected extremity. The pattern evolves with the disease stage. In the acute stage (stage 1), all three phases are positive. In the dystrophic stage (stage 2), flow and blood pool activity become variable while delayed uptake remains increased. In the atrophic stage (stage 3), uptake is decreased in all phases.

Diagnostic Performance

The sensitivity is 60 to 80%, which is variable, and the specificity is 85 to 95%. Diagnostic performance is best in the acute stage. The clinical diagnosis is supported by the Budapest criteria, and the bone scan serves a confirmatory role.

Prosthetic Joint Evaluation

Loosening vs. Infection

The three-phase bone scan alone cannot reliably distinguish aseptic loosening from periprosthetic infection, as both conditions may show increased uptake around the prosthesis on the delayed phase. Combined imaging with a WBC-labeled scan or FDG PET/CT improves specificity. Normal post-arthroplasty bone remodeling can persist for 1 to 2 years after hip replacement or longer after knee replacement. Focal, intense periprosthetic uptake at the tips of the prosthesis or at the cement-bone interface suggests loosening. Diffuse periprosthetic uptake with three-phase positivity favors infection.

<image>Three-phase bone scan of bilateral knee prostheses showing normal post-surgical uptake on the right versus focally increased three-phase uptake around the left tibial component concerning for infection or loosening</image>

Fourth Phase (24-Hour Delayed Images)

Some institutions obtain 24-hour delayed images. These offer an improved target-to-background ratio because the blood pool has further cleared. They may help characterize equivocal findings on standard delayed images and are useful in renal osteodystrophy and metabolic bone disease.

Clinical Pearls

Three-phase positivity is not specific for osteomyelitis. Fracture, surgery, and neuropathic arthropathy can all produce the same pattern.

In the diabetic foot, always combine the bone scan with a WBC-labeled scan to achieve adequate specificity.

Bone scintigraphy has high sensitivity but limited specificity. It detects that something is wrong with the bone but often cannot determine exactly what.

The Honda sign (H-sign) in the sacrum is virtually pathognomonic for sacral insufficiency fractures.

Post-surgical bone remodeling can cause false-positive periprosthetic uptake for 1 to 2 years after arthroplasty.

Superscan and diffuse metabolic uptake patterns should be recognized as distinct from focal disease.

Cold lesions on bone scan (photopenic defects) may indicate aggressive disease, including avascular necrosis, early osteomyelitis in neonates, or purely lytic metastases.

References

• SNMMI Procedure Standard for Bone Scintigraphy.
• Love, C., et al. "Three-Phase Bone Scan for Osteomyelitis." Clinical Nuclear Medicine, 2003.
• Defined Role of Three-Phase Bone Scan in Musculoskeletal Disease. Seminars in Nuclear Medicine, 2010.
• ACR Appropriateness Criteria: Suspected Osteomyelitis, Septic Arthritis, and Soft Tissue Infection.

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