# Skeletal Scintigraphy: Bone Scan Interpretation

## Introduction

Skeletal scintigraphy (bone scan) is a highly sensitive technique for detecting **osteoblastic activity** throughout the entire skeleton. Although partially supplanted by cross-sectional imaging and PET in some applications, it remains a workhorse study for evaluating metastatic disease, occult fractures, infection, and metabolic bone disease.

## Radiopharmaceutical and Mechanism

### Technetium-99m Methylene Diphosphonate (Tc-99m MDP)

**Tc-99m MDP** is the most widely used bone-seeking radiopharmaceutical. It binds to **hydroxyapatite crystals** in bone matrix at sites of active bone formation (osteoblastic activity). Uptake depends on two factors: **regional blood flow** and **osteoblastic activity**. The administered dose is approximately **20-25 mCi IV** in adults. The **three-phase bone scan** consists of the flow phase (dynamic, first 60 seconds), blood pool phase (3-5 minutes), and delayed phase (2-4 hours). Standard delayed whole-body imaging at **2-4 hours** allows clearance of soft tissue activity.

### Image Acquisition

**Whole-body planar images** in anterior and posterior projections are the standard acquisition. **Spot views** of areas of interest provide improved resolution. **SPECT** or **SPECT/CT** offers improved localization for structures like the spine and temporomandibular joints. Pinhole collimator imaging is used for small structures such as the hips in children with suspected Legg-Calve-Perthes disease.

## Normal Scan Appearance

A normal scan shows symmetric uptake throughout the axial and appendicular skeleton, with increased uptake at sites of **high metabolic activity** such as growth plates in children, sacroiliac joints, and sternoclavicular joints. The **kidneys** are normally visualized due to renal excretion; absent renal visualization suggests a **superscan**. **Bladder** activity is prominent, and post-void images may be needed for pelvic evaluation. Growth plates in children are symmetric and linear; asymmetry or focal irregularity warrants investigation.

## Patterns of Abnormality

### Focal Increased Uptake

**Metastatic disease** produces multiple random foci of increased uptake, most commonly in the axial skeleton (spine, pelvis, ribs). **Fractures** show linear or focal uptake at fracture sites, with rib fractures appearing in a linear pattern. **Degenerative disease** produces uptake at facet joints, acromioclavicular joints, and weight-bearing joints. **Paget disease** shows markedly increased uptake involving an entire bone or large segment with cortical expansion.

### Diffusely Increased Skeletal Uptake (Superscan)

A superscan shows diffusely increased skeletal uptake with **absent or faint renal visualization**. A **metabolic superscan** results from hyperparathyroidism, renal osteodystrophy, or osteomalacia and shows relatively uniform uptake with prominent calvarium, mandible, and sternum involvement. A **metastatic superscan** from diffuse osseous metastatic disease (prostate, breast) is often more heterogeneous. The metabolic superscan often shows prominent periarticular uptake in a **beading pattern**.

### Photopenic (Cold) Lesions

Photopenic areas represent **decreased uptake** relative to surrounding bone. Causes include early avascular necrosis, purely lytic metastases (multiple myeloma, renal cell carcinoma, thyroid carcinoma), radiation therapy, and metallic hardware artifact. Multiple myeloma often produces a **normal or near-normal bone scan** despite extensive disease, making skeletal survey or PET/CT preferred.

### Flare Phenomenon

The flare phenomenon is a **paradoxical increase** in the number or intensity of lesions on bone scan 2-3 months after initiating effective therapy. It represents a **healing response** with increased osteoblastic activity at treatment sites and should not be confused with disease progression. It usually resolves on subsequent scans at 6 months.

## Three-Phase Bone Scan

### Indications

The primary indication is distinguishing **osteomyelitis from cellulitis**. | Phase | Osteomyelitis | Cellulitis |
| --- | --- | --- | --- |
| Flow (dynamic) | Positive (increased) | Positive (increased) |  |
| Blood pool (3-5 min) | Positive (increased) | Positive (increased) |  |
| Delayed (2-4 hrs) | Positive (focal uptake) | Normal |  |

**Osteomyelitis** is positive in all three phases (increased flow, blood pool, and delayed uptake). **Cellulitis** is positive in the first two phases (flow and blood pool) but shows a normal delayed phase. Sensitivity for osteomyelitis is approximately **95%**, though specificity is reduced in the setting of fractures, neuropathic joints, or recent surgery.

### Specific Applications

**Stress fractures** show focal delayed-phase uptake, and SPECT or MRI may be needed for confirmation. **Complex regional pain syndrome (CRPS)** shows increased periarticular uptake on delayed images in a characteristic pattern in the affected extremity. **Shin splints versus stress fracture** can be distinguished because shin splints show longitudinal cortical uptake while stress fractures show focal fusiform uptake.

## Specific Clinical Scenarios

### Metastatic Disease Screening

Bone scans are indicated for staging of **prostate, breast, and lung cancer** and for any cancer with bone pain or elevated alkaline phosphatase. Predominantly **osteoblastic metastases** are well detected (prostate, breast). Purely **lytic metastases** may be missed (myeloma, renal cell carcinoma), making PET/CT or CT preferred. A solitary rib lesion is more likely benign (fracture), while multiple random rib lesions suggest metastases.

### Prosthetic Joint Evaluation

**Loosening** appears as increased uptake at the bone-prosthesis interface, particularly on delayed images. **Infection** shows increased uptake on all three phases; combined with **In-111 WBC scan** or **Tc-99m sulfur colloid scan**, specificity improves. Normal post-operative uptake around prostheses can persist for **12-18 months** (cemented) to **2 years** (uncemented).

### Pediatric Applications

In **Legg-Calve-Perthes disease**, pinhole imaging shows a photopenic femoral epiphysis representing early avascular necrosis. In **child abuse**, bone scans may detect occult fractures not seen on radiographs, though skeletal survey remains the primary imaging study. **Osteoid osteoma** shows focal intense uptake with a characteristic **double-density sign** on SPECT.

## Clinical Pearls

A **superscan** shows diffusely increased skeletal uptake with absent kidney visualization; distinguishing metabolic from metastatic causes is important. Bone scan sensitivity for **purely lytic lesions** (myeloma, RCC) is poor, and PET/CT or skeletal survey should be used instead. The **flare phenomenon** after therapy initiation mimics progression but actually indicates treatment response. Three-phase bone scan differentiates osteomyelitis (positive all three phases) from cellulitis (positive flow and blood pool only).

## References

1. Society of Nuclear Medicine Procedure Guideline for Bone Scintigraphy. *J Nucl Med Technol*. 2018;46(4):398-404.
2. Skeletal Scintigraphy: An Update on Current Concepts and Applications. *Radiographics*. 2020;40(5):1430-1451.
3. Bone Scan Interpretation: A Systematic Approach. *Semin Nucl Med*. 2015;45(1):3-15.
4. The Flare Phenomenon on Bone Scintigraphy. *Clin Nucl Med*. 2019;44(5):390-396.