Bone metastases

Bone metastases are secondary malignant bone tumors, most commonly caused by metastasis of breast, lung, or prostate primary malignancies. They are classified as osteoblastic, osteolytic, or mixed metastases depending on whether they cause bone formation, bone destruction, or both. Patients are usually asymptomatic, but they may present with bone pain, local deformity, pathological fractures, and/or spinal cord compression. Diagnosis is primarily based on imaging studies; laboratory findings (e.g., hypercalcemia) can help support the diagnosis but are nonspecific. Biopsy is indicated when the primary malignancy is unknown or imaging findings are atypical. Treatment requires a multidisciplinary approach and includes pain control, management of complications, and bone-targeted agents (e.g., denosumab).

• More common than primary bone tumors ^[1]
• Bones are the third most common site of metastases, after the lung and the liver. ^[1]

Epidemiological data refers to the US, unless otherwise specified.

Bone metastases typically result from hematogenous metastasis or, less commonly, via direct extension (e.g., breast cancer to ribs). ^[2][3]

• Most common causes
  • Breast cancer
  • Prostate cancer
  • Lung cancer
• Other causes, e.g.:
  • Multiple myeloma
  • Kidney cancer
  • Thyroid cancer
  • Gastrointestinal cancer

Bone metastases are often present at diagnosis of the primary malignancy in patients with lung cancer and esophageal adenocarcinoma. ^[2]

Bone metastases are often asymptomatic but may manifest with: ^[1][3]

• Bone pain (e.g., back pain)
• Local deformity
• Pathological fractures
• Features of spinal cord compression and/or radiculopathy
• Features of hypercalcemia

General principles ^[4]

• Diagnosis is primarily based on imaging studies.
• Laboratory findings (e.g., hypercalcemia) can help support the diagnosis but are nonspecific.
• Additional studies are used to diagnose the primary malignancy.
• Bone biopsy is used when imaging is inconclusive and no other lesion is available for biopsy.

Imaging studies ^[3][4]

The choice of imaging modality is guided by several factors, including:

• Need for whole-skeleton assessment (e.g., during primary tumor staging)
• Anatomical location of suspected lesion in symptomatic patients ^[3][5]
• Type of bone metastasis typically associated with the primary malignancy, i.e.:
  • Osteoblastic metastasis (e.g., in prostate cancer)
  • Osteolytic metastasis (e.g., in lung cancer, multiple myeloma, or renal cell carcinoma)
  • Mixed metastasis (e.g., in breast cancer)
• Imaging method availability and/or local hospital protocols

Imaging studies are essential for diagnosing bone metastases, identifying the primary malignancy, and evaluating for complications.

PET-CT scan ^[3][4][5]

• Indications
  • Preferred method for suspected bone metastases and whole-skeleton assessment (e.g., breast cancer staging, lung cancer staging)
  • Identification of occult primary malignancy
• Findings: Sites of bone formation appear as focal areas of increased tracer (e.g., FDG) uptake. ^[4]

PET-CT is preferred to bone scan due to higher specificity; however, due to lower availability of PET-CT, bone scan remains widely used. ^[3]

Bone scan ^[1][3][5]

• Indications
  • Most widely used initial modality for suspected bone metastases and whole-skeleton assessment
  • Suspected osteoblastic metastases not located in the spine ^[3]
• Findings: Osteoblastic and mixed bone metastases appear as focal areas with increased tracer uptake.

Plain radiography ^[1][5]

Plain radiography has low sensitivity and should be complemented with more sensitive methods (e.g., CT, MRI). ^[1][5]

• Indications: initial test in patients with bone pain in extremities ^[1][5]
• Findings
  • Osteolytic and/or osteoblastic lesions
  • Disrupted or absent trabecular bone structure
  • Cortical compromise
  • Pathological fractures

CT scan ^[4][5][6]

• Indications
  • Suspicious findings on bone scan or plain radiography
  • Suspected soft tissue metastases
  • Surgical and/or radiotherapy planning
  • Percutaneous biopsies of bone lesions
• Findings
  • Osteolytic and/or osteoblastic lesions
  • Periosteal reaction
  • Soft tissue involvement
  • Pathological fractures (complete or impending)

MRI ^[4][5]

• Indications
  • First-line modality for suspected spine involvement (e.g., in patients with back pain)
  • Suspected spinal cord compression or radiculopathy
  • Suspicious findings on bone scintigraphy or plain radiography
  • Surgical and/or radiotherapy planning
• Findings
  • Osteolytic and/or osteoblastic lesions
  • Early metastatic changes (e.g., small skeletal lesion, bone marrow infiltration)
  • Spinal cord compression
  • Vertebral body collapse and pathological fractures
  • Soft tissue involvement

Laboratory studies ^[3]

• CBC: may show cytopenias (due to bone marrow infiltration)
• CMP: ↑ serum calcium, ↑ ALP

Biopsy ^[3][5][7]

Image-guided percutaneous biopsy of the most accessible lesion is indicated in patients with any of the following:

• Metastatic cancer of unknown primary
• Solitary or few bone lesions
• Metastases confined to the skeleton
• Inconclusive or atypical imaging findings

Bone metastases are classified based on radiological findings. ^[1][3]

• Osteoblastic metastasis
  • New bone formation by osteoblasts outweighs osteolytic processes → increase in radiographic density
  • Examples: prostate cancer, small cell lung cancer
• Osteolytic metastasis
  • Osteolytic processes outweigh new bone formation → decrease in radiographic density
  • Examples: multiple myeloma, thyroid cancer, kidney cancer, melanoma, non-small cell lung cancer
• Mixed metastasis: e.g., breast cancer, gastrointestinal cancer

General principles ^[3][5]

• The main goal is symptomatic treatment and prevention of complications to preserve quality of life.
• The choice of systemic anticancer treatment depends on:
  • The type of underlying primary malignancy and its staging
  • The extent of bone metastases
• All patients require a multidisciplinary team approach.

Symptomatic treatment ^[3][5]

• Bone-targeted agents
  • Indicated for all patients to prevent bone disease progression
  • Options include zoledronic acid and denosumab
  • Monitor adverse effects (e.g., hypocalcemia, acute kidney injury, osteonecrosis of the jaw).
• Local external beam radiotherapy
  • For moderate to severe pain management
  • For management of compressive spinal emergencies
  • Consider adjunctive glucocorticoid therapy (e.g., dexamethasone). ^[1][5]
• Surgical management ^[3][5]
  • Excision of solitary lesions in patients with severe pain
  • Stabilization of impending or established pathological fractures
  • Management of spinal cord compression or radiculopathy
• Other measures
  • Analgesics as needed (e.g., NSAIDs and/or opioids)
  • Treatment of vitamin D deficiency
  • Treatment of hypercalcemia