Orthopaedic Surgery - Metastatic Bone Disease

Basics

Metastatic bone disease is the most common cause of destructive skeletal lesions in adults.

The degree of osseous involvement varies widely, ranging from small areas of marrow infiltration to extensive cortical destruction and complete pathologic fracture.

Bone metastases are considerably less common in children than in adults.

Almost any malignant tumor can spread to bone, although certain cancers—particularly breast and prostate cancer—have a strong tendency to involve the skeleton in advanced disease.

Clinical Alert

A patient with metastatic bone disease who develops:

Severe back pain

Weakness

Numbness

Difficulty walking

Bowel or bladder dysfunction

may have metastatic spinal cord or cauda equina compression.

This is an oncologic emergency because untreated neural compression may result in permanent paralysis.

Geriatric Considerations

Metastatic skeletal disease is particularly common in older adults.

Persistent unexplained bone pain in an elderly patient should prompt consideration of malignancy, especially when there is:

A previous cancer history, weight loss, night pain, or abnormal imaging.

Pediatric Considerations

Bone metastases are uncommon in children.

Nevertheless, a child with malignancies such as:

Neuroblastoma or rhabdomyosarcoma

who develops focal or persistent bone pain should be evaluated for metastatic disease.

Epidemiology

Cancers with a particularly high propensity for skeletal metastasis include:

Breast cancer

Prostate cancer

Renal cell carcinoma

Lung cancer

Other tumors, including thyroid carcinoma and many additional solid malignancies, may also spread to bone.

Incidence

In advanced high-grade malignancy, skeletal involvement is common.

Historical reports suggest that as many as approximately 50% of patients with advanced aggressive cancers may eventually develop bone metastases, although the actual incidence depends strongly on tumor type and stage.

Risk Factors

The principal risk factors are:

Presence of a malignancy

and

Advanced-stage disease.

Genetics

There is no single inherited genetic abnormality associated with metastatic bone disease as a general entity.

Molecular features of the primary tumor may, however, influence its tendency to spread to bone.

Pathophysiology

Skeletal destruction in metastatic disease results from abnormal interaction between tumor cells and normal bone-remodeling pathways.

Osteoclast-Mediated Bone Destruction

In many osteolytic metastases, tumor cells release factors that stimulate osteoclast formation and activity.

These osteoclasts then resorb normal bone, progressively weakening the skeleton.

RANK–RANKL Pathway

An important pathway involves:

Receptor activator of nuclear factor-κB ligand, or RANKL.

Tumor-related signals stimulate osteoblast-lineage cells to increase RANKL expression.

RANKL then binds to the RANK receptor on osteoclast precursor cells, causing them to differentiate into mature, bone-resorbing osteoclasts.

Breast Cancer and PTHrP

Some breast cancer cells produce:

Parathyroid hormone-related peptide, or PTHrP, and other signaling molecules.

These factors stimulate osteoclast activity indirectly through the RANKL pathway and promote osteolytic bone destruction.

Osteoblastic Disease

Not all metastases are predominantly lytic.

Some tumors, particularly prostate cancer, induce excessive abnormal bone formation and produce:

Sclerotic or osteoblastic lesions.

Many metastases demonstrate a mixture of lytic and blastic features.

Etiology

Bone metastases develop primarily through hematogenous dissemination of tumor cells into bone marrow.

The axial skeleton is commonly affected because of its abundant marrow blood supply.

Frequent sites include:

Spine

Pelvis

Proximal femur

Proximal humerus

Ribs

Skull

Diagnosis

Signs and Symptoms

The most common symptom is bone pain.

Pain may be:

Dull and constant

Present at rest

Severe at night

Sharp with weight bearing

Severe enough to prevent ambulation

Mechanical Pain

Pain that becomes worse with:

Standing, walking, lifting, or movement

may indicate weakening of the bone and an impending pathologic fracture.

Night Pain

Pain that occurs at night or persists at rest is concerning for malignant disease, although it is not specific to metastasis.

Pathologic Fracture

Some patients first present after a fracture through metastatic bone.

The fracture may occur after:

Minimal trauma or routine daily activity because the involved bone has lost structural strength.

History

Patients with known malignancy should be asked routinely about new skeletal symptoms.

Important questions include:

Is the pain constant?

Does weight bearing worsen it?

Does it occur at night?

Can the patient localize it precisely?

Has walking ability deteriorated?

Are weakness, numbness, or bowel/bladder changes present?

Previous Cancer

Patients older than approximately 40 years with unexplained focal bone pain or a destructive bone lesion should be asked specifically about:

Any previous or current malignancy.

Physical Examination

Examination should be performed gently because abrupt or forceful maneuvers may precipitate fracture in severely weakened bone.

Palpation

Assess for:

Localized bony tenderness

Swelling

Soft-tissue masses

Range of Motion

Evaluate adjacent joints carefully.

Pain with motion may reflect:

Tumor extension, mechanical instability, articular involvement, or pathologic fracture.

Neurologic Examination

A complete neurologic examination is essential when spinal involvement is possible.

Assess:

Motor strength

Sensation

Deep tendon reflexes

Gait

Upper motor neuron signs when appropriate

Bowel and bladder function

Laboratory Tests

Laboratory testing supports the diagnostic evaluation but is not specific for skeletal metastases.

Complete Blood Count

A CBC may show anemia caused by:

Bone marrow replacement, chronic disease, chemotherapy, or radiation treatment.

Marked anemia with multiple lytic lesions should also raise suspicion for multiple myeloma.

Serum Calcium

Serum calcium should be measured because skeletal metastases may cause:

Hypercalcemia, especially in patients with extensive osteolytic disease.

Serum Phosphate

Serum phosphate may be useful when distinguishing metastatic disease from metabolic conditions such as hyperparathyroidism.

Additional Laboratory Studies

Depending on the situation, evaluation may also include:

Renal function

Liver function

Alkaline phosphatase

ESR or CRP

Serum and urine protein electrophoresis

Tumor-specific markers

Imaging

Imaging is used to:

Identify skeletal metastases

Determine fracture risk

Assess cortical destruction

Evaluate neurologic compromise

Plan treatment

Monitor response to therapy

Plain Radiographs

AP and lateral radiographs of symptomatic areas are essential.

They help evaluate:

Amount of cortical destruction

Fracture

Alignment

Lesion morphology

Possible soft-tissue extension

Radiographic Classification

Metastatic lesions may be described as:

Lytic

Mixed lytic-blastic

Blastic or sclerotic

Lytic Lesions

Lytic lesions primarily destroy bone.

They are classically associated with cancers such as:

Renal cell carcinoma

Lung cancer

Thyroid carcinoma

and many breast cancers.

Blastic Lesions

Blastic metastases produce increased bone formation and sclerosis.

They are particularly characteristic of:

Prostate cancer.

Technetium Bone Scan

Bone scintigraphy allows imaging of almost the entire skeleton.

Areas of increased osteoblastic activity typically appear as:

Foci of increased radionuclide uptake.

Advantages

Bone scanning is useful for detecting:

Multifocal skeletal involvement.

False-Positive Results

Increased uptake can also occur with:

Degenerative disease

Old fractures

Infection

Other causes of increased bone turnover

False-Negative Results

Bone scintigraphy may miss lesions that produce little osteoblastic response.

Examples include some:

Renal cell carcinoma metastases

Rapidly destructive lung metastases

Multiple myeloma lesions

CT

CT is particularly useful for evaluating:

Cortical bone destruction

Fracture anatomy

Pelvic lesions

Spinal osseous anatomy

It is frequently used for:

Preoperative planning and image-guided biopsy.

MRI

MRI is highly sensitive for detecting bone marrow replacement and may show metastatic disease before radiographs become abnormal.

It is particularly valuable for:

Spinal metastases

Marrow involvement

Soft-tissue extension

Epidural disease

Neural compression

Occult pathologic fracture

Spinal MRI

When spinal cord compression is suspected, MRI is the preferred study.

It demonstrates:

Vertebral involvement

Epidural tumor

Spinal cord compression

Cauda equina compression

Pathologic vertebral fracture

Multilevel disease

FDG-PET/CT

FDG-PET/CT is useful for detecting metabolically active tumor in many malignancies.

It is particularly sensitive in many cases of:

Lung cancer

Renal cell carcinoma

Multiple myeloma

Lytic or mixed breast cancer metastases

Purely sclerotic prostate metastases and some treated sclerotic breast lesions may be less conspicuous with FDG.

Diagnostic Workup

A systematic approach is important when skeletal metastasis is suspected.

Imaging Studies

The evaluation may include:

Plain radiographs of painful sites

CT of the chest, abdomen, and pelvis

Whole-body skeletal imaging

MRI of suspicious regions

Imaging is tailored according to the likely primary tumor and symptoms.

Blood Tests

Common tests include:

Complete blood count

Calcium

Phosphate

Renal and liver function

Alkaline phosphatase

Serum protein electrophoresis when myeloma is suspected

Biopsy

Biopsy is often necessary when:

The primary malignancy is unknown

The lesion has unusual imaging features

A primary bone tumor cannot be excluded

Histologic confirmation would alter treatment

CT-Guided Needle Biopsy

A CT-guided core needle biopsy is commonly used because it provides diagnostic tissue with relatively low morbidity.

The biopsy tract should be planned carefully in case the lesion proves to be a primary bone sarcoma.

Pathological Findings

Metastatic tumor commonly replaces normal marrow with:

Malignant cells and fibrous tissue.

Osteoclast activation causes progressive destruction of the surrounding bone.

Tumor Morphology

Metastatic carcinoma often forms:

Clusters or organoid arrangements of malignant epithelial cells.

Appearance varies according to the primary cancer.

Immunohistochemistry

Special stains and immunohistochemical markers are used to:

Confirm epithelial origin and help identify the primary tumor site.

Differential Diagnosis

Multiple Myeloma

Multiple myeloma may produce:

Diffuse lytic lesions, pathologic fractures, marrow replacement, anemia, and hypercalcemia.

It is an especially important differential diagnosis in older adults.

Lymphoma

Lymphoma can infiltrate bone marrow and mimic metastatic carcinoma radiographically and on MRI.

Definitive diagnosis may require biopsy.

Bone Infarction

Multiple bone infarcts, particularly in patients who have received chemotherapy or other treatments, may resemble metastatic lesions.

Enchondroma

Enchondromas are common benign cartilage lesions.

They may demonstrate increased radionuclide uptake and occasionally be mistaken for metastases.

Primary Bone Tumor

A solitary destructive lesion should not automatically be assumed to represent metastasis.

Primary bone tumors, including sarcoma, must remain in the differential diagnosis until appropriately excluded.

Treatment

Initial Stabilization

Early treatment priorities include:

Preventing pathologic fracture

Protecting neurologic function

Controlling pain

Maintaining mobility and independence

Weight-Bearing Pain

Patients with pain on weight bearing should undergo prompt radiographic assessment for structural weakening.

Protected Weight Bearing

When a long bone demonstrates substantial cortical destruction, historically around 25–50%, activity should be restricted.

Patients may require:

Crutches, a walker, or another assistive device.

Spinal Emergency

A patient with:

Back pain plus weakness, numbness, gait disturbance, or bowel/bladder symptoms

requires urgent MRI.

If neural compression is identified, emergency consultation with:

Spine surgery or neurosurgery

is required, together with oncologic evaluation.

General Measures

Treatment should be multidisciplinary and directed toward:

Slowing tumor progression

Controlling pain

Preventing skeletal failure

Preserving neurologic function

Maintaining activity and independence

Activity Modification

The degree of permitted activity depends on the extent of bone destruction.

Long Bones

With substantial cortical involvement, patients should avoid:

Jumping, twisting, heavy lifting, running, and unprotected weight bearing.

Vertebral Disease

When a vertebral body has major tumor destruction, heavy activities and excessive spinal loading should be avoided until stability has been assessed.

Nursing Goals

Important goals include:

Pain control

Safe transfers

Fall prevention

Preservation of mobility

Maintenance of activities of daily living

Radiotherapy

External-beam radiotherapy is commonly used to:

Relieve pain and control local tumor growth.

Conventional Regimens

Common effective schedules include:

30 Gy in 10 fractions

20 Gy in 5 fractions

8 Gy in a single fraction

Single-Fraction Radiotherapy

A single 8-Gy treatment is often useful for pain control, especially for patients who cannot tolerate repeated visits.

Stereotactic Body Radiotherapy

Stereotactic body radiotherapy delivers highly focused, ablative doses in approximately 1–5 fractions.

It may be used for:

Selected spinal metastases

Limited metastatic disease

Radioresistant tumors

Reirradiation

Higher-dose treatment may increase the risk of fracture, especially in structurally weakened vertebrae.

Systemic Radiopharmaceuticals

Systemic radiopharmaceutical therapy may be considered for selected patients with:

Diffuse painful osteoblastic skeletal disease.

Choice of agent depends on the primary malignancy and overall treatment strategy.

Physical Therapy

Physical therapy aims to preserve:

Mobility

Transfers

Activities of daily living

Functional independence

Safety During Therapy

Rehabilitation must remain within safe loading limits.

Forceful manipulation of an involved limb or spine should be avoided because of the risk of:

Pathologic fracture or neurologic compromise.

Medication

Pain medication should be used adequately to maintain comfort and function.

Treatment may include:

Acetaminophen

NSAIDs when appropriate

Opioids

Adjuvant analgesic medications

Opioid Therapy

Long-acting opioids may be used to maintain baseline pain control.

Short-acting opioids may be used for:

Breakthrough pain.

Bone-Targeted Therapy

Antiresorptive therapy plays an important role in many patients with metastatic skeletal disease.

Bisphosphonates

Bisphosphonates reduce osteoclast-mediated bone resorption.

They can decrease:

Pathologic fractures and other skeletal-related events.

Denosumab

Denosumab inhibits RANKL and suppresses osteoclast activity.

It is another important option for preventing skeletal complications in selected malignancies.

Osteonecrosis of the Jaw

Potent antiresorptive drugs may rarely cause:

Medication-related osteonecrosis of the jaw.

Patients with significant dental disease should undergo dental assessment and treatment before therapy when feasible.

Surgery

Orthopaedic surgery is important for preventing or treating:

Pathologic fracture

Mechanical instability

Neurologic compromise

Long-Bone Prophylactic Fixation

Prophylactic stabilization should be considered when fracture risk is high.

Historical teaching considered more than approximately 50% cortical destruction particularly concerning.

Modern assessment also incorporates:

Pain

Lesion size

Location

Lytic versus blastic character

Functional demand

Overall prognosis

Scoring systems such as Mirels criteria

Internal Fixation

When sufficient bone remains for stable fixation, options include:

Intramedullary nailing

Plate-and-screw fixation

Cement augmentation

Prosthetic Reconstruction

Endoprosthetic replacement may be preferred when:

The joint surface has been destroyed

Bone loss is too extensive for reliable fixation

A periarticular lesion cannot support conventional implants

Spine Surgery

Surgical stabilization and decompression may be indicated for:

Mechanical instability

Severe vertebral collapse

Progressive neurologic deficit

Spinal cord compression

Intractable mechanical pain

Follow-Up

Prognosis

Outcome depends primarily on:

Tumor histology

Extent of systemic disease

Response to treatment

Functional status

Presence of visceral metastases

Modern systemic therapies have improved survival for many cancers, so older survival figures should be interpreted cautiously.

Historical Survival After Pathologic Fracture

Older studies reported approximate survival of:

6–12 months for lung cancer, renal cell carcinoma, and melanoma

and

24–48 months for breast, prostate, and thyroid cancer.

Individual survival varies considerably.

Complications

Complications arise both from the malignancy and from skeletal involvement.

Hypercalcemia

Hypercalcemia is especially common with:

Lung cancer

Breast cancer

Multiple myeloma

Lymphoma

Treatment may include:

Intravenous hydration, antiresorptive therapy, and treatment of the underlying malignancy.

Anemia

Anemia may result from:

Marrow replacement

Chemotherapy

Radiotherapy

Chronic inflammation

Pathologic Fracture

Progressive weakening may produce fracture with:

Severe pain, loss of mobility, and reduced independence.

Spinal Cord Compression

Spinal metastatic disease may cause:

Paralysis

Sensory loss

Gait dysfunction

Bowel or bladder impairment

Prompt recognition and treatment are essential.

Patient Monitoring

Patients are followed according to the tempo of their malignancy.

Intervals may range from approximately 1–6 months, with closer surveillance for rapidly progressive disease.

Monitoring Parameters

Follow-up should assess:

Pain

Walking ability

Weight-bearing tolerance

Neurologic status

Fracture risk

Radiographic progression

Response to radiotherapy or systemic treatment

Laboratory abnormalities such as hypercalcemia

Key Principle

The central orthopaedic objective in metastatic bone disease is to identify impending skeletal failure before fracture or irreversible neurologic injury occurs.

Optimal management combines:

Careful imaging, protected activity, adequate pain control, radiotherapy, systemic oncologic treatment, bone-targeted medication, and timely prophylactic or reconstructive surgery when indicated.