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Metastatic Bone Disease

  • The most common cause of destructive bone lesions in the adult
  • The amount of bone destruction varies from small amounts to complete fracture.
  • Bone metastases occur less commonly in children than in adults.
  • Virtually any malignancy may metastasize to bone.
    • With some cancers (such as breast and prostate cancer), virtually all patients have bone metastases at the time of death.
A patient who has metastatic bone disease with severe back pain and numbness or weakness may be at risk for paralysis and should be evaluated carefully for spinal cord compression.
Geriatric Considerations
  • Metastatic bone disease is common in the geriatric patient.
  • This diagnosis should be considered in the older patient with bone pain.
Pediatric Considerations
  • Metastatic bone disease is rare in the pediatric patient.
  • Children with rhabdomyosarcoma or neuroblastoma who have bone pain should be evaluated for the presence of metastatic disease.
  • Some cancers are prone to bone metastases:
    • Breast cancer
    • Prostate cancer
    • Kidney cancer
    • Lung cancer
Up to 50% of patients with high-grade cancers may develop bone metastases when they have advanced disease.
Risk Factors
  • Any cancer
  • Advanced disease
No specific genetic associations are known.
  • The bone destruction in metastatic bone disease is directly caused by osteoclasts.
  • The tumor cells secrete factors that cause osteoclast activation.
    • Breast cancer and parathyroid hormone-related protein:
      • Parathyroid-hormone-related peptide or other factors causes the release of receptor activator of nuclear factor β-ligand from the osteoblasts.
      • The receptor activator of nuclear factor β-ligand attaches to the receptor activator of nuclear factor β receptor on the osteoclast precursor cells and signals the cell to differentiate into an osteoclast.
Hematogenous dissemination of cancer cells into the bone marrow
Signs and Symptoms
  • Patients present with bone pain.
    • May be dull and occur at rest
    • May be sharp and occur with weightbearing
    • May occur at night and be intense
  • Patients may be unable to walk secondary to the pain.
  • Patients with a history of cancer should be queried as to whether they have any bone pain.
  • Patients >40 years old with bone pain should always be asked about any previous cancer.
  • Elicit a careful history of the bone pain:
    • Is the pain constant?
    • Does the pain occur with weightbearing?
    • Does the pain occur at night?
    • Can the patient localize the site of the pain?
Physical Exam
  • The clinician should examine the patient gently (abrupt maneuvers may cause a fracture).
    • Palpate for bone tenderness.
    • Palpate for soft-tissue masses.
    • Check ROM.
    • Perform careful neurologic examination.
    • Evaluate motor weakness.
    • Check sensation.
    • Check deep tendon reflexes.
Serum tests to evaluate for anemia, hypercalcemia
  • To detect metastases, assess for impending fracture or neurologic compromise, or check the response to treatment.
  • Radiography:
    • AP and lateral views to assess the amount of cortical bone destruction
    • Involvement can be categorized as purely lytic, mixed lytic-blastic, or purely blastic.
  • Technetium bone scans:
    • Areas of involvement show increased activity.
    • The entire skeleton is imaged.
    • False positives may be caused by degenerative disease or old fractures.
    • False negatives may be caused by rapidly destructive lesions (some lung and kidney cancers).
  • CT:
    • Excellent for defining the amount of cortical bone loss
    • Often used for preoperative planning for the pelvis and spine
  • MRI:
    • Excellent for detecting marrow involvement when the plain radiographs are normal
    • Often used to determine if positive bone scan findings represent true metastatic involvement
      • Bone metastases are low signal on T1-weighted images and high signal on T2-weighted images.
Diagnostic Procedures/Surgery
  • A systematic approach must be used to evaluate the patient with suspected bone metastases.
    • Imaging studies:
      • Plain radiographs of painful sites
      • CT of the chest and abdomen to detect lung and kidney cancer, adenopathy
      • Technetium bone scan to look for multiple bone sites
    • Blood tests:
      • Complete blood cell count: Low hemoglobin is suggestive of myeloma.
      • ESR: High rate is suggestive of myeloma.
      • Calcium/PO4: Elevated calcium, low PO4 is suggestive of hyperparathyroidism.
    • Biopsy is necessary to establish or confirm the diagnosis.
      • CT-guided needle biopsy is the most commonly performed procedure.
Pathological Findings
  • Marrow is replaced with cancer cells and fibrous tissue.
    • Osteoclasts resorb the bone.
    • Tumor cells are characteristically in clumps in an organoid pattern.
    • Special stains (e.g., keratin stain) are used to confirm the epithelial nature of the tumor.
Differential Diagnosis
  • Metastatic bone disease can be confused with several entities:
    • Multiple myeloma may cause diffuse lytic bone destruction.
    • Lymphoma often causes replacement of the bone marrow in a manner similar to that of metastatic disease.
    • Bone infarcts can cause multiple lesions, especially after chemotherapy, and these may be confused with metastatic disease.
    • Enchondromas (common and inactive) may show increased uptake on the technetium bone scan and be confused with bone metastases.
Initial Stabilization
  • Patients with weightbearing pain are assessed with plain radiographs to determine the fracture risk.
    • If the cortical bone destruction is >25-50%, a walking aid such as crutches or a walker is advised.
    • If the patient has back pain and a neurologic deficit, an emergent MRI is performed to assess the risk of spinal cord compression.
      • If the MRI shows compression of the neural elements, an orthopaedic spine or neurosurgery consultation is obtained.
General Measures
A systematic treatment plan is developed to halt progression of bone metastases, control pain, and maintain the patient’s activity level and independence.
  • The activity level is modified based on the degree of bone destruction.
    • 25-50% cortical bone destruction (long bone): Activity is restricted to ambulating with a walking aid and avoiding heavy activities (e.g., jumping, twisting, lifting).
    • 25-50% vertebral body destruction: Activity is modified to avoid heavy activities.
Major goal: Control pain, maintain patient independence
Special Therapy
  • External beam irradiation often is used to control pain and halt bone destruction.
  • Several regimens are efficacious:
    • 3,000 cGy in 10 daily fractions
    • 2,000 cGy in 5 daily fractions
    • 800 cGy in a single fraction:
      • Chosen for the very ill patient who cannot tolerate numerous trips to the radiation oncology unit
      • Used mainly for pain control
    • Systemic radiopharmaceuticals are used occasionally in diffuse blastic disease.
    • Strontium
Physical Therapy
  • To maintain activities of daily living and independence
  • Care must be taken not to push patients beyond their capacity or to cause a fracture.
  • Manipulation of the limbs or spine should never be performed.
  • Medications must be used liberally to control pain.
    • Long-acting narcotics are used to achieve basal serum levels.
    • Short-acting narcotics are used to control breakthrough pain.
First Line
  • Diphosphonate therapy has become an integral component of therapy.
    • Halts bone destruction and facilitates healing of the defect
    • Skeletal events (e.g., fractures) decrease in patients on diphosphonate therapy.
    • Osteonecrosis of the jaw rarely occurs as a side effect of diphosphonates.
    • Patients with poor dentition should be referred to an oral surgeon before beginning diphosphonate therapy.
  • Stabilization of long bones and the spine is important to prevent fracture or spinal cord paralysis.
    • Long bones:
      • Prophylactic fixation is recommended when cortical bone destruction is >50%.
      • Internal fixation devices are used when rigid fixation can be achieved.
      • Prosthetic devices are chosen when rigid fixation cannot be achieved or the joint surfaces have been destroyed.
    • Spine:
      • When severe destruction occurs in the vertebral body and/or posterior elements, stabilization is recommended to prevent fracture and neural element compromise.
  • Virtually all patients will succumb to their disease.
  • The prognosis depends on histologic type.
  • Survival after fracture secondary to metastatic bone disease:
    • Lung, kidney, melanoma: 6-12 months
    • Breast, prostate: 24-48 months
  • Systemic complications and complications directly related to the bone metastases may occur.
  • Hypercalcemia:
    • Common in lung and breast cancer, myeloma, and lymphoma
    • Treated with hydration and diphosphonates
  • Anemia:
    • Common secondary to marrow replacement and chemotherapy/radiation therapy
Patient Monitoring
Patients are followed at 1-6-month intervals depending on the temporal progression of their disease.
198.5 Secondary malignant neoplasm, bone and bone marrow, all sites
Patient Teaching
  • Patients must be taught to recognize the warning signs of spinal cord paralysis and impending fracture of a long bone.
  • Paralysis:
    • Numbness/tingling
    • Weakness
    • Change in bowel/bladder habits
  • Impending fracture:
    • Lower extremity long bones:
      • Pain with ambulation
      • Inability to stand or bear weight
    • Upper extremity long bones:
      • Pain with activities of daily living
    • Spine:
      • Severe pain
      • Neurologic symptoms/signs
  • No methods of preventing bone metastases exist.
  • Spinal cord paralysis can be prevented by preventing neurologic compression and stabilizing the unstable spinal segments.
  • Long-bone fractures can be prevented by prophylactic internal fixation or prosthetic arthroplasty.
Q: Can fractures be stabilized so that patients can walk again?
A: Because many techniques and devices exist, almost any fracture can be stabilized so that the patient can bear full weight after the surgery.
Q: Is irradiation necessary after surgery for a fracture?
A: Irradiation is always necessary. Up to 15-20% of patients will need additional surgery because of disease progression when postoperative irradiation is not used.
Q: Will irradiation stop the bone pain?
A: External beam irradiation is very effective, controlling pain in 80-90% of patients.

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