Residency · Residency · Orthopedic Surgery
Metastatic Bone Disease: Prophylactic Fixation and Palliative Management
Introduction
Metastatic bone disease is far more common than primary bone tumors, occurring in approximately 60-70% of patients with advanced cancer. The skeleton is the third most common site of metastasis after lung and liver. Orthopedic surgeons play a critical role in preventing and treating pathologic fractures, managing pain, and maintaining function in patients with limited life expectancy. Treatment decisions must balance oncologic prognosis, functional goals, and surgical morbidity.
Epidemiology
The most common primary cancers metastasizing to bone are breast, prostate, lung, kidney, and thyroid (mnemonic: BLT with Kosher Pickle). Breast and prostate cancers account for over 80% of bone metastases. The most common locations are the spine (most common overall), proximal femur, pelvis, ribs, and proximal humerus. Pathologic fractures occur in approximately 10-30% of patients with bone metastases, and the femur is the most common site of pathologic fracture in long bones.
Pathophysiology
Metastatic tumor cells reach bone via hematogenous spread through the Batson venous plexus (paravertebral veins) and arterial circulation. Tumor cells disrupt normal bone homeostasis through several mechanisms. Osteolytic metastases involve tumor-secreted factors (PTHrP, RANKL, IL-6) that activate osteoclasts, characteristic of breast, lung, kidney, and thyroid cancers. Osteoblastic metastases involve tumor cells stimulating osteoblast activity, characteristic of prostate cancer and some breast cancers. A mixed pattern combining elements of both is most common with breast cancer. Osteolytic lesions weaken the bone, predisposing to pathologic fracture.
Clinical Evaluation
Presentation
Pain is the most common symptom, often progressive, worse at night, and unrelated to activity. Pathologic fracture may be the presenting symptom of an unknown primary cancer. Hypercalcemia produces fatigue, confusion, nausea, constipation, and polyuria. Cord compression presents with back pain and progressive neurologic deficit and constitutes an oncologic emergency.
Workup
The workup includes plain radiographs of the symptomatic area, bone scan (technetium-99m) for whole-body screening, CT chest/abdomen/pelvis for staging and primary tumor identification, CT of the lesion to evaluate cortical integrity and fracture risk, MRI to assess the extent of marrow involvement and soft tissue mass, and PET-CT for staging and monitoring treatment response. Laboratory studies include CBC, metabolic panel, calcium, phosphorus, alkaline phosphatase, PSA, and protein electrophoresis (SPEP/UPEP to exclude myeloma). Biopsy is required if the primary cancer is unknown or if there is any diagnostic uncertainty, and tissue must be obtained before fixation.
Assessing Fracture Risk: Mirels Scoring System
| Variable | 1 Point | 2 Points | 3 Points |
|---|---|---|---|
| Site | Upper extremity | Lower extremity | Peritrochanteric |
| Pain | Mild | Moderate | Functional |
| Lesion type | Blastic | Mixed | Lytic |
| Size (cortex involved) | < 1/3 | 1/3 to 2/3 | > 2/3 |
Interpretation: Score 7 or less = observe + radiation; Score 8 = borderline, consider prophylactic fixation; Score 9+ = prophylactic fixation recommended (fracture risk > 33%).
The Mirels scoring system predicts the risk of pathologic fracture in long bones using four variables, each scored 1-3 points. Site is scored as upper extremity (1), lower extremity (2), or peritrochanteric (3). Pain is scored as mild (1), moderate (2), or functional (3). Lesion type is scored as blastic (1), mixed (2), or lytic (3). Size is scored as less than 1/3 cortex (1), 1/3 to 2/3 (2), or greater than 2/3 (3). A total score of 7 or less indicates observation and radiation therapy. A score of 8 is borderline, and prophylactic fixation should be considered. A score of 9 or greater recommends prophylactic fixation (fracture risk exceeds 33%). CT-based structural analysis (CTRA) is emerging as a more precise tool for fracture risk assessment.
Prophylactic Fixation
Principles
Prophylactic stabilization is biomechanically superior and has lower morbidity than fixation after fracture. The construct must be durable enough to last the patient's remaining lifetime without failure. Fixation should be planned to span the entire bone or the entire region at risk, avoiding unprotected segments.
Surgical Options
Intramedullary nailing is preferred for diaphyseal and peritrochanteric lesions, providing load-sharing fixation of the entire bone. Cephalomedullary nails (trochanteric femoral nail) are used for proximal femur lesions, and curettage with cementation may be performed through a cortical window. Endoprosthetic reconstruction is preferred for periarticular lesions (femoral head/neck) where nailing is insufficient; options include cemented long-stem hemiarthroplasty or total hip arthroplasty, and proximal femoral replacement for extensive proximal femoral destruction. Plate fixation with cement augmentation is used for periarticular humeral, distal femoral, or tibial lesions. Adjuvant cementation with polymethylmethacrylate (PMMA) fills the defect and provides immediate structural support.
Management of Established Pathologic Fractures
General Principles
Pathologic fractures through metastatic deposits rarely heal with nonoperative treatment. Surgical stabilization provides immediate pain relief and functional restoration, and the goal is to allow immediate weight-bearing postoperatively. Construct selection follows the same principles as prophylactic fixation but must account for the fracture pattern.
Femoral Shaft
The intramedullary nail (reamed, locked, full-length) is the treatment of choice, providing immediate load-sharing and protecting the entire femur from additional metastases.
Femoral Neck and Peritrochanteric Region
Endoprosthetic reconstruction (cemented long-stem hemiarthroplasty or THA) is standard. Conventional fracture fixation (sliding hip screw, cephalomedullary nail) is generally avoided due to high failure rates from impaired healing. Proximal femoral replacement (tumor prosthesis) is used for extensive bone loss.
Proximal Humerus
Cemented long-stem hemiarthroplasty or proximal humeral replacement is used for periarticular lesions, and intramedullary nailing for diaphyseal lesions.
Spine
Cord compression is an oncologic emergency requiring urgent evaluation. Treatment options include radiation, decompressive surgery with stabilization, or both. Surgical decompression and stabilization are indicated for mechanical instability, radio-resistant tumors, or progressive neurologic deficit despite radiation.
Adjuvant Treatments
Radiation Therapy
External beam radiation is standard adjuvant after prophylactic fixation or fracture stabilization, typically delivered as a single 8 Gy fraction or 30 Gy in 10 fractions. It provides pain relief in 60-80% of patients and delays or prevents progression of the metastatic deposit.
Systemic Therapy
Bisphosphonates (zoledronic acid) and denosumab (RANKL inhibitor) reduce skeletal-related events (fractures, radiation, surgery, hypercalcemia). Hormonal therapy, chemotherapy, and targeted therapy are directed by medical oncology based on the primary tumor.
Interventional Radiology
Embolization of hypervascular metastases (renal cell carcinoma, thyroid) before surgery reduces intraoperative blood loss. Radiofrequency ablation and cryoablation are used for selected painful lesions.
Estimating Prognosis and Survival
Survival estimation is essential for guiding treatment intensity and construct selection. Factors associated with better prognosis include breast or prostate primary, solitary metastasis, long disease-free interval, and good performance status. Factors associated with worse prognosis include lung primary, visceral metastases, multiple skeletal lesions, and poor performance status. Validated scoring systems (Katagiri, PATHFx) aid in estimating survival and guiding surgical decision-making. Patients with expected survival of less than 6 weeks may be better served with nonoperative palliation.
Key Clinical Pearls
A Mirels score of 9 or greater indicates a high risk of pathologic fracture and warrants prophylactic fixation; stabilization before fracture is associated with lower morbidity than post-fracture fixation. Always obtain a tissue diagnosis before fixation if the primary cancer is unknown; failing to do so may result in treating a primary bone sarcoma as a metastasis, with potentially catastrophic consequences. Constructs must be designed to last the patient's lifetime and allow immediate weight-bearing; underfixation is the most common surgical error in pathologic fracture management. Renal cell carcinoma and thyroid carcinoma metastases are hypervascular; preoperative embolization should be considered to reduce intraoperative blood loss.
References
- Mirels H. Metastatic disease in long bones: a proposed scoring system for diagnosing impending pathologic fractures. Clin Orthop Relat Res. 1989;(249):256-264.
- Damron TA, Sim FH, Shives TC, et al. Intercalary spacers in the treatment of segmentally destructive diaphyseal humeral lesions in disseminated malignancies. Clin Orthop Relat Res. 1996;(324):233-243.
- Katagiri H, Takahashi M, Wakai K, et al. Prognostic factors and a scoring system for patients with skeletal metastasis. J Bone Joint Surg Br. 2005;87(5):698-703.
- Willeumier JJ, van der Linden YM, van de Sande MAJ, Dijkstra PDS. Treatment of pathological fractures of the long bones. EFORT Open Rev. 2016;1(5):136-145.