Fraktur Patologis
Published on September 10, 2026
Risk Factors
Known malignancy (breast, lung, prostate, thyroid, renal cell carcinoma), osteoporosis, Paget disease, multiple myeloma, osteogenesis imperfecta, chronic corticosteroid use, metabolic bone disease, benign bone lesions (unicameral bone cyst, giant cell tumor)
Etiology
Fracture through bone structurally weakened by an underlying disease; metastatic carcinoma is the most common cause in adults, while benign bone lesions (e.g., unicameral bone cyst) are the most common cause in children
Presentation
Pain and loss of function after minimal or no trauma ("low-energy mechanism"); may present with sudden inability to bear weight, deformity, or swelling in a patient with a history of cancer or known bone lesion
Classic Exam
Localized bony tenderness, deformity or shortening of the affected limb, palpable mass at the fracture site, limited range of motion; look for signs of underlying disease such as cachexia, lymphadenopathy, or hepatomegaly
Diagnostics
Plain radiograph showing fracture through an area of abnormal bone (lytic lesion, moth-eaten pattern, periosteal reaction, cortical destruction); elevated alkaline phosphatase (ALP), hypercalcemia; MRI for soft tissue and marrow extent; bone biopsy for definitive tissue diagnosis
Management
Orthopedic stabilization (internal fixation or arthroplasty for impending/complete fractures in long bones), followed by treatment of the underlying condition: radiation therapy for radiosensitive tumors, bisphosphonates or denosumab for skeletal protection, chemotherapy per tumor type, and pain management
01Pathophysiology
Pathological fracture occurs when a bone breaks through a region that has been structurally compromised by a preexisting disease process. Unlike traumatic fractures that require a significant force, pathological fractures happen with minimal or no trauma, sometimes even during routine activities like standing from a chair or rolling in bed.
The mechanism centers on the replacement or destruction of normal bone architecture. In metastatic disease, tumor cells reach bone via hematogenous spread and disrupt the tightly regulated balance between osteoblastic bone formation and osteoclastic bone resorption. Most metastases are osteolytic (breast, lung, renal, thyroid), meaning tumor cells secrete factors such as parathyroid hormone-related peptide (PTHrP), receptor activator of nuclear factor kappa-B ligand (RANKL), and various cytokines that stimulate osteoclast activity. This leads to focal bone destruction, cortical thinning, and eventual mechanical failure. Some tumors (notably prostate and breast) can produce osteoblastic (sclerotic) metastases by stimulating abnormal new bone formation, but this new bone is disorganized and structurally inferior, still predisposing to fracture.
In multiple myeloma, malignant plasma cells infiltrate the marrow and produce osteoclast-activating factors while simultaneously suppressing osteoblast activity. This is why myeloma lesions are purely lytic on imaging and why a bone scan may be falsely negative in myeloma, since bone scans detect osteoblastic activity, which is suppressed here.
In metabolic bone diseases such as osteoporosis, the total bone mass is reduced but the remaining bone is normally mineralized. In contrast, osteomalacia features normal bone mass but defective mineralization, and Paget disease produces excessive but architecturally chaotic bone remodeling. Each of these weakens the bone through a different mechanism, but the clinical endpoint is the same: fracture under physiologic or minimal load.
Understanding the mechanism explains the presentation. Bone pain that worsens at night and is unrelieved by rest suggests a neoplastic process because tumor growth and cytokine release continue regardless of activity level. Hypercalcemia develops when osteolysis releases calcium into the bloodstream faster than the kidneys can excrete it, producing the classic syndrome of "stones, bones, groans, thrones, and psychiatric overtones."
02Classification and Clinical Manifestation
Pathological fractures can be classified by the nature of the underlying bone lesion:
CATEGORY | COMMON CAUSES | TYPICAL LOCATION | KEY CLINICAL FEATURES |
|---|---|---|---|
Metastatic carcinoma | Breast, lung, prostate, renal, thyroid | Proximal femur, vertebral bodies, humerus, pelvis, ribs | Most common cause in adults over 40; night pain preceding fracture; history of known primary cancer or weight loss and fatigue suggesting occult malignancy |
Primary malignant bone tumor | Osteosarcoma, Ewing sarcoma, chondrosarcoma | Distal femur/proximal tibia (osteosarcoma), diaphysis of long bones (Ewing), pelvis and proximal femur (chondrosarcoma) | Younger patients (osteosarcoma: 10 to 25 years; Ewing: 5 to 15 years); localized swelling, warmth, and pain; "onion-skin" periosteal reaction (Ewing), "sunburst" pattern or Codman triangle (osteosarcoma) |
Multiple myeloma | Malignant plasma cell neoplasm | Vertebral bodies, skull, pelvis, ribs | Patients over 60; diffuse bone pain; punched-out lytic lesions on skull X-ray; anemia, renal insufficiency, hypercalcemia; elevated total protein with monoclonal spike on serum protein electrophoresis |
Benign bone lesions | Unicameral (simple) bone cyst, aneurysmal bone cyst, giant cell tumor, fibrous dysplasia, enchondroma | Proximal humerus and proximal femur (unicameral cyst); distal femur around the knee (giant cell tumor); diaphysis (fibrous dysplasia) | Most common cause in children and young adults; often discovered incidentally or after a trivial fall; "fallen fragment sign" (unicameral cyst); "soap bubble" appearance (giant cell tumor or aneurysmal bone cyst) |
Metabolic bone disease | Osteoporosis, osteomalacia, hyperparathyroidism, Paget disease, renal osteodystrophy | Vertebral bodies and distal radius (osteoporosis), femoral neck, subtrochanteric femur | Elderly or postmenopausal women (osteoporosis); proximal muscle weakness and bone pain (osteomalacia); "brown tumors" and subperiosteal bone resorption (hyperparathyroidism); bowing deformity, increased hat size, hearing loss (Paget disease) |
Infection (osteomyelitis) | Staphylococcus aureus (most common), Salmonella (sickle cell disease), tuberculosis | Metaphysis in children, vertebral bodies in adults (TB) | Fever, localized erythema, warmth, and tenderness; elevated ESR and CRP; sequestrum (dead bone) visible on imaging |
Impending Pathological Fracture (Mirels Scoring System)
Vignettes may describe a patient with a known bone lesion who has not yet fractured. The concept of an impending fracture is tested and managed prophylactically. The Mirels scoring system assigns points (1 to 3) based on four variables:
VARIABLE | 1 POINT | 2 POINTS | 3 POINTS |
|---|---|---|---|
Site | Upper extremity | Lower extremity | Peritrochanteric |
Pain | Mild | Moderate | Functional (weight-bearing pain) |
Lesion type | Blastic | Mixed | Lytic |
Size (cortical involvement) | Less than 1/3 | 1/3 to 2/3 | Greater than 2/3 |
A total score of 9 or greater indicates a high risk of fracture and warrants prophylactic surgical stabilization rather than observation.
03Diagnostic Workup
TEST | ROLE | KEY FINDINGS |
|---|---|---|
Plain radiograph (X-ray) | Best initial test | Fracture line through an abnormal area of bone; lytic or blastic lesion; cortical destruction; periosteal reaction; "moth-eaten" or "permeative" pattern suggests aggressive process |
MRI of affected region | Most accurate for local extent | Defines soft tissue mass, marrow infiltration, and relationship to neurovascular structures; essential for surgical planning |
Bone scintigraphy (bone scan) | Screening for multifocal disease | Identifies additional skeletal metastases; areas of increased uptake ("hot spots"); recall that multiple myeloma may show false negatives because of suppressed osteoblastic activity |
CT of chest, abdomen, and pelvis | Search for primary tumor | Indicated when pathological fracture is the first presentation and no primary cancer is known |
Serum labs | Evaluate metabolic and hematologic status | Calcium (hypercalcemia), ALP (elevated in bony metastases and Paget disease), phosphorus, PTH, 25-hydroxyvitamin D, CBC (anemia in myeloma), ESR, serum protein electrophoresis (SPEP) with immunofixation, urine Bence Jones protein |
Biopsy of the lesion | Gold standard for tissue diagnosis | Confirms histologic type; must be performed before definitive surgical fixation in cases of unknown primary to avoid contaminating tissue planes; coordinate with orthopedic oncologist for biopsy tract planning |
When a patient presents with a fracture through abnormal bone, the first step is always a plain radiograph. This will confirm the fracture and reveal the underlying bone abnormality. The appearance of the lesion on X-ray provides initial clues: a well-defined lytic lesion with a sclerotic rim suggests a benign or slow-growing process, while a permeative or moth-eaten pattern with cortical breakthrough and soft tissue mass points toward a malignant or aggressive lesion.
The next step depends on the clinical scenario. If there is a known history of cancer, you can reasonably assume the lesion is metastatic, but a biopsy is still often required to confirm, especially if more than five years have passed since the primary diagnosis or if the histology would change management. If this is a new presentation without a known malignancy, a full oncologic workup is indicated, including CT of the chest, abdomen, and pelvis to find the primary, along with laboratory tests including SPEP to rule out myeloma.
MRI of the affected limb is ordered to evaluate the full extent of marrow involvement and any soft tissue component, which is critical for surgical planning. A bone scan is used to survey the entire skeleton for additional lesions, keeping in mind that it relies on osteoblastic reaction and therefore underestimates the burden in purely lytic conditions like myeloma.
A critical testing pearl: in a patient with a lytic bone lesion, elevated total protein, anemia, renal failure, and hypercalcemia, think multiple myeloma first and order SPEP, urine protein electrophoresis, and serum free light chains. Do not rely on a bone scan alone in this setting.
04Management and Treatment
CLINICAL SCENARIO | MANAGEMENT |
|---|---|
Complete pathological fracture through metastatic lesion (long bone) | Orthopedic stabilization (intramedullary nailing or endoprosthetic replacement) followed by postoperative radiation therapy (typically 8 Gy in a single fraction or 30 Gy in 10 fractions); systemic therapy per tumor type |
Impending fracture (Mirels score 9 or greater) | Prophylactic internal fixation before fracture occurs; this reduces morbidity and improves functional outcomes compared to fixing an already completed fracture |
Vertebral pathological fracture without spinal cord compression | Pain management, bracing, radiation therapy, kyphoplasty or vertebroplasty for persistent pain; bisphosphonates |
Vertebral fracture with spinal cord compression | Oncologic emergency: high-dose dexamethasone (10 mg IV bolus, then 4 mg every 6 hours), urgent MRI of the entire spine, then surgical decompression followed by radiation, or radiation alone if surgery is not feasible |
Multiple myeloma | Chemotherapy (bortezomib-based regimens such as VRd: bortezomib, lenalidomide, dexamethasone); bisphosphonates (zoledronic acid 4 mg IV every 3 to 4 weeks or denosumab 120 mg subcutaneously every 4 weeks); surgical fixation of fractures as needed |
Fracture through benign lesion (e.g., unicameral bone cyst) | Allow fracture to heal first (the fracture itself may stimulate cyst resolution); if the cyst persists, intralesional corticosteroid injection or curettage with bone grafting |
Osteoporotic pathological fracture | Treat the fracture per standard orthopedic protocol; then address osteoporosis with calcium (1000 to 1200 mg/day), vitamin D (800 to 1000 IU/day), and antiresorptive therapy such as alendronate (70 mg orally once weekly) or zoledronic acid (5 mg IV once yearly); consider anabolic agents (teriparatide 20 mcg subcutaneously daily for up to 2 years) for severe osteoporosis, but teriparatide is contraindicated in patients with bone metastases, Paget disease, unexplained elevated ALP, prior radiation to the skeleton, or open epiphyses |
The immediate priority in any pathological fracture is pain control and stabilization. For long bone fractures, the goal is to restore function and allow the patient to bear weight as soon as possible. This is especially important in patients with metastatic disease whose life expectancy may be limited and who benefit from maintaining mobility and quality of life.
Surgical fixation in metastatic pathological fractures differs from traumatic fracture fixation in a critical way: the surgeon must assume the bone will not heal normally because tumor infiltration impairs the biologic healing response. Therefore, the construct chosen must be load-bearing (not load-sharing), meaning it must be strong enough to support the limb indefinitely without relying on bone union. This is why intramedullary nails that span the entire bone (prophylactic nailing of the whole femur, for instance) or endoprosthetic replacement (replacing the diseased segment with a metal prosthesis) are preferred over plates and screws alone.
Postoperative radiation (adjuvant radiotherapy) is given to the surgical site to control residual tumor, reduce pain, and prevent local progression. The two most common regimens are 8 Gy in a single fraction (for patients with limited life expectancy) or 30 Gy in 10 fractions (for patients with longer expected survival).
Bisphosphonates (zoledronic acid) and denosumab (a RANKL inhibitor) are used as skeletal-protective agents in patients with bone metastases. They reduce the incidence of future skeletal-related events (pathological fractures, spinal cord compression, hypercalcemia, need for radiation or surgery). An important side effect of both agents with prolonged use is osteonecrosis of the jaw, and patients should have a dental evaluation before starting treatment.
For spinal cord compression, the key teaching point is that this is an oncologic emergency. The first step when cord compression is suspected is dexamethasone, not imaging. Steroids are given immediately to reduce edema around the cord and buy time while imaging and definitive treatment are arranged. MRI of the entire spine (not just the symptomatic level) is then obtained urgently because up to one-third of patients will have additional levels of epidural disease.
05Differential Diagnosis and Distractors
DIFFERENTIAL | WHY IT IS SIMILAR | KEY DISCRIMINATOR |
|---|---|---|
Stress fracture (fatigue fracture) | Both can present with pain and fracture without high-energy trauma | Stress fractures occur in normal bone subjected to repetitive loading (runners, military recruits); no underlying bone lesion on imaging; periosteal callus formation is visible rather than a lytic or destructive lesion |
Osteoporotic insufficiency fracture | Also a "fragility fracture" from minimal trauma; elderly patient | No focal bone lesion; diffuse osteopenia on imaging; DEXA scan shows T-score of negative 2.5 or lower; no lytic or blastic lesion; compression fractures of the vertebral body show uniform wedging, not focal destruction |
Non-accidental trauma (child abuse) | Fracture in a child with a mechanism that does not match the injury | Multiple fractures at different stages of healing, metaphyseal corner fractures ("bucket handle"), rib fractures in an infant; no underlying bone abnormality such as a cyst or tumor |
Osteomyelitis with fracture | Bone destruction on imaging can mimic a malignant process | Fever, elevated WBC, elevated ESR/CRP; periosteal elevation (involucrum); clinical history of recent surgery, open wound, or bacteremia; culture and biopsy confirm infection, not neoplasm |
Primary bone malignancy (osteosarcoma) | Aggressive bone lesion with pathological fracture | Younger patient (adolescent), metaphyseal location, sunburst periosteal reaction or Codman triangle, elevated ALP; biopsy shows osteoid production by malignant cells, not metastatic carcinoma |
Paget disease with fracture | Bone pain, elevated ALP, and fracture in an elderly patient | Bone is enlarged and deformed (not destroyed); classic findings include bowing of the tibia, increased hat size, hearing loss; X-ray shows cortical thickening, trabecular coarsening, and mixed lytic/sclerotic phases; markedly elevated ALP with normal calcium and phosphorus |
06Traps and High-Yield Pearls
The most common way students lose points on pathological fracture questions is by failing to recognize the fracture as pathological in the first place. The vignette will describe an older patient who falls from standing height and sustains a femur fracture or a vertebral compression fracture, and the student treats it as a routine traumatic fracture without investigating the underlying bone. The critical clue is the mismatch between the mechanism and the injury severity: a fall from standing should not break a femoral shaft in a healthy adult. Whenever the force does not match the fracture, you must investigate the bone.
A second common trap involves biopsy timing. When a patient has a destructive bone lesion of unknown etiology, you must obtain a tissue diagnosis before proceeding to definitive surgical fixation. If the surgeon fixes the fracture with a nail or plate before biopsy, the surgical approach may contaminate tissue planes and compromise future limb-salvage surgery if the lesion turns out to be a primary bone sarcoma. The correct sequence in an unknown lesion is: stabilize the patient, image the lesion, stage the disease, biopsy, then plan definitive treatment.
A third trap targets myeloma. Students see multiple lytic lesions on a skeletal survey and order a bone scan, which comes back normal or near-normal. They then incorrectly conclude the disease is limited. The pearl is that bone scan is unreliable in multiple myeloma because the osteoblastic response is suppressed. Skeletal survey (plain radiographs) or low-dose whole-body CT is the correct imaging modality for myeloma staging, not bone scintigraphy.
Finally, be alert for the vignette that describes a patient on long-term bisphosphonate therapy (more than 5 years) who presents with a subtrochanteric or femoral shaft fracture after minimal trauma with prodromal thigh pain. This is an atypical femoral fracture, a complication of prolonged bisphosphonate use, and is itself a form of pathological fracture. The X-ray will show a transverse or short oblique fracture with lateral cortical thickening ("beaking"). The correct management includes surgical fixation and discontinuation of the bisphosphonate.
The core competency being tested across these questions is the ability to recognize when a fracture is not simply traumatic, to initiate an appropriate oncologic and metabolic workup, and to sequence management correctly: stabilize, image, biopsy (when needed), then treat both the fracture and the underlying disease.