Fraktur Patologis

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:

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:

A total score of 9 or greater indicates a high risk of fracture and warrants prophylactic surgical stabilization rather than observation.

03Diagnostic Workup

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

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

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.