What are the risk factors for pathologic fractures?

Risk Factors for Pathologic Fracture

Pathologic fractures occur when bone is weakened by underlying disease processes, with the most critical risk factors being bone metastases (particularly lytic lesions >2.5 cm or involving >50% of bone diameter), osteoporosis, primary bone tumors, and cancer-related bone loss from hormone-deprivation therapies. 1

Malignancy-Related Risk Factors

Metastatic Bone Disease

• Lytic bone lesions greater than 2.5 cm in diameter represent high fracture risk 1
• Lesions encompassing more than 50% of the bone diameter are at imminent risk for fracture 1
• Lesser trochanter avulsion indicates pathologic involvement requiring intervention 1
• Lesions in weight-bearing areas carry substantially higher fracture risk regardless of size 1
• Bone metastases from breast cancer, prostate cancer, lung cancer, and renal cell carcinoma are the most common causes of pathologic fractures 1, 2

Primary Bone Tumors

• Pathological fracture in osteosarcoma is associated with poorer survival and higher local recurrence rates 1
• Giant cell tumors (GCT) and aneurysmal bone cysts (ABC) are locally aggressive benign tumors that frequently present with pathologic fracture 3
• Pathological fracture in chondrosarcoma may indicate higher tumor grade 1
• Solitary enchondromas are the most common cause of pathologic fractures in the hand 4

Hematologic Malignancies

• Plasmocytoma and multiple myeloma cause diffuse bone weakening with high fracture risk 1, 5, 2
• Radiographic evidence of lytic bone disease is the primary stratification criterion for fracture risk in multiple myeloma 1

Osteoporosis and Bone Loss

Age and Hormonal Factors

• Postmenopausal women face 50-fold increased hip fracture risk and 15-30-fold increased vertebral fracture risk from age 50 to 90 1
• Men aged 70 years and older require bone mineral density screening due to age-related bone loss 1
• Prior fracture increases subsequent fracture risk regardless of whether it was traumatic or nontraumatic 1
• Fracture risk is highest in the immediate 1-2 years following a major osteoporotic fracture (imminent fracture risk) 1

Cancer Treatment-Induced Bone Loss

• Androgen-deprivation therapy (ADT) in prostate cancer patients substantially increases fracture risk 1
• Aromatase inhibitor therapy in breast cancer causes accelerated bone loss 1
• Chemotherapy-induced menopause accelerates bone resorption 1
• GnRH suppression of gonadal function depletes sex steroids critical for bone maintenance 1

Glucocorticoid Use

• Glucocorticoids used as premedications for taxanes or antiemetics significantly increase fracture risk 1
• Prolonged corticosteroid therapy, particularly in cholestatic liver disorders (PBC, PSC), increases osteoporosis risk 1

Lifestyle and Metabolic Risk Factors

Modifiable Risk Factors

• Smoking increases fracture risk through multiple mechanisms 1
• Excess alcohol intake compromises bone quality 1
• Inadequate calcium intake prevents optimal bone mineralization 1
• Vitamin D deficiency impairs calcium absorption and bone metabolism 1
• Inadequate exercise reduces mechanical loading necessary for bone maintenance 1

Genetic and Constitutional Factors

• Parental history of hip fractures indicates genetic predisposition 1
• Body weight less than 70 kg increases fracture risk in women with breast cancer 1
• Prior non-traumatic fracture is a powerful predictor of future fractures 1

Medication-Related Risk Factors

Non-Cancer Medications

• Proton pump inhibitors interfere with calcium absorption 1
• Anticoagulants may increase fracture risk 1
• Certain antidepressants affect bone metabolism 1
• Agents that lower sex steroids or block their effects accelerate bone loss 1

Site-Specific Risk Factors

High-Risk Anatomic Locations

• Proximal femoral shaft lesions are at highest risk due to weight-bearing stress 1
• Acetabular disease presents technical challenges and high complication rates (20-22%) even with surgical stabilization 1
• Periarticular fractures have unpredictable functional consequences 1
• Vertebral fractures are the most common fragility fractures in adults over 50 years, with prevalence increasing from 3% in those under 60 to 20% in those over 70 1

Clinical Context Factors

Disease Burden

• Metastatic disease in multiple bones compromises rehabilitation potential after fracture stabilization 1
• Widespread bisphosphonate use has decreased fracture incidence in bone metastases, but identification of at-risk bones remains challenging with evolving cancer therapies 1

Patient Factors

• Life expectancy influences treatment decisions for impending fractures 1
• Mental status, mobility status, and nutritional status affect fracture healing and rehabilitation 1
• Fracture risk remains high even in individuals with normal bone mineral density—10% fracture incidence was observed in postmenopausal women with normal BMD receiving placebo 1

Critical Pitfalls

• Differentiating pathologic fractures from traumatic fractures is essential—fractures occurring without adequate trauma should trigger evaluation for underlying bone disease 6, 3, 2
• Pain preceding the fracture is a critical historical feature suggesting pathologic etiology 3
• Treatment of impending fractures is preferable to treating completed fractures—it results in shorter hospital stays, greater likelihood of discharge home, and better ambulatory outcomes 1
• Internal fixation is contraindicated in suspected primary malignant bone tumors until biopsy confirms diagnosis, as premature treatment causes tumor contamination and worsens oncological outcomes 1, 3