Pathologic fractures correlate with reduced survival in patients with malignant bone disease

• Published in: Cancer Vol. 110; no. 8; pp. 1860 - 1867
• Main Authors: Saad, Fred, Lipton, Allan, Cook, Richard, Chen, Yin‐Miao, Smith, Matthew, Coleman, Robert
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.10.2007; Wiley-Liss
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; bisphosphonate; breast carcinoma; Double-Blind Method; Female; Fractures, Bone - mortality; Gynecology. Andrology. Obstetrics; Humans; lung carcinoma; Male; Mammary gland diseases; Medical sciences; Middle Aged; multiple myeloma; Neoplasms - mortality; prostate carcinoma; Retrospective Studies; Risk Factors; skeletal metastases; Survival Rate; Tumors; zoledronic acid; Antineoplastic agent; Prostate carcinoma; Pathologic fracture; Prostate disease; lung carcinoma; Lung cancer; Diseases of the osteoarticular system; Diphosphonic acid derivatives; skeletal metastases; Metastasis; Myeloma; Bronchopulmonary carcinoma; Bisphosphonates; Osteoarticular system; Breast carcinoma; Cancerology; Immunoglobulinopathy; Lymphoproliferative syndrome; Zoledronic acid; bisphosphonate; Bronchus disease; Skeleton; Male genital diseases; Human; Immunopathology; Lung disease; multiple myeloma; Urinary system disease; Respiratory disease; Malignant hemopathy; Breast cancer; Malignant tumor; Survival; Mammary gland diseases; Bone; Prostate cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22991

BACKGROUND. Data from randomized, controlled trials of zoledronic acid were retrospectively analyzed to assess the effect of pathologic fractures on survival in patients with malignant bone disease. METHODS. A Cox regression model was used to estimate the effect of fractures (time‐dependent variable) on survival in patients with stage III multiple myeloma or bone metastases from solid tumors enrolled in 3 large trials. Patients were randomized to receive zoledronic acid, pamidronate, or placebo every 3–4 weeks for up to 24 months (prostate cancer, breast cancer, and multiple myeloma) or up to 21 months (lung and other solid tumors). RESULTS. A total of 3049 patients with multiple myeloma (n = 513), breast (n = 1130), prostate (n = 640), or lung cancer or other solid tumors (n = 766) were included in this analysis. Patients with multiple myeloma had the highest fracture incidence (43%), followed by breast (35%), prostate (19%), and lung cancer (17%). In all tumor types except lung, pathologic fracture was associated with a significant increase in risk of death, and breast cancer patients had the greatest increased risk. After adjustment for baseline characteristics, including performance status and prior skeletal complications, breast cancer patients who developed a pathologic fracture on study had a significant 32% increased risk of death relative to patients without a fracture (hazard ratio = 1.32; P < .01); patients with multiple myeloma or prostate cancer had a >20% increased risk of death. CONCLUSIONS. These results suggest that fractures are associated with increased risk of death in patients with malignant bone disease. Therefore, preventing fractures is an important goal of therapy. Cancer 2007. © 2007 American Cancer Society. Data from 3 randomized, double‐blind, controlled phase 3 trials of zoledronic acid were retrospectively analyzed to assess the association between the occurrence of pathologic fractures and survival in patients with bone metastases secondary to breast cancer, multiple myeloma, prostate cancer, or nonsmall‐cell lung cancer or other solid tumors. The results suggest that an increased risk of death is associated with the occurrence of fractures in patients with malignant bone disease.