Hospitalizations for fracture in patients with metastatic disease: primary source lesions in the United States

It has been well established that metastatic disease to bone has major significance in the morbidity associated with the diagnosis of cancer.¹ More than 75% of patients with metastatic cancer will have bone involvement at the time of death.^2-4 Moreover, there is a reported 8% incidence of a pathologic fracture in patients who carry the diagnosis of cancer.⁵ Common sites of involvement include the spine, ribs, pelvis, and long bones such as humerus and femur.⁶ Pathologic fracture is fracture caused by disease rather than injury or trauma (referred to here as nonpathologic). In any bone, pathologic fracture will be associated with increased morbidity for the patient, but it is the spine and long bones that frequently require surgical intervention and are associated with high mortality and morbidity. Advanced cancer can also increase fracture risk through increasing falls; in one prospective study of patients with advanced cancer, more than half the patients experienced a fall.⁷

Based on historical studies of patients who have died from common cancers,^4,6 it is commonly believed that breast, lung, thyroid, kidney, and prostate cancers are the most common sources of metastasis to bone, and that other common cancers, such as colorectal carcinoma (CRC), have lower rates of metastasis to bone.^6,8,9 It has been inferred from this data that cancers such as CRC thereby have lower rates of pathologic fracture.

Presence of bone metastasis at time of death may be less clinically relevant than occurrence of pathologic fracture and, especially, pathologic fracture requiring hospitalization. The authors are aware of no studies that have determined the number of patients hospitalized as a result of pathologic fracture from common tumors. Despite cadaveric findings, clinical experience dictates that colorectal carcinoma is not an uncommon primary tumor in patients presenting with metastatic disease and pathologic fracture, whereas thyroid carcinoma is more rare.

Despite lower rates of metastasis to bone from CRC, progression to advanced disease is common, with projected 50,000 deaths in the United States in 2014, and tumor progression is associated with metastasis to bone.¹⁰ Patterns of health care use and costs associated with skeletal-related events in more common metastatic prostate and breast cancer are well documented.^11-13 The authors are aware of no population-based studies examining the burden from metastatic fractures or hospitalization incidence attributed to CRC.
 

Methods

This is a retrospective study of patients hospitalized in the United States with metastatic disease. Data for this study were obtained from the 2003-2010 National (Nationwide) Inpatient Sample (NIS), the Healthcare Cost and Utilization Project (HCUP), and the Agency for Healthcare Research and Quality.¹⁴ The NIS is a stratified sample of approximately 20% of inpatient hospitalization discharges in the United States with more than 7 million hospital stays each year. The dataset contains basic patient demographics, dates of admission, discharge, and procedures, as well as diagnosis and procedure codes for unique hospitalizations. The numbers of new cases of each type of cancer diagnosed in the United States during 2003-2010 were determined from fact sheets published by the American Cancer Society.¹⁵

In all, 1,008,641 patients with metastatic disease in the NIS database, were identified by the presence of International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) diagnosis codes 196.0-199.1. Patients were then classified by primary cancer type based on the presence of additional ICD-9-CM codes for a specific cancer type (140.x-189.x) or for a history of a specific cancer type (V10.00 – V10.91). The analysis was limited to the 10 most common types of cancer. Multiple myeloma, leukemia, lymphoma, and primary cancers of bone also cause pathologic fractures, but they were purposefully excluded from the analysis because they do not represent truly metastatic disease. Patients were excluded if they were younger than 18 years (n = 9,425), had been admitted with major significant trauma (Major Diagnostic Category 24; n = 287), or if the cancer type was either not listed in discharge billing data or not one of the 10 most common types (n = 324,249). Therefore, the final study sample consisted of 674,680 hospitalizations.

The primary outcome assessed was pathologic fracture, identified with ICD-9-CM codes 733.10-733,19. Fractures not due to bone metastasis can occur in patients with metastatic disease owing to falls and general debility; therefore, the secondary outcome was nonpathologic fracture, identified with ICD-9-CM codes for fracture (805.0-829.0) in the absence of a code for pathologic fracture. Fractures classified as a “stress fracture” (ICD-9-CM code 733.9x) or where there was a concomitant diagnosis of osteoporosis (ICD-9-CM cod 733.0x) were also considered nonpathologic for the purpose of this study. Thus there were 3 groups of hospitalized patients identified: metastatic disease without fracture (No Fracture); Pathologic Fracture; and Nonpathologic Fracture. The study was limited to the 10 types of cancer with the highest numbers of pathologic fracture, leaving 647,680 hospitalizations for analysis.

Univariate analyses comparing the Pathologic, Nonpathologic, and No Fracture groups were performed with the Student t test for continuous characteristics and chi-square test for categorical characteristics. All analyses were performed with use of Stata 13.1 (StataCorp, College Station, TX).

This study protocol (RSRB00055625) was reviewed by the Office for Human Subject Protection Research Subjects Review Board at the University of Rochester and was determined to meet exemption criteria.