Increased incidence of bone metastases in hepatocellular carcinoma

OBJECTIVES: Recently, we often encounter hepatocellular carcinoma patients with bone metastases. We therefore examined the changes in the incidence of bone metastases in hepatocellular carcinoma from 1978 to 1997 and tried to identify the characteristic clinical features. We also discuss the reasons for the increased incidence of bone metastasis in hepatocellular carcinoma. METHODS: A total of 673 patients with hepatocellular carcinoma during the period 1978-1997 were studied. Bone metastasis was screened by bone scintigraphy, and bone lesions were confirmed by plain radiography, computed tomography and/or magnetic resonance imaging. The serum levels of the C-terminal telopeptide of type 1 collagen, which represent osteoclastic bone resorption, were also measured. RESULTS: The incidence of bone metastasis during the decade 1988-1997 was significantly higher than that during the period 1978-1987. The median survival time of patients with hepatocellular carcinoma during 1988-1997 was also significantly longer than that during 1978-1987. Portal thrombus was found in about half of the patients with bone metastases. The most common site of bone metastases was the vertebra followed by the pelvis, rib and skull in that order. All bone lesions depicted by plain radiograph, computed tomography and/or magnetic resonance imaging were of the osteolytic type, and the serum levels of C-terminal telopeptide of type 1 collagen were significantly elevated in the patients with bone metastases. CONCLUSIONS: The increased incidence of bone metastasis in hepatocellular carcinoma in the decade 1988-1997 is first attributed to the prolonged survival rate of hepatocellular carcinoma patients due to recent progress in both the diagnosis and treatment of the disease. Dissemination of hepatocellular carcinoma cells to the vertebra through the portal vein-vertebral vein plexuses due to the presence of portal thrombus and/or portal hypertension may be related to a higher incidence of bone metastasis in hepatocellular carcinoma. Both an early diagnosis and timely treatment of bone metastases are thus called for in the follow-up of hepatocellular carcinoma patients.