SummaryThe relationship between interleukin 6 (IL-6) levels and clinical parameters was studied in 25 patients with malignant pleural mesothelioma. The serum levels of IL-6, C-reactive protein, a,-acid glycoprotein and fibrinogen were significantly higher in mesothelioma than in lung adenocarcinoma with cytology-positive pleural effusion. Serum IL-6 levels correlated with the levels of the acute-phase proteins. We demonstrated a high incidence of thrombocytosis (48%) and a significant correlation between platelet count and the serum IL-6 level. The level of IL-6 in the pleural fluid of patients with mesothelioma was significantly higher than in the pleural fluid of patients with adenocarcinoma, and was about 60-1400 times higher than in the serum. However, even higher levels of IL-6 in the pleural fluid and of thrombocytosis were found in patients with tuberculous pleurisy. These results indicate that large amounts of IL-6 from the pleural fluid of patients with mesothelioma leak into the systemic circulation and induce clinical inflammatory reactions. These profiles are not specific to mesothelioma as similar profiles are found in patients with tuberculous pleurisy. However, the detection of a markedly increased level of IL-6 in pleural fluid argues against a diagnosis of adenocarcinoma.

Although further studies need to be performed on a large number of patients with histologically proven IPF or CVD-IP, it would seem that serum sFasL levels may reflect the activity of IPF and CVD-IP.

Abstract. Osteoporosis has been linked with arteriosclerotic vascular diseases, suggesting that hypercholesterolemia or dyslipidemia may be a common pathogenetic factor underlying these diseases. However, little is known about the relationship between osteoporosis and hypercholesterolemia. The purpose of this study was, therefore, to investigate the effects of hypercholesterolemia upon bone metabolism, by measuring bone turnover markers in hypercholesterolemic patients. This study included 281 Japanese patients with hypercholesterolemia, and 267 control subjects. Serum bonespecific alkaline phosphatase (BAP) of the patients was significantly higher than that of the controls in women. Serum N-terminal telopeptide of type I collagen (NTx) of the patients was significantly higher than that of the controls in both men and women. In addition, both BAP and NTx in men showed a significantly negative correlation with high density lipoprotein cholesterol (HDL-C). On the other hand, in women, both BAP and NTx showed a significantly positive correlation with total cholesterol and low density lipoprotein cholesterol (LDL-C). These results indicate increased bone turnover in hypercholesterolemic or dyslipidemic patients regardless of gender, and suggest the importance of treating hypercholesterolemia or dyslipidemia in order to prevent not only arteriosclerotic complications but also osteoporotic bone loss and subsequent fractures.

Abstract. No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on bone health. The purpose of our study was to evaluate the effects of atorvastatin on bone metabolism by means of measuring bone turnover markers in male patients with hypercholesterolemia both at diagnosis and prospectively after 3 months of treatment. Twenty-two Japanese male patients (mean age 62.36 ± 10.1 years) with untreated hypercholesterolaemeia were selected for this study. After 3-months treatment of atorvastatin, total cholesterol and low density lipoprotein cholesterol significantly decreased as expected (p<0.001 for both parameters). Bone-specific alkaline phosphatase (BAP) did not change significantly (p = 0.444). However, serum N-terminal telopeptide of type I collagen (NTx) significantly decreased by -19.86 ± 26.4% (p = 0.020). In addition, ∆NTx during the course of this study was negatively correlated with NTx at baseline (r = -0.645, p = 0.0008). Although there was a tendency of positive correlations of ∆NTx with ∆total cholesterol, ∆triglycerides, and ∆low density lipoprotein cholesterol, and of negative correlations of ∆NTx and ∆BAP with ∆high density lipoprotein cholesterol, none of them reached statistical significance. Our findings suggest that atorvastatin may have potentially beneficial effects on bone metabolism in patients with hypercholesterolemia mostly by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.

Abstract. Because both raloxifene (RLX) and alfacalcidol (ALF) have been established as therapeutic agents for osteoporosis, it is tempting to speculate that the combination therapy of RLX and ALF might provide benefits over that of either one alone. However, the efficacy of the combination therapy has not been reported yet. The purpose of this study was thus to assess the efficacy of the combination therapy on bone mineral density (BMD) and bone turnover in patients with postmenopausal osteoporosis. Sixty postmenopausal patients (mean age 71.62 ± 9.9 years) with untreated osteoporosis were selected for this study, and were randomly divided into two groups by therapeutic regimen. Group A consisted of 28 patients treated with RLX plus ALF, while Group B consisted of 32 patients with RLX alone. Among them, 20 in group A and 22 in group B completed this study. Contrary to our expectations, at either 6 months or 12 months after the initiation of treatment, RLX plus ALF did not increase BMD at any of the skeletal sites measured, including lumbar spine, femur, and radius, nor did it reduce bone-specific alkaline phosphatase or N-terminal telopeptide of type I collagen more than RLX alone. Our results do not support the hypothesis that the combination therapy of RLX and ALF exerts more beneficial effects on bone compared than with RLX alone. However, it still remains unclear from this study whether the combination therapy of RLX and ALF is more efficacious in preventing fractures compared with RLX alone. Further studies are needed to clarify these issues.