Alendronate and raloxifene affect the osteoprotegerin/RANKL system in human osteoblast primary cultures from patients with osteoporosis and osteoarthritis.

The osteoprotegerin/RANKL system modulates bone remodelling. Alendronate and raloxifene are anti-resorptive drugs effective in osteoporotic disease. They reduce fracture risk, the activity of bone remodelling and increase bone mineral density. It is not known if they can exert a direct effect in osteoblasts via the osteoprotegerin/RANKL system. Our objective was to assess the effects of alendronate and raloxifene among osteoprotegerin production (ELISA), as well as osteoprotegerin and RANKL expression (RT-PCR), in primary cultures of human osteoblasts (hOB). We compared 17 osteoporotic patients with 16 patients affected by osteoarthritis in basal conditions and after incubation with alendronate (10(-6) M), raloxifene (10(-7) M) or 17-ß estradiol (10(-7) M) for 24 h. The statistical analysis was determined by ANOVA. Osteoprotegerin protein secretion in hOB cultures was higher in patients with osteoporosis than osteoarthritis. Osteoprotegerin secretion levels remained unchanged after each treatment. The osteoporotic group was more sensitive to treatment. Both raloxifene (34%) and estradiol (37%) increased osteoprotegerin mRNA expression, and alendronate (118%) and raloxifene (61%) increased the mRNA expression of RANKL. The RANKL/osteoprotegerin mRNA ratio was higher in osteoporotic than osteoarthritic patients. In the osteoporotic group, the RANKL/osteoprotegerin mRNA ratio was significantly increased after treatment with alendronate (112%) and after treatment with raloxifene (60%). These results indicate a direct action of alendronate and raloxifene on hOB cultures from osteoporotic patients, and the cited drugs are able to modulate the osteoprotegerin/RANKL system.

The use of transient elastometry for assessing liver fibrosis in patients with HIV and hepatitis C virus coinfection.

BACKGROUND: Transient elastometry (TE) is accurate for detecting significant liver fibrosis and cirrhosis in hepatitis C virus (HCV)-monoinfected patients. However, this procedure has been insufficiently validated in patients with human immunodeficiency virus (HIV) and HCV coinfection. The purpose of this study was to validate reported cutoff values of TE that discriminate significant liver fibrosis and cirrhosis in HIV-HCV-coinfected subjects. METHODS: Liver stiffness measurements were obtained for 169 HIV-HCV-coinfected adult patients who had undergone a liver biopsy or who had received a nonhistologic diagnosis of cirrhosis within 12 months before or after a liver stiffness measurement. Patients had received no prior therapy for HCV infection. RESULTS: TE measurements ranged from 3.6 kPa to 75 kPa. The area under the receiver operating characteristic curve was 0.87 (95% confidence interval, 0.84-0.93) for significant liver fibrosis and 0.95 (95% confidence interval, 0.92-0.99) for cirrhosis. To diagnose significant liver fibrosis, a cutoff value of 7.2 kPa was associated with a positive predictive value of 88% and a negative predictive value of 75%. Thirty-four patients (20%) were misclassified when this cutoff value was used. Thirteen (24%) of 54 patients with liver stiffness values <7.2 kPa had significant liver fibrosis detected by liver biopsy. To diagnose cirrhosis, a cutoff value of 14.6 kPa was associated with a positive predictive value of 86% and a negative predictive value of 94%. Thus, 13 patients (10%) had disease that was misclassified using this cutoff value. CONCLUSIONS: We found that the diagnostic accuracy of TE was high for detecting cirrhosis and good for diagnosis of significant liver fibrosis. However, the performance of TE was low for discriminating mild fibrosis from significant liver fibrosis, which might limit the applicability of this technique in clinical practice.