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-β 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.
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