Raloxifene therapy interacts with serum osteoprotegerin in postmenopausal women

Objectives: Osteoprotegerin (OPG) is a protein expressed by osteoblasts that, linking the receptor activator of nuclear factor *B (RANK) ligand (RANKL), produced by osteoblasts, blocks the process of osteoclastic differentiation and modulates osteoclastic apoptosis. Raloxifene (RAL) stimulates the production of OPG from osteoblasts, as demonstrated in vitro, carring out their antiresorption activity, at least in part, as means of the OPG/RANK/RANKL system. The aim of this study was to evaluate in vivo if the RAL treatment of postmenopausal women was associated to changes in serum OPG; moreover, to evaluate the serum changes of bone turnover modulators interleukin-6 (IL-6) and C-telopeptides of type-1 collagen (Cross- Laps). Methods: A prospective, randomized, placebo-controlled study was designed. A group of consecutive healthy postmenopausal women (n = 40) referred to II Menopause Centre of the Department of Gynaecology of Second University of Naples for climacteric syndrome was enrolled and divided in two groups: (n = 20) postmenopausal women received for 6 months oral raloxifene (60 mg/day) versus (n = 20) postmenopausal women received placebo tablets. Results: Serum OPG levels in postmenopausal women after RAL treatment are statistically significant increased (P < 0.001) versus baseline (P = 0.007) versus placebo. Conclusions: These in vivo data demonstrate that RAL could improve osteoporosis, also through an increase of OPG production by osteoblasts.