Atorvastatin Reduces Circulating Osteoprogenitor Cells and T-Cell RANKL Expression in Osteoporotic Women: Implications for the Bone-Vascular Axis

AimCirculating osteoprogenitors and receptor activator of nuclear factor kappa-B ligand (RANKL) expression in immune cells have been implicated in the pathogenesis of osteoporosis and vascular calcification. The role played by statin therapy in the bone-vascular axis is unknown. MethodsTwenty naive postmenopausal osteoporotic hypercholesterolemic women were treated with Atorvastatin 40mg/day for 3months. Gene expression analysis was performed to assess modification in osteoprotegerin (OPG)/RANK/RANKL expression in isolated T cells and monocytes. A flow cytometry analysis was used to study changes in the levels of circulating osteoprogenitor cells. ResultsAfter 3months of treatment, Atorvastatin significantly reduced total cholesterol and LDL-C, without affecting HDL-C and triglycerides. Among circulating bone and phosphocalcium homeostasis markers, we found a significant increase in OPG levels (P<0.01) and a modest reduction in osteocalcin (OCN) (P<0.05). We also observed a significant reduction in RANKL expression in T cells (P<0.05). No differences were found in the expression of RANK in T cells and RANKL and RANK in monocytes. OPG expression was low in both immune cell types and was not affected by the treatment. As for circulating osteoprogenitors, we found a significant reduction of CD34(+)BAP(+) (P<0.05) and CD34(+)OCN(+)BAP(+) (P<0.05) cells. In vitro studies showed that Atorvastatin reduced RANKL expression in activated human T-lymphoblastoid cells (Jurkat cell line). ConclusionsThree-month Atorvastatin treatment leads to a reduction in circulating osteoprogenitor cells and RANKL expression in T cells, as well as increase in OPG serum levels. These data suggest that statins could have protective effects in the bone-vascular axis.