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


METHODS
Twenty naïve postmenopausal osteoporotic hypercholesterolemic women were treated with Atorvastatin 40 mg/day for 3 months. 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.


RESULTS
After 3 months 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).


CONCLUSIONS
Three-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.
Department of Medicine, University of Padova, Padova, Italy.|Medicina Interna I^, Ca' Foncello Hospital, Treviso, Italy.
Marcello
M
Rattazzi
Department of Medicine, University of Padova, Padova, Italy.
Elisabetta
E
Faggin
Department of Medicine, University of Padova, Padova, Italy.|Medicina Interna I^, Ca' Foncello Hospital, Treviso, Italy.
Roberta
R
Buso
Medicina Interna I^, Ca' Foncello Hospital, Treviso, Italy.
Roberto
R
Di Virgilio
Department of Medicine, University of Padova, Padova, Italy.
Massimo
M
Puato
Department of Medicine, University of Padova, Padova, Italy.
Mario
M
Plebani
Department of Medicine, University of Padova, Padova, Italy.
Martina
M
Zaninotto
Department of Medicine, University of Padova, Padova, Italy.
Tiziana
T
Palmosi
Department of Medicine, University of Padova, Padova, Italy.
Elisa
E
Bertacco
Department of Medicine, University of Padova, Padova, Italy.
Gian Paolo
GP
Fadini
Department of Medicine, University of Padova, Padova, Italy.|Medicina Interna I^, Ca' Foncello Hospital, Treviso, Italy.
Paolo
P
Pauletto
D000368:Aged; D000069059:Atorvastatin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D019169:Jurkat Cells; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000175:diagnosis / Q000378:metabolism*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000069059:Atorvastatin
Atorvastatin; Osteoporosis; Osteoprogenitors; RANKL; T cells