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

Abstract

SUMMARYAim: 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 na€ ıve 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.

Atorvastatin, a double weapon in osteoporosis treatment: an experimental and clinical study

“…Uzzan et al found that statins showed a better action on cortical bone and positive effect on BMD in various sites, and there was a modest but statically significant favorable effect of statins on BMD; however, the reason was not understood 10. Molecular biology and genetics reveal that both vascular and osteoblast biology have a common pathway RANK/RANKL/OPG 48,49. With regard to this issue, there is growing interest concerning the possible mechanism and the impact of statins on bones on either the experimental or the clinical level.…”

Harnessing Endogenous Cellular Mechanisms for Bone Repair

“…Interestingly, the percentage of myeloid OC+BAP+ cells was higher in peripheral blood and bone marrow of type 2 diabetic patients, and in diabetic carotid endarterectomy specimens, a higher degree of calcification and amounts of OC and BAP-expressing cells were detected in the α-smooth muscle actin-negative areas surrounding calcified nodules, where CD68+ macrophages colocalized (Fadini et al, 2011 ). The increased percentage of COPs in pathological conditions was evidenced also in other clinical studies and it is supposed to be “linked to the presence of vascular damage, such as arterial stiffness and aortic calcification” (Pal et al, 2010 ; Pirro et al, 2011 ; Rattazzi et al, 2016 ). However, in 2005, Eghbali-Fatourechi et al ( 2005 ) showed that the presence of a population of osteoblast-lineage cells circulating in physiological condition endowed with expression of markers of bone formation and markedly increasing during pubertal growth, thus representing a previously unknown component of bone formation process (Table 1 ).…”

Does short preoperative statin therapy prevent infectious complications in adults undergoing cardiac or non-cardiac surgery?

“…Statins can modulate the function of different immune cells, including T cells, and endothelial cells. 26 , 27 Many cell receptors and cytokines can be reduced by statins, such as MCH-II, P-selectin, and MCP-1. 28 In addition, statins exert direct antibacterial and antiviral effects.…”