Vascular effects of drugs employed in osteoporosis treatment

CAMPELO, ADRIÁN; CUTINI, PABLO; CEPEDA, SABRINA; SANDOVAL, MARISA; RAUSCHEMBERGER, MARÍA BELÉN; MASSHEIMER, VIRGINIA

Buenos Aires

Congreso; XXXII Annual Meeting of the Argentine Association of Osteology and Mineral Metabolism.; 2015

Asociación Argentina de Osteología y Metabolismo Mineral

A higher prevalence of bone and vascular disease in postmenopausal women hasbeen well established. Bone and vascular systems are tightly integrated and manydrugs employed for osteoporosis treatment may impact on vascular homeostasis.Nitric oxide (NO) bioavailability and vascular cell proliferation and migrationaffect blood vessel health. The aim of this study was to evaluate whether the anti-osteoporotic drugs strontium ranelate (SrR 1 mM), the SERM raloxifene (Ral 10 nM) or the bisphosphonate alendronate (ALN 5μM) could affect vascular cellular homeostasis. Treatment of endothelial cells (EC) with ALN or Ral induced a rapid increase on NO production, while SrR did not affect the synthesis of the vasoactive (0.45 ± 0.15, 0.79 ± 0.05, 0.81 ± 0.09, 0.47 ± 0.09 nmol NO/mg protein; control, Ral, ALN, SrR; pb0.01). Ral stimulated EC proliferation (MTT assay), whereas the bisphosphonate exerted an opposite effect, and no effect was observed with SrR (↑72%,↓45% above control; Ral, ALN; pb0.05). We observed that 48?72 h treatment with Ral stimulated EC motility, while ALN and SrR inhibited and do not affect it respectively (212 ± 23, 345 ± 31, 190 ± 29, 216 ± 27 cells/field; control, Ral, ALN, SrR; pb0.05). Vascular smooth muscle cells (VSMC) proliferation and migration are key processes involved in vascular injury indicators of an impaired vascular function.ALN and SrR treatment (24 h), unlike Ral, significantly increased cell growth (110%, 120%, 51% above control; ALN, SrR, Ral; pb0.01). Wound healing assay showed that 72 h exposure to Ral inhibits cell motility (47% vs control; pb0.01), whereas SrR and ALN showed no significant change compared with control. These results suggest that SrR, ALN and Ral: exhibit selectively vascular actions. From the standpoint of vascular homeostasis, Ral has a more beneficial effect, promoting EC activity and reducing VSMC infiltration, while ALN exert dual actions.