Differential effects of strontium ranelate on bone microarchitecture in vivo and osteogenic diffrenciation in vitro Role of vitamin D

SEDLINSKY, CLAUDIA; FERNANDEZ JM; MOLINUEVO MS; SCHURMAN L; CORTIZO AM; MCCARTHY AD

Congreso; ASBMR, 2014 Annual Meeting; 2014

Diabetes mellitus can induce vascular and bone alterations. In particular, the collagen accumulation of advanced glycation end products (AGEs) has been associated both with bone fragility and vascular calcifications. Although bone loss is frequently treated with antiresorptive drugs such as bisphosphonates, there are other therapeutic options available such as strontium ranelate (SrRan), which has been demonstrated to improve bone quality and biomechanical properties in osteoporotic patients. In the present year, restrictions have been imposed on SrRan use in relation with its cardiovascular safety. Thus diabetic patients should only be treated with SrRan after careful considerations and regular cardiovascular evaluations. we have recently demonstrated that SrRan can prevent the deleterious effects of AGEs on osteoblasts in vitro. The present work aimed to investigateSrRan effects on bone microarchitecture in diabetic rats in vivo, and SrRan and/or 25-OH-vitamin D (VD) on the osteogenic potential on vascular smooth muscle cells (VSMC) in vitro. Diabetes was induced by consecutive i.p. administration of streptozotocin and nicotinamide to 10 adult male Sprague-Dawley rats. Diabetic animals were divided into two groups: diabetic (D, water ad libitum) and diabetic plus 625 mg/kg/day SrRan in drinking water (DR). For comparison, a group of non-diabetic rats without treatment (control, C) was also included. After 2 weeks animals were sacrificed and femora were isolated for histologic examination. VSMC were isolated from the aorta of non-diabetic (control, C) animals and cultured in DMEM-10% FBS. Cells were incubated with either 100 µg/ml bovine serum albumin (BSA) or 100 µg/ml AGEs-modified BSA (AGE-BSA), in the presence or absence of 100 µM SrRan and/or 70 ng/ml VD. Cell proliferation was determined by the MTT bioassay and cell migration by an in vitro wound assay. Osteogenic trans-differentiation of VSMC was induced by culturing cells in the above medium plus ascorbic acid and beta-glycerol phosphate for 7 days, after which collagen production and extracellular mineral nodule accumulation were determined. Expression of Runx-2 as an osteogenic differentiation factor and alpha-actin as a VSMC phenotypic marker were also assessed. The in vivo study on diabetic rats demonstrated that bone microarchitecture and cellularity were altered in D group (trabecular area: 71% vs. C, p