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      Dual effect of strontium ranelate: stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro.

      1 , , ,
      Bone
      Elsevier BV

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          Abstract

          Strontium ranelate is a newly developed drug that has been shown to significantly reduce the risk of vertebral and non-vertebral fractures, including those of the hip, in postmenopausal women with osteoporosis. In contrast to other available treatments for osteoporosis, strontium ranelate increases bone formation and decreases resorption. In this study, the dual mode of action of strontium ranelate in bone was tested in vitro, on primary murine osteoblasts and osteoclasts derived from calvaria and spleen cells, respectively. We show that strontium ranelate treatment, either continuously or during proliferation or differentiation phases of mouse calvaria cells, stimulates osteoblast formation. Indeed after 22 days of continuous treatment with strontium ranelate, the expression of the osteoblast markers ALP, BSP and OCN was increased, and was combined with an increase in bone nodule numbers. On the other hand, the number of mature osteoclasts strongly decreased after strontium ranelate treatment. Similarly to previous studies, we confirm that osteoclasts resorbing activity was also reduced but we found that strontium ranelate treatment was associated with a disruption of the osteoclast actin-containing sealing zone. Therefore, our in vitro assays performed on primary murine bone cells confirmed the dual action of strontium ranelate in vivo as an anabolic agent on bone remodeling. It stimulates bone formation through its positive action on osteoblast differentiation and function, and decreases osteoclast differentiation as well as function by disrupting actin cytoskeleton organization.

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          Author and article information

          Journal
          Bone
          Bone
          Elsevier BV
          8756-3282
          1873-2763
          Jan 2008
          : 42
          : 1
          Affiliations
          [1 ] Laboratoire de Génomique Fonctionelle de Lyon, Université de Lyon-UMR5242, CNRS/INRA/ENS/Université Lyon1. IFR 128 Biosciences Lyon-Gerland, 46, allée d'Italie, 69007 Lyon, France.
          Article
          S8756-3282(07)00666-7
          10.1016/j.bone.2007.08.043
          17945546
          1f7142ff-b47c-4615-b456-5e8241eed444
          History

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