Searchable abstracts of presentations at key conferences on calcified tissues
Bone Abstracts (2013) 1 PP414 | DOI: 10.1530/boneabs.1.PP414

ECTS2013 Poster Presentations Osteoporosis: treatment (64 abstracts)

Treatment with eldecalcitol (ED-71) and raloxifene combined increases cancellous and cortical bone strength in ovariectomized rats

Sadaoki Sakai , Satoshi Takeda , Ayako Shiraishi , Nobuo Koike , Masahiko Mihara & Koichi Endo


Chugai Pharmaceutical Co., Ltd., Gotemba, Japan.


Eldecalcitol (ED-71; ELD), a 2β-hydroxypropyloxy derivative of 1α,25(OH)2D3, was approved to treat osteoporosis in Japan in 2011. Raloxifene (RAL), a selective estrogen receptor modulator, is available to treat or prevent postmenopausal osteoporosis. In this study, we compared the effects of combining ELD and RAL against each monotherapy in osteoporotic rats.

Eight-month-old female Wistar–Imamichi rats were ovariectomized (OVX) and administered either ELD (7.5 ng/kg), RAL (0.3 mg/kg) or ELD plus RAL daily by oral gavage for 12 weeks. Urinary deoxypyridinoline (DPD), a marker of bone resorption, was reduced significantly in the combination therapy group compared to either the ELD or RAL groups after 4 weeks of treatment. DPD in combination therapy group remained a lower level than in the RAL monotherapy group until the end of experiment. Both lumber spine and distal femur bone mineral density (BMD) were higher in combination group than either monotherapy group. Bone strength of lumbar vertebra in compression and the femoral midshaft in three-point bending were significantly higher in combination group than vehicle treatment group. Bone histomorphometric analysis revealed that osteoblast surface (Ob.S/BS) and osteoclast surface (Oc.S/BS) decreased in all the agent-treated groups. Ob.S/BS in the combination group was significantly lower than in both monotherapy groups, but not less than sham control group. Mineral apposition rate (MAR) and bone formation rate (BFR) were significantly reduced in the combination group to sham control level. ELD (10−7 M) and RAL (10−6 M) inhibited in vitro osteoclastgenesis of mouse bone marrow cells, and ELD combined with RAL more potently inhibited osteoclast differentiation than RAL.

In summary, the simultaneous administration of ELD and RAL enhanced cancellous and cortical bone strength in ovariectomized rats. It reduced bone turnover in vivo and inhibited bone marrow osteoclastogenesis in vitro, without excess suppression of bone formation.

Volume 1

European Calcified Tissue Society Congress 2013

Lisbon, Portugal
18 May 2013 - 22 May 2013

European Calcified Tissue Society 

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