Effetto del risedronato nell'osteoporosi cortisonica su modello animale

Starting date
January 1, 2006
Duration (months)
24
Departments
Medicine
Managers or local contacts
Dalle Carbonare Luca Giuseppe

The purpose of this study was to evaluate the effects of risedronate (Ris) in the modulation of bone formation in rats with glucocorticoid (GC)-induced osteoporosis by histomorphometric, immunohistochemical and gene expression analyses.
We analyzed structure, turnover and microarchitecture, cyclooxygenase 2 (COX-2) levels and osteocyte apoptosis in 40 female rats divided as follows: 1) vehicle of methylprednisolone (vGC) + vehicle of risedronate (vRis); 2) Ris 5 μg/Kg + vGC; 3) methylprednisolone (GC) 7 mg/Kg + vRis; 4) GC 7 mg/Kg +Ris 5 μg/Kg. In addition, we evaluated cell proliferation and expression of COX-2 and bone alkaline phosphatase (b-ALP) genes in bone marrow cells and MLO-y4 osteocytes treated with Ris alone or in co-treatment with the selective COX-2 inhibitor NS-398 or with dexametasone.
Ris reduced apoptosis induced by GC of osteocytes (41% vs 86%, P < 0.0001) and increased COX-2 expression with respect to controls (Immuno-Hystochemical Score (IHS): 8.75 vs 1.00, P < 0.0001). These positive effects of Ris in bone formation were confirmed by in vitro data as the viability and expression of b-ALP gene in bone marrow cells resulted increased in a dose dependent manner.
These findings suggest a positive effect of Ris in bone formation and support the hypothesis that the up-regulation of COX-2 could be an additional mechanism of anabolic effect of Ris.

Sponsors:

Procter & Gamble
Funds: assigned and managed by the department

Project participants

Francesco Bertoldo
Associate Professor
Luca Giuseppe Dalle Carbonare
Associate Professor
Luca Donatelli
Maria Teresa Valenti
Technical-administrative staff
Publications
Title Authors Year
The effect of risedronate on osteogenic lineage is mediated by cyclooxygenase-2 gene upregulation. Valenti MT; Giannini S; Donatelli L; Zanatta M; Bertoldo F; Sella S; Vilei MT; Ossi E; Realdi G; Lo Cascio V; Dalle Carbonare L. 2010
Risedronate prevents the loss of microarchitecture in glucocorticoid-induced osteoporosis in rats. Dalle Carbonare L.; Bertoldo F.; Valenti M.T.; Zordan S.; Sella S.; Fassina A.; Turco G.; Realdi G.; Lo Cascio V.; Giannini S. 2007

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