Effetto del risedronato nell'osteoporosi cortisonica su modello animale

Data inizio
1 gennaio 2006
Durata (mesi) 
24
Dipartimenti
Medicina
Responsabili (o referenti locali)
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.

Enti finanziatori:

Procter & Gamble
Finanziamento: assegnato e gestito dal Dipartimento

Partecipanti al progetto

Francesco Bertoldo
Professore associato
Luca Giuseppe Dalle Carbonare
Professore associato
Luca Donatelli
Maria Teresa Valenti
Tecnico-Amministrativo
Pubblicazioni
Titolo Autori Anno
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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