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Risedronate prevents the loss of microarchitecture in glucocorticoid-induced osteoporosis in rats

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Abstract

Osteoporosis is a severe complication of glucocorticoid treatment. Bisphosphonates are a powerful therapeutic option to prevent osteoporotic fractures. The aims of this study were: a) to determine bone alterations induced by therapy with glucocorticoids (GC); b) to establish the efficacy of risedronate (Ris) in the prevention of these effects. We studied 40 female Sprague-Dawley rats randomly divided into 4 groups of treatment, administered 3 times a week sc: 1. Control: vehicle of methylprednisolone (GC) + vehicle of Ris; 2. Ris: Ris 5 μg/kg body weight vehicle of GC; 3. GC: GC 7 mg/kg + vehicle of Ris; 4. GC+Ris: GC 7 mg/kg, Ris 5 μg/kg. Animals were treated for 30 days and then were sacrificed. Densitometry was performed at baseline and at the end of the treatment. Right tibiae were removed for histomorphometric analyses. The GC group showed a 7% decrease in bone density vs controls (p<0.05), while the GC+Ris group was associated with a 3.5% increase in bone density vs controls (p<0.05). In the GC group, histomorphometric evaluations showed reduced bone volume (BV/TV) and thinning of trabeculae (Tb.Th) vs controls (BV/TV: 31±1 vs 35±1%, p<0.05; Tb.Th: 43±2 vs 50±3 μm, p<0.01; Ac.f: 1.8±0.2 vs 1.6±0.3 N/yr). The GC+Ris group had increased BV/TV and Tb.Th, and reduced Ac.f vs the GC group. Ris also maintained trabecular microarchitecture. At the histological level, glucocorticoid-induced osteoporosis was characterized by decreased bone volume, reduced osteoblastic activity, and deterioration of microarchitecture. Ris counteracted these effects both by prolonging osteoblast activity, and by maintaining bone microarchitecture.

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Authors and Affiliations

  1. Clinic of Internal Medicine D, Department of Biomedical and Surgical Sciences, University of Verona, Verona, Italy

    L. Dalle Carbonare MD, F. Bertoldo, M. T. Valenti & V. Lo Cascio

  2. Medical Clinic I, Department of Medical and Surgical Sciences, University of Padua, Padua, Italy

    S. Zordan, S. Sella, G. Realdi & S. Giannini

  3. Section of Pathology, Department of Oncology and Surgical Sciences, University of Padua, Padua, Italy

    A. Fassina & G. Turco

Authors
  1. L. Dalle Carbonare MD
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  2. F. Bertoldo
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  3. M. T. Valenti
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  4. S. Zordan
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  5. S. Sella
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  6. A. Fassina
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Correspondence to L. Dalle Carbonare MD.

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Dalle Carbonare, L., Bertoldo, F., Valenti, M.T. et al. Risedronate prevents the loss of microarchitecture in glucocorticoid-induced osteoporosis in rats. J Endocrinol Invest 30, 739–746 (2007). https://doi.org/10.1007/BF03350811

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