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Research ArticleArticle

Bisphosphonate Effects in Rat Unloaded Hindlimb Bone Loss Model: Three-Dimensional Microcomputed Tomographic, Histomorphometric, and Densitometric Analyses

Odile Barou, Marie-Hélène Lafage-Proust, Catherine Martel, Thierry Thomas, Fabrice Tirode, Norbert Laroche, Alain Barbier, Christian Alexandre and Laurence Vico
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 321-328;
Odile Barou
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Marie-Hélène Lafage-Proust
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Catherine Martel
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Thierry Thomas
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Fabrice Tirode
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Norbert Laroche
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Alain Barbier
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Christian Alexandre
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Laurence Vico
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Abstract

The effects of antiresorptive drugs on bone loss remain unclear. Using three-dimensional microtomography, dual X-ray/densitometry, and histomorphometry, we evaluated tiludronate effects in the bone loss model of immobilization in tail-suspended rats after 7, 13, and 23 days. Seventy-eight 12-week-old Wistar male rats were assigned to 13 groups: 1 baseline group, and for each time point, 1 control group treated with vehicle and three tail-suspended groups treated with either tiludronate (0.5 or 5 mg/kg) or vehicle, administered s.c. every other day, during the last week before sacrifice. In primary spongiosa (ISP), immobilization-induced bone loss plateaued after day 7 and was prevented by tiludronate. In secondary spongiosa (IISP), bone loss appeared at day 13 with a decrease in trabecular thickness and trabecular number (Tb.N) as assessed by three-dimensional microtomography. Osteoclastic parameters did not differ in tail-suspended rats versus control rats, whereas bone formation showed a biphasic pattern: after a marked decrease at day 7, osteoblastic activity and recruitment normalized at days 13 and 23, respectively. At day 23, the 80% decrease in bone mass was fully prevented by high-dose tiludronate with an increase in Tb.N without preventing trabecular thinning. In summary, at day 7, tiludronate prevented bone loss in ISP. After day 13, tiludronate prevented bone loss in ISP and IISP despite a further decrease in bone formation. Thus, the preventive effects of tiludronate in this model may be related to the alteration in bone modeling with an increase in Tb.N in ISP and subsequently in IISP.

Footnotes

  • Send reprint requests to: Prof. Christian Alexandre, Laboratoire de Biologie du Tissu Osseux, Faculté de Médecine, 15, rue Ambroise Paré, 42023 Saint-Etienne Cedex 2, France. E-mail:lbto{at}univ-st-etienne.fr

  • ↵1 Recipient of a doctoral research grant from Sanofi Recherche (Montpellier, France) and Center National d’Etudes Spatiales (Paris, France).

  • Abbreviations:
    Tb.N
    trabecular number
    3D-μCT
    three-dimensional microtomography
    ISP
    primary spongiosa
    IISP
    secondary spongiosa
    Tb.Th
    trabecular thickness
    Tb.Sp
    trabecular separation
    MAR
    mineral apposition rate
    BFR/BS
    bone formation rate, surface referent
    HM
    histomorphometry
    BMD
    bone mineral density
    Ctr
    control rats
    Susp
    tail-suspended rats
    Susp Til 0.5
    suspended rats treated with 0.5 mg/kg b.wt. tiludronate s.c
    Susp Til 5
    suspended rats treated with 5 mg/kg b.wt. tiludronate s.c
    BV/TV
    trabecular bone volume/tissue volume
    OS/BS
    osteoid surfaces
    N.Oc/B.Pm
    osteoclast number
    Oc.S/BS
    osteoclastic surfaces
    MS/BS
    mineralizing surfaces
    LGR
    longitudinal growth rate
    • Received March 23, 1999.
    • Accepted June 16, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
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Research ArticleArticle

Bisphosphonate Effects in Rat Unloaded Hindlimb Bone Loss Model: Three-Dimensional Microcomputed Tomographic, Histomorphometric, and Densitometric Analyses

Odile Barou, Marie-Hélène Lafage-Proust, Catherine Martel, Thierry Thomas, Fabrice Tirode, Norbert Laroche, Alain Barbier, Christian Alexandre and Laurence Vico
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 321-328;

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Research ArticleArticle

Bisphosphonate Effects in Rat Unloaded Hindlimb Bone Loss Model: Three-Dimensional Microcomputed Tomographic, Histomorphometric, and Densitometric Analyses

Odile Barou, Marie-Hélène Lafage-Proust, Catherine Martel, Thierry Thomas, Fabrice Tirode, Norbert Laroche, Alain Barbier, Christian Alexandre and Laurence Vico
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 321-328;
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