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OtherENDOCRINE PHARMACOLOGY

The Effect of Orally Administered Clodronate on Bone Mineral Density and Bone Geometry in Ovariectomized Rats

T. Österman, L. Laurén, P. Kuurtamo, R. Hannuniemi, P. Isaksson, K. Kippo, Z. Peng, H. K. Väänänen and R. Sellman
Journal of Pharmacology and Experimental Therapeutics January 1998, 284 (1) 312-316;
T. Österman
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L. Laurén
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P. Kuurtamo
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R. Hannuniemi
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P. Isaksson
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K. Kippo
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Z. Peng
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H. K. Väänänen
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R. Sellman
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Abstract

The effects of clodronate administered p.o. on bone mineral density (BMD), bone geometry and strength of bone were investigated in 6-month-old ovariectomized rats. Sixty Sprague-Dawley rats were randomized into four groups. Three groups were ovariectomized (OVX) and one group was sham-operated (SHAM). The OVX groups were given p.o. either clodronate (100 mg/kg/d or 500 mg/kg/d) or a vehicle. The SHAM group received the vehicle. Treatments started on the day of OVX and continued for 3 months. BMD of proximal tibial metaphysis was measured by computed tomography in vivo 1 day before OVX and 6 and 12 weeks after OVX. At the end of the study, left tibiae and femora were removed for ex vivo BMD and bone geometry measurement. A three-point bending test of the tibial shaft was carried out, and ash weights of femur and tibia were determined. OVX induced a marked decrease in total and trabecular BMD over time at the proximal tibial metaphysis. This bone loss was prevented by clodronate. Clodronate also prevented the decrease in BMD and change in bone geometry at distal and proximal femur, as well as the decrease in total ash weight of femur and tibia. OVX did not cause any marked changes in cortical BMD or bone geometry at the level of mid-diaphysis of tibia or femur over a 3-month period. Neither were there any changes between groups in bending strength in the tibial diaphysis. However, a positive correlation (n = 58, r = 0.51, P < .001) was found between bending strength and calculated density-weighted polar moment of resistance of tibial diaphysis. We conclude that clodronate administered p.o. in adult rats prevents changes due to estrogen deficiency in BMD and bone geometry.

Footnotes

  • Send reprint requests to: Thua Österman, Leiras Oy, Biomedical Research Center, P.O. Box 415, FIN-20101 Turku, Finland.

  • Abbreviations:
    BMD
    bone mineral density
    BMC
    bone mineral content
    OVX
    ovariectomy, ovariectomized
    SHAM
    sham-operated
    pQCT
    peripheral quantitative computed tomography
    SSI
    stability index
    • Received February 7, 1997.
    • Accepted September 22, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 1
1 Jan 1998
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OtherENDOCRINE PHARMACOLOGY

The Effect of Orally Administered Clodronate on Bone Mineral Density and Bone Geometry in Ovariectomized Rats

T. Österman, L. Laurén, P. Kuurtamo, R. Hannuniemi, P. Isaksson, K. Kippo, Z. Peng, H. K. Väänänen and R. Sellman
Journal of Pharmacology and Experimental Therapeutics January 1, 1998, 284 (1) 312-316;

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OtherENDOCRINE PHARMACOLOGY

The Effect of Orally Administered Clodronate on Bone Mineral Density and Bone Geometry in Ovariectomized Rats

T. Österman, L. Laurén, P. Kuurtamo, R. Hannuniemi, P. Isaksson, K. Kippo, Z. Peng, H. K. Väänänen and R. Sellman
Journal of Pharmacology and Experimental Therapeutics January 1, 1998, 284 (1) 312-316;
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