Osteoporosis International

, Volume 8, Issue 2, pp 97–103 | Cite as

Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats

  • S. Lalla
  • L. A. Hothorn
  • N. Haag
  • R. Bader
  • F. Bauss
Original Article


As part of a long-term safety study the bisphosphonate ibandronate was investigated for its effects on bone quality in lumbar vertebrae in rats. Bone area, bone density and mechanical properties were assessed by peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA) and compression tests. Female and male groups of Wistar rats received either vehicle or 3, 7 or 15 mg/kg per day of ibandronate over 104 weeks orally by gavage. Compared with the control group, bone mineral density, compressive strength and stiffness were significantly higher in ibandronate-treated animals, whereas no changes occurred in strain or modulus of elasticity. The increase in vertebral body stress was significant in some of the ibandronate-treated groups. The changes in mechanical properties appear to be due mainly to an increase in bone mass. A highly significant correlation was found between bone mineral density measured either by DXA (r=0.86) or pQCT (r=0.85) and maximal strength in vertebral bodies (p<0.0001 each). In conclusion, we demonstrated that lifelong administration of doses of ibandronate far in excess of any therapeutically intended dose not only increases bone mass and apparent density, but also maintains or even slightly improves bone quality. Bone mineral density measured either by pQCT or DXA can be used as a predictor for ultimate strength in rat lumbar vertebral bodies after treatment with ibandronate.


Bone quality Bone mineral density Mechanical properties Ibandronate Rats 


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  1. 1.
    Fleisch H. Bisphosphonates in bone disease. 3rd ed. New York: Parthenon Publishing, 1997.Google Scholar
  2. 2.
    Mühlbauer RC, Bauss F, Schenk R, et al. BM 21.0955, a potent new bisphosphonate to inhibit bone resorption. J Bone Miner Res 1991;6:1003–11.PubMedGoogle Scholar
  3. 3.
    Bauss F. Ibandronate in malignant bone diseases and osteoporosis preclinical results. Onkologie 1997;20:204–8.CrossRefGoogle Scholar
  4. 4.
    Pecherstorfer M, Herrmann Z, Body J-J, et al. Randomized phase II trial comparing different doses of the bisphophonate ibandronate in the treatment of hypercalcemia of malignancy. J Clin Oncol 1996;14:268–76.PubMedGoogle Scholar
  5. 5.
    Yoneda T, Sasaki A, Dunstan C, et al. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest 1997;99:2509–17.PubMedCrossRefGoogle Scholar
  6. 6.
    Monier-Faugere M-C, Friedler RM, Bauss F, Malluche HH. A new bisphosphonate, BM 21.0955, prevents bone loss associated with cessation of ovarian function in experimental dogs. J Bone Miner Res 1993;8:1345–55.PubMedGoogle Scholar
  7. 7.
    Bauss F, Kling L, Sponer G. Comparison of continuous and cyclical administration of ibandronate on bone mass in ovariectomized rats. J Bone Miner Res 1996;11(Suppl 1): No. M 618, page S336.Google Scholar
  8. 8.
    Geng Z, Faugere M-C, Qi Q, Bauss F, Malluche HH. Ibandronate reverses bone loss after cessation of ovarian function in beagle dogs. J Bone Miner Res 1995, 10(Suppl 1): No P283, page S199.Google Scholar
  9. 9.
    Borchers RE, Gibson LJ, Burchardt H, Hayes WC. Effects of selected thermal variables on the mechanical properties of trabecular bone. Biomaterials 1995;16:545–51.PubMedCrossRefGoogle Scholar
  10. 10.
    Dunnett CW. A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 1955;50:1096–121.CrossRefGoogle Scholar
  11. 11.
    Shaffer JP. Modified sequentially rejective multiple test procedures. J Am Stat Assoc 1986;81:826–31.CrossRefGoogle Scholar
  12. 12.
    Guy JA, Shea M, Peter CP, Morrissey R, Hayes WC. Continuous alendronate treatment throughout growth, maturation, and aging in the rat results in increases in bone mass and mechanical properties. Calcif Tissue Int 1993;53:283–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Lepola VT, Hannuniemi R, Kippo K, Laurén L, Jalovaara P, Väänänen HK. Long-term effects of clodronate on growing rat bone. Bone 1996;18:191–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Mosekilde L, Danielsen CC, Knudsen UB. The effect of aging and ovariectomy on the vertebral bone mass and biomechanical properties of mature rats. Bone 1993;14:1–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Toolan BC, Shea M, Myers ER, et al. Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats. J Bone Miner Res 1992;7:1399–406PubMedGoogle Scholar
  16. 16.
    Li M, Mosekilde Li, Søgaard CH, et al. Parathyroid hormone monotherapy and cotherapy with antiresorptive agents restore vertebral bone mass and strength in aged ovariectomized rats. Bone 1995;16:629–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Jowsey J, Riggs BL, Kelly PJ, Hoffman DL, Bordier P. The treatment of osteoporosis with disodium ethane-1-hydroxy-1,1-diphosphonate. J Lab Clin Med 1971;78:574–84.PubMedGoogle Scholar
  18. 18.
    Jiang Y, Zhao J, Van Audekercke R, Dequeker J, Geusens P. Effects of low-dose long-term sodium fluoride preventive treatment on rat bone mass and biomechanical properties. Calcif Tissue Int 1996;58:30–9.PubMedGoogle Scholar
  19. 19.
    Fratzl P, Schreiber S, Roschger P, Lafage M-H, Rodan G, Klaushofer K. Effects of sodium fluoride and alendronate on the bone mineral in minipigs: a small-angle X-ray scattering and backscattered electron imaging study. J Bone Miner Res 1996;11:248–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Keaveny TM, Hayes WC. A 20-year perspective on the mechanical properties of trabecular bone. J Biomech Eng 1993;115:534–42.PubMedGoogle Scholar
  21. 21.
    Moro M, Hecker AT, Bouxsein ML, Myers ER. Failure load of thoracic vertebrae correlates with lumbar bone mineral density measured by DEXA. Calcif Tissue Int 1995;56:206–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Burr DB. Remodeling and the repair of fatigue damage. Calcif Tissue Int 1993;53(Suppl 1):S75–81.PubMedCrossRefGoogle Scholar
  23. 23.
    Flora L, Hassing GS, Parfitt AM, Villanueva AR. Comparative skeletal effects of two diphosphonates in dogs. Metab Bone Dis Rel Res 1980;2(Suppl):389–407.Google Scholar

Copyright information

© European Foundation for Osteoporosis and the National Osteoporosis Foundation 1998

Authors and Affiliations

  • S. Lalla
    • 1
  • L. A. Hothorn
    • 2
  • N. Haag
    • 1
  • R. Bader
    • 1
  • F. Bauss
    • 1
  1. 1.Department of Preclinical Research and DevelopmentBone Metabolism, Boehringer Mannheim GmbHMannheimGermany
  2. 2.Department of BioinformaticsUniversity of HannoverHannoverGermany

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