Osteoporosis International

, Volume 3, Supplement 3, pp 7–12 | Cite as

Preclinical pharmacology of alendronate

  • G. A. Rodan
  • J. G. Seedor
  • R. Balena


This brief review summarizes some of the preclinical findings of studies aimed at assessing the efficacy and safety of the aminobisphosphonate alendronate (ALN) in preventing or restoring the bone loss caused by calcium or estrogen deficiency. Mode of action studies show that ALN localizes at sites of bone resorption and inhibits osteoclastic activity. In secondary hyperparathyroidism caused by calcium-deficient diets in the rat, ALN reduced the bone loss. For low doses, daily administration proved most efficient. In ovariectomized rats, ALN both prevented and reversed the bone changes produced by estrogen deficiency at oral doses equivalent to 0.1 mg/kg per day or higher, and also maintained the mechanical strength of vertebrae. In ovariectomized baboons, which show bone changes similar to those seen in ovariectomized women, ALN also prevented the increase in bone turnover and increased both bone volume and bone strength in vertebrae. In a comparative study between ALN and etidronate, we found that ALN was 1000-fold more potent in inhibiting bone resorption and had at least a 1000-fold higher safety margin with respect to inhibition of mineralization and osteomalacia.


Bisphosphonates Estrogen deficiency Secondary hyperparathyroidism 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Weiss NS, Ure CL, Ballard JH, Williams AR, Daling JR. Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen. N Engl J Med 1980;303:1195–8.Google Scholar
  2. 2.
    Fleisch, H. Bisphosphonates: history and experimental basis. Bone (NY) 1987;8:523–8.Google Scholar
  3. 3.
    Fleisch H. Bisphosphonates in osteoporosis: an introduction. Osteoporosis Int 1993;3(Suppl 3):S3–5.Google Scholar
  4. 4.
    Schenk R, Eggli P, Fleisch H, Rosini S. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat. Calcif Tissue Int 1986;34:342–9.Google Scholar
  5. 5.
    Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, et al. Bisphosphonate action: alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 1991;88:2095–105.Google Scholar
  6. 6.
    Masarachia P, Balena R, Rodan GA. Long term fate of tritiated alendronate in the skeleton of adult mice in vivo. Calcif Tissue Int 1993;52(Suppl 1):S60.Google Scholar
  7. 7.
    Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ. Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 1993;91:2004–11.Google Scholar
  8. 8.
    Wronski TJ, Cintron J, Dann LM. Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 1988;43:179–83.Google Scholar
  9. 9.
    Seedor JG, Quartuccio HA, Thompson DD. The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats. J Bone Miner Res 1991;6:339–346.Google Scholar
  10. 10.
    Toolan BC, Shea M, Myers ER, Borchers RE, Seedor JG, Quartuccio H, et al. Effects of 4-amino-1-hydroxybutylidene bisphosphonate on bone biomechanics in rats. J Bone Miner Res 1992;7:1399–406.Google Scholar
  11. 11.
    Jerome CP, Kimmel DB, McAlister JA, Weaver DS. Effects of ovariectomy on iliac trabecular bone in baboons (Papio anumbis). Calcif Tissue Int 1986;39:206–8.Google Scholar
  12. 12.
    Reeves DM. A stochastic analysis of iliac trabecular bone dynamics. Clin Orthop Rel Res 1986;213:264–78.Google Scholar
  13. 13.
    Thompson DD, Seedor JG, Quartuccio H, Solomon H, Fioravanti C, Davidson J, et al. The bisphosphonate, alendronate, prevents bone loss in ovariectomized baboons. J Bone Miner Res 1992;7:951–60.Google Scholar
  14. 14.
    Balena R, Markatos A, Lafage M-H, Masarachia P, Gentile M, Rodan GA. The long term effects of alendronate on bone remodeling in the spine of ovariectomized baboons. J Bone Miner Res 1992;7 (Suppl 1):S113.Google Scholar
  15. 15.
    Toolan BC, Shea M, Myers ER, Hayes WC, Thompson DD, Seedor JG, et al. The effect of long term alendronate treatment on vertebral strength in ovariectomized baboons and rats. J Bone Miner Res 1991;6 (Suppl 1):S248.Google Scholar
  16. 16.
    Schenk R, et al. Effect of EHDP and Cl2MDP on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif Tissue Res 1973;11:196–214.Google Scholar

Copyright information

© European Foundation for Osteoporosis 1993

Authors and Affiliations

  • G. A. Rodan
    • 1
  • J. G. Seedor
    • 1
  • R. Balena
    • 1
  1. 1.Merck Research LaboratoriesWest PointUSA

Personalised recommendations