Skip to main content
Log in

Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Summary

Three new bisphosphonates of various chain length, namely, 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 5-amino-1-hydroxypentylidene-1,1-bisphosphonate (AHPeBP), and 6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) were compared with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylene bisphosphonate as to their effect on metaphyseal bone remodeling in the rat. The parameters assessed were growth in length, mineralization, metaphyseal density, mean trabecular diameter, and number of trabeculae. Both metaphyseal density, an index of metaphyseal Ca balance, and number of trabeculae, an index of bone resorption, showed the following sequence of potency: AHBuBP>AHPrBP=AHPeBP=AHHexBP>Cl2MBP. All compounds decreased trabecular diameter somewhat, an index of bone formation, with AHBuBP decreasing the least. AHBuBP and possibly AHHexBP appear to be interesting new bisphosphonates for future clinical use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Reynolds JJ, Minkin C, Morgan DB, Spycher D, Fleisch H (1972) The effect of two diphosphonates on the resorption of mouse calvaria in vitro. Calcif Tissue Res 10:302–313

    Article  PubMed  CAS  Google Scholar 

  2. Fleisch H, Russell RGG, Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262–1264

    Article  PubMed  CAS  Google Scholar 

  3. Russell RGG, Mühlbauer RC, Bisaz S, Williams DA, Fleisch H (1970) The influence of pyrophosphate, condensed phosphates, phosphonates and other phosphate compounds on the dissolution of hydroxyapatite in vitro and on bone resorption induced by parathyroid hormone in tissue culture and in thyroparathyroidectomized rats. Calcif Tissue Res 6:183–196

    Article  PubMed  CAS  Google Scholar 

  4. Gasser AB, Morgan DB, Fleisch H, Richelle LJ (1972) The influence of two diphosphonates on calcium metabolism in the rat. Clin Sci 43:31–45

    PubMed  CAS  Google Scholar 

  5. Schenk R, Merz WA, Mühlbauer R, Russell RGG, Fleisch H (1973) Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl2MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats. Calcif Tissue Res 11:196–214

    Article  PubMed  CAS  Google Scholar 

  6. Smith R, Russell RGG, Bishop M (1971) Diphosphonates and Paget's disease of bone. Lancet i:945–947

    Article  Google Scholar 

  7. Altman RD, Johnston CC, Khairi MRA, Wellman H, Serafini AN, Sankey RR (1973) Influence of disodium etidronate on clinical and laboratory manifestations of Paget's disease of bone (osteitis deformans). N Engl J Med 289:1379–1384

    Article  PubMed  CAS  Google Scholar 

  8. De Vries HR, Bijvoet OLM (1974) Results of prolonged treatment of Paget's disease of bone with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). Neth J Med 17:281–298

    PubMed  Google Scholar 

  9. Canfield R, Rosner W, Skinner J, McWorther J, Resnick L, Feldman F, Kammerman S, Ryan K, Kunigonis M, Bohne W (1977) Diphosphonate therapy of Paget's disease of bone. J Clin Endocrinol Metab 44:96–106

    Article  PubMed  CAS  Google Scholar 

  10. Meunier PJ, Alexandre C, Edouard C, Mathieu L, Chapuy MC, Bressot C, Vignon E, Trechsel U (1979) Effects of disodium dichloromethylenediphosphonate on Paget's disease of bone. Lancet ii:489–492

    Article  Google Scholar 

  11. Frijlink WB, Te Velde J, Bijvoet OLM, Heynen G (1979) Treatment of Paget's disease with (3-amino-1-hydroxy-propylidene)-1,1-bisphosphonate (A.P.D.). Lancet i:799–803

    Article  Google Scholar 

  12. Jung A (1982) Comparison of two parenteral diphosphonates in hypercalcemia of malignancy. Am J Med 72:221–226

    Article  PubMed  CAS  Google Scholar 

  13. Siris ES, Sherman WH, Baquiran DC, Schlatterer JP, Osserman EF, Canfield RE (1980) Effects of dichloromethylene diphosphonate on skeletal mobilization of calcium in multiple myeloma. N Engl J Med 302:310–315

    Article  PubMed  CAS  Google Scholar 

  14. Van Breukelen FJM, Bijvoet OLM, Oosterom AT (1979) Inhibition of osteolytic bone lesions by (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (A.P.D.). Lancet i:803–805

    Article  Google Scholar 

  15. Chapuy MC, Meunier PJ, Alexandre C, Vignon E (1980) Effects of disodium dichloromethylene diphosphonate on hypercalcemia produced by bone metastases. J Clin Invest 65:1243–1247

    Article  PubMed  CAS  Google Scholar 

  16. Elomaa I, Blomqvist C, Gröhn P, Parkka L, Kairento AL, Selander K, Lamberg-Allardt C, Holmström T (1983) Long-term controlled trial with diphosphonate in patients with osteolytic bone metastases. Lancet 1:146–149

    Article  PubMed  CAS  Google Scholar 

  17. Minaire P, Bérard E, Meunier PJ, Edouard C, Goedert G, Pilonchéry G (1981) Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients. J Clin Invest 68:1086–1092

    PubMed  CAS  Google Scholar 

  18. Shinoda H, Adamek G, Felix R, Fleisch H, Schenk R, Hagan P (1983) Structure-activity relationships of various bisphosphonates. Calcif Tissue Int 35:87–99

    Article  PubMed  CAS  Google Scholar 

  19. Lemkes HHPJ, Reitsma PH, Frijlink W, Verlinden-Ooms H, Bijvoet OLM (1978) A new diphosphonate: dissociation between effects on cells and mineral in rats and a preliminary trial in Paget's disease. Adv Exp Med Biol 103:459–469

    PubMed  CAS  Google Scholar 

  20. Reitsma PH, Bijvoet OLM, Verlinden-Ooms H, van der Wee-Pals LJA (1980) Kinetic studies of bone and minral metabolism during treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in rats. Calcif Tissue Int 32:145–147

    Article  PubMed  CAS  Google Scholar 

  21. Fast DK, Felix R, Dowse C, Neuman WF, Fleisch H (1978) The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture. Biochem J 172:97–107

    PubMed  CAS  Google Scholar 

  22. Burkhardt R (1966) Präparative Voraussetzungen zur klinischen Histologie des menschlichen Knochenmarks, 1. Mitteilung. Blut 13:337–357

    Article  PubMed  CAS  Google Scholar 

  23. Krutsay M (1963) Methode zur Darstellung einzelner Kalzium-verbindungen in histologischen Schnitten. Acta histochem (Jena) 15:189–191

    CAS  Google Scholar 

  24. Olah AJ, Simon A, Gaudy M, Hermann H, Schenk RK (1977) Differential staining of calcified tissues in plastic-embedded microtome sections by a modification of Movat's pentachrome stain. Stain Technol 53:331–337

    Google Scholar 

  25. Schenk RK, Olah AJ, Herrmann W (1984) Preparation of calcified tissues for light microscopy. In: Dickson GR (ed) Methods of calcified tissue preparation. Elsevier Science Publishers B.V. Amsterdam, New York, Oxford, p 199

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schenk, R., Eggli, P., Fleisch, H. et al. Quantitative morphometric evaluation of the inhibitory activity of new aminobisphosphonates on bone resorption in the rat. Calcif Tissue Int 38, 342–349 (1986). https://doi.org/10.1007/BF02555748

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02555748

Key words

Navigation