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. 1986 Feb;111(1):35–41. doi: 10.1007/BF00402773

Effects of new bisphosphonic acids on tumor-induced bone destruction in the rat

Franz Wingen 1,✉, Thomas Eichmann 2, Christian Manegold 3, Burkhard Krempien 2
PMCID: PMC12253181  PMID: 3949849

Abstract

This report is concerned with therapeutic studies utilizing new bisphosphonic acids on tumor-induced osteolytic metastases. The bone metastases on SD rats were induced by intraarterial and intraosseous transplantation of Walker carcinosarcoma 256B ascites cells. The treatment was carried out using disodium-3-amino-1-hydroxypropylidene-1,1-bisphophonate (APD), diglycidyl-[3-(3,3-bisphosphono-3-hydroxy-propylamino)-2-hydroxypropyl-]urazol-Na2 (DDU) and 1,2,4-triglycidylurazol (TGU). The extent of bone metastases was determined by X-ray on the 5th and 10th days following tumor inoculation, as well as both microradiographically and histologically upon termination of the experiment.

High dose DDU produced a clear reduction of the tumor osteolysis, but these positive results were surpassed using APD. The best results were achieved by pretreatment with APD 24 h prior to tumor inoculation.

Key words: Bisphosphonic acids, Osteolytic metastases, Bone metastases

References

  • 1.Abrams HL (1950) Skeletal metastases in carcinoma. Radiology 55:534 [DOI] [PubMed] [Google Scholar]
  • 2.Atassi G, Dumont P, Fisher U, Zeidler M, Budnowski M (1984) Preclinical evaluation of the anti tumor activity of new epoxyde derivatives. Cancer Treat Rev, 11:99–110 [DOI] [PubMed] [Google Scholar]
  • 3.van Breukelen FJM, Bijvoet OLM, Oosterom AT (1979) Inhibition of osteolytic bone lesions by 3-amino-1-hydroxy-propylidene-1,1-bisphosponate (APD). Lancet I (8120):803–805 [DOI] [PubMed] [Google Scholar]
  • 4.Douglas DL, Cundy T, Hanis JA, Preston FE, Rusel RGG, Woodhead S (1980) Inhibitory action of dichloromethylene diphosphonate on bone resorption in man. In: Donath A, Courvoisier B (eds) Bone and tumors. Edition Medicine and Hygiene, Geneve, pp 161–165 [Google Scholar]
  • 5.Elomaa I, Blomquist C, Gröhn P (1983) Long-term controlled trial with diphosphonate in patients with osteolytic bone metastases. Lancet I (8317):146–149 [DOI] [PubMed] [Google Scholar]
  • 6.Felix R, Fleisch H (1982) Chemie und Wirkung der Bisphosphonate. In: Ziegler R (ed) EHDP. Ein neues therapeutisches Prinzip bei Osteopathien und Calciumstoffwechselstörungen. Urban & Schwarzenberg, München Wien Baltimore [Google Scholar]
  • 7.Fleisch H, Russel RGG, Francis MD (1969) Diphosphonates inhibit hydroxylapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262–1264 [DOI] [PubMed] [Google Scholar]
  • 8.Frijlink WB, Bijvoet OLM, te Velde J, Heynen G (1979) Treatment of Paget's disease with (3-amino-1-hydroxypropylidene)-1,1-biphosphonate (APD). The Lancet I (8120):799–803 [DOI] [PubMed] [Google Scholar]
  • 9.Galasko CSB (1981) Bone metastases studied by experimental models. Schweiz Med Wochenschr 111:1862–1868 [PubMed] [Google Scholar]
  • 10.Guatani A, Polentarutti N, Filippeschi S, Marmonti L, Corti F, Italia C, Coccioli G, Donelle MG, Montovani A, Garattini S (1984) Effects of disodium etidronate in murine tumor models. Eur J Cancer Clin Oncol 20 (5):685–693 [DOI] [PubMed] [Google Scholar]
  • 11.Johnson KF, Wesseler MA, Martodam RR, Olson HM, Poser JW (1982) The effects of diphosphonates on tumor-induced hypercalcemia and osteolysis in Walker carcinosarcoma 256 (WLSG) in rats. Proc Am Assoc Cancer Res 23:896 [Google Scholar]
  • 12.Jung A, Fleisch H (1981) Les diphosphonated dans le traitement des metastases osseuses. Schweiz Med Wochenschr 111, 49:1878–1882 [PubMed] [Google Scholar]
  • 13.Jung A, Barres C, Mermillod B, Courvoisier B (1979) Effet de deux diphosphonates sur la lyse osseuse induite par des extraits tumoraux. Schweiz Med Wochenschr 109:1888–1890 [PubMed] [Google Scholar]
  • 14.Jung A, Bornand I, Mermillod B, Evuard C, Meunier PI (1984) Inhibition by diphosphonates of bone resorption induced by the Walker tumor of the rat. Cancer Res 44:3007–3011 [PubMed] [Google Scholar]
  • 15.Krempien B, Pfeilschifter I, Minne H (1982) Influence of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) on bone remodelling. In: Silbermann M, Slavkin HC (eds) Current advances in skeletogenesis. Proc 5th int workshop on calcified tissues. Diryat-Anarim, Israel, 117–122 [Google Scholar]
  • 16.Krempien B, Diel I, Jockle-Kretz B, Büchele R, Andre L (1984) Das Walker Carcino-Sarkom 256 als Modell für die Entwicklung von Knochenmetastasen. Untersuchungen zum Einfluß des Knochenstoffwechsels auf die Entwicklung von Knochenmetastasen. Verh Dtsch Ges Pathol 68:211–216 [Google Scholar]
  • 17.Manegold C, Krempien B (1984) Beckenkammnadelbiopsie in der Diagnostik von Knochen- und Knochenmarkserkrankungen. Dtsch Med Wochenschr 24:954–956 [DOI] [PubMed] [Google Scholar]
  • 18.Martodam RR, Johnson KY, Jung A (1981) The effects of diphosphonates (bone seeking agents) on hypercalcemia and increased bone resorption in the rat Walker 256 tumor and in humans. 4th Annual San Antonio breast cancer symposium, Texas cancer therapy and research center of South Texas, USA
  • 19.Minne HW, Rane F, Klär H, Ziegler R, Bijvoet OLM (1980) Treatment of paraneoplastic hypercalcemia with a new diphosphonate (APD) in the animal experiment. In: Donath A, Convoisier B (eds) Bone and tumors, Medicine and Hygiene, Geneve, pp 166–169 [Google Scholar]
  • 20.Peto R, Pike MC, Armitage P, Brelow NE, Cox PR, Howard SV, Mantel N, McPherson U, Peto J, Smith PG (1977) Design and analysis of randomized clinical trials requiring prolonged observation of each patient. Br J Cancer 35:1–39 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Rade J, Croese JW, Zurcher C, Enden-Vieveen MHM, van den Brondigh RJ, Hazil M, Haaijman JJ, Reitsma PH, Bijvoet OLM (1985) Influence of treatment with APD-bisphosphonate on the bone lesions in the mouse 5T2 multiple myeloma. Cancer 55:1030–1040 [DOI] [PubMed] [Google Scholar]
  • 22.Reitsma PH, Bijvoet OLM, Verlinden-Ooms H, Wee-Pals van der LIA (1980) Kinetic studies of bone and mineral metabolism during treatment with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in rats. Calcif Tissue Int 32:145–157 [DOI] [PubMed] [Google Scholar]
  • 23.Reitsma PH, Teitelbaum SL, Bijvoet OLM, Hahn AJ (1982) Differential action of the bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichlormethylidene bisphosponate (Cl2MDP) on rat macrophage mediated bone resorption in vitro. 2. Clin Invest 70:927–933 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Samuel AW, Rushton S, Galasko CS (1979) Effects of prostaglandin inhibitors and diphosphonates on tumor-mediated osteolysis. Br J Surg 66:901 [DOI] [PubMed] [Google Scholar]
  • 25.Schürer CC, Peters U, Tischer JT (1981) Therapeutische Möglichkeiten bei paraneoplastischer Hypercalcämie. Med Welt 32:1219 [PubMed] [Google Scholar]
  • 26.Sleebohm HP, Bijvoet OLM, van Oosterom AT, Gleed JH, O'Riordan JL (1983) Comparison of intravenous (3-amino-1-hydroxypropylidene)-1,1-bisphosponate and volume repletion in tumor-induced hypercalcemia. Lancet II (8344):239–243 [DOI] [PubMed] [Google Scholar]
  • 27.Wingen F, Schmähl D (1985) Distribution of 3-amino-1-hydroxypropane-1,1-diphosphonic acid (APD) in rats and effects on rat osteosarcoma. Arzneimittelforsch 35 (II) 10, 1565–1571 (1985) [PubMed] [Google Scholar]
  • 28.Wingen F, Schmähl D (in preparation) Effects of new bisphosphonic acids in subcutaneously growing Walker carcinomas in rats
  • 29.Wingen F, Schmähl D, Berger MR, Spring H (1984) Intraosseosly transplantable osteosarcoma with regularly disseminating pulmonary metastases in rats. Cancer Lett 23:201–211 [DOI] [PubMed] [Google Scholar]

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