Advertisement

Disodium Pamidronate Therapy of Paget’s Disease

  • Olav L. M. Bijvoet

Abstract

Several bisphosphonate analogues are currently in use for the treatment of bone disorders, with the best known being etidronate disodium, disodium clodronate (Cl2 MDP), and disodium pamidronate, also known as disodium APD.1 APD is chemically disodium (3-amino-1-hydroxy-propylidene)-1, 1-bisphosphonate. The inhibitory action of the bisphosphonates on bone resorption requires prior chemisorption to the calcified bone matrix,2–4 which is achieved through two phosphonate groups connected by a central carbon atom, the P-C-P bond, which all the bisphosphonates have in common. The two phosphonates form complexes with calcium salts and with the hydroxyapatite crystals embedded in bone matrix.1 Their presence on crystal surfaces changes the energy distribution on these surfaces and the chemical composition of the mineral, according to the nature of the nonbisphosphonate groups of the bisphosphonate, so that some of them make crystals grow more slowly and also dissolve more slowly. In addition, several bisphosphonates alter biologic processes taking place at the surface of bone crystals. Some may inhibit bone resorption by direct inhibition of bone-resorbing cells, others by impairing accession to bone of these cells. The high affinity of bisphosphonates for Bone Mineral is exploited in scintigraphy, in which bisphosphonates bound to radioactive tracers localize to bony areas having increased turnover. Phosphonate bonds are not hydrolyzable by alkaline phosphatases or pyrophosphatases. This, together with their strong chemisorption to Bone Mineral, is responsible for a long half-life once deposited there.

Keywords

Osteoclast Precursor Serum Alkaline Phosphatase Level Central Carbon Atom Serum Alkaline Phosphatase Activity Etidronate Disodium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fleisch H: Bisphosphonates: Mechanism of action and clinical application. In: WA Peck (ed.) Bone and Mineral Research. Annual 1. Amsterdam, Excerpta Medica, 1983, pp. 319–357.Google Scholar
  2. 2.
    Boonekamp PM, Löwik CWGM, van der Wee-Pals LJA, et al: Enhancement of the inhibitory action of APD on the transformation of osteoclast precursors into resorbing cells after dimethylation of the amino group. Bone Mineral 1987; 2: 29–42.Google Scholar
  3. 3.
    Boonekamp PM, van der Wee-Pals LJA, van Wijk-van Lennep M, et al: Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Mineral 1986; 1: 27–40.Google Scholar
  4. 4.
    Löwik CWGM, van der Pluym G, van der Wee-Pals LJA, et al: Migration and phenotypic transformation of osteoclast precursors into mature osteoclasts: The effects of a bisphosphonate. J Bone Mineral Res 1988; 2: 185–192.Google Scholar
  5. 5.
    Shinoda H, Adamek G, Felix R, et al: Structure-activity relationships of various bisphosphonates. Calif Tiss Int 1983; 35: 87–99.CrossRefGoogle Scholar
  6. 6.
    Reitsma PH, Bijvoet OLM, Verlinden-Ooms H, van der Wee-Pals L: Kinetic studies of bone and mineral metabolism during treatment with (3-amino-l-hydroxypropylidene) -1,1-bisphosphonate (APD) in rats. Calcif Tissue Int 1980; 32: 145–157.PubMedCrossRefGoogle Scholar
  7. 7.
    Reitsma PH, Bijvoet OLM, Potokar M, et al: Apposition and resorption of bone during oral treatment with (3-amino-l-hydroxypropylidene)-1,1-bisphosphonate (APD). Calcif Tissue Int 1983; 35: 357–361.PubMedCrossRefGoogle Scholar
  8. 8.
    Harinck HIJ, Bijvoet OLM, Blanksma HJ, Dahlinghaus-Nienhuis PJ: Efficaceous management with aminobisphosphonate (APD) in Paget’s disease of bone. Clin Orthop 1987; 217: 79–98.PubMedGoogle Scholar
  9. 9.
    Douglas DL, Duckworth T, Kanis JA, et al: Biochemical and clinical responses to dichloromethylene diphosphonate (Cl2MDP) in Paget’s disease of bone. Arthritis Rheum 1980; 23: 1185–1192.PubMedCrossRefGoogle Scholar
  10. 10.
    McCloskey EV, Yates AJP, Beneton MNC, et al: Comparative effects of intravenous diphosphonates on calcium and skeletal metabolism in man. Bone 1987; 8: [Suppl 1] pp 35–41.Google Scholar
  11. 11.
    Attardo-Parrinello G, Merlini G, Pavesi F, et al: Effects of a new aminodiphosphonate (aminohydroxybutylidene-diphosphonate) in patients with osteolytic lesions from metastases and myelomatosis. Arch Int Med 1987; 147: 1629–1633.CrossRefGoogle Scholar
  12. 12.
    Bijvoet OLM, Frijlink WB, Jie K, et al: APD in Paget’s disease of bone: Role of the mononuclear phagocyte system? Arthr Rheum 1980; 23: 1193–1204.CrossRefGoogle Scholar
  13. 13.
    Harinck HIJ, Papapoulos SE, Blanksma HJ, et al: Paget’s disease of bone: Early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD). Brit Med J 1987; 295: 1301–1305.CrossRefGoogle Scholar
  14. 14.
    Bijvoet OLM, Vellenga CJLR, Harinck HIJ. Paget’s disease of bones: Assessment, therapy, and secondary prevention. In Kleerekoper M, Krane SM (eds.): Clinical Disorders of Bone and Mineral Metabolism. New York, Mary Ann Liebert, Publishers, 1989, pp 525–542.Google Scholar
  15. 15.
    Frijlink WB, TeVelde J, Bijvoet OLM, Heynen G: Treatment of Paget’s disease of bone with (3-amino-l-hydroxy-propylidene)-l,l-bisphosphonate (APD). Lancet 1979;i: 799–803.CrossRefGoogle Scholar
  16. 16.
    Dodd GW, Ibbertson HK, Fraser TR, et al: Radiological assessment of Paget’s disease of bone after treatment with the bisphosphonates EHDP and APD. Br J Radiol 1987; 60: 849–860.PubMedCrossRefGoogle Scholar
  17. 17.
    Maldague B, Malghem J: Dynamic radiologic patterns of Paget’s disease of bone. Clin Orthop Rel Res 1987; 217: 126–151.Google Scholar
  18. 18.
    Vellenga CJLR, Bijvoet OLM, Pauwels EKJ: Bone scintigraphy and radiology in Paget’s disease of bone. Amer J Physiol Imaging 1988; 3: 154–168.Google Scholar
  19. 19.
    Adami S, Frijlink WB, Bijvoet OLM, et al: Regulation of calcium absorption by 1, 25 dihydroxyvitamin D3. Studies of the effect of bisphosphonate treatment. Calc Tiss Int 1983; 35: 357 - 361.CrossRefGoogle Scholar
  20. 20.
    Papapoulos SE, Harinck HIJ, Bijvoet OLM, et al: Effects of decreasing serum calcium on circulating parathyroid hormone and vitamin D metabolites in normocalcaemic and hypercalcaemic patients treated with APD. Bone Mineral 1986; 1: 59–78.Google Scholar
  21. 21.
    Vellenga CUR, Pauwels EKJ, Bijvoet OLM, et al: Quantitative bone scintigraphy in Paget’s disease treated with APD. Brit J Radiol 1985; 58: 1165–1172.PubMedCrossRefGoogle Scholar
  22. 22.
    Dinarello CA: Interleukin-1 and the pathogenesis of the acute phase response. N Engl J Med 1984; 311: 1413–1418.PubMedCrossRefGoogle Scholar
  23. 23.
    Heynen G, Delwaide P, Bijvoet OLM, Franchimont P: Clinical and biological effects of low dose of (3-amino-l-hydroxypropylidene)-1,1-bisphosphonate (APD) in Paget’s disease of bone. Europ J Clin Invest 1982; 12: 29–35.PubMedCrossRefGoogle Scholar
  24. 24.
    Gallacher SJ, Ralston SH, Pastel U, Boyle IT: Side effects of pamidronate. Lancet 1988;ii:42–43.Google Scholar

Copyright information

© Elsevier Science Publishing Co., Inc. 1991

Authors and Affiliations

  • Olav L. M. Bijvoet

There are no affiliations available

Personalised recommendations