Skip to main content

Effect of gallium on thein vitro formation, growth, and solubility of hydroxyapatite

Calcified Tissue International volume 45, pages 81–87 (1989)Cite this article

Summary

Gallium (Ga) is an effective treatment for the hypercalcemia of malignancy. The mechanism of action of the metal in blocking bone resorption in humans is not well understood. This paper examines the effect of Ga on thein vitro formation of hydroxyapatite (HA) in three test systems that have possible biological relevance in a pH-stat at pH 7.4, 37°C, and 0.15 M NaCl: (1) the direct precipitation of HA; (2) the transformation of amorphous calcium phosphate to HA; and (3) the growth of HA seeds. In addition, the effect of Ga on HA solubility was measured at pH 5.0, the approximate pH of osteoclastic bone resorption. Ga decreased the HA formation and/or growth kinetics in a dose-related manner in all three test systems. In addition, the time to the onset of HA formation was increased in systems 1 and 2. Also, the adsorption of Ga on the surface of HA crystals was measured. Ga reduced the dissolution kinetics of HA compared with Ga-free control. The mechanism reported herein—the significant adsorption of Ga on forming and growing HA nuclei and on the surface of HA crystals—is believed to be responsible for the effects of the metal on HA proliferation and solubility. Accumulation of the metal on newly formed metaphyseal bone can now be explained by this adsorption of Ga. Thesein vitro results partly explain thein vivo action of Ga in treating hypercalcemia by decreasing bone apatite solubility. The similarities in reducingin vitro HA formation rates of aluminum and Ga suggest that patients on long-term Ga therapy for any bone pathology should be carefully monitored for possible osteomalacic complication.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Warrell RP Jr, Bockman RS, Coonley CJ, Isaacs M, Staszewski HJ (1984) Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcemia. J Clin Invest 73:1487–1490

    PubMed  CAS  Article  Google Scholar 

  2. Bockman RS, Warrell RP, Alcock NW (1985) Gallium blocks accelerated bone resorption in patients with metastatic cancer and increases calcium content of bone. Clin Res 33:576A

    Google Scholar 

  3. Bockman RS, Boskey AL, Blumenthal NC, Alcock NW, Warrell RP Jr (1986) Gallium increases bone calcium and crystallite perfection of hydroxyapatite. Calcif Tissue Int 39:376–381

    PubMed  Article  CAS  Google Scholar 

  4. Boskey AI, Posner AS (1973) Conversion of amorphous calcium phosphate to microcrystalline hydroxyapatite: a pH-dependent solution-mediated, solid-solid conversion. J Phys Chem 77:2313–2317

    Article  CAS  Google Scholar 

  5. Blumenthal NC, Posner AS, Holmes JM (1972) Effect of preparation conditions on the properties and transformation of amorphous calcium phosphate. Mat Res Bull 7:1181

    Article  CAS  Google Scholar 

  6. Betts F, Posner AS (1974) A structural model for amorphous calcium phosphate. Trans Am Cryst Assoc 10:73

    CAS  Google Scholar 

  7. Blumenthal NC, Betts F, Posner AS (1977) Stabilization of amorphous calcium phosphate by Mg and ATP. Calcif Tissue Res 23:245

    PubMed  Article  CAS  Google Scholar 

  8. Betts F, Blumenthal NC, Posner AS, Becker GL, Lehringer AL (1975) Atomic structure of ultracellular amorphous calcium deposits. Proc Nat Acad Sci 72:2088

    PubMed  Article  CAS  Google Scholar 

  9. McGann TCA, Kearney RD, Bucheim W, Posner AS, Betts F, Blumenthal NC (1983) Amorphous calcium phosphate in casein micelles of bovine milk. Calcif Tissue Int 35:821

    PubMed  Article  CAS  Google Scholar 

  10. Gay CV (1977) The ultrastructure of the extracellular phase of bone as observed in frozen thin sections. Calcif Tissue Res 23:215–223

    PubMed  Article  CAS  Google Scholar 

  11. Landis WJ, Glimcher MF (1978) Electron diffraction and electron probe microanalysis of the mineral phase of bone tissue prepared by anhydrous techniques. J Ultrastruct Res 63:188

    PubMed  Article  CAS  Google Scholar 

  12. Walton AG (1967) The formation and properties of precipitates. Interscience, New York, p 30

    Google Scholar 

  13. Jackson SA, Cartwright AG, Lewis D (1978) The morphology of bone mineral crystals. Calcif Tissue Res 25:217–222

    PubMed  Article  CAS  Google Scholar 

  14. Blumenthal NC, Posner AS (1987) Surface poisoning of synthetic and biological apatites. Colloids and Surfaces 26:123

    Article  CAS  Google Scholar 

  15. Blumenthal NC, Betts F, Posner AS (1975) Effect of carbonate and biological macromolecules on formation and properties of hydroxyapatites. Calcif Tissue Res 18:81

    PubMed  Article  CAS  Google Scholar 

  16. Cho PW, Fox JL, Higuchi WJ, Pithayanukul P (1984) Influence of dodecylamine hydrochloride adsorption on the dissolution kinetics of hydroxyapatite. In: Miska DN (ed) Adsorption on and surface chemistry of hydroxyapatite. Plenum Press, New York, pp 51–70

    Google Scholar 

  17. Hodsman AB, Sherrard DJ, Alfrey AC, Ott S, Brickman AS, Miller ML, Maloney NA, Coburn JW (1982) Bone aluminum and histomorphometric features of renal osteodystrophy. J Clin Endo Metab 54:539–546

    CAS  Article  Google Scholar 

  18. Blumenthal NC, Posner AS (1984) In vitro model of aluminum-induced osteomalacia: inhibition of hydroxyapatite formation and growth. Calcif Tissue Int 36:439–441

    PubMed  Article  CAS  Google Scholar 

  19. Blumenthal NC (1985) Binding of aluminum to hydroxyapatite and amorphous calcium phosphate as a model for aluminum-associated osteomalacia. In: Butler WT (ed) The chemistry and biology of mineralized tissues. EBSCO Media, Birmingham, AL, pp 385–388

    Google Scholar 

  20. Fleisch H, Russell RGG, Francis MD (1969) Diphosphonates inhibit hydroxyapatite dissolution. Science 165:1262

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. New York University Medical School, New York, New York, USA

    Stuart Levine

  2. Department of Bioengineering, Hospital for Joint Diseases Orthopaedic Institute, 10003, New York, NY, USA

    Norman C. Blumenthal & Vera Cosma

Authors
  1. Norman C. Blumenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vera Cosma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stuart Levine
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Blumenthal, N.C., Cosma, V. & Levine, S. Effect of gallium on thein vitro formation, growth, and solubility of hydroxyapatite. Calcif Tissue Int 45, 81–87 (1989). https://doi.org/10.1007/BF02561406

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02561406

Key words

  • Gallium
  • Hydroxyapatite
  • Nucleation
  • Inhibition
  • Solubility