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Related Experiment Videos

The acute-phase response after bisphosphonate administration.

S Adami1, A K Bhalla, R Dorizzi

  • 1Istituto di Semeiotica e Nefrologia Medica, University of Verona, Italy.

Calcified Tissue International
|December 1, 1987
PubMed
Summary

Amino-bisphosphonates induce an acute-phase response (APR) in patients, characterized by fever and changes in CRP and zinc levels. This response desensitizes patients to further bisphosphonate treatment for several months.

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Area of Science:

  • Pharmacology
  • Immunology
  • Bone Biology

Background:

  • Bisphosphonates are commonly used to treat bone diseases.
  • The acute-phase response (APR) is a systemic reaction to inflammation.
  • The interaction between bisphosphonates and the immune system is not fully understood.

Purpose of the Study:

  • To investigate the acute-phase response induced by amino-bisphosphonates.
  • To determine the dose-dependency and duration of the APR.
  • To explore the potential for desensitization to bisphosphonate therapy.

Main Methods:

  • Intravenous administration of various amino-bisphosphonates (AHButBP, AHPrBP, AHHexBP) and dichloromethanebisphosphonate (Cl2MBP) to patients.
  • Monitoring of clinical signs (fever) and laboratory parameters (lymphocyte count, serum zinc, CRP).

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  • Subsequent challenge with bisphosphonates after varying intervals to assess desensitization.

    • Main Results:

    • Amino-bisphosphonates induced an APR, including fever, decreased lymphocytes, and zinc, with increased CRP.
    • The APR was dose-dependent and resolved within 2-3 days.
    • Patients receiving effective doses or suboptimal doses became desensitized to subsequent bisphosphonate challenges for up to 160 days.

    Conclusions:

    • Bisphosphonates interact with skeletal macrophage-like cells, stimulating IL-1 release and causing the APR.
    • This interaction leads to temporary insensitivity of these cells to further stimulation.
    • Understanding this mechanism is crucial for optimizing bisphosphonate therapy and managing potential side effects.