Interleukin-6 and the acute phase response during treatment of patients with Paget's disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate

J Bone Miner Res. 1995 Jun;10(6):956-62. doi: 10.1002/jbmr.5650100617.


Bisphosphonates suppress bone resorption and are used in the management of bone diseases with increasing frequency. In some patients treated for the first time with potent nitrogen-containing bisphosphonates, there is a transient febrile reaction and transient hematological changes suggestive of an acute phase response. Because IL-6 is considered to be an important mediator of the acute phase response, we examined the changes in circulating IL-6 bioactivity in 38 patients with Paget's disease treated with the nitrogen-containing bisphosphonate (3-dimethyl-amino-1-hydroxypropylidene)-1,1-bisphosphonate (dimethyl-APD). 16 patients who had never received such bisphosphonate were treated with oral dimethyl-APD (100-400 mg/day) and 22 (9 for the first time) with intravenous dimethyl-APD 4 mg/day. Treatment was given for 10 days. Eleven of 38 patients, all first treatments, showed an increase in body temperature of more than 0.5 degrees C exceeding 37 degrees C associated with a significant decrease in lymphocyte count and an increase in serum CRP values. These changes were transient and did not occur in the patients with no febrile response. In patients with a febrile reaction circulating IL-6 bioactivity increased significantly and this increase generally preceeded the rise in temperature. Moreover, patients with an acute phase response had significantly higher peak IL-6 values than those without (128 +/- 30 vs. 31 +/- 4 U/ml, p < 0.001). The peaks in plasma IL-6 were further correlated with the peaks in temperature and in serum CRP values (r = 0.49, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / chemically induced*
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Animals
  • Blood Proteins / metabolism
  • Body Temperature / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / immunology
  • C-Reactive Protein / metabolism
  • Diphosphonates / administration & dosage
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use*
  • Female
  • Humans
  • Injections, Intravenous
  • Interleukin-6 / metabolism*
  • Lymphocyte Count / drug effects
  • Male
  • Mice
  • Middle Aged
  • Organ Culture Techniques
  • Osteitis Deformans / drug therapy*
  • Osteitis Deformans / immunology
  • Parathyroid Hormone / blood
  • Radioimmunoassay


  • Blood Proteins
  • Diphosphonates
  • Interleukin-6
  • Parathyroid Hormone
  • olpadronic acid
  • C-Reactive Protein