1. Interleukin-6 and the acute phase response during treatment of patients with Paget's disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate.
- Author
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Schweitzer DH, Oostendorp-van de Ruit M, Van der Pluijm G, Löwik CW, and Papapoulos SE
- Subjects
- 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, Female, Humans, Injections, Intravenous, Lymphocyte Count drug effects, Male, Mice, Middle Aged, Organ Culture Techniques, Osteitis Deformans immunology, Parathyroid Hormone blood, Radioimmunoassay, Acute-Phase Reaction chemically induced, Diphosphonates therapeutic use, Interleukin-6 metabolism, Osteitis Deformans drug therapy
- Abstract
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)
- Published
- 1995
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