title: Interleukin-6 and the acute phase response during treatment of patients with Paget's disease with the nitrogen-containing bisphosphonate dimethylaminohydroxypropylidene bisphosphonate.
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)
authors.affiliation: Department of Endocrinology and Metabolic Diseases, University Hospital Leiden, The Netherlands.
authors.forename: D H
authors.initials: DH
authors.lastname: Schweitzer
authors.forename: M
authors.initials: M
authors.lastname: Oostendorp-van de Ruit
authors.forename: G
authors.initials: G
authors.lastname: Van der Pluijm
authors.forename: C W
authors.initials: CW
authors.lastname: Löwik
authors.forename: S E
authors.initials: SE
authors.lastname: Papapoulos
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced*; D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism*; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D009924:Organ Culture Techniques; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000276:immunology; D010281:Parathyroid Hormone / Q000097:blood; D011863:Radioimmunoassay
chemical_list: D001798:Blood Proteins; D004164:Diphosphonates; D015850:Interleukin-6; D010281:Parathyroid Hormone; C055774:olpadronic acid; D002097:C-Reactive Protein