title: Acute effects of intravenous administration of pamidronate in patients with osteoporosis.
abstract: We investigated acute effects of intermittent large dose bisphosphonate therapy in osteoporotic patients. Peripheral blood mononuclear cells were incubated with alendronate (100 microM) for 18 hr, in vitro and cytokine expressions were measured by real-time RT-PCR. Pamidronate 30 mg was administered on 26 osteoporotic patients; and acute phase reactants, inflammatory cytokines and bone biomarkers were measured. The in vitro study showed significant increase in mRNA expression of IL-6, TNF-alpha and IFN-gamma. A notable rise in serum C-reactive protein (CRP) was observed over 3 days after pamidronate infusion (P=0.026). Serum levels of TNF-alpha, IL-6 and IFN-gamma were also significantly increased (P=0.009, 0.014, 0.035, respectively) and the increase in IL-6 levels were strongly correlated with CRP levels (P=0.04). Serum calcium and c-telopeptide levels rapidly decreased after the treatment (P=0.02, <0.001, respectively). This study showed that mRNA expression of inflammatory cytokines at peripheral blood mononuclear cells (PBMC) level were observed within 18 hr and marked elevation of inflammatory cytokines and acute phase reactants were demonstrated after pamidronate infusion at the dose for osteoporosis. Our studies confirmed that intermittent large dose aminobisphosphonate causes acute inflammation.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea.
authors.forename: Mie Jin
authors.initials: MJ
authors.lastname: Lim
authors.forename: Seong Ryul
authors.initials: SR
authors.lastname: Kwon
authors.forename: Shin-Goo
authors.initials: SG
authors.lastname: Park
authors.forename: Won
authors.initials: W
authors.lastname: Park
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D001773:Blood Cells / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy*; D000077268:Pamidronate; D010455:Peptides / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D015850:Interleukin-6; D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; D007371:Interferon-gamma; D002097:C-Reactive Protein; D000077268:Pamidronate; D002118:Calcium; D019386:Alendronate
references.citation: J Immunol. 2001 Feb 15;166(4):2276-82
references.pmid: 11160282
references.citation: Rheumatology (Oxford). 2007 Jul;46(7):1049-51
references.pmid: 17500074
references.citation: Clin Cancer Res. 2002 May;8(5):1080-4
references.pmid: 12006522
references.citation: Cancer. 2000 Jun 15;88(12 Suppl):2961-78
references.pmid: 10898340
references.citation: J Bone Miner Res. 1995 Jun;10(6):956-62
references.pmid: 7572320
references.citation: J Interferon Cytokine Res. 2003 Nov;23(11):649-54
references.pmid: 14651779
references.citation: Leuk Lymphoma. 2007 Sep;48(9):1852-4
references.pmid: 17786724
references.citation: Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6222s-6230s
references.pmid: 17062705
references.citation: Clin Exp Immunol. 2004 Jun;136(3):472-82
references.pmid: 15147349
references.citation: Arthritis Rheum. 1980 Oct;23(10):1193-204
references.pmid: 6448605
references.citation: Ann Oncol. 2007 Jan;18(1):201-202
references.pmid: 17021272
references.citation: Calcif Tissue Int. 1997 Nov;61(5):386-92
references.pmid: 9351880
references.citation: Clin Exp Immunol. 2005 Jan;139(1):101-11
references.pmid: 15606619
references.citation: Oncology. 2005;69(1):35-43
references.pmid: 16088233
references.citation: Clin Exp Immunol. 2006 Dec;146(3):371-80
references.pmid: 17100755
references.citation: Biochem Biophys Res Commun. 1988 Aug 30;155(1):112-7
references.pmid: 3261980
references.citation: Calcif Tissue Int. 1987 Dec;41(6):326-31
references.pmid: 3124942
references.citation: Bone. 1996 Feb;18(2):133-9
references.pmid: 8833207
references.citation: J Clin Densitom. 2004 Spring;7(1):1-6
references.pmid: 14742881
references.citation: J Pharmacol Exp Ther. 2001 Feb;296(2):235-42
references.pmid: 11160603
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Clin Cancer Res. 2003 Aug 1;9(8):2893-7
references.pmid: 12912933
references.citation: J Immunol. 2001 May 1;166(9):5508-14
references.pmid: 11313389
references.citation: J Oncol Pharm Pract. 2007 Dec;13(4):223-9
references.pmid: 18045781