title: No effect of rosuvastatin in the zoledronate-induced acute-phase response.
abstract: The acute-phase response (APR) is frequently observed in patients treated with intravenous (iv) zoledronate (ZOL). We investigated whether a short course of rosuvastatin (ROSU) could attenuate the ZOL--induced APR through blocking the mevalonate pathway at a proximal level. Twenty-eight osteoporotic postmenopausal women with no prior bisphosphonate use (mean age 65.3 ± 1.9 years) were subjected to ZOL iv infusion. Patients were randomly assigned into either a ROSU+ group (n = 12), which received ROSU 10 mg/day starting 5 days before the infusion of ZOL for a total period of 11 days, or a ROSU- group (n = 16), which did not receive ROSU. The visual analog pain scale (VAS) for musculoskeletal symptoms and body temperature was used to define clinically APR. In addition, white blood cell (WBC) count, leukocytic subpopulations, and C-reactive protein (CRP) were obtained before and 48 h following the infusion. Seven (58.3%) patients in the ROSU+ group and 13 (81.3%) in the ROSU- group experienced APR (P = not significant). No difference was found in fever and VAS measurements. CRP and granulocytes increased significantly in both groups; WBC count increased, while lymphocytes and eosinophils decreased significantly only in the ROSU- group. In a post hoc analysis of only patients with an APR, all laboratory parameters exhibited a similar significant change solely within the ROSU- group. In conclusion, our data suggest that a short course of ROS at this dose cannot prevent the ZOL-induced APR among osteoporotic women. Milder changes in acute-phase laboratory parameters in ROSU+ patients suggest that studies with higher doses may be warranted.
authors.affiliation: Department of Endocrinology and Diabetes, 251 Hellenic Air Force and VA General Hospital, 3 Kanellopoulou St, 115 25 Athens, Greece. makras@internet.gr
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Ilias
authors.initials: I
authors.lastname: Bisbinas
authors.forename: Grigorios T
authors.initials: GT
authors.lastname: Sakellariou
authors.forename: Socrates E
authors.initials: SE
authors.lastname: Papapoulos
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced* / Q000188:drug therapy*; D000368:Aged; D001831:Body Temperature / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D004164:Diphosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D007093:Imidazoles / Q000009:adverse effects* / Q000627:therapeutic use; D007958:Leukocyte Count; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007093:Imidazoles; D011743:Pyrimidines; D013449:Sulfonamides; D000077211:Zoledronic Acid; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein