title: Intravenous bisphosphonates for postmenopausal osteoporosis: safety profiles of zoledronic acid and ibandronate in clinical practice.
abstract: BACKGROUND
  Intravenous bisphosphonates are widely used for treatment of postmenopausal osteoporosis. They are associated with transient influenza-like symptoms, predominantly after the first zoledronic acid (up to 32 %) or ibandronate (up to 5 %) administration. The experience in clinical practice suggests that the incidence of post-dose symptoms is higher than has been reported in clinical trials. We assessed the safety of annual infusions of zoledronic acid and 3-monthly injections of ibandronate in women with postmenopausal osteoporosis.
  
  
  METHODS
  In this retrospective study we analysed safety data from 272 postmenopausal women treated with zoledronic acid (n = 127; mean age 68.6 ± 9.4 years) or intravenous (IV) ibandronate (n = 145; mean age 69.1 ± 9.0 years). Safety data (including occurrence of acute-phase reactions and osteonecrosis of the jaw) were gathered in phone call interviews by using a standardized questionnaire.
  
  
  RESULTS
  The number of patients with adverse events was significantly higher in zoledronic acid as compared to ibandronate-treated patients, primarily because of a larger number of post-dose symptoms after bisphosphonate administrations (54.3 % vs. 33.1 %, p < 0.001). Except for occurrence of fever (more common after zoledronic acid infusion), other influenza-like symptoms (myalgia, arthralgia, headache) appeared in a similar proportion of patients after IV treatment (within 24-36 h). Symptoms lasted for >3 days in approximately 50 % of patients. The incidence of symptoms decreased after subsequent infusions. The rate of influenza-like symptoms was more frequent after zoledronic acid than after IV ibandronate in bisphosphonate-naïve patients but comparable in patients pretreated with oral bisphosphonates. There were no spontaneous reports of osteonecrosis of the jaw, arrhythmia or delayed fracture healing.
  
  
  CONCLUSIONS
  Although IV bisphosphonates are generally safe, the occurrence of transient influenza-like symptoms after IV bisphosphonates seems to be more frequent in clinical practice than has been reported in clinical trials.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Missionsstrasse 24, 4055 Basel, Switzerland.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sieber
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lardelli
authors.forename: Claude A
authors.initials: CA
authors.lastname: Kraenzlin
authors.forename: Marius E
authors.initials: ME
authors.lastname: Kraenzlin
authors.forename: Christian
authors.initials: C
authors.lastname: Meier
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000453:epidemiology; D000368:Aged; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000453:epidemiology / Q000209:etiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077557:Ibandronic Acid; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D012189:Retrospective Studies; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid; D000077557:Ibandronic Acid