I R Reid1, G D Gamble, P Mesenbrink, P Lakatos, D M Black. 1. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, 1142 Auckland, New Zealand. i.reid@auckland.ac.nz
Abstract
CONTEXT: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied. OBJECTIVE: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development. DESIGN: The study was an analysis of adverse events from a large randomized trial. SETTING: This was a multicenter international trial. PATIENTS: Patients included 7765 postmenopausal women with osteoporosis. INTERVENTION: Zoledronic acid 5 mg annually or placebo was the intervention. MAIN OUTCOME MEASURE: Adverse events occurring within 3 d of zoledronic acid infusion were measured. RESULTS: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all). CONCLUSION: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study.
RCT Entities:
CONTEXT: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied. OBJECTIVE: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development. DESIGN: The study was an analysis of adverse events from a large randomized trial. SETTING: This was a multicenter international trial. PATIENTS: Patients included 7765 postmenopausal women with osteoporosis. INTERVENTION: Zoledronic acid 5 mg annually or placebo was the intervention. MAIN OUTCOME MEASURE: Adverse events occurring within 3 d of zoledronic acid infusion were measured. RESULTS: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all). CONCLUSION: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study.
Authors: Melissa P Wasserstein; Simon A Jones; Handrean Soran; George A Diaz; Natalie Lippa; Beth L Thurberg; Kerry Culm-Merdek; Elias Shamiyeh; Haig Inguilizian; Gerald F Cox; Ana Cristina Puga Journal: Mol Genet Metab Date: 2015-05-30 Impact factor: 4.797
Authors: Nam-Kyong Choi; Daniel H Solomon; Theodore N Tsacogianis; Joan E Landon; Hong Ji Song; Seoyoung C Kim Journal: J Bone Miner Res Date: 2017-02-07 Impact factor: 6.741
Authors: D V Patel; M Bolland; Z Nisa; F Al-Abuwsi; M Singh; A Horne; I R Reid; C N J McGhee Journal: Osteoporos Int Date: 2014-09-04 Impact factor: 4.507
Authors: Ian R Reid; Jacques P Brown; Naomi Levitt; José A Román Ivorra; Javier Bachiller-Corral; Ian L Ross; Guoqin Su; Oscar Antunez-Flores; R Paul Aftring Journal: Bonekey Rep Date: 2013-11-06