Raymond E Cole1, Steven T Harris. 1. Department of Internal Medicine, Michigan State University College of Osteopathic Medicine, Michigan, USA. Recfcc@aol.com
Abstract
CONTEXT: Nonvertebral fractures (NVFs) are the most costly and disabling type of osteoporotic fractures. Bisphosphonate therapy effectively reduces the risk for NVFs; however, fracture protection depends critically on adherence and persistence. Approved bisphosphonate regimens with extended dosing intervals increase patient convenience, help patients remain on therapy, and improve fracture protection in clinical practice. EVIDENCE ACQUISITION: To assess evidence for NVF reduction with extended-interval bisphosphonates, we searched PubMed for phase 3 clinical trials, meta-analyses, and reviews of approved nitrogen-containing bisphosphonate regimens with monthly or less frequent dosing (monthly oral ibandronate, monthly or intermittent oral risedronate, quarterly intravenous [IV] ibandronate, and yearly IV zoledronic acid). These references were augmented by ISI Web of Science cited reference searches, ISI Proceedings searches, and hand searches of relevant conference proceedings and review bibliographies. EVIDENCE SYNTHESIS: Monthly oral and quarterly IV ibandronate reduce NVF risk significantly more than daily oral ibandronate and placebo, as shown by meta-analyses stratified by ibandronate dose (annual cumulative exposure). Intermittent and monthly oral risedronate have shown bone density gains similar to those seen with daily oral risedronate. Incidence rates of NVF, reported as adverse events, were also similar. Yearly IV zoledronic acid reduced NVF risk by 25% and hip fracture risk by 41% compared with placebo in its pivotal trial for postmenopausal osteoporosis. CONCLUSIONS: Extended-interval bisphosphonates offer similar or superior NVF protection with less lifestyle disruption compared with daily or weekly treatment. By removing obstacles to adherence and persistence, extended-interval oral and IV bisphosphonate regimens provide valuable therapeutic options to enhance real-world effectiveness and reduce NVF incidence.
CONTEXT: Nonvertebral fractures (NVFs) are the most costly and disabling type of osteoporotic fractures. Bisphosphonate therapy effectively reduces the risk for NVFs; however, fracture protection depends critically on adherence and persistence. Approved bisphosphonate regimens with extended dosing intervals increase patient convenience, help patients remain on therapy, and improve fracture protection in clinical practice. EVIDENCE ACQUISITION: To assess evidence for NVF reduction with extended-interval bisphosphonates, we searched PubMed for phase 3 clinical trials, meta-analyses, and reviews of approved nitrogen-containing bisphosphonate regimens with monthly or less frequent dosing (monthly oral ibandronate, monthly or intermittent oral risedronate, quarterly intravenous [IV] ibandronate, and yearly IV zoledronic acid). These references were augmented by ISI Web of Science cited reference searches, ISI Proceedings searches, and hand searches of relevant conference proceedings and review bibliographies. EVIDENCE SYNTHESIS: Monthly oral and quarterly IV ibandronate reduce NVF risk significantly more than daily oral ibandronate and placebo, as shown by meta-analyses stratified by ibandronate dose (annual cumulative exposure). Intermittent and monthly oral risedronate have shown bone density gains similar to those seen with daily oral risedronate. Incidence rates of NVF, reported as adverse events, were also similar. Yearly IV zoledronic acid reduced NVF risk by 25% and hip fracture risk by 41% compared with placebo in its pivotal trial for postmenopausal osteoporosis. CONCLUSIONS: Extended-interval bisphosphonates offer similar or superior NVF protection with less lifestyle disruption compared with daily or weekly treatment. By removing obstacles to adherence and persistence, extended-interval oral and IV bisphosphonate regimens provide valuable therapeutic options to enhance real-world effectiveness and reduce NVF incidence.
Authors: Pierre D Delmas; Silvano Adami; Cezary Strugala; Jacob A Stakkestad; Jean-Yves Reginster; Dieter Felsenberg; Claus Christiansen; Roberto Civitelli; Marc K Drezner; Robert R Recker; Michael Bolognese; Claire Hughes; Daiva Masanauskaite; Penelope Ward; Philip Sambrook; David M Reid Journal: Arthritis Rheum Date: 2006-06
Authors: Ronald Emkey; William Koltun; Kathleen Beusterien; Larry Seidman; Alan Kivitz; Vipul Devas; Daiva Masanauskaite Journal: Curr Med Res Opin Date: 2005-12 Impact factor: 2.580
Authors: Ethel S Siris; Steven T Harris; Clifford J Rosen; Charles E Barr; James N Arvesen; Thomas A Abbott; Stuart Silverman Journal: Mayo Clin Proc Date: 2006-08 Impact factor: 7.616
Authors: J-Y Reginster; S Adami; P Lakatos; M Greenwald; J J Stepan; S L Silverman; C Christiansen; L Rowell; N Mairon; B Bonvoisin; M K Drezner; R Emkey; D Felsenberg; C Cooper; P D Delmas; P D Miller Journal: Ann Rheum Dis Date: 2005-12-08 Impact factor: 19.103