Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 30, Issue 5, Pages 934-944Publisher
WILEY
DOI: 10.1002/jbmr.2442
Keywords
RANDOMIZED CLINICAL TRIALS; FRACTURE PREVENTION; OSTEOPOROSIS; ANTIRESORPTIVES; BIOCHEMICAL MARKERS OF BONE TURNOVER
Categories
Funding
- Novartis
- Merck
- Lilly
- Amgen
- Radius
- Enteris
- Asahi-Kasei
- Medscape
- Omnia
- Servier
- Roche
- MSD
- Takeda
- Department of Health
- AstraZeneca
- Immunodiagnostic Systems
- Canadian Institute of Health Research
- National Osteoporosis Society
- ARUK/MRC Centre of Excellence in Musculoskeletal Ageing Research
- National Institute for Health Research
- Cancer Research UK
- MRC/AZMechanism of Diseases Call
- Sheffield Teaching Hospitals Foundation Trust
- Procter Gamble
- Sanofi Aventis
- Queen Mary University of Landon
- Arthritis Research UK
- PRP Department of Health
- Alexion
- Otsuka
- IBMS
- Johnson Johnson
- SPD Development
- Fonterra Brands
- Janssen Research
- Lily
- Ono Pharma
- Alere (Unipath)
- Chronos
- European Calcified Tissue Society
- Efficacy & mechanism Evaluation Board of Medical Research Council
- IOF CSA
- MRC [MR/K006312/1] Funding Source: UKRI
- Medical Research Council [MR/K006312/1] Funding Source: researchfish
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While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n=95) and Z6P3 (n=95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p=0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. (c) 2015 American Society for Bone and Mineral Research.
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