The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON‐Pivotal Fracture Trial (PFT) |
| |
| Authors: | Dennis M. Black Ian R. Reid Jane A. Cauley Felicia Cosman Ping Chung Leung Peter Lakatos Kurt Lippuner Steven R. Cummings Trisha F. Hue Amitava Mukhopadhyay Monique Tan R. Paul Aftring Richard Eastell |
| |
| Affiliation: | 1. University of California, San Francisco, CA, USA;2. University of Auckland, Auckland, New Zealand;3. University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA;4. Helen Hayes Hospital, New York, NY, USA;5. Chinese University of Hong Kong, Hong Kong, China;6. Semmelweis University Medical School, Budapest, Hungary;7. Bern University Hospital, Bern, Switzerland;8. San Francisco Coordinating Center, San Francisco, CA, USA;9. Novartis Healthcare Pvt. Ltd., Hyderabad, India;10. Novartis Pharmaceutical Corporation, East Hanover, NJ, USA;11. University of Sheffield, Sheffield, UK |
| |
| Abstract: | 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) 5 mg 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. © 2015 American Society for Bone and Mineral Research. |
| |
| Keywords: | RANDOMIZED CLINICAL TRIALS FRACTURE PREVENTION OSTEOPOROSIS ANTIRESORPTIVES BIOCHEMICAL MARKERS OF BONE TURNOVER |
|
|
