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The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)†‡

  1. Dennis M Black1,*,
  2. Ian R Reid2,
  3. Steven Boonen3,
  4. Christina Bucci-Rechtweg4,
  5. Jane A Cauley5,
  6. Felicia Cosman6,
  7. Steven R Cummings7,
  8. Trisha F Hue1,
  9. Kurt Lippuner8,
  10. Peter Lakatos9,
  11. Ping Chung Leung10,
  12. Zulema Man11,
  13. Ruvie Lou Maria Martinez4,
  14. Monique Tan4,
  15. Mary Ellen Ruzycky4,
  16. Guoqin Su4,
  17. Richard Eastell12

Article first published online: 23 JAN 2012

DOI: 10.1002/jbmr.1494

Issue

Journal of Bone and Mineral Research

Journal of Bone and Mineral Research

Volume 27, Issue 2, pages 243–254, February 2012

Additional Information

How to Cite

Black, D. M., Reid, I. R., Boonen, S., Bucci-Rechtweg, C., Cauley, J. A., Cosman, F., Cummings, S. R., Hue, T. F., Lippuner, K., Lakatos, P., Leung, P. C., Man, Z., Martinez, R. L. M., Tan, M., Ruzycky, M. E., Su, G. and Eastell, R. (2012), The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res, 27: 243–254. doi: 10.1002/jbmr.1494

Author Information

  1. 1

    University of California, San Francisco, CA, USA

  2. 2

    University of Auckland, Auckland, New Zealand

  3. 3

    Katholieke Universiteit Leuven, Leuven, Belgium

  4. 4

    Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

  5. 5

    University of Pittsburgh, Pittsburgh, PA, USA

  6. 6

    Helen Hayes Hospital, West Haverstraw, NY, USA

  7. 7

    California Pacific Medical Center, San Francisco, CA, USA

  8. 8

    Bern University Hospital, Bern, Switzerland

  9. 9

    Semmelweis University Medical School, Budapest, Hungary

  10. 10

    Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China

  11. 11

    Centro Médico TIEMPO, Buenos Aires, Argentina

  12. 12

    University of Sheffield, Sheffield, UK

*University of California, San Francisco, Department of Epidemiology and Biostastistics, 185 Berry Street, Lobby 5, Suite 5700, San Francisco, CA 94107, USA.

  1. †

    For a Commentary on this article, please see Compston and Bilezikian (J Bone Miner Res. 2012;27:240–242. DOI: 10.1002/jbmr.1542).

  2. ‡

    http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms.

Publication History

  1. Issue published online: 23 JAN 2012
  2. Article first published online: 23 JAN 2012
  3. Accepted manuscript online: 8 DEC 2011 10:50AM EST
  4. Manuscript Accepted: 25 OCT 2011
  5. Manuscript Revised: 20 OCT 2011
  6. Manuscript Received: 13 AUG 2011

Funded by

  • Unknown funding agency
Corrected by:

Errata: The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Vol. 27, Issue 12, 2612, Article first published online: 19 NOV 2012

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Keywords:

  • FRACTURE;
  • POSTMENOPAUSAL OSTEOPOROSIS;
  • ZOLEDRONIC ACID;
  • BISPHOSPHONATES;
  • EXTENSION STUDY

Abstract

Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment. (ClinicalTrials.gov identifier: NCT00145327). © 2012 American Society for Bone and Mineral Research

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