Efficacy and Safety of a Once-Yearly Intravenous Zoledronic Acid 5 mg for Fracture Prevention in Elderly Postmenopausal Women with Osteoporosis Aged 75 and Older

Authors

  • Steven Boonen MD, PhD,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Dennis M. Black PhD,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Cathleen S. Colón-Emeric MD, MHSc,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Richard Eastell MD,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Jay S. Magaziner PhD,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Erik Fink Eriksen MD, DMSc,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Peter Mesenbrink PhD,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Patrick Haentjens MD, PhD,

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Kenneth W. Lyles MD

    1. From the *Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine, University of Leuven, Leuven, Belgium; Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California; Department of Medicine, Duke University, Durham, North Carolina; §Veterans Affairs Medical Center, Durham, North Carolina; Academic Unit of Bone Metabolism, Metabolic Bone Centre, University of Sheffield, Sheffield,United Kingdom; #Department of Epidemiology and Preventive Medicine, University of Maryland, Baltimore, Maryland; **Department of Endocrinology, Oslo University Hospital Aker, Oslo, Norway; ††Novartis Pharmaceuticals, East Hanover, New Jersey; ‡‡Center for Outcomes Research, Laboratory for Experimental Surgery, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium; and §§Department of Medicine, Carolinas Center for Medical Excellence, Cary, North Carolina
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  • Submitted to or presented at American Geriatrics Society, April 29 to May 2, 2009, Chicago, IL; International Bone and Mineral Society, March 21 to March 25, 2009, Sydney, Australia; European Congress on Clinical and Economic Aspects of Osteoporosis, March 18 to March 21, 2009, Athens, Greece; and International Osteoporosis Foundation, December 3 to December 7, 2008, Bangkok, Thailand.

Address correspondence to Steven Boonen, Leuven University Centre for Metabolic Bone Diseases & Division of Geriatric Medicine, University Hospital Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: Steven.Boonen@uz.kuleuven.ac.be

Abstract

OBJECTIVES: To determine the efficacy of once-yearly intravenous zoledronic acid (ZOL) 5 mg in reducing risk of clinical vertebral, nonvertebral, and any clinical fractures in elderly osteoporotic postmenopausal women.

DESIGN: A post hoc subgroup analysis of pooled data from the Health Outcome and Reduced Incidence with Zoledronic Acid One Yearly (HORIZON) Pivotal Fracture Trial and the HORIZON Recurrent Fracture Trial.

SETTING: Multicenter, randomized, double-blind, placebo-controlled trials.

PARTICIPANTS: Postmenopausal women (aged ≥75) with documented osteoporosis (T-score ≤−2.5 at femoral neck or ≥1 prevalent vertebral or hip fracture) or a recent hip fracture.

INTERVENTION: Patients were randomized to receive an intravenous infusion of ZOL 5 mg (n=1,961) or placebo (n=1,926) at baseline and 12 and 24 months.

MEASUREMENTS: Primary endpoints were incidence of clinical vertebral and nonvertebral and any clinical fracture after treatment.

RESULTS: At 3 years, incidence of any clinical, clinical vertebral, and nonvertebral fracture were significantly lower in the ZOL group than in the placebo group (10.8% vs 16.6%, 1.1% vs 3.7%, and 9.9% vs 13.7%, respectively) (hazard ratio (HR)=0.65, 95% confidence interval (CI)=0.54–0.78, P<.001; HR=0.34, 95% CI=0.21–0.55, P<.001; and HR=0.73, 95% CI=0.60–0.90, P=.002, respectively). The incidence of hip fracture was lower with ZOL but did not reach statistical significance. The incidence rate of postdose adverse events were higher with ZOL, although the rate of serious adverse events and deaths was comparable between the two groups.

CONCLUSION: Once-yearly intravenous ZOL 5 mg was associated with a significant reduction in the risk of new clinical fractures (vertebral and nonvertebral) in elderly postmenopausal women with osteroporosis.

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