Zoledronic Acid for the Prevention of Bone Loss in Postmenopausal Women With Low Bone Mass: A Randomized Controlled Trial

McClung, Michael MD1; Miller, Paul MD2; Recknor, Chris MD3; Mesenbrink, Peter PhD4; Bucci-Rechtweg, Christina MD4; Benhamou, Claude-Laurent MD5

doi: 10.1097/AOG.0b013e3181bdce0a
Original Research

OBJECTIVE: To evaluate the efficacy of zoledronic acid in the prevention of bone loss in postmenopausal women with low bone mass.

METHODS: In this 2-year, randomized, multicenter, double-blind, placebo-controlled study, postmenopausal women with low bone mass were selected randomly to receive either zoledronic acid 5 mg intravenously at randomization and at month 12 (zoledronic acid 2×5 mg), zoledronic acid 5 mg intravenously only at randomization and placebo at month 12 (zoledronic acid 1×5 mg), or placebo at randomization and at month 12 (placebo). The primary efficacy endpoint was the percentage change in lumbar spine bone mineral density (BMD) (lumbar spine BMD) at month 24 relative to baseline.

RESULTS: Both zoledronic acid 2×5 mg and zoledronic acid 1×5 mg regimens significantly increased mean lumbar spine BMD compared with placebo at month 24 (5.18% and 4.42% compared with −1.32%, respectively, both P<.001). Similarly, significantly greater increases for both zoledronic acid regimens relative to placebo were observed for lumbar spine BMD at month 12 and for BMD at the proximal femur sites (total hip, femoral neck, trochanter) at month 12 and 24 (all P<.001). Both zoledronic acid regimens significantly reduced bone turnover markers over time relative to placebo (all P<.001), although changes with zoledronic acid 2×5 mg regimen were sustained greater during the second year relative to zoledronic acid 1×5 mg. The overall incidence of adverse events and serious adverse events were similar across all treatment groups.

CONCLUSION: Both once-yearly dosing and a single dose of intravenous zoledronic acid 5 mg prevented bone loss for 2 years and were well-tolerated in postmenopausal women with low bone mass.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00132808.

LEVEL OF EVIDENCE: I

Zoledronic acid is an effective and well-tolerated agent in the prevention of bone loss in postmenopausal women with low bone mass. SUPPLEMENTAL DIGITAL CONTENT AVAILABLE ONLINE IN THE TEXT.

From the 1Oregon Osteoporosis Center, Portland, Oregon; the 2Colorado Center for Bone Research, Lakewood, Colorado; the 3United Osteoporosis Centers, Gainesville, Gainesville Georgia; 4Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; and 5Centre Hospitalier Régional d’Orléans, Orléans, France.

For a list of investigators who participated in this study, see the Appendix online at http://links.lww.com/AOG/A132.

Supported by Novartis Pharma AG, Basel, Switzerland.

Abstract and poster presented at the 8th International Symposium on Osteoporosis: Translating Research into Clinical Practice, April 1–5, 2009, Washington, DC, and the 4th International Workshop on Advances in the Molecular Pharmacology and Therapeutics of Bone Disease, July 6–8, 2009, Oxford, United Kingdom.

Corresponding author: Dr Michael R. McClung, Oregon Osteoporosis Center, 5050 NE Hoyt Street, Suite 651, Portland, OR 97213-2954; e-mail: mmcclung@orost.com.

Financial Disclosure Dr. McClung has received grant support from Amgen Inc. (Thousand Oaks, CA), Eli Lilly & Co. (Indianapolis, IN), Merck & Co. Inc. (Whitehouse Station, NJ), Novartis (East Hanover, NJ), and Proctor & Gamble (Cincinnati, OH). He has served as a speaker, consultant, or advisor to Amgen Inc., Eli Lilly & Co., Merck & Co. Inc., Novartis, Proctor & Gamble, and Sanofi-Aventis (Bridgewater, NJ). Dr. Miller has received grant support from Amgen, Eli Lilly & Co., Hoffmann-LaRoche, Inc. (Nutley, NJ), Merck & Co. Inc., Novartis Pharma AG (Basel, Switzerland), Proctor & Gamble, and Sanofi-Aventis. He has served as a speaker, consultant, or advisor to Amgen, Eli Lilly, GlaxoSmithKline (Philadelphia, PA), Hoffmann-LaRoche, Merck, Novartis, NPS Pharmaceuticals Inc. (Bedminster, NJ), Proctor & Gamble, and Sanofi-Aventis. Dr. Mesenbrink is a Novartis employee and owns shares and stock options in Novartis. Dr. Recknor has received consulting fees from Proctor & Gamble, Hoffmann-LaRoche, and Eli Lilly. He has received lecture fees from Proctor & Gamble, Eli Lilly, Hoffmann-LaRoche, GlaxoSmithKline, Merck, and Sanofi-Aventis. He has received grant support from Proctor & Gamble. He also has served as a steering committee member in the HORIZON Recurrent Fracture Trial conducted by Novartis Pharma AG. Dr. Bucci-Rechtweg is an employee of Novartis Pharma AG. Dr. Benhamou has either worked as a conference speaker, been a board member, or been an investigator for Amgen Inc., Merck, Novartis, Proctor & Gamble, Hoffmann-LaRoche, Servier (Neuilly-sur-Seine, France), and Wyeth (Madison, NJ).

© 2009 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.