Systematic Review: Comparative Effectiveness of Treatments to Prevent Fractures in Men and Women with Low Bone Density or Osteoporosis

5 February 2008 | Volume 148 Issue 3

Background: Although several agents are available to treat osteoporosis, the relative efficacy and toxicity of these agents when used to prevent fractures has not been well described.

Purpose: To compare the benefits in fracture reduction and the harms from adverse events of various therapies for osteoporosis.

Data Sources: MEDLINE (1966 to November 2007) and other selected databases were searched for English-language studies.

Study Selection: For the efficacy analysis, investigators selected studies that reported the rate or risk for fractures. For the adverse event analysis, they selected studies that reported the relationship between an agent and cardiovascular, thromboembolic, or upper gastrointestinal events, malignant conditions, and osteonecrosis.

Data Extraction: Using a standardized protocol, investigators abstracted data on fractures and adverse events, agents and comparators, study design, and variables of methodological quality.

Data Synthesis: Good evidence suggests that alendronate, etidronate, ibandronate, risedronate, zoledronic acid, estrogen, parathyroid hormone (1-34), and raloxifene prevent vertebral fractures more than placebo; the evidence for calcitonin was fair. Good evidence suggests that alendronate, risedronate, and estrogen prevent hip fractures more than placebo; the evidence for zoledronic acid was fair. The effects of vitamin D varied with dose, analogue, and study population for both vertebral and hip fractures. Raloxifene, estrogen, and estrogen–progestin increased the risk for thromboembolic events, and etidronate increased the risk for esophageal ulcerations and gastrointestinal perforations, ulcerations, and bleeding.

Limitation: Few direct comparisons have been conducted between different agents or classes of agents used to treat osteoporosis.

Conclusion: Although good evidence suggests that many agents are effective in preventing osteoporotic fractures, data are insufficient to determine the relative efficacy or safety of these agents.

Editors' Notes Context Sorting through the proven benefits and harms of the multiple agents available for treating osteoporosis is difficult. Contribution This systematic review of 76 randomized trials and 24 meta-analyses found good evidence that multiple agents, including alendronate, zoledronic acid, and estrogen, prevented vertebral and hip fractures more than placebo. Harms included increased risk for thromboembolic events with raloxifene and estrogen compared with and esophageal symptoms with bisphosphonates. No large trials directly compared 2 or more agents and established superiority of any agent. Implication Available data insufficiently characterize the relative benefits and harms of various therapies for osteoporosis. —The Editors

 

Author and Article Information

From the Southern California Evidence-based Practice Center, which includes RAND, Santa Monica, and the Greater Los Angeles Veterans Administration Healthcare System and the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California.

Disclaimer: Dr. MacLean is employed by WellPoint: This paper and its content reflect the views of Dr. MacLean and has not been reviewed or endorsed by WellPoint.

Acknowledgment: The authors acknowledge the guidance provided by the Technical Expert Panel members: Marc C. Hochberg, MD, MPH; Lee J. Melton III, MD, MPH; Paul D. Miller, MD; Marcel E. Salive, MD, MPH; and Katherine Sherif, MD. They also acknowledge the careful work of the reviewers, and the invaluable assistance of Julie Newell, Jianglai Zhang, Scott Hiromoto, Yuyan (Sabrina) Shi, and Zhen (Frank) Wang.

Grant Support: Prepared under contract with the Agency for Healthcare Research and Quality (contract no. 290-02-003).

Potential Financial Conflicts of Interest: Stock ownership or options (other than mutual funds: J. Grossman (Johnson & Johnson).

Requests for Single Reprints: Margaret Maglione, MPP, RAND Corporation, 1776 Main Street, Santa Monica, CA 90401; e-mail, maglione{at}rand.org.

Current Author Addresses: Dr. MacLean: WellPoint, 4553 LaTienda Drive, M/S CAT102-C003, Thousand Oaks, CA 91362.

Dr. Newberry, Ms. Maglione, Ms. Suttorp, Ms. Timmer, Ms. Zhou, Ms. Chen, Mr. Carter, Mr. Tringale, Ms. Johnsen, and Ms. Valentine: RAND Corporation, 1776 Main Street, Santa Monica, CA 90407-2138.

Drs. McMahon, Ranganath, Desai, and Grossman: University of California, Los Angeles, 1000 Veteran Avenue 32-59, Los Angeles, CA 90095.

Dr. Mojica: Kaiser Permanente, 393 Walnut Center, Pasadena, CA 91188.

Dr. Alexander: c/o Margaret Maglione, MPP, RAND Corporation, 1776 Main Street, Santa Monica, CA 90401.

Dr. McNamara: Arthritis and Rheumatology Center, 5601 Norris Canyon Road, Suite 340, San Ramon, CA 94583.

Read all Rapid Responses

All the data that doesn't FIT

Robert Karis

Annals Online, 9 Jan 2008 [Full text]

Meta-analysis of Osteoporosis Therapies

Dennis M. Black, et al.

Annals Online, 14 Jan 2008 [Full text]

MacLean et al. 2008; Ann Intern Med. 2008; 148:197-213.

John L Stock, et al.

Annals Online, 5 Feb 2008 [Full text]

Calcium an orphan treatment

Richard L Prince

Annals Online, 7 Feb 2008 [Full text]

Musculoskeletal adverse effects of bisphosphonate therapy

Lionel S Lim

Annals Online, 8 Feb 2008 [Full text]

Comment

Harold Rosen

Annals Online, 3 Mar 2008 [Full text]

Non-skeletal Effects of Osteoporosis Treatments: Does the evidence support the conclusions?

Laura N Kuhl, et al.

Annals Online, 11 Mar 2008 [Full text]

The authors' reply

Catherine H MacLean, et al.

Annals Online, 21 Mar 2008 [Full text]