Relative Effectiveness of Osteoporosis Drugs for Preventing Nonvertebral Fracture

6 May 2008 | Volume 148 Issue 9 | Pages 637-646

Background: Little information is available on the comparative effectiveness of osteoporosis pharmacotherapies.

Objective: To compare the relative effectiveness of osteoporosis treatments to reduce nonvertebral fracture risk among older adults.

Design: Cohort study.

Setting: Enrollees in 2 statewide pharmaceutical benefit programs for persons age 65 years or older.

Patients: 43 135 new recipients of oral bisphosphonates, nasal calcitonin, and raloxifene who began treatment from 2000 to 2005. The mean age was 79 years (SD, 6.9), and 96% were women.

Measurements: The primary outcome was nonvertebral fracture (hip, humerus, or radius or ulna) within 12 months of treatment initiation. Cox proportional hazard models stratified by state and adjusted for risk factors for fracture were used to compare fracture rates. Alendronate was the reference category in all analyses.

Results: A total of 1051 nonvertebral fractures were observed within 12 months (2.62 fractures per 100 person-years). No large differences in fracture risk were found between risedronate (hazard ratio [HR], 1.01 [95% CI, 0.85 to 1.21]) or raloxifene (HR, 1.18 [CI, 0.96 to 1.46]) and alendronate. However, among those with a fracture history, raloxifene recipients experienced more nonvertebral fractures within 12 months (HR, 1.78 [CI, 1.20 to 2.63]) compared with alendronate recipients. Patients who received calcitonin experienced more nonvertebral fractures than those who received alendronate (HR, 1.40, [CI, 1.20 to 1.63]). Results were similar in sensitivity analyses that examined different lengths of follow-up (6 months and 24 months), were restricted to hip fracture as the outcome, and were completed in various subgroups.

Limitation: Confounder adjustment was limited to health care utilization data, and the confidence bounds of some comparisons were too wide to rule out potential clinically important differences between agents.

Conclusion: Differences in fracture risk between risedronate or raloxifene and alendronate were small. Nasal calcitonin recipients may have a higher risk for nonvertebral fractures compared with alendronate recipients. Future studies that can better adjust for possible confounding may further clarify these relationships.

Editors' Notes Context Few studies have evaluated the relative effectiveness of drug therapies for osteoporosis. Contribution This study compared nonvertebral fractures that occurred within 1 year of initiating osteoporosis pharmacotherapy among 43 135 enrollees in 2 statewide pharmaceutical benefit programs. Differences in fracture risk between adults prescribed risedronate or raloxifene and those prescribed alendronate were small. Fracture risk seemed to be higher with calcitonin than alendronate. Caution Wide confidence bounds around risk estimates did not rule out potentially important differences between some agents. No adherence data were available, and the ability to account for confounders was limited. Implication There probably is no single clearly superior drug therapy for osteoporosis. —The Editors

 

Author and Article Information

From Brigham and Women's Hospital, Harvard Medical School, and Boston University, Boston, Massachusetts.

Acknowledgment: The authors thank Raisa Levin, MS, for preparing the study data for analysis.

Grant Support: By grant K25 AG027400 from the National Institute on Aging (Dr. Brookhart), a Canadian Institutes of Health Research Post-Doctoral Fellowship (Dr. Cadarette), grants K24 AR02123 and P60 AR47782 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (Dr. Katz), grants from the Arthritis Foundation and grants R21 AG027066 and P60 AR47782 from the National Institutes of Health (Dr. Solomon), and grant RO1 AG023178 from the National Institute on Aging (Dr. Stürmer).

Potential Financial Conflicts of Interest: Grants received: M.A. Brookhart (Amgen), D.H. Solomon (Merck). Grants pending: M.A. Brookhart (Amgen).

Reproducible Research Statement: Study protocol, statistical code, and data set: Not available.

Requests for Single Reprints: Suzanne M. Cadarette, PhD, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120.

Current Author Addresses: Drs. Cadarette, Brookhart, and Stürmer and Ms. Stedman: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Harvard Medical School, 1620 Tremont Street, Suite 3030, Boston, MA 02120.

Dr. Katz: Department of Orthopaedic Surgery and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115.

Dr. Solomon: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115.

Author Contributions: Conception and design: S.M. Cadarette, M.A. Brookhart, T. Stürmer, D.H. Solomon.

Analysis and interpretation of the data: S.M. Cadarette, J.N. Katz, M.A. Brookhart, T. Stürmer, M.R. Stedman, D.H. Solomon.

Drafting of the article: S.M. Cadarette, T. Stürmer, D.H. Solomon.

Critical revision of the article for important intellectual content: S.M. Cadarette, J.N. Katz, M.A. Brookhart, T. Stürmer, M.R. Stedman, D.H. Solomon.

Final approval of the article: S.M. Cadarette, J.N. Katz, M.A. Brookhart, T. Stürmer, M.R. Stedman, D.H. Solomon.

Provision of study materials or patients: D.H. Solomon.

Statistical expertise: M.A. Brookhart, T. Stürmer, M.R. Stedman.

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