Reviews
11 April 2017

Benefits and Harms of Osteoporosis Medications in Patients With Chronic Kidney Disease: A Systematic Review and Meta-analysis

Publication: Annals of Internal Medicine
Volume 166, Number 9

Abstract

Background:

Complications of chronic kidney disease (CKD) include weak bones and increased fracture risk.

Purpose:

To review the benefits and harms of osteoporosis medications (bisphosphonates, teriparatide, raloxifene, and denosumab) compared with placebo, usual care, or active control in terms of bone mineral density (BMD), fractures, and safety in patients with CKD.

Data Sources:

PubMed and the Cochrane Central Register of Controlled Trials from December 2006 through December 2016.

Study Selection:

Paired reviewers independently screened abstracts and full-text articles for English-language, randomized, controlled trials that had at least 6 months of follow-up; evaluated osteoporosis medications among patients with CKD; and reported on BMD, fractures, or safety (mortality and adverse events).

Data Extraction:

Two reviewers serially abstracted data and independently assessed risk of bias and graded the strength of evidence (SOE).

Data Synthesis:

There were 13 trials (n = 9850) that included kidney transplant recipients (6 trials), patients who had stage 3 to 5 CKD or were receiving dialysis (3 trials), or postmenopausal women with CKD (4 trials). Evidence showed that bisphosphonates may slow loss of BMD among transplant recipients (moderate SOE), but their effects on fractures and safety in transplant recipients and others with CKD are unclear. Raloxifene may prevent vertebral fractures but may not improve BMD (low SOE). Effects of teriparatide and denosumab on BMD and fractures are unclear (very low SOE), and these medications may increase risk for some safety outcomes.

Limitation:

Unclear rigor of evidence, possible reporting biases, and scant evidence among patients with stage 3 to 5 CKD.

Conclusion:

Effects of osteoporosis medications on BMD, fracture risk, and safety among patients with CKD are not clearly established.

Primary Funding Source:

Kidney Disease: Improving Global Outcomes.

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Information & Authors

Information

Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 166Number 92 May 2017
Pages: 649 - 658

History

Published online: 11 April 2017
Published in issue: 2 May 2017

Keywords

Authors

Affiliations

Lisa M. Wilson, ScM
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Casey M. Rebholz, PhD, MPH, MS
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Ermias Jirru, MD, MPH
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Marisa Chi Liu, MD, MPH
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Allen Zhang, BS
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Jessica Gayleard, BS
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Yue Chu, MSPH
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Karen A. Robinson, PhD
From Johns Hopkins University Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland; Mount Sinai St. Luke's and Mount Sinai West, Icahn School of Medicine at Mount Sinai, New York, New York; and University of Vermont College of Medicine, Burlington, Vermont.
Financial Support: By Kidney Disease: Improving Global Outcomes.
Disclosures: Dr. Rebholz reports a grant from the National Institute of Diabetes and Digestive and Kidney Diseases outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2752.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement: Study protocol: The document specifying the research questions is available from the authors. Statistical code and data set: See the Methods and the appendix tables.
Corresponding Author: Lisa M. Wilson, ScM, Johns Hopkins University Bloomberg School of Public Health, 1830 East Monument Street, Room 8066, Baltimore, MD 21205; e-mail, [email protected].
Current Author Addresses: Ms. Wilson: Research Associate, Johns Hopkins University Bloomberg School of Public Health, 1830 East Monument Street, Room 8066, Baltimore, MD 21205.
Dr. Rebholz: Assistant Professor, Johns Hopkins University Bloomberg School of Public Health, 2024 East Monument Street, Room 2-611, Baltimore, MD 21287.
Dr. Jirru: Icahn School of Medicine at Mount Sinai, 1000 Tenth Avenue, Suite 3A-09, New York, NY 10019.
Dr. Liu: University of California, Irvine Medical Center, 101 The City Drive, Orange, CA 92868.
Mr. Zhang, Ms. Gayleard, and Ms. Chu: Department of Health Policy and Management, Johns Hopkins University Bloomberg School of Public Health, 624 North Broadway, 6th Floor, Baltimore, MD 21205.
Dr. Robinson: Associate Professor, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 8068, Baltimore, MD 21205.
Author Contributions: Conception and design: L.M. Wilson, E. Jirru, K.A. Robinson.
Analysis and interpretation of the data: L.M. Wilson, E. Jirru, M.C. Liu, A. Zhang, K.A. Robinson.
Drafting of the article: L.M. Wilson, K.A. Robinson.
Critical revision of the article for important intellectual content: L.M. Wilson, C.M. Rebholz, E. Jirru, K.A. Robinson.
Final approval of the article: L.M. Wilson, C.M. Rebholz, E. Jirru, M.C. Liu, A. Zhang, J. Gayleard, Y. Chu, K.A. Robinson.
Provision of study materials or patients: L.M. Wilson, A. Zhang.
Statistical expertise: L.M. Wilson.
Obtaining of funding: K.A. Robinson.
Administrative, technical, or logistic support: L.M. Wilson, M.C. Liu, A. Zhang, J. Gayleard, Y. Chu.
Collection and assembly of data: L.M. Wilson, C.M. Rebholz, E. Jirru, M.C. Liu, A. Zhang, J. Gayleard, Y. Chu, K.A. Robinson.
This article was published at Annals.org on 11 April 2017.

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