Implications of expanding indications for drug treatment to prevent fracture in older men in United States: cross sectional and longitudinal analysis of prospective cohort study
BMJ 2014; 349 doi: https://doi.org/10.1136/bmj.g4120 (Published 03 July 2014) Cite this as: BMJ 2014;349:g4120
- Kristine E Ensrud, professor1, core investigator2,
- Brent C Taylor, associate professor1, core investigator2,
- Katherine W Peters, statistician3,
- Margaret L Gourlay, assistant professor4,
- Meghan G Donaldson, research associate5,
- William D Leslie, professor6,
- Terri L Blackwell, statistician3,
- Howard A Fink, associate professor1, core investigator2,
- Eric S Orwoll, professor7,
- John Schousboe, rheumatologist8, assistant professor9
- for the Osteoporotic Fractures in Men (MrOS) Study Group
- 1Department of Medicine and Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA
- 2Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN, USA
- 3California Pacific Medical Center Research Institute, San Francisco, CA, USA
- 4Department of Family Medicine, University of North Carolina, Chapel Hill, NC, USA
- 5Centre for Clinical Epidemiology and Evaluation, University of British Columbia, Vancouver, BC, Canada
- 6Department of Medicine, University of Manitoba, Winnipeg, MB, Canada
- 7Bone and Mineral Unit, Oregon Health and Science University, Portland, OR, USA
- 8Park Nicollet Clinic, St Louis Park, MN, USA
- 9Division of Health Policy and Management, University of Minnesota, Minneapolis, MN, USA
- Correspondence to: K E Ensrud, One Veterans Drive (111-0), Minneapolis, MN 55417, USA ensru001{at}umn.edu
- Accepted 5 June 2014
Abstract
Objectives To quantify incremental effects of applying different criteria to identify men who are candidates for drug treatment to prevent fracture and to examine the extent to which fracture probabilities vary across distinct categories of men defined by these criteria.
Design Cross sectional and longitudinal analysis of a prospective cohort study.
Setting Multicenter Osteoporotic Fractures in Men (MrOS) study in the United States.
Participants 5880 untreated community dwelling men aged 65 years or over classified into four distinct groups: osteoporosis by World Health Organization criteria alone; osteoporosis by National Osteoporosis Foundation (NOF) but not WHO criteria; no osteoporosis but at high fracture risk (at or above NOF derived FRAX intervention thresholds recommended for US); and no osteoporosis and at low fracture risk (below NOF derived FRAX intervention thresholds recommended for US).
Main outcome measures Proportion of men identified for drug treatment; predicted 10 year probabilities of hip and major osteoporotic fracture calculated using FRAX algorithm with femoral neck bone mineral density; observed 10 year probabilities for confirmed incident hip and major osteoporotic (hip, clinical vertebral, wrist, or humerus) fracture events calculated using cumulative incidence estimation, accounting for competing risk of mortality.
Results 130 (2.2%) men were identified as having osteoporosis by using the WHO definition, and an additional 422 were identified by applying the NOF definition (total osteoporosis prevalence 9.4%). Application of NOF derived FRAX intervention thresholds led to 936 (15.9%) additional men without osteoporosis being identified as at high fracture risk, raising the total prevalence of men potentially eligible for drug treatment to 25.3%. Observed 10 year hip fracture probabilities were 20.6% for men with osteoporosis by WHO criteria alone, 6.8% for men with osteoporosis by NOF (but not WHO) criteria, 6.4% for men without osteoporosis but classified as at high fracture risk, and 1.5% for men without osteoporosis and classified as at low fracture risk. A similar pattern was noted in observed fracture probabilities for major osteoporotic fracture. Among men with osteoporosis by WHO criteria, observed fracture probabilities were greater than FRAX predicted probabilities (20.6% v 9.5% for hip fracture and 30.0% v 17.4% for major osteoporotic fracture).
Conclusions and relevance Choice of definition of osteoporosis and use of NOF derived FRAX intervention thresholds have major effects on the proportion of older men identified as warranting drug treatment to prevent fracture. Among men identified with osteoporosis by WHO criteria, who comprised 2% of the study population, actual observed fracture probabilities during 10 years of follow-up were highest and exceeded FRAX predicted fracture probabilities. On the basis of findings from randomized trials in women, these men are most likely to benefit from treatment. Expanding indications for treatment beyond this small group has uncertain value owing to lower observed fracture probabilities and uncertain benefits of treatment among men not selected on the basis of WHO criteria.
Footnotes
Contributors: KEE and ESO were involved in the design and conduct of the study and the collection of data. All authors were involved in the analysis and/or interpretation of data. KWP did the statistical analyses; she had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. KEE was responsible for preparation of the manuscript. KWP, BCT, MLG, MGD, WDL, TLB, HAF, and ESO critically reviewed and approved the manuscript. KEE and ESO are the guarantors.
Funding: The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health (NIH) funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute on Aging, the National Center for Research Resources, and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01 AG027810, and UL1 TR000128. The funding agencies had no direct role in the conduct of the study; the collection, management, analyses, and interpretation of the data; or the preparation or approval of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: KEE serves as a consultant on a data monitoring committee for Merck Sharpe & Dohme; WDL has served as a speaker for Amgen, Eli Lilly, and Novartis and received research grants from Novartis, Amgen, and Genzyme; ESO receives research support from Merck Sharpe & Dohme and Eli Lilly and provides consultation to Amgen, Merck Sharpe & Dohme, and Eli Lilly; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The institutional review board at each participating institution approved the study protocol, and all participants gave informed consent.
Transparency statement: The first author (KEE) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.
Data sharing: The Osteoporotic Fractures in Men (MrOS) technical appendix, statistical code, and dataset are maintained at the Data Coordinating Center (California Pacific Medical Center Research Institute, San Francisco, CA, USA) and are available from Kathy Peters (KPeters{at}sfcc-cpmc.net).
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