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

Kristine E. Ensrud, Brent C. Taylor, Katherine W. Peters, Margaret L. Gourlay, Meghan G. Donaldson, William D. Leslie, Terri L. Blackwell, Howard A. Fink, Eric Orwoll, John Schousboe

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberg4120
JournalBMJ (Online)
Volume349
DOIs
StatePublished - Jul 3 2014

Fingerprint

Osteoporosis
Cohort Studies
Cross-Sectional Studies
Prospective Studies
Pharmaceutical Preparations
Therapeutics
Osteoporotic Fractures
Hip
Hip Fractures
Independent Living
Femur Neck
Humerus
Wrist

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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. / Ensrud, Kristine E.; Taylor, Brent C.; Peters, Katherine W.; Gourlay, Margaret L.; Donaldson, Meghan G.; Leslie, William D.; Blackwell, Terri L.; Fink, Howard A.; Orwoll, Eric; Schousboe, John.

In: BMJ (Online), Vol. 349, g4120, 03.07.2014.

Research output: Contribution to journalArticle

Ensrud, Kristine E. ; Taylor, Brent C. ; Peters, Katherine W. ; Gourlay, Margaret L. ; Donaldson, Meghan G. ; Leslie, William D. ; Blackwell, Terri L. ; Fink, Howard A. ; Orwoll, Eric ; Schousboe, John. / 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. In: BMJ (Online). 2014 ; Vol. 349.
@article{82e689027cc340e5a13bda0620eadc09,
title = "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",
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.",
author = "Ensrud, {Kristine E.} and Taylor, {Brent C.} and Peters, {Katherine W.} and Gourlay, {Margaret L.} and Donaldson, {Meghan G.} and Leslie, {William D.} and Blackwell, {Terri L.} and Fink, {Howard A.} and Eric Orwoll and John Schousboe",
year = "2014",
month = "7",
day = "3",
doi = "10.1136/bmj.g4120",
language = "English (US)",
volume = "349",
journal = "BMJ (Online)",
issn = "0267-0623",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Implications of expanding indications for drug treatment to prevent fracture in older men in United States

T2 - Cross sectional and longitudinal analysis of prospective cohort study

AU - Ensrud, Kristine E.

AU - Taylor, Brent C.

AU - Peters, Katherine W.

AU - Gourlay, Margaret L.

AU - Donaldson, Meghan G.

AU - Leslie, William D.

AU - Blackwell, Terri L.

AU - Fink, Howard A.

AU - Orwoll, Eric

AU - Schousboe, John

PY - 2014/7/3

Y1 - 2014/7/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84903643294&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903643294&partnerID=8YFLogxK

U2 - 10.1136/bmj.g4120

DO - 10.1136/bmj.g4120

M3 - Article

VL - 349

JO - BMJ (Online)

JF - BMJ (Online)

SN - 0267-0623

M1 - g4120

ER -