Evidence Synthesis Pilot Program 

Screening Men for Osteoporosis: 

Who & How

Department of Veterans Affairs

Health Services Research & Development Service

May 2007

Investigators:

Paul Shekelle, MD, PhD 

Director

 

Brett Munjas, BA

Project Manager/Literature Database Manager

Hau Liu, MD

Elaine Wong, MD

Content Experts/Physician Reviewers

Neil Paige, MD

Caroline Goldzweig, MD

Physician Reviewers/Health Services Researchers

Annie Zhou, MS

Marika Suttorp, MS

Statisticians

Prepared for: 

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420 

Prepared by:

Greater Los Angeles Veterans Affairs Healthcare 

System/Southern California/RAND Evidence-based 

Practice Center 

Los Angeles, CA
ii 

Suggested Citation 

Shekelle P, Munjas B, Liu H, Paige N, and Zhou A. “Screening Men for Osteoporosis: 

Who & How.” Department of Veterans Affairs. May 2007. 

Technical Experts & Consultants* 

Eric Orwoll, MD, Oregon Health Sciences University, Portland, OR. 

William Duncan, MD, VA Central Office, Washington, DC. 

* Service as a technical expert for this report does not imply endorsement of 

the report’s findings. 

This information is distributed solely for the purposes of pre-dissemination peer review. It has 

not been formally disseminated by the Department of Veterans Affairs and does not represent 

an official or non-official VA determination or policy.

This report is based on research conducted by the Greater Los Angeles Veterans Affairs 

Healthcare System and Southern California Evidence-based Practice Center (EPC) under 

contract to the Department of Veterans Affairs. The findings and conclusions in this document 

are those of the author(s) who are responsible for its contents and do not necessarily represent 

the views of the Department of Veterans Affairs. Therefore, no statement in this article should 

be construed as an official position of the Department of Veterans Affairs. 

This report is intended as a reference and not as a substitute for clinical judgment. 

This report may be used, in whole or in part, as the basis for the development of clinical 

practice guidelines and other quality enhancement tools, or as a basis for reimbursement and 

coverage policies. The Department of Veterans Affairs endorsement of such derivative 

products may not be stated or implied. 

FINANCIAL DISCLOSURE: No investigators have any affiliations or financial involvement (e.g., 

employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or 

patents received or pending, or royalties) that conflict with material presented in the report. 
iii 

PREFACE 

VA’s Health Services Research and Development Service (HSR&D) works to improve the cost, 

quality, and outcomes of health care for our nation’s veterans. Collaborating with VA leaders, 

managers, and policy makers, HSR&D focuses on important health care topics that are likely to 

have significant impact on quality improvement efforts. One significant collaborative effort is 

HSR&D’s Evidence-based Synthesis Pilot Project (ESP). Through this project, HSR&D 

provides timely and accurate evidence syntheses on targeted health care topics. These products 

will be disseminated broadly throughout VA and will: inform VA clinical policy, develop 

clinical practice guidelines, set directions for future research to address gaps in knowledge, 

identify the evidence to support VA performance measures, and rationalize drug formulary 

decisions. 

HSR&D provided funding for the two Evidence Based Practice Centers (EPCs) supported by the 

Agency for Healthcare Research and Quality (AHRQ) that also had an active and publicly 

acknowledged VA affiliation—Southern California EPC and Portland, OR EPC—so they could 

develop evidence syntheses on requested topics for dissemination to VA policymakers. A 

planning committee with representation from HSR&D, Patient Care Services, Office of Quality 

and Performance, and the VISN Clinical Management Officers, has been established to identify 

priority topics and to insure the quality of final reports. 

Comments on this evidence report are welcome and can be sent to Susan Schiffner, ESP Program 

Manager, at Susan.Schiffner@va.gov . 
iv 

TABLE OF CONTENTS 

(Click the titles or page numbers below 

 to go directly to the desired page) 

EXECUTIVE SUMMARY .........................................................................................................................................1

INTRODUCTION .......................................................................................................................................................4

BACKGROUND ...........................................................................................................................................................4

METHODS...................................................................................................................................................................6

TOPIC DEVELOPMENT................................................................................................................................................6

SEARCH STRATEGY ...................................................................................................................................................6

STUDY SELECTION.....................................................................................................................................................7

DATA ABSTRACTION .................................................................................................................................................7

QUALITY ASSESSMENT ..............................................................................................................................................7

RATING THE BODY OF EVIDENCE ...............................................................................................................................8

DATA SYNTHESIS ......................................................................................................................................................9

PEER REVIEW ............................................................................................................................................................9

RESULTS...................................................................................................................................................................10

LITERATURE FLOW..................................................................................................................................................10

KEY QUESTION #1:

What are the prevalence of and risk factors for osteopenia, osteoporosis and osteoporotic fractures among men in 

general and among male Veterans specifically? .....................................................................................................12

KEY QUESTION #2:

Are there any validated tools (outside of DXA-determined central bone density) to screen for osteoporosis in 

men?........................................................................................................................................................................23

KEY QUESTION 3:

What values of BMD determined by DXA (and by different DXA techniques) have been used to diagnose 

osteopenia and osteoporosis; and what is the evidence regarding the relationship between differing definitions 

and the development of osteoporotic fractures?......................................................................................................37

SUMMARY AND DISCUSSION.............................................................................................................................41

LIMITATIONS ...........................................................................................................................................................41

CONCLUSIONS .........................................................................................................................................................42

FUTURE RESEARCH..............................................................................................................................................44

REFERENCES ..........................................................................................................................................................45

TABLES

Table 1. Classification of risk factors for fracture related to bone mass loss ..............................................................13 

Table 2. Risks for osteoporotic fractures.....................................................................................................................14 

Table 3. Descriptive Data about Risk Factor Articles .................................................................................................19 

Table 4a. Cohort Studies Assessing Alcohol as a Risk Factor, Outcome Measure: Fracture Occurence....................20 

Table 4b. Cohort Studies Assessing Alcohol as a Risk Factor, Outcome Measure: BMD..........................................20 

Table 4c. Cohort Studies Assessing Diabetes Type II or NOS as a Risk Factor, Outcome Measure: BMD...............21 

Table 5. Studies Assessing Spinal Cord Injury as a Risk Factor, Outcome Measure: BMD and/or Fracture 

Occurrence ....................................................................................................................................................22 

Table 6a. Study Test: Ultrasound vs. Reference Test: cDXA detailed comparison ....................................................26 

Table 6b. Study Test: Questionnaire vs. Reference Test: cDXA detailed comparison................................................27 

Table 6c. Study Test: Ultrasound vs. Reference Test: Fracture Occurrence detailed comparison ..............................28 

Table 7. Entry Criteria of Trials Reporting Efficacy of Osteoporosis Treatment in Men............................................40 
v 

FIGURES

Figure 1. Male OP Literature Flow..............................................................................................................................11 

Figure 2a. Bone Mineral Density-Centric Simple Model............................................................................................23 

Figure 2b. Multiple Risk Factor Model .......................................................................................................................23 

Figure 3a. Sensitivity versus 1-Specificity: Pooled Results of Heel Ultrasound or OSTA Compared to cDXA.........31 

Figure 3b. ROC Curve Comparing Quantitative Ultrasound to cDXA Using Three Different T-scores.....................31 

Figure 3c. ROC Curve Comparing Quantitative Ultrasound to cDXA from Meta-Analysis of Nayak (2006) .......... 31 

Figure 3d. ROC Curves Comparing Quantitative Ultrasound to cDXA, a Comparison of Figures 3a-c.................... 31 

Figure 4. ROC Curve Comparing OST to cDXA using Two Different T-scores.........................................................32 

Figure 5. ROC Curves and Individual Study Sensitivity versus 1-Specificty (All Studies) ................................33 

APPENDIX

Appendix A. Data Collection Forms ...........................................................................................................................53 

Appendix B. Evidence Table.......................................................................................................................................58 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 1

EXECUTIVE SUMMARY

BACKGROUND

Although 25% of men over the age of 60 will sustain osteoporotic fractures during their lifetime, data 

suggest that male osteoporosis is underdiganosed and undertreated. In order to help inform decisions 

about whether the Veterans Health Administration should develop screening guidelines for male 

osteoporosis, summaries of what is known about 1) the epidemiology of male osteoporosis, and 2) the 

validity of tools to screen and diagnose male osteoporosis are needed. 

The Key Questions were: 

Key Question 1. What are the prevalence of and risk factors for osteopenia, osteoporosis and 

osteoporotic fractures among men in general and among male Veterans specifically? 

Key Question 2. Are there any validated tools (outside of central bone density) to screen for 

osteoporosis in men? 

Key Question 3. What values of BMD determined by Dual energy X-ray Absorptiometry (DXA) (and 

by different DXA techniques) have been used to diagnose osteopenia and osteoporosis; and what is the 

evidence regarding the relationship between differing definitions and the development of osteoporotic 

fractures? 

METHODS

We searched PubMed from 1990-2006 using standard search terms. Titles, abstracts, and articles were 

reviewed in duplicate by physicians trained in the critical analysis of literature. Data were extracted by 

quantitative analysts. Pooled analyses were performed for the comparison of either calcaneal ultrasound 

or the Osteoporosis Screening Tool compared to central DXA; all other data were narratively 

summarized. 

RESULTS

We screened 564 titles and performed a more detailed review on 378 articles. From this, we identified 

173 articles that addressed risk factors for osteoporosis, 27 articles that addressed diagnostic tools, and 

31 articles about differing DXA levels and fracture risk. We identified an older high quality metaanalysis of risk factors for osteoporosis. Of the risk factors assessed in this review that the authors 

classified as something other than high risk, VA policymakers selected alcohol use, diabetes mellitus 

type II, and spinal cord injury as the factors for assessment in this review. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 2

KEY QUESTION #1: What are the prevalence of and risk factors for osteopenia, osteoporosis and 

osteoporotic fractures among men in general and among male Veterans specifically? 

PREVALENCE

 There are no VA specific data on prevalence of osteopenia and osteoporosis in men. 

 Applying NHANES III estimates of prevalence to veteran-specific enrollee data we estimate the 

prevalence of osteoporosis in male veterans of 200,000 – 400,000; and of osteopenia in male 

veterans of 2-3 million. 

RISK FACTORS

 We found a high quality meta-analysis, and a limited number of articles specific to the risk factors 

alcohol use, diabetes mellitus type II and spinal cord injury. Based on these findings, our review 

suggests the following. 

 Strong predictors of an increased risk of osteoporosis in men include age, low body weight, 

physical inactivity, and weight loss. (GRADE quality of evidence = High; further research is very 

unlikely to change our confidence on the estimate of effect.) 

 Certain health conditions and medications also are strong or moderate predictors of an increased 

risk of osteoporosis in men. The most relevant to VA are prolonged systemic corticosteroid 

therapy and androgen deprivation (in the context of prostate cancer treatment). (GRADE quality of 

evidence = Moderate; further research is likely to have an important impact on our confidence in 

the estimate of effect and may change the estimate.) 

 Alcohol use is probably associated with an increase in osteoporotic fractures, but is not clearly 

associated with an increase in osteoporosis as measured by BMD. (GRADE quality of evidence: 

Fractures = Moderate; further research is likely to have an important impact on our confidence in 

the estimate of effect and may change the estimate; BMD = Very Low; any estimate of effect is 

very uncertain.) 

 There is no evidence that diabetes mellitus type II is a significant risk factor for osteoporosis in 

men. (GRADE quality of evidence: Low; further research is very likely to have an important 

impact on our confidence in the estimate of effect and is likely to change the estimate.) 

 Spinal Cord Injury is likely associated with an increase risk of osteoporosis and possibly 

osteoporotic fractures. (GRADE quality of evidence: BMD=Moderate; further research is likely to 

have an important impact on our confidence in the estimate of effect and may change the estimate; 

Fractures=Low; further research is very likely to have an important impact on our confidence in 

the estimate of effect and is likely to change the estimate.) 

KEY QUESTION #2: Are there any validated tools (outside of central bone density) to screen for 

osteoporosis in men? 

 The evidence for screening tools for men is much more limited than for women. We were only able 

to synthesize evidence on two screening tools: calcaneal ultrasound and the Osteoporosis Screening 

Tool (OST). 

 There is no evidence to suggest that calcaneal ultrasound performs differently in men than in 

women. (GRADE quality of evidence = Moderate; further research is likely to have an important 

impact on our confidence in the estimate of effect and may change the estimate.) 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 3

 The OST appears to have comparable (and possibly better) test characteristics than calcaneal 

ultrasound in diagnosing DXA-determined osteoporosis. (GRADE quality of evidence = Low; 

further research is very likely to have an important impact on our confidence in the estimate of 

effect and is likely to change the estimate.) 

 Although calcaneal ultrasound does not appear to be a particularly good test at diagnosing DXAdetermined osteoporosis, it is a strong, independent predictor of fractures in men. (GRADE quality 

of evidence = Moderate; further research is likely to have an important impact on our confidence in 

the estimate of effect and may change the estimate.) 

 Limited data are available on other screening modalities and there is a large gap in our 

understanding of osteoporosis screening tests in men. 

KEY QUESTION #3: What values of BMD determined by DXA (and by different DXA 

techniques) have been used to diagnose osteopenia and osteoporosis; and what is the evidence 

regarding the relationship between differing definitions and the development of osteoporotic 

fractures? 

 The values of BMD determined by DXA that have been used are based on standard deviations (Tscore) away from a reference standard, either young female or young male. 

 Whether to use a young female or a young male reference range in order to identify men as “at 

risk” for osteoporotic fractures is an area of controversy that is not possible to resolve with existing 

data. 

 Until more definitive evidence is available, we believe it is most logically consistent for VA to use 

for the identification of men who might potentially benefit from treatment for osteoporosis the 

same conditions as were used in the randomized controlled trials (RCT), in other words use of the 

young male reference standard. (GRADE quality of evidence = Low; further research is very likely 

to have an important impact on our confidence in the estimate of effect and is likely to change the 

estimate.) 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 4

INTRODUCTION 

Background 

Although the Surgeon General’s recent report on osteoporosis stated that, “Strong bones (are) essential 

to overall health and quality of life,” it warned that, “The bone health status of Americans... is in 

jeopardy.”1

 Traditionally, osteoporosis was viewed as a disease of women, but it has become clear that 

osteoporotic fractures result in substantial morbidity, mortality, and costs in men.2-6 A 60-year old man 

has a 25% lifetime risk of sustaining an osteoporotic fracture.7 The consequences of this fracture can be 

severe as the one-year mortality rate in men after hip fracture is twice that of women.8 With the aging of 

the population, rates of osteoporosis in men are expected to increase nearly 50% in the next 15 years and 

hip fractures rates are projected to double or triple by 2040.1

Furthermore, annual U.S. direct medical costs for osteoporosis exceed $17 billion9

 and are expected to 

increase rapidly with an aging population.1 The percentage of costs directly attributable to men or 

veterans is unclear, although 25% of hip fractures, the fracture type associated with greatest costs due to 

hospitalization and long-term care, occur in men.5

 This large and growing clinical and cost burden, 

combined with an environment of increasingly limited health care resources, strongly underlies the need 

to develop rational, evidence-based osteoporosis management strategies to obtain maximum benefit for 

every health care dollar spent. 

Osteoporotic fractures may be particularly devastating in the veteran population as post-fracture 

inpatient mortality rates for Veterans are more than double that of the general population.10 An analysis 

of femoral bone mineral density data from the National Health and Nutrition Examination Survey 

(NHANES) III, a nationally-representative dataset, reported that 1 to 2 million American men over the 

age of 50 have osteoporosis and 8 to 13 million similarly-aged men have osteopenia, or low bone 

density.11 Applying prevalence data from this analysis to VA-specific enrollee data,12 it is possible that 

200,000 to 400,000 veterans have osteoporosis and 2 to 3 million veterans have osteopenia. These 

estimates are likely conservative as Veterans have increased rates of co-morbid conditions compared to 

the general population.13

Despite the substantial advances in our understanding of osteoporosis over the last decade, there are no 

consensus guidelines on the assessment and management of male osteoporosis. Although osteoporosis 

management strategies have been evaluated in women,1,14-19 much less work has been done in this area 

in men.10,20,21 Lack of research in this area has led to considerable uncertainty regarding optimal 

osteoporosis strategies in men and Veterans. The VA Office of Quality and Performance and the U.S. 

Preventive Services Task Force offer no clinical practice guidelines on the management of osteoporosis 

in men. The National Osteoporosis Foundation offers no guidelines on screening for men, although it 

suggests that that all individuals be treated with osteoporosis medications if they have a pre-existing 

fragility fracture.22 The International Society for Clinical Densitometry suggests that all men over the 

age of 70 receive a DXA exam,23 although the effects of this recommendation have not been evaluated. 

As such, a significant gap in our understanding exists on how best to evaluate and manage osteoporosis 

in men. 

As the largest integrated health care system in the U.S., serving a population that is more than 95% male 

and 80% over the age of 50,12 these issues are of particular concern and importance to the VA. In 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 5

particular, identifying and implementing optimal strategies for osteoporosis management will be 

critically important over the next five to ten years as the “baby boomers” begin to reach retirement, an 

age when fracture risk dramatically increases in men. Given the large number of male veterans at high 

risk for osteoporosis who receive care through the VA, the VA is uniquely positioned and qualified to 

dramatically preserve and improve veteran and male skeletal health 

In order to inform decision-making regarding potential VA screening guidelines for male osteoporosis, 

William Duncan, MD, PhD, the Acting Director of the VA Medical Service, and the VA HSR&D 

Service commissioned this literature review of the epidemiology and risk factors for osteoporosis, and 

validity of screening tools for male osteoporosis. This review is being performed as part of the Evidence 

Synthesis Project, an HSR&D-organized initiative to provide VA policymakers with high quality 

evidence reviews. 

The purpose of this review is to analyze the literature in order to answer three key questions: 1) What is the 

epidemiology and what are the key risk factors for male osteoporosis?; 2) Are there any validated screening 

tools for osteoporosis in men (beyond DXA-assessed central bone density)?; and 3) What is the evidence 

regarding bone mineral density and fracture risk? The results of this review will be used to assist VA 

policy-makers in making evidence-based decisions on how best to preserve and improve skeletal health in 

the veteran population. In specific, their report is not meant to be a guideline. The role of guideline 

development is that of the VA guidelines committee, which will use this evidence synthesis in its 

deliberation. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 6

METHODS 

Topic Development 

This project was nominated by William Duncan, MD, for the Evidence Synthesis Project. Key questions 

were discussed and finalized during a conference call that included the Steering Committee of the 

Evidence Synthesis Project, Dr. Duncan, and the VA Greater Los Angeles project site director. The final 

key questions are: 

1. What are the prevalence of and risk factors for osteopenia, osteoporosis and osteoporotic 

fractures among men in general and among male Veterans specifically? 

2. Are there any validated tools (outside of central bone density) to screen for osteoporosis in men? 

3. What values of BMD determined by DXA (and by different DXA techniques) have been used to 

diagnose osteopenia and osteoporosis; and what is the evidence regarding the relationship 

between differing definitions and the development of osteoporotic fractures? 

Search Strategy 

Our library searches began in June, 2006, with a search of PubMed. 

The search strategy is listed below: 

DATABASE SEARCHED & TIME PERIOD COVERED: 

 PUBMED – 1990-2006 

LIMITERS: ENGLISH, HUMAN, MALE 

SEARCH STRATEGY: 

osteoporosis[majr] OR osteoporosis[ti] 

AND 

male[tiab] OR men[tiab] OR gender 

AND 

risk factors[majr] OR risk*[tiab] 

AND 

bone mineral density OR bone*[ti] OR risk*[ti] OR fractur*[ti] 

NOT 

Results of previous searches 

NUMBER OF ITEMS RETRIEVED: 508 

In addition to our PubMed search, we performed reference mining of retrieved articles, references of 

prior reviews, and solicited articles from experts. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 7

Study Selection 

Four trained researchers (working in groups of two) reviewed the list of titles and selected articles for 

further review. Each group of two consisted of an endocrinologist trained in the critical examination of 

literature and a fellowship-trained health services research general internist. Each article retrieved was 

reviewed with a brief screening form (see Appendix A) that collected data on prevalence and incidence, 

risk fractures, diagnostic tools, associations between bone mass density levels (BMD) as determined by 

dual energy X-ray absorptiometry (DXA), study design, and whether or not the subjects in the study 

were Veterans. To be included in our evidence report, a study had to measure incidence, prevalence, or 

risk factors for osteoporosis in men; or, a comparison of two different methods of assessing for the 

presence of osteoporosis in men; or, provide data on different values of BMD as determined by DXA 

and risk of osteoporotic fractures in men. Eligible study designs included controlled clinical trials, 

cohort studies and case series, case control studies, and systematic reviews/meta-analyses. Case reports, 

non-systematic reviews, letters to the editor and other similar contributions were excluded. 

Data Abstraction 

Data were independently abstracted by an endocrinologist and a general internist/health services 

researcher, with consensus resolution. The following data were abstracted from included trials: study 

test and site, reference test and site, population, sample size, patient characteristics, region, and outcome 

reporting. Data abstraction forms are provided in Appendix A.

For diagnostic accuracy studies, a statistician extracted data. For each selected study, the sample size, 

sensitivity and specificity at each quantitative ultrasound or questionnaire threshold were extracted. The 

standard error of sensitivity and specificity were calculated as variancesens = pi*(1-pi)/ni where pi is the 

sensitivity for study i and ni is the number of people classified as having the disease for study i. If a 

study did not report the sensitivity or specificity and if they could not be calculated from the given data, 

the study was excluded from analysis. We contacted the original authors of some studies to obtain the 

sample sizes per group needed to perform this calculation. 

Quality assessment 

To assess internal validity of diagnostic studies, we used the QUADAS, a tool for Quality Assessment of 

studies of Diagnostic Accuracy included in Systematic Reviews (see Appendix A). We abstracted data 

on representativeness of patients to those who will receive the test in practice; clarity of selection 

criteria; likelihood of reference test to correctly classify the condition; time frame between reference test 

and study test; whether or not the entire or randomized group of the sample received verification using 

the reference test; whether patients received the same reference test regardless of the study test result; 

independence of the reference test from the study test; ability to replicate study and reference test based 

on detail provided in the article; study test results interpreted blinded from reference standard and vice 

versa; replicability of results when test is used in practice; and whether intermediate test results were 

reported; withdrawals from the study explained. 

To assess internal validity of studies of risk or prognosis, we used the criteria proposed by Hayden and 

colleagues24 (see Appendix A). We abstracted data on study participation; study attrition, prognostic 

factor measurement; outcome measurement; confounding measurement and account; and analysis. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 8

Rating the body of evidence 

We assessed the overall quality of evidence for outcomes using a method developed by the Grade 

Working Group, which classified the grade of evidence across outcomes according to the following 

criteria:25

o High = Further research is very unlikely to change our confidence on the estimate of effect. 

o Moderate = Further research is likely to have an important impact on our confidence in the 

estimate of effect and may change the estimate. 

o Low = Further research is very likely to have an important impact on our confidence in the 

estimate of effect and is likely to change the estimate. 

o Very Low = Any estimate of effect is very uncertain. 

GRADE also suggests using the following scheme for assigning the “grade” or strength of evidence: 

Criteria for assigning grade of evidence 

Type of evidence 

Randomized trial = high 

Observational study = low 

Any other evidence = very low

Decrease grade if: 

• Serious (-1) or very serious (-2) limitation to study quality 

• Important inconsistency (-1) 

• Some (-1) or major (-2) uncertainty about directness 

• Imprecise or sparse data (-1) 

• High probability of reporting bias (-1) 

Increase grade if: 

• Strong evidence of association-significant relative risk of > 2 (< 0.5) 

based on consistent evidence from two or more observational studies, 

with no plausible confounders (+1) 

• Very strong evidence of association-significant relative risk of > 5 

(< 0.2) based on direct evidence with no major threats to validity (+2) 

• Evidence of a dose response gradient (+1) 

• All plausible confounders would have reduced the effect (+1) 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 9

For this report, we used both this explicit scoring scheme and the global implicit judgment about 

“confidence” in the result. Where the two disagreed, we went with the lower of the two classifications. 

Data Synthesis 

Of the articles that were determined to be clinically eligible, thresholds for determining osteoporosis (in 

terms of T-scores) were reviewed across studies to see if they were comparable. First, we looked to see if 

the diagnostic method used was similar across studies. Then, within diagnostic method, we looked to see if 

the cutoff points analyzed were consistent across studies. Within comparable measures, we estimated a 

pooled random effects estimate26 of the sensitivity and specificity. ROC (receiver operating characteristic) 

curves were graphed. Pooled estimates from the meta analysis were plotted onto the ROC curves. 

The remaining studies regarding diagnostic assessments were too heterogeneous to statistically pool, and we 

therefore summarized these narratively. 

Peer Review

This report was reviewed by our technical experts. Their comments were taken into consideration in our 

revision. Service as a technical expert does not imply endorsement of the report’s findings. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 10

RESULTS 

Literature Flow 

In total, we examined 580 titles. The electronic literature search identified 508 articles. An additional 68 

articles were identified through reference mining. Content experts identified 4 more articles. 

Of the titles identified through our electronic literature search, 186 were rejected as not relevant to the 

project. This left 394 from all sources. Four articles were excluded at abstract review. One title could not 

be located after contacting many sources. 

Initial screening of the articles resulted in 176 articles that addressed risk factors for osteoporosis. We 

found 27 articles that addressed diagnostic tools for osteoporosis, and 31 articles about differing DXA 

levels and risk of fracture. (Figure 1) 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 11

Figure 1. Male OP Literature Flow 

Literature Searches 

n= 508 

Content Expert 

n= 4 

Reference Mining 

n= 68 

Total number of titles identified for title review 

n= 580 

Literature Searches 

n= 322 

Total number of titles considered possibly relevant and articles ordered 

n= 394 

1 unlocatable 

4 excluded at abstract review 

Total number of articles reviewed 

n= 389 

Articles addressing 

screening tools 

n= 27 

Article addressing the 

relationship between 

differing DXA values 

of fracture 

n= 31 

Content Expert 

n= 4 

Reference Mining 

n= 68 

Articles addressing 

prevalence/ 

incidence/risk of 

fracture 

n= 176 

Articles with 

specific risk factors 

Alcohol n= 38 

Diabetes, Type II or 

NOS n= 15 

Spinal Cord Injury n= 4 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 12

Key Question #1: What are the prevalence of and risk factors for osteopenia, 

osteoporosis and osteoporotic fractures among men in general and among male 

Veterans specifically?

PREVALENCE

We identified 20 articles that compared osteoporosis and men in Veteran populations.10,19,27-44All of the 

articles dealt with patients selected from specific populations such as nursing homes, pulmonary clinic, 

rheumatology clinic, etc.; or, were convenience samples. Thus there are no population-based data on the 

prevalence of osteoporosis in male veterans. 

A study assessing the prevalence of osteoporosis using a T-score of >2.5 standard deviations below the 

young male reference standard, based on data from the National Health and Nutrition Examination 

Survey III (NHANES III), estimated that the prevalence in men was 3%-6% for osteoporosis, and 28%-

27% for osteopenia.11 Applying these estimates of prevalence to VA-specific enrollee data yields 

estimates of 200,000 to 400,000 male veterans with osteoporosis and 2 to 3 million male veterans with 

osteopenia.

RISK FACTORS 

We identified a high quality systematic review and meta-analysis seeking to identify factors to help 

select subjects for bone densitometry assessments.45 This review searched multiple computerized 

databases up to 1997 and identified 94 cohort studies, 72 case control studies, and 1 randomized clinical 

trial. Most studies were performed in subjects older than age 50 and used American or European 

populations. Where feasible, the authors used fixed-effects methods to provide meta-analytic pooled 

estimates of risk. They classified risk factors into the following groups: 

“High risk”: an associated Relative Risk (RR) or Odds Ratio (OR) of greater than or equal to 2. 

“Moderate risk”: risk vales of between 1 and 2. 

“No risk”: risk values close to or equal to the null value, or even a protective effect. 

“Unclassifiable”: the data are insufficient or contradictory to reach a conclusion. 

The authors performed separate analyses for men and for women, found no important differences, and 

presented their results for both sexes combined. Table 1 presents the main results of their study. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 13

Table 1. Classification of risk factors for fracture related to bone mass loss(taken from reference 45) 

High risk (15%)* Moderate risk (18%)* No risk (8%)* Unclassifiable (59%)*

Aging (> 70–80 years) Gender (female) Consumption of caffeine Alcohol intake 

Low body weighta Smoking (active) Consumption of tea Long-term immobilization 

Weight lossb Low sunlight exposure (low or none) Menopausej Type of menopausek

Physical inactivityc

 Family history of osteoporotic fractured Nulliparity Menopausal discomfort 

Corticosteroids Surgical menopausee

 Consumption of fluoridated Prior practice of athletics 

 Water 

Anticonvulsants Early menopause (<45 years)f Thiazide diuretics High number of children 

Primary hyperparathyroidism†

 Short fertile period (<30 years)g Old age at parity 

Diabetes mellitus type I†

 Late menarche (>15 years)h Other reproductive factorsl

Anorexia nervosa†

 No lactation Male hypogonadism 

Gastrectomy†

 Low calcium intake (<500–850 mg/day)i Other hormonal factors in men 

Pernicious anemia† Hyperparathyroidism (N/S) Mineral nutrient intake 

Prior osteoporotic fracture Hyperthyroidism Dietary deficiency of vitamin D 

 Diabetes mellitus (type II or N/S) Dietary deficiency of vitamin C 

 Rheumatoid arthritis High-protein diet 

 Deficient nutritional intake 

 indicators 

 Other dietary habits 

 Prostaglandin inhibitorsm

 Thyroid hormone replacement 

 therapy 

 Non-thiazide diuretics 

 Tamoxifen 

 Anti-ulcer agents 

 Metabolism and gastrointestinal 

 absorption disordersn

 Other thyroid disorderso

 Respiratory diseasesp

 Neoplasmq

 Paget’s disease 

 Peptic ulcer 

 Thalassemia 

 Lithiasis 

N/S, not specified. 

*Percentage of total risk factors identified. 

†There is little available scientific evidence for this risk factor, its quality also being moderate. However, the available studies show a consistent 

and significant increase in fracture risk. 

a

BMI (body mass index) lower than 20–25 kg/m2 or weight under about 40 kg. b

Greater than 10% (compared with the usual young or adult weight, or weight loss in recent years). c

No physical activities are performed regularly (walking, climbing stairs, carrying weights, housework, gardening, or other). d

Hip fracture in first-degree relatives was the most frequently studied risk factor. e

Due to bilateral oophorectomy. 

f

Before 45 years. 

g

Duration less than 30 years. 

h

From 15 years. 

i

Less than 500–850 mg/day (patient’s age and gender should be assessed) or low/no consumption of dairy products such as milk (<1 glass/day) or 

cheese. 

j

Menopause, due to nonspecified cause or by oophorectomy (unspecified uni- or bilateral). k

Surgical vs natural. 

l

Includes those related to menstrual cycle, miscarriages, hysterectomy and tubal ligation. mIncludes aspirin and other nonsteroidal anti-inflammatories. 

n

Includes hepatic cirrhosis, chronic renal failure, regional enteritis, gastrointestinal resection. o

Includes goiter, adenoma and unspecified glandular disorders. 

p

Includes asthma, chronic bronchitis and emphysema. 

q

Includes endometrial carcinoma, breast carcinoma and any type of neoplasm. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 14

We also identified a recent review (2005) that assessed risk factors for fractures.46 While not a 

systematic review, the paper is authored by leaders in the World Health Organization 

osteoporosis community, and presents summaries of data originally presented in research articles 

(primarily by the co-authors). Included in this paper is a table summarizing their assessment of 

risk factors for osteoporotic fractures, with an additional notation indicating those factors that 

confer extra risk over and above that determined by BMD. That table is reproduced here as 

Table 2. 

Table 2. Risks for osteoporotic fractures (taken from reference 46) 

Female gender Premature menopause 

Agea Primary or secondary amenorrhoea 

Primary and secondary 

 hypogonadism in men 

Asian or Caucasian race Previous fragility fracturea

Low BMD Glucocorticoid therapya

High bone turnovera Family history of hip fracturea

Poor visual acuitya Low body weighta

Neuromuscular disordersa

 Cigarette smokinga

Excessive alcohol consumptiona

Prolonged immobilisation 

Low dietary calcium intake 

Vitamin D deficiency 

a

These characteristics capture aspects of fracture risk over and 

above that provided by BMD 

Of the 176 articles that we identified which assessed risk factors for osteoporosis in men, we 

identified those that concentrated on factors for which prior reviews demonstrated an uncertain 

evidence base and factors that might have specific importance to the VA population. 

These data were discussed with the Evidence Synthesis Project Steering Committee. After 

reviewing the risk factors about which there was still some uncertainty, they identified diabetes 

mellitus type II or NOS, spinal cord injury and alcohol use as factors most relevant to the VA 

and directed us to pursue a more detailed evaluation of articles relevant to these factors. 

We therefore selected the 45 articles that measured one of these risk factors and assessed them 

with a brief screening form (Appendix A). Table 3 presents the results. There were 38 articles 

that assessed alcohol use, 15 that assessed diabetes mellitus and 4 that assessed spinal cord 

injury. Eight studies were cohorts, 9 were case control studies, and 28 were cross sectional in 

design. Almost all studies adjusted for, or in some way accounted for confounding by age, body 

weight, cigarette smoking, and physical activity, but adjustments for other potential risk factors 

were rare and variable. 

Because of inherent problems with temporal ambiguity we rejected the cross sectional studies. 

Because of data supporting the superiority of cohort studies over case control studies,47 we 

focused on the cohort studies. We identified seven articles assessing alcohol, but rejected one48
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 15

as data from this cohort were included in another study. Thus there were six articles about 

alcohol use. We identified one cohort assessing diabetes mellitus type II. We identified four 

relevant studies of osteoporosis in patients with spinal cord injury (SCI), one case control study 

and three cross-sectional studies. 

Each study was assessed for quality using criteria suggested by Hayden & colleagues.24 Tables 

4a-c and Table 5 present descriptive details. 

SYNTHESIS

Alcohol Use and Osteoporotic Fracture 

Three articles assessed the relationship between alcohol intake and osteoporotic fractures.49-51 

Use of this outcome measure means that alcohol’s effect on bone density and its known effect on 

predisposing to falls are both included in the association. It was not possible to pool studies as 

the articles measure the exposure variable, alcohol use, in different ways: self report of units per 

day, days per week, or weekly number and kind of drinks. The measurement of alcohol exposure 

is known to be very sensitive to how self-report questions are asked.52 Study size was in general 

large, with 3,000-17,800 participants. On the Hayden items, these three studies scored modestly, 

with only 2 or 3 items being scored as fully satisfied, the remaining, being partly satisfied or 

unsure. 

The two studies that assessed the association of units per day of alcohol intake and hip fracture 

both reported a statistically significant association. In the first of them, which also combined 

several other studies (in Canada, Australia, and the Netherlands) into a single analysis, assessed 

the relationship between self-reported alcohol use and hip fracture or osteoporotic fracture in 

about 6,000 men followed on average about 4 years.49 Alcohol use was measured once at entry 

and fractures were assessed by self-report with medical record verification. In a multivariate 

analysis adjusted for age, body mass index, and smoking (but not physical activity), a 

statistically significant association was seen in alcohol intake exceeding 3 units per day (3 

units/day, RR hip fracture=1.91; 4 units/day, RR hip fracture=2.84, RR any osteoporotic 

fracture=1.81). 

The second study, three cohorts in Copenhagen that were originally assembled to assess 

cardiovascular disease were re-assessed for the incidence of hip fracture as determined by 

inpatient admission for same in a national database of hospital discharges.51 More than 17,000 

men were followed for 10 or more years. Alcohol intake was measured once, at entry into the 

study. In multivariate models adjusted for age, physical activity, body mass index, and other 

variables, a statistically significant association between baseline self-reported alcohol use and hip 

fracture was seen for categories of drinking exceeding 4 units per day (4-6 units/day, RR=1.75; 

6-10 units/day, RR=1.84, >10 units/day, RR=5.28). 

The third study to assess the relationship between alcohol intake and fracture came from the 

European Prospective Osteoporosis Study, which enrolled 3,173 men and followed them for 

about 4 years.50 Alcohol use was measured once at entry and was reported as frequency in days 

per week. Vertebral fractures were assessed with baseline and follow-up spinal radiographs. In 

bivariate analyses, increasing alcohol intake had modest associations with vertebral fractures 

(RR approximately 1.2 to 1.6) but these were not statistically significant. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 16

Alcohol Use and Bone Mineral Density 

Three articles assessed the relationship between alcohol use and bone mineral density as 

measured by DXA.53-55 Again, we could not pool these studies because they measured the use of 

alcohol in different ways. These studies were much smaller than the studies assessing fractures, 

with 150-507 persons being assessed. These studies scored somewhat better on the Hayden 

items, with 3, 4, and 5 items being scored as fully satisfied. 

These three studies reached inconclusive results. A study of 278 from Framingham reported a 

statistically significant association between self-reported alcohol intake greater than seven 

ounces per week and decreased BMD only at the radial shaft. There were nonsignificant 

decreases in BMD at the trochanter and the lumbar spine.55

A study of the Rancho Bernardo cohort assessed 811 white men and reported a moderate positive 

effect of consuming alcohol three or more times per week on femoral neck BMD measured four 

years later. Non-significant positive associations were also reported for BMD measured at the 

spine and total hip.54 The third study in this group assessed 308 men in Spain.53 Participants 

completed a postal survey at entry and again at four years regarding health habits, including units 

per week of alcohol consumption. BMD was measured by DXA and performed at baseline and 

again at four years. No statistically significant association between alcohol intake and change in 

BMD was found. 

Summary of Alcohol Use and Osteoporotic Fracture Evidence 

Taken together, this group of studies suggests that alcohol intake is probably associated with an 

increase in hip fractures, but only at high rates of consumption. The lack of association reported 

in the European Prospective Osteoporotic study could be due to lack of specificity in the 

classification of alcohol consumption, as this study could not assess high rates of consumption. 

The available evidence fall short of proof because the strength of the association is modest 

(RR<2) and within the level where confounding is still a serious concern, and imprecision in the 

classification of alcohol consumption by self-report is present in all studies. With regard to 

BMD, these is no compelling evidence that alcohol intake is associated with lower BMD. 

(GRADE quality of evidence: Alcohol and Fractures = Low; Further research is very likely to 

have an important impact on our confidence in the estimate of effect and is likely to change the 

estimate; Alcohol and BMD = Very Low; any estimate of effect is very uncertain.) 

Diabetes Mellitus Type II 

We identified only one cohort study that assessed the association between Type II diabetes 

mellitus and osteoporosis.56 This study assessed 998 older male participants in the Health ABC 

study, which was conducted in Pittsburgh and Memphis. The presence of diabetes was assessed 

by self-report and a fasting blood glucose (and follow-up two hour oral glucose tolerance test in 

selected participants). Bone density was determined using DXA at the proximal femur at entry 

and at follow-up. Duration of follow-up was four years. In multivariable models adjusting for 

age, baseline BMD, weight change, smoking status, renal status, and other variables, there was 

no association between the presence of diabetes and femoral neck or total hip BMD. On the 

Hayden criteria, this study scored very strongly, fully satisfying all six items. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 17

Spinal Cord Injury 

We identified four relevant studies of osteoporosis in patients with SCI, one case control study 

and three cross-sectional studies43,57-59 (Table 5). A large body of literature was also identified 

that assessed changes in BMD over time in patients with SCI. 

The case control study compared 17 New Zealander SCI male patients between the ages of 17 

and 52 who were matched for age, height, weight and time spent in physical activity with ablebodied male controls (many of the participants were elite sportsmen)57. Eleven of the SCI 

patients were tetraplegic and six paraplegic. BMD by DXA was measured for the total body, 

arms, legs, left hip and lumbar spine. There were significant differences in mean T-scores of the 

legs and hip between the SCI and control groups; and, mean t-scores in the SCI patients were 

consistent with osteoporosis in the legs and trochanter and osteopenia in the femoral neck and 

Wards triangle. 

Further supporting the association between SCI and bone loss were the three cross-sectional 

studies. The first evaluated 41 veteran SCI patients with a mean age of 55 for predictors of 

osteoporotic fractures in SCI patients43. This study found a high prevalence of osteoporosis 

(61%) and osteopenia (19.5%) in the patients studied as well as a high prevalence of previous 

fracture (34%). Controlling for age and duration of SCI, BMD was a strong predictor of fracture 

with the risk of fracture increasing 2.6 times for each unit decrease in BMD T-score. Another 

cross-sectional study evaluated the BMD of 46 male SCI patients with a mean age of 32 and 

compared this to age-matched reference values and found significantly lower BMD Z-scores in 

the proximal femur and distal forearm but not in the lumbar spine58. Patients with a history of at 

least two weeks of immobilization after spine surgery had significantly lower BMD Z-scores in 

the proximal femur but not in the lumbar spine or distal forearm. Patients with complete SCI had 

lower BMD Z-scores in the lumbar spine compared to patients with incomplete SCI. 

The last cross-sectional study evaluated 41 Turkish SCI patients of which 32 were male with a 

mean age of 34.4 years59. BMD Z-scores were significantly higher in the upper extremities for 

paraplegic patients when compared to tetraplegic patients; and, when evaluating paraplegic 

patients alone, BMD Z-scores were significantly higher in the upper extremities than the lower 

extremities. This study also demonstrated that BMD Z-scores were significantly higher in SCI 

patients with incomplete injuries versus those with complete injuries, in those with spastic versus 

flaccid paralysis, and in those with a shorter duration of injury. 

As mentioned above, there were a number of longitudinal studies which evaluated changes in 

BMD for patients with SCI. These studies did not meet our criteria for in-depth review but 

overall were consistent in demonstrating decreasing BMD over time in SCI patients. Four of 

these studies assessed veterans with SCI.40-42,44 These studies support the hypothesis that SCI is 

a risk factor for osteoporosis. 

Summary of Spinal Cord Injury and Osteoporosis or Osteoporotic Fracture 

Taken together, these case-control and cross-sectional studies of SCI patients indicate that 

osteoporosis is significantly more likely in patients with SCI compared to non-SCI patients; that 

BMD worsens with duration of SCI ; and, that decreases in BMD are more significant in bones 

distal to the SCI level. Fracture risk also appears elevated but the evidence is less robust. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 18

CONCLUSIONS

We found an older high quality meta analysis assessing numerous risk factors, and a limited 

number of articles specific to the risk factors alcohol use, diabetes mellitus type II and spinal 

cord injury. Based on these findings, our review suggests the following. 

1. Strong predictors of an increased risk of osteoporosis in men include age, low body 

weight, physical inactivity, and weight loss. (GRADE quality of evidence = High; further 

research is very unlikely to change our confidence on the estimate of effect.) 

2. Certain health conditions and medications also are strong or moderate predictors of an 

increased risk of osteoporosis in men. The most relevant to VA are prolonged systemic 

corticosteroid therapy and androgen deprivation (in the context of prostate cancer 

treatment). (GRADE quality of evidence = Moderate; further research is likely to have an 

important impact on our confidence in the estimate of effect and may change the 

estimate.) 

3. Alcohol use is probably associated with an increase in osteoporotic fractures, but is not 

clearly associated with an increase in osteoporosis as measured by BMD. (GRADE 

quality of evidence: Fractures = Moderate; further research is likely to have an important 

impact on our confidence in the estimate of effect and may change the estimate; BMD = 

Very Low; any estimate of effect is very uncertain.) 

4. There is no evidence that diabetes mellitus type II is a significant risk factor for 

osteoporosis in men. (GRADE quality of evidence: Low; further research is very likely to 

have an important impact on our confidence in the estimate of effect and is likely to 

change the estimate.) 

5. Spinal cord injury is associated with an increase risk of osteoporosis and possibly 

osteoporotic fractures. (GRADE quality of evidence: BMD=Moderate; further research 

is likely to have an important impact on our confidence in the estimate of effect and may 

change the estimate; Fractures=Low; further research is very likely to have an important 

impact on our confidence in the estimate of effect and is likely to change the estimate.) 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 19

 

Table 3. Descriptive Data about Risk Factor Articles 

Risk Factor Assessed: Number of Articles

Alcohol............................................................ 38 

Diabetes Type II or NOS..................................15 *includes 12 articles that also assessed alcohol

Spinal Cord Injury..............................................4

Study Design: 

 Cohort.................................................................8 

Case-Control.......................................................9 

 Cross Sectional.................................................28 

Outcomes Assessed:

cDXA................................................................28 

 Site: 

 Spine.....................................17 

 Femur....................................23 

 Other.....................................9 

Osteoporotic Fracture.....................................19

 Assessed by: 

 X-ray.....................................11 

 Medical Record Review.........8 

 Administrative data................4 

 Diary.......................................4 

Other Bone Measurements...............................8 

 Ultrasound.............................................2 

 Other......................................................8 

Covariates Adjusted for: Percent of Articles

 Age...................................................................82% 

 Low body weight.............................................84% 

 Weight loss........................................................9% 

 

Physical inactivity/prolonged immobilization.71% 

 Corticosteroid use............................................36% 

 Anticonvulsant use..........................................16% 

 

Hyperparathyroidism........................................9% 

 Diabetes Type I.................................................0% 

 Gastrectomy.....................................................13% 

 

Hypogonadism, primary or secondary.............16% 

 Poor visual acuity..............................................2% 

 Previous osteoporotic fracture..........................29% 

 

Cigarette smoking.............................................89% 

 Vitamin D deficiency........................................16% 

 Low dietary calcium intake...............................60% 

 

Family history of osteoporosis..........................31% 

 Hyperthyroidism................................................20% 

 Rheumatoid arthritis..........................................18% 

 High bone turnover rate.......................................4% 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 20

Table 4a. Cohort Studies Assessing Alcohol as a Risk Factor, Outcome Measure: Fracture Occurrence 

BMD=Bone Mass Density, NR=Not Reported, OP=Osteoporosis, RR=Relative Risk Table 4b. Cohort Studies Assessing Alcohol as a Risk Factor, Outcome Measure: BMD BMD=Bone Mass Density, NR=Not Reported, NA=Not applicable, OP=Osteoporosis

Quality Measurement

Study Participation (SP) Outcome Measurement 

(OM) 

Study Attrition (SA) Confounding Measurement 

(CM) 

Article Population Enrolled 

/Include

d in 

analysis 

Duration 

of follow 

up 

Alcohol 

Consumption

Definition 

Fracture 

Occurrence 

assessed

Covariates 

adjusted for 

Prognostic Factor 

Measurement (PFM) 

Analysis (A) 

SP: Partly OM: Partly 

SA: Unsure CM: Partly 

Kanis, 200549

3 cohort populations with mean ages 60, 70, 67 years 

5939 / 5939 

27,968 

person yrs

Units / day Diary 

Medical Record Review 

Age Low body weight Smoking 

PFM: Yes A: Yes 

i

int

of 

SP: Partly OM: Yes 

SA: Unsure CM: Yes 

Roy, 200350 European 

men mean age 63.1 years 

NR / 3173 

3.8 years 5-6, 3-4, 1-2 

days/wk 

X-ray Age 

Low body weight Inactivity Smoking Low calcium intake 

PFM: Yes A: Partly 

s

SP: Partly OM: Yes 

SA: Partly CM: Partly 

Holdrup, 199951

Pooled data from 3 Danish cohorts mean age 50.5 years 

17,868 / 17,868 

13.6 years Weekly 

number & 

kind of 

drinks 

Administrative data Medical Record Review 

Age Low body weight Inactivity Smoking PFM: Yes A: Yes 

Th

(R

BMD Quality Measurement

Study Participation 

(SP) 

Outcome Measurem

(OM) 

Study Attrition (SA) Confounding Measur

(CM) 

Article Population Enrolled 

/Included 

in analysis 

Duration 

of follow 

up 

Alcohol 

Consumption 

Definition Site T-score Reference 

Standard

Covariates 

adjusted for 

Prognostic Factor 

Measurement (PFM) 

Analysis (A) 

SP: Yes OM: Partly 

SA: Yes CM: Yes 

Naves, 200553 Spanish 

men with mean age of 64 years 

229 / 150 4 years Units, 

unit= 

10grams

Femur 

Spine 

<-2.5=OP Unclear Age 

Low body weight Inactivity Smoking Low Calcium Intake Family History of OP fracture

PFM: Yes A: Partly 

SP: Yes OM: Yes 

SA: Partly CM: Yes 

Bakhireva 200454

American men with mean age of 70.8 years 

818 / 507 4 years Drink >=3 

days/wk v. 

<=2 

days/wk 

Femur 

Spine 

<=-2=OP Male Age 

Low body weight Weight loss Inactivity Smoking Low calcium intake PFM: Partly A: Partly 

SP: Yes OM: Yes 

SA: Partly CM: Yes 

Hannan, 200055

Elderly American men 

NR / 278 4 years Current vs. 

non user, 

grams/wk 

Femur 

Spine 

NR NA Age 

Low body weight Weight loss Inactivity Smoking Vitamin D deficiency Low calcium intake

PFM: Yes A: Yes 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 21

Table 4c. Cohort Studies Assessing Diabetes Type II or NOS as a Risk Factor, Outcome Measure: BMD 

BMD=Bone Mass Density, NR=Not Reported, NA=Not Applicable, OP=Osteoporosis, FBG=Fasting Blood Glucose, OGTT=Oral Glucose Tolerance Test 

BMD Quality Measurement

Study Participation 

(SP) 

Outcome Measurem

(OM) 

Study Attrition (SA) Confounding Measur

(CM) 

Article Population Enrolled 

/Included 

in analysis 

Duration 

of follow 

up 

Presence of 

Diabetes 

Defined 

Site T-score Reference 

Standard

Covariates 

adjusted for 

Prognostic Factor 

Measurement (PFM) 

Analysis (A) 

SP: Yes OM: Yes 

SA: Yes CM: Yes 

Schwartz, 200556

American men with mean age of 73.8 years 

NR / 998 4 years History 

Blood work 

(FBG) 

(75gOGTT) 

Femur NR NA Age, Inactivity 

Low body weight Weight Loss Corticosteroid use Smoking Low calcium intake 

PFM: Yes A: Yes 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 22Table 5. Studies Assessing Spinal Cord Injury as a Risk Factor, Outcome Measure: BMD and/or Fracture OccurreSCI=Spinal Cord Injury, BMD=Bone Mass Density, NR=Not Reported, NA=Not applicable, OP=Osteoporosis

BMD Quality Measurem

Study Participation 

(SP) 

Mea

Study Attrition (SA) 

Me

Article Population Study 

Design 

Cases 

/Controls 

Included 

OR 

Sample 

Size 

Spinal Cord 

Injury Definition Site T-score Reference 

Standard

Fracture 

Occurrence 

Assessed 

Covariates 

adjusted for 

Prognostic Factor 

Measurement (PFM) 

SP: Partly 

NA 

Jones, 2002[#1083] 

SCI patients in New Zealand, mean age 32 years 

Case Control 

17 cases 17 controls 

Descriptive: 

Number of 

quadriplegic/para

plegic; incomplete 

v. complete 

Spine, Femur Radius, Finger Calcaneus Total body, arms, legs 

 <-2.5=OP Young 

Adult Mean 

Not assessed Age 

Low body weight Inactivity 

PFM: Partly 

SP: Partly 

NA 

Lazo, 2001[#1386] 

Veteran SCI patients associated with the Hines VA, median age 55 years 

Cross Sectional

45 American Spinal 

Injury Association 

Classification 

Femur NR Male X-ray 

Diary 

Age 

PFM: Yes 

SP: No 

NA 

Sabo, 2001[#1380] 

Caucasian SCI patients <50 years living in Germany ; mean age 32 

Cross 

Sectional

46 Frankel Score, 

Neuro Level 

Assessment 

Spine, Femur, Radius 

Z-score, 

NR 

Agerelated 

Reference 

 Not assessed 

PFM: Yes 

SP: Partly 

NA 

Demirel, 1998[#1382] 

SCI patients from the Istanbul Physical Medicine and Rehabilitation Centre; mean age 36 

Cross Sectional

32 American Spinal 

Injury Association 

criteria for level 

of injury 

Arms, Legs Z-score, 

NR 

Agematched 

Z-score 

Not assessed Age 

Low body weight High bone turnover rate 

PFM: Yes 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 23

Key Question #2: Are there any validated tools (outside of DXAdetermined central bone density) to screen for osteoporosis in men? 

CONCEPTUAL FRAMEWORK

The clinical diagnosis of osteoporosis in men can be made in two ways: through the 

occurrence of a fragility fracture or based on bone density criteria. Fragility fractures 

typically occur after a prolonged decrease in bone density and quality and are the hallmark of 

osteoporotic bone disease. In 1994, the World Health Organization defined osteoporosis as a 

bone mineral density of greater than 2.5 standard deviations (T-score, -2.5) below that of a 

young healthy population. While this definition was originally proposed for postmenopausal 

women, it has also been used to define osteoporosis in men. 

Use of the WHO-recommended threshold T-score of -2.5 has substantially simplified the 

clinical diagnosis of osteoporosis. Establishing a T-score threshold is useful and practical 

because substantial evidence suggests that each standard deviation decrement in bone density 

roughly doubles fracture risk. As such, bone density is an excellent tool for identifying those 

at high risk for future fracture. A simple causal pathway with bone density as the key 

determining factor for fracture risk (i.e., from normal bone density, to osteoporotic bone 

density, to fracture) is one way to conceptualize the progression of osteoporotic bone disease 

(Figure 2a). However, while bone density measurement is one of the best tools currently 

available to assess fracture risk, it is at best an imperfect predictor of future fracture. 

Recent evidence, particularly from the National Osteoporosis Risk Assessment (NORA), 

which evaluated bone density and fracture history in over 200,000 postmenopausal women, 

reveals that the majority of osteoporotic fractures actually occur in those with a bone density 

T-score greater than -2.5. This is principally due to the poor sensitivity of central bone 

densitometry (reported to be around 70%) in identifying those who fracture. Although those 

without “osteoporosis” by T-score have lower rates of fracture than those with osteoporosis 

by T-score, there are much greater numbers of people with T-scores in the former category. 

These findings suggest that an alternate model of osteoporosis disease progression, one 

which incorporates multiple risk factors, is necessary to fully understand osteoporosis and 

identify those who will ultimately fracture (Figure 2b). 

CONCEPTUAL FRAMEWORK FOR PROGRESSION OF OSTEOPOROSIS 

Figure 2a. Bone Mineral Density-Centric Simple Model 

Figure 2b. Multiple Risk Factor Model 

“Normal” 

Bone Density 

(T-score > -2.5) 

“Osteoporotic” 

Bone Density 

(T-score = -2.5) 

Osteoporotic 

Fragility Fracture 

Occurrence 

“Normal” 

Risk for 

Fracture 

Decrease in 

Bone 

Density

Decrease in 

Bone 

“Quality”

Worsened 

Balance 

and Gait

Other 

Factors? 

Osteoporotic 

Fragility Fracture 

Occurrence 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 24

In this context, screening is defined as performing a test to identify the condition in persons 

who are asymptomatic. An evaluation of a screening test requires its comparison to a “gold 

standard” method for identifying the condition. 

As there are two commonly used “gold standard” reference tests (i.e., bone mineral density 

and fracture occurrence) for the diagnosis of osteoporosis, studies evaluating osteoporosis 

screening tests can be broadly divided into two categories: 1) those that assess a test against a 

bone density measurement; and 2) those that assess a test against a fracture occurrence. As 

such, diagnostic studies that evaluate screening tests against both bone density and studies 

that evaluate screening tests against fracture occurrence are important for review and 

included in our analysis. 

As bone mineral density is often employed as a “gold standard” reference test, we do not 

specifically examine the test characteristics of central bone density (DXA) as a screening 

modality in this section. A recent cost-effectiveness analysis was presented in abstract form, 

at the American Society of Bone and Mineral Research60. This study used microsimulation 

Markov modeling to assess a policy of universal DXA screening in men combined with five 

years of bisphosphonate therapy for those men found to have osteoporosis (using the young 

female reference standard). For patients without a prior non-spine fracture, estimated costs 

per year of quality-adjusted life year varied from $248,000 to $143,000 to $78,000 to 

$30,000 by the age at which screening was done (65, 70, 75 and 80 years of age, 

respectively.) This indicates that universal screening with DXA is unlikely to be costeffective. An evaluation of DXA, and the values used to diagnose osteoporosis and the 

evidence regarding the relationship with osteoporotic fracture occurrence, is the topic of Key 

Question #3, found on page 37. 

The published literature suggests that male osteoporosis is a significantly underdiagnosed 

condition. While osteoporosis screening tools, such as quantitative ultrasound, have been 

assessed in women, little research has been performed on validating such screening tools in 

men. We reviewed the literature to identify studies that evaluated a screening osteoporosis 

index test against a reference test (i.e., bone density or fracture occurrence) in men. Our goal 

was to assess the test performance characteristics of tests in men and determine the validity 

of these tests for screening in male osteoporosis. 

DESCRIPTION OF EVIDENCE 

Our search of PubMed identified 27 potentially relevant studies (See Figure 1, page 9). 

Descriptive information about these studies is displayed in Evidence Table 1 (see Appendix 

B). Of the 27 studies, 4 identified a veteran population. Twenty-one of the studies did not 

report the characteristics of the population; four had an Asian population; one had a Filipino 

population; one was other. The male sample size ranged from 33 to 6,860. In ten of the 

articles the population was unselected; eight included an elderly population; six used 

referrals; and three recruited patients from a specific clinic. Seven studies evaluated 

ultrasound (index test) against central dual x-ray absorptiometry (DXA, reference test); five 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 25

studies evaluated osteoporosis screening questionnaires versus central DXA; and nine studies 

evaluated ultrasound versus fracture occurrence. 

QUALITY EVALUATION

Quality as assessed using the QUADAS instrument showed that almost all of the articles 

scored adequately on description of the selection criteria, the ability of the reference test to 

correctly classify the condition, the time period between the index test and the reference test, 

the sample receiving the reference test, the independence of the reference test, the description 

of the index test and the reference test, the generalizability to clinical practice, the reporting 

of uninterruptible test results. Conversely, almost no report indicated that interpretation of 

either the reference test or the index test was performed without knowledge (or “blind”) to 

the other test results. In 13 of 27 (48%), the representativeness of the enrolled population to a 

VA population was not clear. In almost half of studies (12 of 27), withdrawals from the 

study were either not explained or unclear, and in only half of studies (14 of 27) were 

patients selected representative of a population that might be eligible for screening in the VA. 

Thus, in this application, the QUADAS instrument had limited ability to distinguish between 

studies based on quality. 

In terms of total score, none of the studies met all of the QUADAS criteria. However, 24 out 

of the 27 articles (88%) scored positive on at least 60% or more of the criteria. In studies of 

the efficacy of treatments, validation studies of the criteria of Jadad and of the Delphi list 

both found empirical evidence that a threshold of 60% of the criteria being met distinguished 

better quality studies from lesser quality studies.61,62 Until such time as empirical studies 

with QUADAS are available, it seems reasonable to use the 60% threshold for classifying 

studies with QUADAS. Hence, most of the studies we evaluated were of good quality. 

SCREENING TEST GROUPINGS

We found substantial heterogeneity in the original authors’ use of thresholds both for the 

index test and reference test. Additionally, several studies did not provide key information, 

such as sample size by group. We reviewed available data and used clinical judgment to 

group studies into categories of comparisons for further quantitative analysis (Tables 6a-c). 

Using central DXA as the reference standard, we analyzed studies evaluating: ultrasound 

versus central DXA; and questionnaires versus central DXA. Using fracture occurrence as 

the reference standard, we reviewed studies evaluating ultrasound versus fracture 

occurrence. We did not pool data for other index and reference test combinations because of 

the heterogeneous nature of the data. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 26Table 6a. Study Test: Ultrasound vs. Reference Test: cDXA detailed comparison

Sens=Sensitivity, Spec=Specificity, LS=Lumbar Spine, FN=Femoral Neck, TH=Total Hip, PF=Proximal Femur, SI=Stiffness Index, BUA=Broad-band ultrasound attenuation, SOS=Speed of sound, BMD=Bone MIndex, US=Quantitative Ultrasound 

STUDIES INCLUDED IN ANALYSIS

Study Test: Ultrasound Reference Test: cDXA Data Pooling 

Variance 

Article Population Machine Location 

Measurement Units Machine Location Units Sens Spec Sens Spec Osteoporosis 

Total hip DXA T-sco

<-2.5 vs >=-2.5 

Femoral neck BMD 

score <=-2.5 vs >-2

Gudmundsdottir, 200520

Unselected Lunar 

Achilles+ 

Calcaneus L 

SI T Score Hologic 

QDR 4500 

LS, FN, TH 

T Score X X 

Central DXA T-sco

 <-1.5 vs >=-1.5 

Kung, 200563

Elderly Hologic 

Sahara 

Calcaneus R 

QUI(SI?) 

T Score Hologic 

QDR 2000+ 

LS, F T Score X X X X Femoral Neck BMD 

T-score <=-2.5 vs >-

Adler, 2003a 19

Referral Hologic 

Sahara 

Calcaneus QUI 

(SI?) 

T Score Hologic 

QDR 4500 

LS, FN, TH 

T Score X X X X 

T-score <=-2.0 vs >-

BMD (FN, LS, TH

<-2.5 vs >=-2.5 

SI T-score 

<-2.5 vs >=-2.5 

BMD (FN, LS, TH

<-1.0 vs >=-1.0 

Mulleman, 2002 64

Referral Lunar 

Achilles 

Calcaneus BUA, 

SOS & SI 

T Score Hologic 

QDR 2000 

LS, PF T Score X X 

SI T-score 

<-1.0 vs >=-1.0 

Central DXA T-sco

 <-1.5 vs >=-1.5 

Central DXA T-sco

<-2.0 vs >=-2.0

Adler, 200127

Referral Hologic 

Sahara 

Calcaneus QUI

(SI?) 

T Score Hologic 

1000-W 

LS, FN, TH 

T Score X X X X 

Central DXA T-sco

<-2.5 vs >=-2.5

STUDIES NOT INCLUDED IN ANALYSIS (no data on sensitivity/specificity) 

Lynn, 200565 Elderly Hologic 

Sahara 

Calcaneus R 

QUI (SI?) Unitless Hologic QDR 4500 W LS, PF T Score 

Grampp, 200166

Unselected Lunar 

Achilles 

Calcaneus SI T Score Hologic QDR 

4500 

LS, FN T Score 

Montagnani, 200167

NR DBM Sonic Phalanx UBPI, QUS Unitless Hologic QDR 4500 LS, FN, TH T Score 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 27

Table 6b. Study Test: Questionnaire vs. Reference Test: cDXA detailed comparison 

Sens=Sensitivity, Spec=Specificity, LS=Lumbar Spine, FN=Femoral Neck, TH=Total Hip, PF=Proximal Femur, BMD=Bone Mass Density 

STUDIES INCLUDED IN ANALYSIS 

Study Test: Questionnaire Reference Test: cDXA Data P

Variance 

Article Population Name Key Inputs Units Machine Location Units Sens Spec Sens Spec 

Kung, 200563 Elderly 

Clin Risk Assess Tool Age, Weight 

Score -11-10 Hologic QDR 2000 + LS, F T Score 

X X Femo

score 

Li-Yu, 200515 Referral 

Osteoporosis Screening Tool for Asians (OSTA) Age, Weight 

Lo, Med, Hi Risk GE Lunar DPX-IQ FN T Score 

X X X X BMD 

Lynn, 200565 Elderly 

Male Osteoporosis Screening Tool (MOST) Weight, QUI*

Score 0 - 8 

Hologic QDR 4500 W LS, PF T Score 

X X 

Lumba

Fem

 <

Adler, 2003b35 Referral 

Osteoporosis Screening Tool (OST ) Age, Weight 

Cutoff 3,2,1 Hologic QDR 4500 

LS, FN, TH T Score 

X X X X D

<

STUDIES NOT INCLUDED IN ANALYSIS (no data on sensitivity/specificity)

Adler, 2003a19 Referral Questionnaire 

Weight, Heel BMD, steroids, race 

Score 0 -14 Hologic QDR 4500 

LS, FN, TH T Score 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 28

Table 6c. Study Test: Ultrasound vs. Reference Test: Fracture Occurrence detailed comparison 

Sens=Sensitivity, Spec=Specificity, LS=Lumbar Spine, FN=Femoral Neck, TH=Total Hip, PF=Proximal Femur, BMD=Bone Mass Density 

Study Test: Ultrasound Referen

Article Population Machine Location Measurement Units 

Gonnelli, 200568 Referral Lunar Achilles + Calcaneus SI percent Fragility Fractures: verteVarenna, 200569 Other Lunar Achilles Calcaneus SI, BUA, SOS unitless, db/Mhz, m/s Low energy fractures sincRothenberg, 200470 Other Hologic Sahara Calcaneus Estimated BMD gm/cm2, T score Self reported fractures, foWelch, 200471 Other McCue CUBA Calcaneus BUA db/MHz Self reported vertebral, hiMulleman, 200264 Referral Lunar Achilles Calcaneus nondom SI T Score 

Vertebral, other; low traudecrease in vertebral heig

Donaldson, 199972 Elderly Walker Sonix 1001 Calcaneus BUA db/MHz Any since 50, By recall; mStewart, 199573 Other Walker Sonix UBA 575 Calcaneus BUA db/MHz Patients with vertebral fraTravers-Gustafson,. 199574 Elderly Osteo-Technology Signet Patella AVU m/sec Fractures since age 40, exBauer200475 Elderly Hologic Sahara Calcaneus BUA db/MHz Hip and non-spine fractur
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 29

CENTRAL DXA AS REFERENCE TEST

Ultimately, we were able to pool only studies evaluating calcaneal ultrasound versus central 

DXA and those evaluating Osteoporosis Self-Assessment Tool (OST) versus central DXA 

(Table 6a-b). There were studies comparing ultrasound to cDXA that we could not include 

in our pooled analysis because they lacked data to calculate the sensitivity and specificity.65-

67 Details of these analyses are presented below and in graphical format, along with a pooled 

ROC curve from a recently published meta-analysis of the utility of calcaneal ultrasound 

versus central DXA in women,76 in the following series of figures (Figures 3a-d, 4, 5). 

Calcaneal Ultrasound versus Central DXA 

Calcaneal ultrasound, in which an ultrasound probe is placed on either heel, has the 

advantages of being portable, inexpensive, and radiation-free. Ultrasound measurements are 

often reported as T-scores (standardized units) of the quantitative ultrasound index (QUI). 

However, there is no commonly accepted threshold for a positive QUI reading, and our 

review showed that thresholds from 0 to -2.5 have been used. 

Given this heterogeneity in thresholds, we were able to incorporate data from only 3 studies 

for our summary sensitivity and specificity measurements.19,27,63 We found that using a 

calcaneal ultrasound T-score of -1.0, calcaneal ultrasound had a sensitivity of 75% and a 

specificity of 66% to diagnose bone density-determined osteoporosis (central DXA T-score 

of < -2.5) (Figure 3a). When the calcaneal ultrasound threshold was decreased to -1.5, 

specificity improved to 78% but sensitivity dropped to 47%. We were able to construct a 

ROC curve from one study evaluating male veterans27 (Figure 3b), which varied calcaneal 

ultrasound thresholds from -1.5 to -2.5. Superimposing these ROC curves onto a recently 

reported ROC curve of calcaneal ultrasound in primarily women (Figure 3c) showed these 

curves to be similar, suggesting that calcaneal ultrasound likely performs comparably in men 

as in women (Figure 3d). 

The Osteoporosis Self-Assessment Tool (OST) versus Central DXA 

The Osteoporosis Self-Assessment Tool, which uses a subject’s age and weight to develop a 

risk score (equation: [(weight in kilograms – age in years) x 0.2], truncated to an integer), is 

a simple test which has been primarily evaluated and validated in women. More recently, a 

number of evaluations have been performed in men, with particular attention to the veteran 

population.35 Similarly to calcaneal ultrasound, there is no commonly accepted OST risk 

score threshold. Our review showed that thresholds from -1 to 3 have been used (Table 6b). 

Pooling data from two studies of evaluations of Asian men (Chinese and Filipino), we found 

that at an OST risk score of -1, the OST had a sensitivity of 81% and specificity of 68% to 

diagnose bone density-determined osteoporosis. In the only study of OST in Veterans 

(Figure 4), the authors found that at an OST threshold of 3, the OST had a sensitivity of 93% 

and specificity of 66%. Sensitivity decreased to 75% and specificity increased to 80% when 

the OST threshold was decreased to 1. Of note, at all thresholds evaluated, the OST had 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 30

higher sensitivity and specificity than calcaneal ultrasound, although this analysis is limited 

by the paucity of data points available and therefore no definitive conclusions can be drawn. 

Summary Figure 5 graphs all results from all articles with relevant data, and the metaanalytic result for the ROC curve in primarily women76 (data in red). The figure shows that 

all studies assessing ultrasound reported results that are close to the pooled ROC curve for 

primarily women. The studies assessing OST reported results above the pooled ROC curve, 

suggesting OST may be more accurate than ultrasound. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 31

0 0.1 0.2 0.3 0.4 0.5 0.6 

0

0.10.20.30.40.50.60.70.80.9

1

1 - Sp

Sensitivity

AH

AH

AH

Figure 3b. ROC Curve Comparing Quantitat

cDXA Using Three Different T-

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0

0.10.20.30.40.50.60.70.80.9

1

1 - Specificity

Sensitivity

Figure 3c. ROC Curve Comparing Quantative Ultrasound

to cDXA from Meta-Analysis of Nayak (2006)

Nayak et al. (2006)

0 0.1 0.2 0.3 0.4 0.5 0.6 

0

0.10.20.30.40.50.60.70.80.9

1

1 - Sp

Sensitivity

Figure 3d. ROC Curves Comparing Quantita

to cDXA: A Comparison of Figure

NaAdHeAdHeAdHeKu& BMAd& DXAd& ADX

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0

0.10.20.30.40.50.60.70.80.9

1

1 - Specificity

Sensitivity

Figure 3a. Sensitivity versus 1-Specificity:

Pooled Results of Heel Ultrasound or OSTA Compared to cDXA

Kung et al. (2005)& Li-Yu et al. (2005)BMD T=-2.5, OSTA = -1

Adler et al. (2001)& Kung et al. (2005)DXA T =-2.5, Heel T=-1.0

Adler et al.. (2001)& Adler et al. (2003a)DXA T=-2.0, Heel T=-1.5
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 32

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0

0.10.20.30.40.50.60.70.80.9

1

1 - Specificity

Sensitivity

Adler et al. (2003b)BMD T=-2.0

Adler et al. (2003b)BMD T=-2.5

Figure 4. ROC Curve Comparing OST to cDXA

using Two Different T-Scores
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 33

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0

0.10.20.30.40.50.60.70.80.9

1

1 - Specificity

Sensitivity

Nayak et al. (2006)

Adler et al. (2001), Heel T=-1.5

Adler et al. (2001), Heel T=-2.0Adler et al. (2001), Heel T=-2.5

Adler et al. (2003b), BMD T=-2.0Adler et al. (2003b), BMD T=-2.5

Kung et al. (2005) & Li-Yu et al. (20OSTA = -1

Adler et al. (2001) & Kung et al. (200Heel T=-1.0

Adler et al. (2001) & Adler et al. (200Heel T=-1.5

Lynn et al. (2005)

Figure 5. ROC Curves and Individual Study Sensitivity versus 1-Specificity

(All Studies)

Mullemen et al. (2002)
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 34

FRACTURE OCCURRENCE AS REFERENCE TEST

Eighteen studies used fractures occurrence as the reference test, with: ten evaluating 

ultrasound as the index test; two evaluating quantitative CT, and one each evaluating 

peripheral bone density, central bone density, x-ray, bone structural parameters, linear photon 

absorptiometry, and a multivariate scoring model (Table 6c). However, we could not pool 

data from these studies given the heterogeneity of the data although we provide a qualitative 

assessment of studies evaluating ultrasound against fracture occurrence below. We 

narratively summarized the nine studies that assessed ultrasound to occurrence of fragility 

fractures.64,68-75

Calcaneal Ultrasound versus Fracture Occurrence 

Calcaneal ultrasound appears to be independently associated with and moderately predictive 

of fragility fracture in men. One study found that each standard deviation reduction in 

ultrasound measurement resulted in an approximate two-fold increase in hip fractures that 

was independent of age and other clinical variables and comparable to findings in elderly 

women.69 Similarly, an abstract published from the ongoing and pivotal MrOS Study, a 

population-based study of older men, found that each SD reduction in calcaneal ultrasound 

measurement was associated with an increased risk of hip (relative hazard, 2.0, 1.3-3.5) and 

non-spine fracture (relative hazard, 1.7, 1.4-2.0).75 Finally, another study found that 

ultrasound stiffness parameters had a strong association (odds ratio 3.2, 2.3-4.5) with prior 

fragility fracture.68 

More controversial is whether the combination of bone density measurements and calcaneal 

ultrasound to assess for fractures is better than either test alone. One study found that both 

bone mineral density of the hip (odds ratio, 3.4) and ultrasound (odds ratio, 3.2) were 

strongly associated with fragility fracture.68 If bone density and ultrasound results were 

combined, the odds ratio for fracture association increased to 6.1. However, an analysis of 

ROC curves for hip fracture prediction from the MrOS study for: ultrasound alone (AUC, 

0.84); bone mineral density alone (AUC, 0.85); and the combination of the two (AUC 0.85) 

suggested that the combining ultrasound and bone mineral density was not superior to using 

either modality alone.75 As such, it remains unclear as to whether an optimal male 

osteoporosis screening program should include bone density, ultrasound, or a combination of 

these two or other test modalities. 

CONCLUSIONS

Although the limited number of studies published on male osteoporosis screening tools 

precludes drawing definitive conclusions on these tests, our review suggests the following: 

1) There is no evidence to suggest that calcaneal ultrasound performs differently in men 

than in women. Our pooled data points and the ROC curve we constructed to evaluate 

calcaneal ultrasound against a reference standard of bone density appeared comparable to a 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 35

recently published ROC curve on calcaneal ultrasound that included studies primarily 

evaluating women. In addition, we found evidence that calcaneal ultrasound measurements 

were predictive of or associated with fractures in men at similar levels as those published for 

women. As such, we find no evidence indicating that calcaneal ultrasound should perform 

any differently in men as it does in women. The available data fall short of proof, but 

suggest that calcaneal ultrasound performs comparably in men as in women. (GRADE 

quality of evidence = Moderate; further research is likely to have an important impact on our 

confidence in the estimate of effect and may change the estimate.) 

2) The OST appears to have comparable (and possibly better) test characteristics than 

calcaneal ultrasound in diagnosing DXA-determined osteoporosis. The OST, a 

questionnaire which incorporates only age and weight, appears to perform as well or better 

than ultrasound in predicting DXA-determined osteoporosis. Supporting this conclusion, one 

of the studies identified assessed Veterans, and found test characteristics similar to our 

pooled analysis. This simple tool appears promising and could potentially be easily 

incorporated into a mass osteoporosis screening program. However, caution must be 

exercised as two of the three studies we quantitatively analyzed enrolled exclusively men 

from Asia. In addition, all of these studies evaluated the OST against DXA, and not against 

fracture occurrence, which is the critical outcome of interest. Our results suggest that more 

evaluation of this test is urgently warranted and necessary. (GRADE quality of evidence = 

Low; further research is very likely to have an important impact on our confidence in the 

estimate of effect and is likely to change the estimate.) 

3) Although calcaneal ultrasound does not appear to be a particularly good test at 

diagnosing DXA-determined osteoporosis, it is a strong, independent predictor of fractures 

in men. Although ultrasound may not perform exceptionally well at predicting a particular 

bone mineral density score, it appears to perform well in identifying a population of patients 

who will fracture, the endpoint that clinicians and patients ultimately care about. Both bone 

density and ultrasound can identify populations who will fracture, although these populations 

do not appear to fully overlap. Ultrasound may be identifying deficits in other bone 

parameters, such as bone quality, which may not be identified through bone density 

measurement. However, as almost all clinical trials of osteoporosis drugs recruited patients 

based on a bone density score and not an ultrasound score, it remains to be determined if 

those identified at risk for fracture by ultrasound will benefit from our current osteoporosis 

drug armamentarium. This finding is likely to be true for all patients identified to be “at risk” 

through the screening modalities (e.g., osteoporosis screening questionnaires) evaluated in 

this review, as it is not clear that current pharmacologic interventions decrease fracture risk 

in such populations given the lack of clinical trial evaluation in these specific groups. 

(GRADE quality of evidence = Moderate; further research is likely to have an important 

impact on our confidence in the estimate of effect and may change the estimate.) 

4) Limited data are available on other screening modalities and there is a large gap in our 

understanding of osteoporosis screening tests in men. Our comprehensive review identified 

only 26 studies in total evaluating osteoporosis screening tests in men. We were only able to 

perform limited quantitative analyses on two screening tests: calcaneal ultrasound and the 

OST. It remains unclear if other screening tests, such as quantitative CT, other types of 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 36

questionnaires, or peripheral bone density measurements, might also be useful as screening 

tests in men. As such, there is a large, and currently unmet, need for additional research in 

this field of study. 

5) A majority of the studies compared a screening test against DXA and not fracture 

occurrence. Most of the studies we identified evaluated a screening test against the gold 

standard of central DXA rather than fracture occurrence. The relevant clinical outcome is 

fracture occurrence, and studies assessing their relationship are needed. In order to interpret 

the clinical utility of such studies, though, evidence is needed about the effectiveness of 

therapies to prevent fracture occurrence in men identified as high risk based on calcaneal 

ultrasound, or OST, etc. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 37

Key Question 3: What values of BMD determined by DXA (and by 

different DXA techniques) have been used to diagnose osteopenia and 

osteoporosis; and what is the evidence regarding the relationship between 

differing definitions and the development of osteoporotic fractures? 

Our review identified 31 articles evaluating the association between BMD as measured by DXA 

and the risk of fractures in men. Most of these articles indicated that BMD is a strong predictor 

of fracture risk in men and femoral neck BMD is a stronger predictor than lumbar spine BMD. 

Almost all studies assessed BMD as a standardized measure (in terms of T-score or Z-score) and 

not in terms of grams of bone mineral content per centimeter squared. 

Risk of fracture per standard deviation decrease in BMD varied by study. One large metaanalysis of 12 cohort studies77 found that the gradient of risk for an osteoporotic fracture per 

standard deviation decrease in z-score in men (“gradient of risk” = RR/SD) was 1.6 and the 

gradient of risk for a hip fracture per standard deviation decrease in z-score in men was 2.42. 

Another large prospective cohort study78 found a 3.2 time increased risk of hip fracture per sexspecific SD decrease in total hip BMD. 

Virtually all studies evaluating the relationship between BMD and osteoporosis in men defined 

osteoporosis as a BMD more than 2.5 standard deviations below the mean for young adults (“Tscore”). However, whether to use a young female or a young male reference range when 

evaluating BMD in men is an area of controversy that is not possible to resolve with existing 

data. In a summary statement from the International Conference on Osteoporosis in Men in 

2002, international experts “agreed to disagree” on this issue, each marshalling data to support 

their own position. 

In an article from this conference, a summary of the evidence favoring use of the female 

reference range was presented. Proponents of this cite studies that have demonstrated that 

measurement of BMD at the hip expressed as a T-score using the female reference standard 

predicts fracture risk similarly in men and women. By far the largest study identified was a 

meta-analysis of 12 cohort studies that collectively included 9891 men, 29082 women and 

168,366 person years.77 The "gradient of risk" (RR/SD) for each SD decrease in BMD using sex 

and age-specific standard deviations (Z-scores) was virtually identical in men and women; and, 

was not significantly different from the "gradient of risk" using the standard deviation of a young 

female reference range (T-scores). For instance, in men the gradient of risk for osteoporotic 

fractures was 1.6 using a sex and age-specific reference range and was 1.55 using a young 

female reference range. In women, the gradient of risk for osteoporotic fractures was 1.53 using 

a sex and age-specific reference range and 1.56 using a young female reference range. Currently, 

this is the primary evidence behind the argument that the reference range used in men and 

women should be the same, and should be the female range. The study shows not only that 

gradient of risk is the same but also that the absolute risk is the same in men and women using 

the female range. 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 38

Additionally, some studies have demonstrated that men and women at the same age with the 

same absolute BMD at the hip have an equal likelihood of hip fracture.79 Thus, these experts 

argue that osteoporosis in men should be defined as it is in women, using T-scores derived from 

a young healthy female reference population. 

Critics of this conclusion, raise several concerns. First, they argue that, despite the large numbers 

of patients included in this pooled analysis, the data are imprecise because different populations 

are mixed together. Important heterogeneity in effect may be obscured. Second, these critics 

point to a large prospective study demonstrating a much stronger relationship in men than in 

women between hip BMD & subsequent fracture78 as evidence that there are important gender 

differences to be discovered and dealt with. Furthermore, they point out that using a young 

female reference range underestimates the expected prevalence of osteoporosis in men. In one 

study by Melton80 evaluating the association of BMD with hip fracture risk, the prevalence of 

osteoporosis in men using a young healthy male reference range was 19.4% versus only 3.4% 

using a young healthy female reference range. In another study by Falkner,81 prevalence 

estimates for osteoporosis in men differed depending on which reference range was utilized. 

This study also raised the question as to whether using the standard definition of osteoporosis 

(more than 2.5 standard deviations below the mean) is appropriate in men since the T-scores that 

best corresponded to the lifetime risk for osteoporotic fracture in men were significantly different 

from -2.5 (-1.9 using young male reference ranges and -1.5 using young female reference 

ranges). Thus, there is evidence that using female-specific reference ranges may significantly 

under detect osteoporosis in men and result in fewer men being identified who may, in fact, be at 

risk for osteoporotic fracture and might benefit from treatment. 

Proponents of the female standard respond to these arguments by highlighting the fact that there 

are few data relating use of the male reference range and the 5- or 10-year risk of fracture. 

Whether to utilize gender-specific reference ranges to determine T-scores when screening for 

osteoporosis remains an area of uncertainty and awaits further prospective studies evaluating the 

association of fracture and BMD. But a principle of screening is that it should be performed only 

when there is an effective health care strategy for early treatment.82 Therefore, when deciding 

which reference range to choose given current limited information, it is helpful to evaluate how 

subjects were identified as candidates for osteoporosis therapies in randomized controlled trials 

that have demonstrated a benefit in reducing risk of osteoporotic fractures. In other words, a 

screening program to identify Veterans with osteoporosis would be rooted in current evidence 

when it identifies persons who are most similar to the subjects enrolled in the RCTs that we rely 

on to guide treatment. Table 7 presents information from all of the RCTs identified in an 

ongoing systematic review of therapies for osteoporosis (Comparative Effectiveness Review of 

Pharmacologic Therapies for Low Bone Density, Southern California Evidence Based Practice 

Center Draft Report) that reported data specific to men, using as outcome either fractures or any 

of several intermediate outcomes. Many of these studies used the existing presence of 

osteoporotic fractures as an entry criterion, and in that case the concept of “screening” does not 

apply. But in those studies that used BMD as measured by DXA as the entry criterion for low 

bone density, all used T-scores using the young male reference standard. Therefore, this is 

evidence that men identified with low bone density/osteoporosis using the young male reference 
HSR&D Evidence Synthesis Pilot Program – 

Screening Men for Osteoporosis: Who & How 39

standard (which is a larger percentage of the potentially osteoporotic population than would be 

identified using the young female standard, as discussed previously) will benefit from treatment. 

This does not account for the potential for heterogeneity in treatment effects.27,66 In some RCTs, 

it has been shown that studies reporting a benefit in the enrolled population actually provided 

large benefit to only a portion of that population – usually the most severely affected – while 

providing no benefit or actually harming other enrolled patients, although the net “overall” result 

was still positive. Whether there is heterogeneity in treatment effects in the RCTs of treatment 

for men with low bone density is not known. However, until more definitive evidence is 

available, we believe it is most logically consistent for VA to identify men who might benefit 

from treatment for osteoporosis by adhering to the same conditions as were used in RCTs of 

osteoporosis treatment; namely, the young male reference standard. (GRADE quality of evidence 

= Low; further research is very likely to have an important impact on our confidence in the 

estimate of effect and is likely to change the estimate.) 
BMD=Bone mass density 40 

Table 7. Entry Criteria of Trials Reporting Efficacy of Osteoporosis Treatment in Men. 

Studies that Use Fracture Reduction as Outcome 

Study DXA Site T-score Reference 

Includes Fragility 

Fracture Treatment Assess

Lumbar Spine <=-2.5 male with or without risedronate 

Ringe 200683 Femoral Neck <=-2.0 male with or without risedronate Kaufman, 200584

Lumbar Spine or Proximal Femur <=-2.0 male no teriparatide 

Ringe, 200485

& Ringe, 200186 Lumbar Spine <-2.5 male no alendronate 

Orwoll, 200354

Proximal Femur or Lumbar Spine <-2.0 male no teriparatide 

Femoral neck and Lumbar Spine 

<=-2.0 FM & <=-1.0 LS male no alendronate 

Orwoll, 200087 Femoral neck <=-1.0 male no alendronate Studies that Use Other Outcomes 

 DXA Site T-score Reference 

Includes Fragility 

Fracture 

Treatment 

Assessed O

Shimon, 200588

Lumbar Spine or Femoral Neck <=-2.0 male 

not inclusion criteria but reported in Table1 alendronate 

BMD lumbfemoral nec

Kurland, 200089

Lumbar Spine or Femoral Neck <=-2.5 male 

not inclusion criteria but reported 

parathyroid hormone 

BMD lumbfemoral nec

Toth, 200557

Lumbar Spine or Femoral Neck <-2.5 

gender specific no 

intranasal salmon calcitonin therapy 

BMD lumbfemoral nec

Femoral Neck and Lumbar Spine 

<-2.0 FM & <-1.0 LS male no alendronate 

Drake, 200390 Femoral Neck <-1.0 male yes alendronate 

BMD lumbspine 

Laroche, 199891 Lumbar Spine <-2.5 

lumbar spine BMD and/or fractures 

fluoride, etidronate, calcitron BMD 

Trovas, 200292

Lumbar Spine or Femoral Neck <-2.5 male no 

nasal spray salmon calcitonin BMD spine 

Gonnelli, 200393

Lumbar Spine or Femoral Neck <=-2.5 male 

not inclusion criteria, but reported alendronate 

BMD lumbneck, total 
41 

SUMMARY AND DISCUSSION 

In this chapter, we describe the limitations of our review and meta-analysis and then present our 

conclusions. We also discuss the implications of our findings for future research. 

Limitations 

PUBLICATION BIAS

Our literature search procedures were extensive and included canvassing experts from academia 

regarding studies we may have missed. It was not possible to conduct formal tests for publication 

bias, but even with such tests it is not possible to exclude the possibility that such bias exists. 

Therefore, readers are cautioned about this possibility. 

STUDY QUALITY 

An important limitation common to systematic reviews is the quality of the original studies. 

Recent attempts to define elements of study design and execution that are related to bias have 

shown that in many cases, such efforts are not reproducible and do not distinguish study results 

based on bias. Therefore, the current approach is to avoid rejecting studies or using quality 

criteria to adjust the meta-analysis results. We did use the QUADAS criteria and those 

suggested by Hayden and colleagues as a descriptive measure of quality. As there is a lack of 

empirical evidence regarding study characteristics and their relationship to bias, we did not 

attempt to use other criteria. Other aspects of the design and execution of a trial may be related to 

bias, but we do not yet have good measures of these elements. Because of the small number of 

studies found, it was not possible to do sensitivity analyses based on study quality. 

HETEROGENEITY 

In our meta-analysis, it was not possible to calculate a test of heterogeneity. Clearly, the 

populations being assessed were different, and there were also important differences in how 

some key variables were measured, which diagnostic tests were used, and which reference 

standard for classifying osteoporosis was used, among others. This heterogeneity further limits 

our ability to draw strong conclusions. 

APPLICABILITY OF FINDINGS 

Green & Glasgow94 provide a framework for evaluating the relevance, generalization, and 

applicability of research. Their framework includes assessing the participation rate, the intended 

target population, the representativeness of the setting, the representativeness of the individuals, 

and evaluating information about implementation and assessment of outcomes. As these data are 

rarely reported in the studies we reviewed, conclusions about applicability are necessarily weak. 
42 

Conclusions 

With the above limitations in mind, we reached the conclusions displayed below. 

KEY QUESTION #1: What are the prevalence of and risk factors for osteopenia, 

osteoporosis and osteoporotic fractures among men in general and among male Veterans 

specifically? 

Prevalence 

 There are no VA specific data on prevalence of osteopenia and osteoporosis in men. 

 Applying NHANES III estimates of prevalence to veteran-specific enrollee data we estimate 

the prevalence of osteoporosis in male veterans of 200,000 – 400,000; and of osteopenia in 

male veterans of 2-3 million. 

Risk Factors 

 We found a high quality meta analysis, and a limited number of articles specific to the risk 

factors alcohol use, diabetes mellitus type II and spinal cord injury. Based on these 

findings, our review suggests the following. 

 Strong predictors of an increased risk of osteoporosis in men include age, low body weight, 

physical inactivity, and weight loss. (GRADE quality of evidence = High; further research 

is very unlikely to change our confidence on the estimate of effect.) 

 Certain health conditions and medications also are strong or moderate predictors of an 

increased risk of osteoporosis in men. The most relevant to VA are prolonged systemic 

corticosteroid therapy and androgen deprivation (in the context of prostate cancer 

treatment). (GRADE quality of evidence = Moderate; further research is likely to have an 

important impact on our confidence in the estimate of effect and may change the estimate.) 

 Alcohol use is probably associated with an increase in osteoporotic fractures, but is not 

clearly associated with an increase in osteoporosis as measured by BMD. (GRADE quality 

of evidence: Fractures = Moderate; further research is likely to have an important impact 

on our confidence in the estimate of effect and may change the estimate; BMD = Very 

Low; any estimate of effect is very uncertain.) 

 There is no evidence that diabetes mellitus type II is a significant risk factor for osteoporosis 

in men. (GRADE quality of evidence: Low; further research is very likely to have an 

important impact on our confidence in the estimate of effect and is likely to change the 

estimate.) 

 Spinal cord injury is associated with an increase risk of osteoporosis and possibly 

osteoporotic fractures. (GRADE quality of evidence: BMD= Moderate; further research is 

likely to have an important impact on our confidence in the estimate of effect and may 

change the estimate; BMD = Very Low; any estimate of effect is very uncertain; Fractures= 
43 

Low; further research is very likely to have an important impact on our confidence in the 

estimate of effect and is likely to change the estimate.) 

KEY QUESTION #2: Are there any validated tools to screen for osteoporosis in men? 

 The evidence for screening tools for men is much more limited than for women. We were 

only able to synthesize evidence on two screening tools: calcaneal ultrasound and the 

Osteoporosis Screening Tool (OST). 

 There is no evidence to suggest that calcaneal ultrasound performs differently in men than in 

women. (GRADE quality of evidence = Moderate; further research is likely to have an 

important impact on our confidence in the estimate of effect and may change the estimate.) 

 The OST appears to have comparable (and possibly better) test characteristics than calcaneal 

ultrasound in diagnosing DXA-determined osteoporosis. (GRADE quality of evidence = 

Low; further research is very likely to have an important impact on our confidence in the 

estimate of effect and is likely to change the estimate.) 

 Although calcaneal ultrasound does not appear to be a particularly good test at diagnosing 

DXA-determined osteoporosis, it is a strong, independent predictor of fractures in men. 

(GRADE quality of evidence = Moderate; further research is likely to have an important 

impact on our confidence in the estimate of effect and may change the estimate.) 

 Limited data are available on other screening modalities and there is a large gap in our 

understanding of osteoporosis screening tests in men. 

KEY QUESTION #3: What values of BMD determined by DXA (and by different DXA 

techniques) have been used to diagnose osteopenia and osteoporosis; and what is the 

evidence regarding the relationship between differing definitions and the development of 

osteoporotic fractures? 

 The values of BMD determined by DXA that have been used are based on standard 

deviations (T-score) away from a reference standard, either young female or young male. 

 Whether to use a young female or a young male reference range in order to identify men as 

“at risk” for osteoporotic fractures is an area of controversy that is not possible to resolve 

with existing data. 

 Until more definitive evidence is available, we believe it is most logically consistent for VA 

to identify men who might benefit from treatment for osteoporosis by adhering to the same 

conditions as were used in the RCTs of osteoporosis treatment; namely, the young male 

reference standard. (GRADE quality of evidence = Low; further research is very likely to 

have an important impact on our confidence in the estimate of effect and is likely to change 

the estimate.) 
44 

FUTURE RESEARCH 

Our review suggests that additional and extensive research is urgently needed to better 

understand the risk factors, prevalence, and application of screening tests for male osteoporosis. 

While osteoporosis has been extensively evaluated in women, comparably little work has been 

done in men. As the largest integrated health care system in the U.S., serving a population that is 

more than 95% male and 80% over the age of 50, these issues are of particular concern and 

importance to the VA. 

In particular, we have identified three areas of future research in male osteoporosis that we 

believe to be of critical importance to the VA: 

1. Determine the scope of the problem within the veteran population. We did not find any 

veteran-specific data on the prevalence of osteoporosis or osteopenia in male veterans. Applying 

our own calculations based on NHANES III data, we estimate up to 400,000 veterans may have 

osteoporosis and 3 million may have osteopenia. However, as the NHANES cohort was a 

relatively healthy sample of the U.S. population, and as Veterans tend on average to have more 

comorbidity than non-Veterans, our calculations may underestimate the prevalence of 

osteoporotic disease in Veterans. Research that attempts to quantify the number of the Veterans 

at risk for osteoporotic disease, such as those that evaluate a representative veteran population, 

will help the VA better understand the burden of current and future osteoporotic disease. Crosssectional studies of association will be helpful to better define which Veterans are most likely to 

have osteoporosis. 

2. Further elucidate the test characteristics of promising screening tests. Based on limited 

evidence, we find the OST to be a promising screening test that could potentially be widely 

employed for male osteoporosis screening. An advantage to the OST is that is can be easily 

applied with existing data and could require minimal effort to program a CPRS clinical reminder 

using age and weight, which could trigger a patient specific request for a DXA scan. However, 

only three studies that evaluated the OST, of which only one in our analysis assessed a Veteran 

population. Additional research effort should be focused on testing the sensitivity, specificity, 

and positive predictive value of the OST in Veterans. 

3. Determine the optimal screening regimen for male osteoporosis in Veterans. Ultimately, the 

goal of a male osteoporosis screening program will be to determine and implement a sensitive 

yet cost-effective screening strategy. Future clinical research efforts should focus on evaluating 

and comparing different screening strategies. In addition, computer modeling, including costeffectiveness analysis, should be used to aid decision-making on optimal resource allocation. 

Avaliable evidence suggests that universal screening with cDXA based on age is unlikely to be 

cost-effective: strategies of targeted screening with cDXA based on other risk factors have not 

been evaluated. 
45 

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 98. Melton LJ 3rd, Beck TJ, Amin S, Khosla S, Achenbach SJ, Oberg AL, et al. 

Contributions of bone density and structure to fracture risk assessment in men and 

women. Osteoporos Int 2005; 16:460-7. 

 99. Odvina CV, Wergedal JE, Libanati CR, Schulz EE, Baylink DJ. Relationship between 

trabecular vertebral body density and fractures: a quantitative definition of spinal 

osteoporosis. Metabolism 1988; 37:221-8. 

 100. Robinson B, Wagstaffe C, Roche J, Clifton-Bligh P, Posen S. Is there a place for forearm 

osteodensitometry in clinical screening studies? Med J Aust 1987; 146:297-300. 

 101. Shin MH, Kweon SS, Park KS, Heo H, Kim SJ, Nam HS, et al. Quantitative ultrasound 

of the calcaneus in a Korean population: reference data and relationship to bone 

mineral density determined by peripheral dual X-ray absorptiometry. J Korean 

Med Sci 2005; 20:1011-6. 
53 

Appendix A. Data Collection Forms 
54 

VA-EPC Male/OP Project Screener 

Reviewers: 

Article ID Assigned on: 

Citation: 

Reviewer: ___________________________ 

First Author:_________________________ 

1. Does the article report original data on the 

prevalence or incidence of any of the following in 

men? 

 (Check all that apply) 

Osteopenia .................................................... 

Osteoporosis.................................................. 

Fractures ....................................................... 

None of the above ......................................... 

2. Does the article report original data on risk factors 

for osteopenia, osteoporosis, or fractures in men? 

 (Circle one) 

Yes................................................................1 

No.................................................................2 

3. Does the article report on a tool to screen for 

osteoporosis in men? 

 [tool=radiologic studies, surveys, etc] 

 (Circle one) 

Yes................................................................ 1 

No.................................................................2 

4. Does the article report associations between BMD 

levels as determined by DXA and fractures in men? 

 (Circle one) 

Yes................................................................ 1 

No.................................................................2 

5. Study design 

 (Circle one) 

RCT/CCT..................................................... 1 

Cohort/case series ........................................2 

Case control .................................................3 

Review article: systematic or M-A ............. 4 

Review article: not systematic ................... 5 (STOP) 

Review article: letter, editorial, 

other syst review......................................... 6 (STOP) 

Other........................................................... 7 (STOP) 

6. Are any of the subjects identified as veterans? 

 (Circle one) 

Yes.......................................................... 1 

No............................................................ 2 

7. Should this article be saved for background? 

(Circle one) 

Yes.......................................................... 1 

No............................................................ 2 

NOTES: 
VA Male OP Project-Detailed Review Form- Diagnostic Studies

49 

Do you think that this article might include the same data as another study? (CIRCLE ONE)Yes 1 No 2 

 If YES enter Trial name and/or IDs: 

Trial name : ___________________________ ID(s) : ________________________________ 

What is the study test? 

(CHECK ALL THAT APPLY)

Ultrasound, BUA ....................................................



Ultrasound, SOS .....................................................



Ultrasound, QUI......................................................



Peripheral bone density, pDXA ..............................



Peripheral bone density, SXA.................................



Peripheral bone density, other: _______________.



Central DXA ..........................................................  Quantitative CT ......................................................  Bone markers .........................................................  

 Questionnaire, OST.................................................

  

Questionnaire, other: ____________________......



Other: ________________________________ .....  Other: ________________________________ .....



If applicable, at what anatomic site was 

Spine........................................

Femur ......................................

Radius......................................

Patella......................................

Calcaneus ................................

Finger ......................................

Other: ___________________Not applicable .........................

Not reported ............................

What is the reference test? 

Ultrasound, BUA.....................

Ultrasound, SOS......................

Ultrasound, QUI......................

Peripheral bone density, pDXA 

Peripheral bone density, SXA .

Peripheral bone density, other: 

Central DXA ..........................Quantitative CT ......................

 Questionnaire, OST..................

Questionnaire, other: ________Prior fractures..........................

Prior self-reported osteoporosi

Other: ___________________Other: ___________________

F

Article ID: Reviewer:______________ 

First Author: ____________________________________ 

 (Last Name Only) Study Number: ___of____Description:________________ 

(Enter ‘1of 1’ if only one) (if more than one study)
VA Male OP Project-Detailed Review Form- Diagnostic Studies

50 

If applicable, at what anatomic site was the reference test performed? 

(CHECK ALL THAT APPLY)

Spine .......................................................................



Femur......................................................................



Radius .....................................................................



Patella......................................................................



Calcaneus ................................................................



Finger......................................................................  Other: _____________________________ ..........  

Not applicable .........................................................



Not reported ............................................................



Who is studied? (CHECK ALL THAT APPLY)A. Not reported 



B. Unselected population 



C. Selected population 



Elderly  

Nursing home  

Referred  Prior glucocorticoid use  COPD  Hypogonadal  

Excess alcohol  

Malabsorption  Other: __________________________ 



What was the male sample size data? (Enter number or 9999 for not reported)

Enrolled: _________ Followed up: _________ 

What were the characteristics of the pa

Caucasian..................

African Ancestry.......

Hispanic....................

Asian (non-Filipino) .

Filipino .....................

Native American.......Eskimo/Inuit .............

Other (_________ _______

Veteran .....................Characteristics not rep

In what region did the study take place

US/Canada................Scandinavia...............

Australia/NZ .............

Western Europe ........

Eastern Europe..........

Latin America...........

Middle East...............

India..........................

Africa........................

Asia...........................

Other : ____________

Not reported..............

Does the article report sensitivity, s

construct 2 X 2 table? 

Sensitivity.................Specificity.................

Correlation................

Other : ____________Not reported..............
VA Male OP QUADAS Quality Review Form

51 

1. Was the spectrum of patients representative of the patients who 

will receive the test in practice? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if based on information reported from study’s authors, you believe the spectrum of patients included in the study is representative of those in whom the test will be used in practice. Judgment should be based on both method of recruitment and the characteristics of those recruited. Score ‘no’ if you think the population studied does not fit into what was specified as acceptable. Score ‘no’ if studies recruit a group of healthy controls and a group known to have the target disorder. 2. Were selection criteria clearly described? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if you think all relevant information regarding how participants were selected for inclusion has been provided. Score ‘no’ if study selection criteria are not clearly reported. 3. Is the reference standard likely to correctly classify the target 

condition? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if you believe the reference standard is likely to correctly classify the target condition or is the best method available. Score ‘no’ if you do not think the reference standard was likely to have correctly classified the target condition. 

4. Is the time period between reference standa

reasonably sure that the target condition dtests? 

(C

Yes 1 No 2 Unclear 3 *How to score: For conditions that progress rapidly, sh

performance of index and ref test if very short. If condiappropriate. You will have to determine what is ‘short eperformance of index test and reference standard was schanged between the performance of the two tests. 

5. Did the whole sample or a random selectio

using a reference standard? 

(C

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if it is clear that all patients received index test went on to receive verification of di

‘no’ if some patients did not receive verification of disereference standard was not random. 

6. Did patients receive the same reference sta

result? 

(C

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if it is clear that patients recusing the same reference standard. Score ‘no’ if some pdifferent reference standard. 

Article ID: Reviewer:______________ 

First Author: ____________________________________ 

 (Last Name Only) Study Number: ___of____Description:________________ 

(Enter ‘1of 1’ if only one) (if more than one study)
VA Male OP QUADAS Quality Review Form

52 

7. Was the reference standard independent of the index test (i.e. the 

index test did not form part of the reference standard)? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if it is clear from the study that the index test did not form part of the reference standard. Score ‘no’ if it appears that the index test formed part of the reference standard. 8. Was the execution of the index test described in sufficient detail to 

permit replication of the test? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: SEE # 9 9. Was the execution of the reference standard described in sufficient 

detail to permit its replication? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if study reports sufficient details or citations to permit replication of the index test and reference standard. Score as ‘no’ in other cases. 10. Were the index test results interpreted without knowledge of the 

results of the reference standard? 

(CIRCLE ONE)

Yes 1 No 2 Unclear 3 *How to score: SEE # 11 

11. Were the reference standard results interp

results of the index test? 

(C

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if study clearly states that th

were interpreted blind to the results of the other test. Scwere interpreted blind to results of the other test. 

12. Were the same clinical data available whe

would be available when the test is used i

(C

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if clinical data would normin practice and similar data were available when interpr in the study and when clinical data would not be availaavailable when the index test results were interpreted. S13. Were uninterruptible/intermediate test res

(C

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if it is clear that all test resuuninterruptible/indeterminate/intermediate results are reresults occurred but have not been reported. 14. Were withdrawals from the study explain

(C

Yes 1 No 2 Unclear 3 *How to score: Score ‘yes’ if it is clear what happened example if a flow diagram of study participants is reporparticipants who entered the study did not completed thstudy (i.e. did not receive both the index test and refere

accounted for).
VA Male OP Project- RISK FACTOR STUDIES

53 

Are data in this article reported for MEN for the risk factors listed below? 

MODERATE RISK FACTORS 

(CHECK ALL THAT APPLY)

Smoking (active)..................................................... 

Low Sunlight Exposure (low or none).................... 

Family History of Osteoporotic Fracture................ 

Low Calcium Intake (<500-850 mg/day)................ 

Hyperparathyroidism (N/S) .................................... 

Hyperthyroidism ..................................................... 

Diabetes mellitus (type II or N/S)........................... 

Rheumatoid arthritis................................................ 

UNCLASSIFIABLE RISK FACT

Alcohol Intake.......................................

Male hypogonadism..............................

Other hormonal factors in men, includin Anti-androgen therapy .........

Prostaglandin inhibitors (NSAIDs and a

Anti-ulcer agents...................................

Thyroid disease including replacement 

Respiratory diseases – independent of s

Dietary deficiency of Vitamin D...........

Metabolism and GI absorption disorder

SCI ........................................................

Hyperhomocysteinemia ........................

 This article does not include any of  listed on this form.

Article ID: Reviewer: Elaine Wong

First Author: ____________________________________ 

 (Last Name Only) 
VA Male OP Project-Detailed Review Form- RISK FACTOR STUDIES

54 

STUDY PARTICIPATION 

YES NO 

Was the source population clearly defined?... 

Was the study population described?............. 

Is the study population representative of  the patients of interest (VA)?.....................  

STUDY DESIGN 

 4. What is the study design? (Check one) 

Case- Control ..........................................................



Cohort .....................................................................



Cross sectional ........................................................



STUDY ATTRITION

 FOR COHORTS ONLY How many subjects were enrolled?  _____ _____ _____ _____ (ND=9999)  6. How many subjects were included in the data analysis?  _____ _____ _____ _____ (ND=9999) 

 7. What is the duration of the follow up? 

 Duration Units 

 OR 

 _____ _____ _____ _____ person-years 

 FOR CASE CONTROL ONLY  8. How many cases were included?  _____ _____ _____ _____  9. How many controls were included?  _____ _____ _____ _____  FOR CROSS SECTIONAL STUDIES ONLY 

10. What is the sample size? 

 _____ _____ _____ _____ 

RISRIRISK FACTOR MEASUREMENT

Which of the following risk factors were asse

Alcohol Consumption .......................

- If yes, how was alcohol consu____________________________

Diabetes Mellitus, type II or NOS ....

- If yes, how was the presence o____________________________

Spinal Cord Injury.............................

- If yes, how was the presence a____________________________

 Article ID: Reviewer: First Author: ____________________________________ 

(Last Name Only) 

F

Units

01. Days 04. Years 02. Weeks 05. NR 03. Months 
VA Male OP Project-Detailed Review Form- RISK FACTOR STUDIES

55 

OUTCOME MEASUREMENT

 12. What outcome was assessed? 

BMD (cDXA).........................................................  

 If yes answer the following: 

- Site (CHECK ALL THAT APPLY)

 Spine ..........................................................



 Femur .........................................................



 Radius ........................................................



 Patella.........................................................



 Calcaneus ...................................................



 Finger .........................................................



 Other: ________________________ .......   Not applicable ............................................



 Not reported ...............................................  

- T-score: _____________________________ - Reference Standard 

 Male ...........................................................



 Female........................................................



 Other .........................................................  

Specify:___________________________ 

Osteoporotic fracture............................................  

If yes, how was the presence of fracture assessed: 

(CHECK ALL THAT APPLY)

 X-ray ..........................................................



 Diary/Self Report.......................................



 Administrative data....................................



 Medical Record Review.............................



Other Bone Measurements...................................   If yes, please specify: (CHECK ALL THAT APPLY)

 Ultrasound..................................................



 Other .........................................................  

Specify:___________________________ 

POTEPOTENTIAL CONFOUNDING PROGNOS

MEASUREMENT 13. Which of the following risk facto

Age....................................................

Low body weight ..............................

Weight loss........................................

Physical inactivity/prolonged immob (Not SCI).........................

Corticosteroid use .............................

Anticonvulsant use............................

Hyperparathyroidism ........................

Diabetes Mellitus, type I ...................

Gastrectomy ......................................

Hypogonadism, primary or secondary 

Poor visual acuity..............................

Previous osteoporotic fracture ..........

Cigarette smoking .............................

Vitamin D deficiency........................

Low dietary calcium intake...............

Family History of Osteoporotic Fract

Hyperthyroidism ...............................

Rheumatoid Arthritis ........................

High bone turnover rate ....................

ANALANALYSIS

14. Does the article present: 

Bivariate............................................Multivariate.......................................Other ................................................

Specify:_______________
VA Male OP Project – RISK FACTOR STUDIES, Quality Measurement 

56 

STUDY PARTICIPATION The study sample represents the population of interest on key characteristics, sufficient to limit potential bias to the results. 

 Yes ........................................................................

 Partly..................................................................... 

 No.......................................................................... 

 Unsure................................................................... 

*Population of interest is adequately described for key characteristics *Sampling frame and recruitment are adequately described, including methods to identity the sample (number and type used, e.g., referral patterns in health care), period of recruitment, and place of recruitment (setting and geographic location). *Inclusion and exclusion criteria are adequately described (e.g., including explicit diagnostic criteria or “zero time” description). * There is adequate participation in the study by eligible individuals. *The baseline study sample (i.e., individuals entering the study) is adequately described for key characteristics. 

STUDY ATTRITIONLoss to follow-up (from sample to study population) is not associated with key characteristics (i.e., the study data adequately represent the sample), sufficient to limit potential bias. 

 Yes ........................................................................ 

 Partly..................................................................... 

 No.......................................................................... 

 Unsure................................................................... 

*Proportion of study sample completing the study and providing outcome data is adequate. 

*Attempts to collect information on participants who dropped out of the study are described. *Reasons for loss to follow-up are provided. *Participants lost to follow-up are adequately described for key characteristics. *There are no important differences between key characteristics and outcomes in participants who completed the study and those who did not. 

PROGPROGNOSTIC FACTOR MEASUREMENT

The prognostic factor of interest is adequately measuresufficiently limit potential bias. 

 Yes.................................................................

 Partly..............................................................

 No ..................................................................

 Unsure............................................................

*A clear definition or description of the prognostic factor measure is level, duration of exposure, and clear specification of the method of m*Continuous variables are reported or appropriate (i.e., not data-depe*The prognostic factor measure and method are adequately valid and 

Bias (e.g. may include relevant outside sources of information on mecharacteristics, such as blind measurement and limited reliance on rec*Adequate proportion of the study sample has complete data for prog*The method and setting of measurement are the same for all study p*Appropriate methods are used if imputation is used for missing prog

OUTCOME MEASUREMENT

The outcome of interest is adequately measured in studsufficiently limit potential bias. 

 Yes.................................................................

 Partly..............................................................

 No ..................................................................

 Unsure............................................................

 *A clear definition of the outcome of interest is provided, including d and extent of the outcome construct. 

*The outcome measure and method used are adequately valid and rel

(e.g., may include relevant outside sources of information on measurecharacteristics, such as blind measurement and confirmation of outco*The method and setting of measurement are the same for all study p

Article ID: Reviewer: 

First Author: ____________________________________ 

 (Last Name Only) 
VA Male OP Project – RISK FACTOR STUDIES, Quality Measurement 

57 

CONFOUNDING MEASUREMENT AND ACCOUNT

Important potential confounders are appropriately accounted for, limiting potential bias with respect to the prognostic factor of interest. 

 Yes ........................................................................

 Partly..................................................................... 

 No.......................................................................... 

 Unsure................................................................... 

*All important confounders, including treatments (key variables in conceptual model), are measured. *Clear definitions of the important confounders measured are provided (e.g., including dose, level and duration of exposures). *Measurement of all important confounders is adequately valid and reliable (e.g., may include relevant outside sources of information on measurement properties, also characteristics, such as blind measurement and limited reliance on recall.) *The method and setting of confounding measurement are the same for all study participants. *Appropriate methods are used if imputation is used for missing confounder data. *Important potential confounders are accounted for in the study design (e.g., matching for key variables, stratification, or initial assembly of comparable groups.) *Important potential confounders are accounted for in the analysis (i.e., appropriate adjustment). 

ANALYSIS

The statistical analysis is appropriate for the design of potential for presentation of invalid results. 

 Yes.................................................................

 Partly..............................................................

 No ..................................................................

 Unsure............................................................

*There is sufficient presentation of data to assess the adequacy of the *The strategy for model building (i.e., inclusion of variables) is approframework or model. * The selected model is adequate for the design of the study. *There is no selective reporting of results. 
58 

Appendix B. Evidence Table 
Evidence Table 1. Diagnostic Test Studies 

Columns 1-10: Article, Population, Characteristics, Sample Size, Study test & site, Reference test & site, QUADAS, R

*QUADAS 1=Yes, 2=No, 3=Unclear; Order is: Spectrum representativeness, Selection criteria, Reference standard, Time period, Verification bias, Use of same reference test, Independe

reference test, Blinding #1, Blinding #2, Usefulness in practice, Intermediate results, Withdrawls NR=Not Reported BUA=Broad-band ultrasound attenuation QUI=Quantitative Ultrasound Index DXA=Dual energy x-ray absorptiometry 

SOS=Speed of sound OST=Osteoporosis Screening Tool BMD=Bone Mass Density QUS=Quantitative Ultrasound SI=Stiffness Index OSTA=Osteoporosis Screening Tool for Asians MOST=Male Osteoporosis Screening Tool AVU=Apparent velocity of ultrasound 

Study Reference 

Author, Year, Region, 

Trial Name Population Characteristics 

Male 

sample 

size Test Site Test Site QUADAS* 

Adler, 2001 27

US/Canada 

Referred for DXA NR, Veteran 185 Ultrasound BUA 

& QUI 

Calcaneus Central DXA Spine, Femur 3,3,1,1,1,1,1, 

1,1,3,3,1,1,3 

Adler, 2003 19US/Canada 

Pulmonary Clinic Asian, Veteran 107 Ultrasound BUA, 

SOS & QUI; questionnaire 

Calcaneus Central DXA Spine, Femur 1,1,1,1,2,1,1, 

1,1,3,3,1,1,3 

Adler, 2003 35

US/Canada 

Pulmonary & Rheumatology Clinic 

Pulmonary & Rheumatology Clinic, Veteran 

181 Questionnaire 

OST 

NA Central DXA Spine, Femur 1,1,1,1,1,1,1, 

1,1,3,3,1,1,1 

Cheng, 1997 95Scandinavia 

Elderly NR 205 Peripheral bone 

density pDXA 

Calcaneus Fracture 

Occurrence 

Multiple Sites 2,1,1,1,2,1,1, 

1,1,3,3,1,1,1 

De Laet, 1998 96

Western Europe 

Elderly NR 2778 Central DXA, 

Hiefy Risk using DCA 

Femur, NA Fracture 

Occurrence 

NA 1,1,1,1,1,1,1, 

1,1,3,3,1,1,1 

Donaldson, 1999 72Western Europe 

Elderly NR 817 Ultrasound BUA Calcaneus Fracture 

Occurrence 

NR 1,1,3,1,2,3,1, 

1,1,3,3,1,1,2 
Evidence Table 1. Diagnostic Test Studies 

Columns 1-10: Article, Population, Characteristics, Sample Size, Study test & site, Reference test & site, QUADAS, R

*QUADAS 1=Yes, 2=No, 3=Unclear; Order is: Spectrum representativeness, Selection criteria, Reference standard, Time period, Verification bias, Use of same reference test, Independe

reference test, Blinding #1, Blinding #2, Usefulness in practice, Intermediate results, Withdrawls NR=Not Reported BUA=Broad-band ultrasound attenuation QUI=Quantitative Ultrasound Index DXA=Dual energy x-ray absorptiometry 

SOS=Speed of sound OST=Osteoporosis Screening Tool BMD=Bone Mass Density QUS=Quantitative Ultrasound SI=Stiffness Index OSTA=Osteoporosis Screening Tool for Asians MOST=Male Osteoporosis Screening Tool AVU=Apparent velocity of ultrasound 

Study Reference 

Author, Year, Region, Population Characteristics

Male 

sample 

size Test Site Test Site QUADAS* 

Gonnelli, 2005 68

Western Europe 

Bone Clinic NR 407 Ultrasound BUA 

& SOS; Central DXA 

Spine, Femur, Calcaneus 

Fracture Occurrence 

Spine, Femur, Radius, Pelvis 

2,1,1,1,1,1,1, 1,1,3,3,1,1,1 

Grampp, 2001 66Western Europe 

Referred for BMD NR 501 Ultrasound QUS Calcaneus Central DXA Spine, Femur 2,1,1,1,1,1,1, 

1,1,3,3,1,1,1 

Gudmundsdottir, 2005 20

Scandinavia 

Unselected NR 589 Ultrasound BUA, 

SOS & SI 

Calcaneus Central DXA Spine, Femur 2,1,1,1,3,1,1, 

1,1,3,3,1,1,2 

Kaptoge, 2004 17Western Europe 

Unselected NR 2653 Simple Score 

Male Multivariate Model 

Spine Fracture 

Occurrence 

Spine, Femur, Radius, Rib, Other 

1,1,1,1,1,1,1, 1,1,3,3,1,1,1 

Karlsson, 1996 14

Scandinavia 

Unselected NR 33 Central DXA; Xray Femur Fracture Occurrence Femur 1,1,1,1,1,1,1, 1,1,3,3,3,1,1 

Kroger, 1999 97Scandinavia, Western Europe 

Referred – PCP NR 68 Central DXA; 

Quantitative CT 

Spine, Femur Fracture 

Occurrence 

Spine, Femur 3,2,1,3,3,3,1, 

1,1,3,3,3,3,3 

Kung, 2005 63

Asia 

Elderly Asian 776 Ultrasound BUA; 

SOS & QUI; OSTA 

Calcaneus NA 

Central DXA Spine, Femur 2,1,1,1,1,1,1, 

1,1,3,3,1,1,3 

Li-Yu, 2005 15Asia 

Unselected Filipino 132 OSTA NA Central DXA Femur 2,1,1,1,1,1,1, 

2,1,3,1,1,3,3 

Lynn, 2005 65

Asia 

Elderly Asian 2000 Ultrasound QUI; 

MOST 

NA Central DXA Spine, Femur 2,1,1,1,3,1,1, 

1,1,3,3,1,1,3 

Melton, 2005 98US/Canada 

Unselected NR 348 Bone Structural 

Parameters 

Femur Central 

DXA, Fracture Occurrence 

Femur 1,1,1,1,1,1,2, 

1,1,3,3,1,1,2 

Montagnani, 2001 67Western Europe 

Unselected NR 182 Central DXA; 

Ultrasound 

Spine, Femur, Finger 

Fracture Occurrence 

NR 1,2,1,1,1,1,1, 

1,1,3,3,1,1,1 
Evidence Table 1. Diagnostic Test Studies 

Columns 1-10: Article, Population, Characteristics, Sample Size, Study test & site, Reference test & site, QUADAS, R

*QUADAS 1=Yes, 2=No, 3=Unclear; Order is: Spectrum representativeness, Selection criteria, Reference standard, Time period, Verification bias, Use of same reference test, Independe

reference test, Blinding #1, Blinding #2, Usefulness in practice, Intermediate results, Withdrawls NR=Not Reported BUA=Broad-band ultrasound attenuation QUI=Quantitative Ultrasound Index DXA=Dual energy x-ray absorptiometry 

SOS=Speed of sound OST=Osteoporosis Screening Tool BMD=Bone Mass Density QUS=Quantitative Ultrasound SI=Stiffness Index OSTA=Osteoporosis Screening Tool for Asians MOST=Male Osteoporosis Screening Tool AVU=Apparent velocity of ultrasound 

Study Reference 

Author, Year, Region, Population Characteristics

Male 

sample 

size Test Site Test Site QUADAS* 

Mulleman, 2002 [#1274] Western Europe 

Referral NR 102 Ultrasound BUA, 

SOS & SI 

Calcaneus Central 

DXA, Fracture Occurrence 

Spine, Femur 2,1,3,1,1,1,1, 

1,1,3,3,1,1,1 

Odvina, 1988 99US/Canada 

Referral for Osteoporosis 

NR, Veteran 38 Quantitative CT Spine Fracture 

Occurrence 

2,1,1,1,1,1,1, 1,1,3,3,1,1,1 

Robinson, 1987 100

Australia 

Referred by Hospital Staff 

NR 31 Linear Photon 

Absorptiometry 

Spine, Radius 

Quantitative CT, Fracture Occurrence 

Spine 2,2,1,1,3,3,1, 

1,1,3,3,1,1,3 

Rothenberg, 2004 70US/Canada 

Unselected NR 301 Ultrasound Bone 

Density 

Calcaneus Fracture 

Occurrence 

Spine, Femur, Radius, Shoulder, Ribs 

1,1,3,1,1,1,1, 1,1,3,3,1,1,1 

Shin, 2005 101

Asia 

Unselected, Elderly 

Asian 1225 Ultrasound BUA, 

SOS & Stiffness 

Calcaneus Peripheral 

bone density pDXA 

Radius, Calcaneus 2,1,1,1,1,1,1, 

1,1,3,3,1,1,2 

Stewart, 1995 73Western Europe 

Unselected NR 247 Ultrasound BUA; 

Central DXA 

Spine, Femur, Calcaneus 

Fracture Occurrence 

Spine 1,3,1,1,1,1,1, 

1,1,3,3,1,1,1 

Travers-Gustafson, 1995 74

US/Canada 

Elderly NR 529 Peripheral Bone 

Density other; AVU 

Radius, Patella 

Fracture Occurrence 

NR 1,1,3,1,1,1,1, 

1,1,3,3,1,1,1 
Evidence Table 1. Diagnostic Test Studies 

Columns 1-10: Article, Population, Characteristics, Sample Size, Study test & site, Reference test & site, QUADAS, R

*QUADAS 1=Yes, 2=No, 3=Unclear; Order is: Spectrum representativeness, Selection criteria, Reference standard, Time period, Verification bias, Use of same reference test, Independe

reference test, Blinding #1, Blinding #2, Usefulness in practice, Intermediate results, Withdrawls NR=Not Reported BUA=Broad-band ultrasound attenuation QUI=Quantitative Ultrasound Index DXA=Dual energy x-ray absorptiometry 

SOS=Speed of sound OST=Osteoporosis Screening Tool BMD=Bone Mass Density QUS=Quantitative Ultrasound SI=Stiffness Index OSTA=Osteoporosis Screening Tool for Asians MOST=Male Osteoporosis Screening Tool AVU=Apparent velocity of ultrasound 

Author, Year, Region, Population Characteristics Male Study Reference sample 

size Test Site Test Site QUADAS* 

Varenna, 2005 69

Western Europe 

Unselected NR 4832 Ultrasound BUA, 

SOS, & SI 

Calcaneus Fracture 

Occurrence 

Femur, Non-spinal 1,1,3,1,1,1,1, 

1,1,3,3,1,1,1 

Welch, 2004 71Western Europe 

Unselected NR 6860 Ultrasound BUA Calcaneus Fracture 

Occurrence 

Spine, Femur, Radius 

1,1,3,1,1,1,1, 1,1,3,3,1,1,1 

Bauer, 2006 75

US/Canada 

Elderly NR 5608 Ultrasound BUA, 

Central DXA 

Femur, Calcaneus 

Fracture Occurrence 

Femur 1,1,1,1,1,1,1, 

3,3,1,1,1,1,3