28. Osteoporosis in Postmenopausal Women: Diagnosis and 

Monitoring

Evidence Report/Technology Assessment

Number 28

Prepared for:

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services

2101 East Jefferson Street

Rockville, MD 20852

http://www.ahrq.gov

Contract No. 290-97-0018

Prepared by:

Oregon Health & Science University Evidence-based Practice Center

Portland, Oregon

Heidi D. Nelson, M.D., M.P.H.

Principal Investigator

Cynthia D. Morris, Ph.D., M.P.H.

Dale F. Kraemer, Ph.D.

Susan Mahon, M.P.H.

Nancy Carney, Ph.D.

Peggy M. Nygren, M.A.

Mark Helfand, M.D., M.P.H., EPC Director

AHRQ Publication No. 01-E032

November 2001

This document is in the public domain and may be used and reprinted without permission except 

those copyrighted materials noted for which further reproduction is prohibited without the 

specific permission of copyright holders.

Suggested Citation:

Nelson HD, Morris CD, Kraemer DF, et al. Osteoporosis in postmenopausal women: diagnosis 
and monitoring. Evidence Report/Technology Assessment No. 28 (Prepared by the Oregon 

Health & Science University Evidence-based Practice Center under Contract No. 290-97-0018). 

AHRQ Publication No. 01-E032. Rockville, MD: Agency for Healthcare Research and Quality. 

January 2001.

Preface

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based Practice 

Centers (EPCs), sponsors the development of evidence reports and technology assessments to 

assist public- and private-sector organizations in their efforts to improve the quality of health 

care in the United States. The reports and assessments provide organizations with 

comprehensive, science-based information on common, costly medical conditions and new 

health care technologies. The EPCs systematically review the relevant scientific literature on 

topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to 

developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and health 

technology assessments, AHRQ encourages the EPCs to form partnerships and enter into 

collaborations with other medical and research organizations. The EPCs work with these partner 

organizations to ensure that the evidence reports and technology assessments they produce will 

become building blocks for health care quality improvement projects throughout the Nation. The 

reports undergo peer review prior to their release.

AHRQ expects that the EPC evidence reports and technology assessments will inform individual 

health plans, providers, and purchasers as well as the health care system as a whole by providing 

important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Acting Director, 

Center for Practice and Technoloy Assessment, Agency for Healthcare Research and Quality, 

6010 Executive Blvd., Suite 300, Rockville, MD 20852.

John M. Eisenberg, M.D. Director, Center for Practice and

Director, Agency for Healthcare Technology Assessment

Research and Quality

The authors of this report are responsible for its content. Statements in the report should not be 

construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. 
Department of Health and Human Services of a particular drug, device, test, treatment, or other 

clinical service.

Robert Graham, M.D.

Acknowledgments

We thank the following members of the Oregon Health & Science University (OHSU) Evidencebased Practice Center staff for their contributions to this project:

Piper Hackett, B.S.

Kathryn Pyle Krages, A.M.L.S., M.A.

Alix E. Seif, M.A.

Patty Davies, M.S.

Patty Davies, M.S.Gary Miranda, M.A.

Connie Levesque, B.S.

Cynthia Davis-O'Reilly

Benjamin Chan, M.S.

Jeani Crichlow, B.S.

Lynne Schwabe

I'eisha Parker

Linda Slattery

Katy Lesowski

Structured Abstract

Objectives.

This report examines the evidence on the effectiveness of various strategies for diagnosing and 

monitoring postmenopausal women with osteoporosis. Specifically, it addresses: (1) the role of 

risk factors in identifying high-risk women and guiding their initial treatment, (2) the advantages 

and disadvantages of various techniques for bone measurement in predicting risk of hip or spine 

fracture, (3) the effectiveness of bone measurement tests for monitoring response to treatment 

and for guiding treatment change, (4) the role of markers of bone turnover in diagnosis and 

treatment management, (5) the evaluation of patients with osteoporosis for secondary causes, and 

(6) the costs and cost-effectiveness of various diagnostic strategies for osteoporosis.

Search Strategy.

The authors conducted a MEDLINE search (covering the years 1966 to 2000), supplemented by 

searches of HealthSTAR (covering 1975 to 2000) of papers published in English, reviewed 

reference lists of review articles, and sought guidance from local and national experts.

Selection of Studies.
The authors included abstracts relevant to one or more topic areas that had original data about 

postmenopausal women and osteoporosis. Two reviewers read each abstract to determine its 

eligibility. Articles were excluded if they did not provide sufficient information to determine the 

methods for selecting subjects and for analyzing data. For some topics, additional eligibility 

criteria were applied. For all topics combined, the authors retrieved 10,174 citations. After 

reviewing these citations for possible relevance, 530 articles about risk factors, 123 about bone 

measurement testing, 23 about monitoring, 277 about biochemical markers, and 53 about costs 

were selected for further review. An additional 242 studies were retrieved after reviewing the 

reference lists of studies and/or by suggestion of others. The search yielded no papers with data 

for the secondary causes topic.

Data Collection and Analysis.

From full-text published studies of fracture or bone density prediction or bone measurement 

methods, the authors extracted selected information about the patient population, interventions, 

clinical endpoints, study design, and study quality, and used this information to construct 

evidence tables. Additional reviews assessed the internal validity of studies of risk factors and 

the diagnostic performance of bone measurement tests and biochemical markers, summarized 

recommendations for testing for secondary causes of osteoporosis, reviewed studies about cost 

and cost-effectiveness, and compared diagnostic strategies.

Main Results.

Epidemiologic studies report clinical risk factors for osteoporosis and fractures, but few studies 

evaluate how to use them to identify individual women at risk for fracture, and no studies 

provide evidence that treatment decisions based on clinical risk factors lead to better or worse 

fracture outcomes than those based on bone measurement tests. Because of differences between 

bone measurement techniques, and because individuals have different rates of bone loss at 

different sites, no one test can exclude osteoporosis at the most important fracture sites -- hip, 

spine, and wrist. Dual-energy X-ray absorptiometry (DXA) of the femoral neck is the best 

validated test to predict hip fracture. Other techniques predict hip fracture less accurately or have 

not been evaluated in prospective studies.

Recent results from clinical trials raise questions about the value of repeated, annual 

densitometry tests for patients on therapy to prevent osteoporosis or bone loss; moreover, there is 

no evidence from clinical trials that adjusting therapy based on serial densitometry at any interval 

improve outcomes. Markers of bone turnover correlate poorly with bone measurement tests and 

are not good predictors of fractures.

Cost and cost-effectiveness studies, which are based solely on economic models, suggest 

targeting treatment to women with the lowest bone density and including a risk factor score or 

less expensive (and more widely available) technology to determine which women should 

receive hip DXA. The authors' supplementary analysis on cost-effectiveness favors a sequential 

strategy of quantitative ultrasound at the heel followed by densitometry of those identified by 

ultrasound as high risk over densitometry alone. In high-risk populations, ultrasound alone may 
also be cost-effective.

Conclusions.

Application of the results from epidemiologic studies to diagnosis and monitoring strategies for 

individual patients in the clinical setting is currently based on extrapolation from models or, for 

most questions addressed in this review, is simply lacking. To be more useful for clinicians and 

patients, future research should focus on the application of these data to the clinical setting.

Summary

Overview

At an international consensus development conference, osteoporosis was defined as "a systemic 

skeletal disease characterized by low bone mass and microarchitectural deterioration of bone 

tissue, leading to enhanced bone fragility and a consequent increase in fracture risk." In 1994, a 

World Health Organization (WHO) working group proposed that, in epidemiologic studies, 

osteoporosis could be determined when bone density at the hip, spine, or forearm is 2.5 standard 

deviations or more below the mean for healthy, young, adult women (a value defined as the Tscore), or when a history of a fracture is present in the absence of trauma. The group also 

proposed that osteopenia be diagnosed when the bone density was 1.0 to 2.5 standard deviations 

below the mean for young, healthy women.

According to the National Health and Nutrition Examination Survey (NHANES III), an 

estimated 14 million American women over age 50 years are affected by low bone density at the 

hip, and 5 million more have bone density that measures -2.5 standard deviations or more below 

the mean at the hip. The prevalence of osteoporosis in Mexican-American women is similar to 

that in white women, while rates in black women are approximately half that of the first two 

groups. The prevalence of osteoporosis increases with age for all sites, and -- by the WHO 

definition -- up to 70 percent of women over age 80 years have osteoporosis. Furthermore, age is 

an important factor in the relationship between bone density and the absolute risk of fracture. An 

increase in age of 13 years increases the risk of hip fracture by the same amount as a decrease in

bone density of one standard deviation. Older women have a much higher fracture rate than 

younger women who have the same bone density, because of increasing risk from other factors, 

such as a change in bone quality and the tendency to fall.

Women with osteoporosis are more likely to experience fractures. Demographic trends for hip 

fracture parallel those for osteoporosis. Hip-fracture incidence in white women rises from 50 per 

100,000 at age 50 years to 237 per 100,000 at age 65 years. White women are generally two to 

three times more likely than nonwhite women to suffer a hip fracture. Hip fractures are 

associated with high rates of mortality and loss of independence. Wrist fracture incidence tends 

to increase at earlier ages than does that of hip fractures.

Vertebral fractures have also been associated with significant morbidity. Sixteen percent of 

postmenopausal women have osteoporosis of the lumbar spine; furthermore, five percent of 50-
year-old white women and 25 percent of 80-year-old women have had at least one vertebral 

fracture. Vertebral fractures can cause severe pain and are associated with more than five million 

days of restricted activity in those age 45 years or older.

The disease burden of osteoporosis extends beyond consequences of low bone density and 

fractures. For example, the act of screening, diagnosis, and subsequent treatment can also affect 

the quality of life. Fear of fracture itself can reduce the quality of life in women who have been 

diagnosed as having osteoporosis.

In 1995, the total direct medical expenditure in the United States for the treatment of 

osteoporotic fractures in adults older than 45 years was estimated at $13.8 billion. The majority 

of this total ($8.6 billion) was spent for inpatient care. Hip fracture alone accounted for $8.7 

billion (63 percent) of osteoporosis-related costs, while fractures at sites other than the hip 

accounted for approximately 37 percent of the total expenditure (about $5.1 billion). In addition 

to these costs is the cost of lost productivity for women with fractures, or for their family or other 

caregivers. As the median age of the U.S. population increases, the costs associated with 

osteoporotic fractures are also likely to increase.

Reporting the Evidence

This evidence report describes the effectiveness of various strategies for diagnosing and 

monitoring postmenopausal women with osteoporosis, as represented by six topic areas:

1. Risk Factors. What is the role of clinical risk factors, in conjunction with bone 

measurement tests, in identifying high-risk women and guiding initial treatment 

decisions? 

2. Bone Measurement Tests. What are the advantages and disadvantages of various bone 

measurement tests at different anatomic sites for identifying women at high risk of 

fracture? 

3. Monitoring. Are bone measurement tests effective for monitoring response to treatment 

and for guiding decisions about changes in management? 

4. Biochemical Markers. What is the role of markers of bone turnover for identifying 

women at risk of bone loss, guiding initial treatment decisions, or monitoring response to 

therapy? 

5. Evaluation for Secondary Causes. What diagnostic or laboratory tests are appropriate for 

evaluating patients with osteoporosis for secondary causes? 

6. Cost. Assuming consistent treatment approaches, what are the costs and costeffectiveness of various diagnostic strategies for identifying women with osteoporosis? 

These topic areas do not include the effectiveness of dietary, lifestyle, hormonal, and medical 

interventions for primary prevention or treatment of osteoporosis. This report is confined to 

diagnostic and monitoring strategies as they apply to individual women, and does not include 

issues regarding mass screening in the general population. Also, while most of the literature 

addressing these topic areas is aimed at an audience of clinical researchers who specialize in 

osteoporosis, we have attempted to assess the research findings from the perspectives of 

clinicians and patients. However, it is not the purpose of this report to propose practice 
recommendations.

Methodology

With input from local and national experts, we developed an analytic framework and key 

questions in each of the six topic areas. Relevant studies were identified from multiple searches 

of MEDLINE (for the years 1966 to 2000) and HealthSTAR (for the years 1975 to 2000), from 

the reference lists of systematic review articles, and from national experts. All searches were 

limited to publications in the English language. The authors excluded articles if they did not 

provide sufficient information to determine the methods for selecting subjects and for analyzing 

data.

Out of 10,174 citations retrieved for all topics combined, the authors selected as possibly 

relevant 530 articles about risk factors, 123 about bone measurement tests, 23 about 

measurement tests for bone monitoring, 277 about biochemical markers, and 53 about costs. An 

additional 242 studies were retrieved after reviewing reference lists of studies and by suggestion 

of the expert panel or leading researchers in the field. The search yielded no papers with data for 

the secondary causes topic, but this topic was addressed by reviewing published guidelines and 

by a supplemental analysis of physician practice patterns for the evaluation of secondary causes 

of osteoporosis. For articles that were included, the authors applied criteria proposed by the U.S. 

Preventive Services Task Force to rate the quality of individual studies. A second supplemental 

analysis investigated the cost-effectiveness of various diagnostic strategies.

Findings

Risk Factors

After a review of the relevant articles, the findings about the risk factors that predict bone 

density, bone loss, and fractures are as follows:

Factors that are consistently associated with increased risks of low bone density and 

fractures in postmenopausal women include increasing age, white race, low weight or 

weight loss, nonuse of estrogen replacement, history of previous fracture, family history 

of fracture, history of falls, and low scores on one or more measures of physical activity 

or function. 

Other factors are less consistent predictors across studies, but also have statistically 

significant associations with low bone density and fractures. These include smoking, 

alcohol use, caffeine use, low calcium and vitamin D intake, and use of certain drugs. 

Predictors of low bone density are similar to those for fracture, except for those factors 

related to physical function and falls. 

Some clinical risk factors, especially those related to physical function and falls, are as 

powerful as bone density in the prediction of hip fracture. 

Women with multiple risk factors and low bone density have an especially high risk of 

hip fracture. 

Most of the strongest risk factors are consistently related to outcomes, regardless of the 

racial and ethnic population, although there are few studies of nonwhite women. 
A second set of findings about risk factors concerned the accuracy of methodologies (also called 

instruments or tools) for assessing risk factors in identifying women at risk of fracture. These 

included:

In contrast to the extensive research about determining clinical risk factors for 

osteoporosis and fractures, there are fewer studies available that evaluate how to use 

these risk factors to identify individual women at risk for fracture. 

Methologies designed to assess risk of low bone density or fractures generally have low 

to moderate sensitivity and specificity. Those that perform well when originally tested 

either have performed less well in other populations or have not yet been widely tested. 

Some methodologies -- especially those developed in large community populations and 

containing variables known to be strong predictors -- may ultimately be applicable to the 

clinical setting once they are tested there. 

A third set of findings, exploring whether risk factors are useful in treatment decisions, included:

The authors did not identify any studies that examined whether treatment decisions based 

on clinical risk factors lead to better or worse health outcomes than those based on bone 

measurement tests or a combination of bone tests and risk factors. 

Bone Measurement Tests

Regarding bone measurement tests, the major findings related to the capacity of different bone 

measurement tests at different sites to predict fractures included:

Among different bone measurement tests at various sites, bone density measured at the 

femoral neck by dual energy x-ray absorptiometry (DXA) is the best predictor of hip 

fracture and is comparable to forearm measurements for predicting fracture at other sites. 

In recent prospective studies, quantitative ultrasound (QUS) measured at the heel 

predicted hip fracture and all nonspine fractures as well or nearly as well as DXA 

measured at the femoral neck. For each of these tests, a result in the osteoporotic range is 

independently associated with an increased short-term probability of hip fracture. 

Individuals who have low scores by one of these tests, but not the other, have a higher 

risk of fracture than those who have higher scores by both tests, and a lower risk of 

fracture than those whose results on both tests are low. 

While other peripheral measures may approach QUS in predicting hip fracture, there are 

no recent prospective studies that directly compare prediction of hip fracture of these 

tests with DXA of the hip. Radiographic absorptiometry (RA) or quantitative 

microdensitometry (QMD) of the hand can predict the risk of nonspine fractures in 

general, many of which are in the forearm, but there are no recent data about the ability 

of hand measurement to predict hip fracture. 

Correlations between different bone measurement tests are generally too low to be 

accepted as evidence that one test will identify patients at similar risk to those identified 

by another test. 
Major findings on identification of the factors related to bone testing that influence diagnosis 

included:

The likelihood of being diagnosed with osteoporosis varies greatly, depending on the site 

and type of the bone measurement test, on the brand of densitometer, and on the 

relevance of the reference range to the local population. 

The likelihood of being diagnosed as having osteoporosis also depends on the number of 

sites tested. Testing in the forearm, hip, spine, or heel will generally identify different 

groups. A physician cannot say, based only on one of these tests, that the patient "does 

not have osteoporosis." 

The results of bone measurement tests are often inaccurately reported to patients. 

Major findings related to how bone measurement test results affect patients' and physicians'

decisions and actions included:

One randomized trial suggests that women who undergo densitometry are more likely to 

start hormone replacement therapy than women who do not. 

In a randomized trial and a large, uncontrolled case series, women who had densitometry 

and were told they had osteoporosis were more likely to start or continue hormone 

replacement therapy than women who were told they had normal bone density. 

In one randomized trial, physicians found densitometry reports confusing and were not

confident that their interpretations of T-scores were correct. 

Monitoring

The major findings regarding whether bone measurement tests are effective for monitoring 

response to therapy and for guiding decisions about changes in management included:

The weight of the evidence is currently against repeating bone density tests within the 

first year of treatment. There is insufficient evidence to determine whether repeating bone 

density tests 2 years after starting therapy is useful. 

There are also no studies about the effect of either monitoring responses to therapy using 

densitometry or the choice of test on the outcome of therapy. 

Biochemical Markers

Findings regarding whether biochemical markers can be used instead of bone measurement tests 

in identifying women at risk for osteoporosis included:

No single marker or cluster of markers accurately predicted the results of densitometry in 

individuals. Densitometry measures current bone status, whereas markers measure the 

process of bone turnover. 

Major findings as to how well biochemical markers predict fracture included:
No marker was associated with increased fracture risk consistently across all studies. One 

study provides evidence that using markers in conjunction with densitometry may 

increase predictability, but this result has not been otherwise confirmed. 

In addition, major findings as to whether markers can help select patients for treatment included:

Studies correlating marker results and bone loss indicated no clear trend. Furthermore, 

sensitivity and specificity of markers were too low to be useful for the purpose of 

selecting patients for treatment. 

Some studies found better test accuracy when a combination of two or more markers 

and/or other risk factors was used to predict bone loss. 

The report also investigated what is known about the adverse effects of using markers to identify 

women at risk for osteoporosis. Major findings for this issue included:

The primary adverse effect of biochemical markers is the potential for false-positive and 

false-negative results. Rates of false-positive and false-negative test results vary widely 

among the biochemical markers. (If markers are used to select women for treatment, a 

false-positive test could lead to the initiation of unnecessary treatment, while a falsenegative result could lead to lack of needed treatment.) 

Major findings regarding whether markers can predict a patient's response to therapy included:

There is a small correlation between response to therapy as measured by densitometry 

and marker results, but no marker is accurate enough to reliably identify those individuals 

who will fail to respond to treatment. 

Evaluation for Secondary Causes of Osteoporosis

Major findings from a literature review, assessment of published guidelines, and a secondary 

analysis regarding which diagnostic or laboratory tests are appropriate for evaluating patients 

with osteoporosis for secondary causes included:

There is no evidence from controlled trials on which to base recommendations for a 

strategy of testing to determine secondary causes of osteoporosis. 

Some guidelines and experts support extensive testing to rule out major concomitant 

disease, while others suggest a limited testing strategy based on findings in the history 

and physical examination. Because the diagnosis of primary osteoporosis is often seen as 

a diagnosis of exclusion, the pattern of diagnostic testing may continue to be costly until 

the diagnostic yield is fully demonstrated. 

Assumptions about the probability of a secondary disease or disorder to explain the 

occurrence of osteoporosis vary by practice type and specialty. 

Thyroid stimulating hormone measurement, chemistry battery, and complete blood count 

were the most frequently ordered tests to rule out secondary causes of osteoporosis cited 

by respondents in our supplemental analysis. These were also the most frequently 
recommended tests in our review of expert guidelines. 

Costs

The report's findings regarding the costs and cost-effectiveness of diagnostic strategies for 

identifying women with osteoporosis included:

Published economic assessments suggested that diagnosis and treatment of women at risk 

for osteoporosis would be more cost-effective by targeting treatment to those with the 

lowest bone measurement results. Inclusion of another assessment, such as a risk profile 

or additional bone measurement test, prior to DXA may improve the cost-effectiveness of 

diagnosis. 

Using data from two large studies, the authors conducted cost-effectiveness analyses to 

estimate cost per hip fracture prevented. These analyses suggested that a sequential 

diagnostic approach may be more cost-effective than DXA alone. The sequential 

approach that the authors considered was QUS of the heel followed by DXA of the 

femoral neck only for those with low values of QUS/BUA. A range of QUS/BUA 

measures was used because there are no established cut points that separate high risk 

from normal risk. The authors used QUS as an example of a less expensive and more 

widely available diagnostic approach than DXA. 

Diagnosis with DXA of the femoral neck alone prevented more fractures, in most cases, 

but at a higher cost per hip fracture prevented compared with the sequential approach. 

All current treatment trials have inclusion criteria based on diagnosis with DXA. In 

sensitivity analyses, if treatment efficacy following diagnosis with QUS (using 

QUS/BUA cut points between 65 and 75 dB/mHz) were 5%-15% less than that following 

diagnosis using DXA, diagnosis with QUS alone would have higher costs to prevent 

fewer hip fractures than other diagnostic options. 

Future Research

Much of the evidence for the diagnosis and monitoring strategies for osteoporosis comes from 

epidemiologic studies. To be more useful for clinicians and patients, future research should focus 

on the application of these data to the clinical setting and include a wider diversity of patient 

populations. Tools for assessing risk factors should be tested in prospective studies to determine 

if their use can correctly stratify women by risk factors, influence treatment decisions, and 

ultimately reduce fracture outcomes.

Clinical trials should be conducted to determine if identifying and reducing modifiable risk 

factors influences fracture outcomes. Addressing some of these modifiable risk factors -- such as 

by supplementation with calcium and vitamin D -- has already demonstrated effects on fracture 

risk after intervention. Examples of additional interventions to test include smoking cessation, 

correcting visual loss, and improving physical function. Randomized, controlled trials of 

treatments for osteoporosis should be done to test the hypothesis that overall fracture risk, rather 

than bone measurement results alone, determines the likelihood that a patient will benefit from 
therapy. Selection of patients for trials should focus on groups of patients who are at high risk of 

fracture based on clinical risk factors and who have relatively normal bone measurement results. 

Trials should also address whether patients who are identified to have bone loss demonstrated by 

different techniques at different sites demonstrate a similar benefit to those identified solely by 

hip DXA measurements.

Additional research is needed to examine the quality of information provided to patients who 

undergo various bone measurement tests, as well as to identify other patient education and 

information needs.

Future research should examine the clinical utility of the WHO working group's criterion for 

diagnosing osteoporosis, specifically:

To determine whether the diagnosis of osteoporosis provides benefits to patients above 

that provided by predicting their risk of fractures; 

To assess the added value of obtaining bone measurement tests at more than one site, and 

the usefulness of using T-scores for different sites; and 

To define the prognosis and treated course in patients who are diagnosed to have 

osteoporosis by a wrist or spine measure, but who are not diagnosed to have osteoporosis 

by a hip measure. 

Studies that use bone measurement tests for monitoring response to therapy could compare 

fracture outcomes in a group of patients who had tailored therapy based on test results versus a 

group in whom changes in therapy, if any, were guided by the history alone. A study could also 

record how often test results in patients on therapy led to a change in therapy or improved 

compliance, to establish the mechanism by which monitoring leads to improved outcomes. By 

comparing patients, such a study could establish that monitoring changes in test results can 

reliably predict fracture risk in individual patients by distinguishing an inadequate response to 

therapy from an adequate response or poor adherence, and that monitoring changes in therapy 

made because of an inadequate test response can reduce the rate of fractures.

Prospective studies of biochemical markers should define, apply, and evaluate criteria for using 

marker results in clinical decision making.

Determining the utility of screening for secondary disorders by use of common laboratory tests 

requires studies of the frequency of abnormal baseline laboratory test results in large cohorts or 

in treatment trials of osteoporosis. Clinical follow-up of these subjects would provide data on 

bone measurement test results or fracture outcomes.

Studies to formally account for the adverse quality-of-life impact of treatment and treatment side 

effects are needed to more accurately determine the balance of risks and benefits of the therapy 

options for patients.

Three areas for additional cost-effectiveness research include:

Identifying a scientifically appropriate cut point for QUS/BUA that can be used in either 
a sequential diagnostic approach or for diagnosis with QUS alone. 

Performing additional cost-effectiveness analyses using data from other large, 

population-based cohorts with various cut points. 

Conducting a more detailed, societal-perspective, cost-effectiveness analysis that would 

address some of the deficiencies in the authors' analysis. 

If these findings can be demonstrated in one or two other populations, and in a more complete 

economic evaluation, a randomized, controlled trial of diagnostic approaches would be a useful 

next step. Alternatively, an observational-design study with randomization of groups of patients 

to diagnostic or monitoring procedures could be conducted.

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