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Original Contribution |

Cost-effectiveness of Bone Densitometry Followed by Treatment of Osteoporosis in Older Men FREE

John T. Schousboe, MD, MS; Brent C. Taylor, PhD, MPH; Howard A. Fink, MD, MPH; Robert L. Kane, MD; Steven R. Cummings, MD; Eric S. Orwoll, MD; L. Joseph Melton, MD, MPH; Douglas C. Bauer, MD; Kristine E. Ensrud, MD, MPH
[+] Author Affiliations

Author Affiliations: Park Nicollet Health Services (Dr Schousboe), Divisions of Health Policy and Management (Drs Schousboe and Kane) and Epidemiology (Drs Fink and Ensrud), School of Public Health, and Clinical Outcomes Research Center (Dr Kane), University of Minnesota, Center for Chronic Disease Outcomes Research (Drs Taylor, Fink, and Ensrud) and Geriatric Research Education and Clinical Center (Dr Fink), Veterans Affairs Medical Center, Department of Medicine, Veterans Administration Medical Center (Drs Fink and Ensrud), Minneapolis, Minnesota; San Francisco Coordinating Center, California Pacific Medical Center Research Institute (Dr Cummings), and Department of Medicine and Epidemiology, University of California at San Francisco (Dr Bauer), San Francisco; Department of Medicine, Oregon Health Sciences University, Portland (Dr Orwoll); and Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota (Dr Melton).

More Author Information
JAMA. 2007;298(6):629-637. doi:10.1001/jama.298.6.629.
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Published online

Context Osteoporotic fractures are common among elderly men.

Objective To evaluate among older men the cost-effectiveness of bone densitometry followed by 5 years of oral bisphosphonate therapy to prevent fractures for those found to have osteoporosis (femoral neck T score ≤−2.5), compared with no intervention.

Design, Setting, and Population Computer Markov microsimulation model using a societal perspective and a lifetime horizon. Simulations were performed for hypothetical cohorts of white men aged 65, 70, 75, 80, or 85 years, with or without prior clinical fracture. Data sources for model parameters included the Rochester Epidemiology Project for fracture costs and population-based age-specific fracture rates; the Osteoporotic Fractures in Men (MrOS) study and published meta-analyses for the associations among prior fractures, bone density, and incident fractures; and published studies of fracture disutility.

Main Outcome Measures Costs per quality-adjusted life-year (QALY) gained for the densitometry and follow-up treatment strategy compared with no intervention, calculated from lifetime costs and accumulated QALYs for each strategy.

Results Lifetime costs per QALY gained for the densitometry and follow-up treatment strategy were less than $50 000 for men aged 65 years or older with a prior clinical fracture and for men aged 80 years or older without a prior fracture. These results were most sensitive to oral bisphosphonate cost and fracture reduction efficacy, the strength of association between bone mineral density and fractures, fracture rates and disutility, and medication adherence.

Conclusions Bone densitometry followed by bisphosphonate therapy for those with osteoporosis may be cost-effective for men aged 65 years or older with a self-reported prior clinical fracture and for men aged 80 to 85 years with no prior fracture. This strategy may also be cost-effective for men as young as 70 years without a prior clinical fracture if oral bisphosphonate costs are less than $500 per year or if the societal willingness to pay per QALY gained is $100 000.

Figures in this Article

As the population ages, osteoporotic fractures are increasingly recognized as a common and serious health problem among elderly men.1,2 White men at age 60 years have a 29% chance of experiencing such a fracture during their remaining lifetimes.3 One-third of all hip fractures occur in men46 and are associated with as much morbidity as and higher mortality than those that occur in women.79 Vertebral fractures are also quite prevalent among older men10,11 and are strongly associated with subsequent hip12 and other clinical fractures13 and probably as much morbidity in men as in women.14

For these reasons, the International Society for Clinical Densitometry15 and the Canadian Osteoporosis Society,16 respectively, have advocated (based on expert opinion) bone densitometry for all men older than 70 and 65 years. However, the US Preventive Services Task Force and the Canadian Task Force on Preventive Health Care have made no recommendations on use of bone densitometry among elderly men. Universal bone densitometry for women older than 65 years has been demonstrated to be cost-effective,17 but the age-specific prevalence of osteoporosis and incident fracture rates are much lower among men than women. Among men, increased age is associated not only with increased prevalence of osteoporosis and fracture rates but also with increased mortality, so it is unclear a priori if bone densitometry followed by treatment of men with osteoporosis is cost-effective at any age. Only 1 modeling study has assessed the cost-effectiveness of pharmacologic therapy to prevent fracture in osteoporotic men, and it included neither the costs of bone densitometry to identify the treatment cohort nor the disutility associated with incident radiographic but clinically unrecognized vertebral fractures.18 Thus, despite the importance of the problem of osteoporosis in men, clinical decision making is hampered by a lack of evidence-based cost-effectiveness analyses of common diagnostic and therapeutic interventions. The lack of consensus concerning this issue is reflected in very low rates of clinical intervention for osteoporosis in men.19

The purpose of this modeling study was to estimate the lifetime costs and health benefits of bone densitometry followed by 5 years of oral bisphosphonate therapy for men found to have osteoporosis (femoral neck T score ≤−2.5, using healthy young white men as the reference) among hypothetical subsets of elderly men with or without prior clinical fracture since age 50 years, compared with no intervention. We chose to stratify the analyses according to self-reported fracture history because self-reports of prior fractures are reasonably accurate20,21 and are an important predictor of subsequent fractures.22,23

We constructed a Markov cost-utility model using Data Pro Healthcare 2005 software, release 0.4 (TreeAge, Williamstown, Massachusetts) to compare bone densitometry followed by oral bisphosphonate therapy for those with osteoporosis vs no intervention.

Model Structure

The model health states were no fracture, post–distal forearm fracture, post–clinical vertebral fracture (ie, clinically evident at onset), post–radiographic vertebral fracture (ie, not recognized clinically at onset), post–hip fracture, post–other fractures (ie, of the proximal forearm, humerus, scapula, clavicle, sternum, ribs, pelvis, distal femur, patella, tibia, or proximal fibula), post–hip and vertebral fracture, and death (Figure 1). Beginning in the no-fracture state, a fracture may occur, at which time transition to that postfracture state occurs. The costs of that fracture are assigned as a transition cost. Fracture disutility is modeled as a lower value of a quality-adjusted life- year (QALY) compared with the no-fracture state. Long-term care costs after hip fracture are assigned in the post–hip fracture and post–vertebral/hip fracture states. Individuals are eligible for (at risk of) transition to a different state once every 3 months and are followed up through the model until death or age 105 years to capture the permanent disutility that may follow hip and clinical vertebral fractures. We assumed discount rates of 3% for both costs and health benefits.

Figure 1. Markov Diagram of Health States and Possible Transitions Among Them During Each 3-Month Cycle
Graphic Jump Location

Transition to death may also occur from any state (not shown by arrows).

Probability of Mortality

Background mortality was estimated from 2003 US vital statistics.24 The mortality for the first year after hip fracture was estimated to be 1.375 times the background rate.25 Because the excess mortality associated with vertebral fracture may be attributable to preexisting comorbidity and not to the fracture itself,26,27 we assumed no excess mortality directly attributable to vertebral or other nonhip fractures.

Fracture Probabilities

The probabilities of each type of fracture due to mild or moderate trauma were established as functions of age, presence of osteoporosis (femoral neck T score ≤−2.5), presence or absence of prior clinical fracture, and presence or absence of bisphosphonate therapy. The risks of each type of fracture as a function of age were developed from comprehensive population-based, age-specific data for men from the Rochester Epidemiology Project,28 which captures virtually all health care utilization within Olmsted County, Minnesota.29 Since the odds ratio of a radiographic vertebral fracture in Olmsted County being clinically unrecognized vs clinically recognized is 1.86,30 the incidence rate of radiographic (but clinically unrecognized) vertebral fracture was set at 1.86 times that of clinical vertebral fracture. Fracture rates were plotted against age, and a best-fitting power curve was determined for each fracture type. These power curves represent fracture rates as continuous functions of age for the entire male population of Olmsted County (90% of which is white), including those with or without osteoporosis and/or prior fracture. Because fracture reduction from bisphosphonates was modeled from direct data rather than indirectly through changes in bone mineral density (BMD), changes in BMD from bisphosphonate therapy were not included in the model.

Fracture Risks Attributable to Osteoporosis and Self-reported Clinical Fracture

The relative risks of hip fracture for each 1-SD decrease in femoral neck BMD, derived from the largest meta-analysis of hip fracture predictors performed to date,31 were assumed to decrease with age from 3.38 for men aged 65 years to 2.26 for men aged 85 years. Based on this same meta-analysis, the relative risks of hip fracture in those with (vs without) prior clinical fracture were assumed to decrease with age from 2.77 for men aged 65 years to 1.61 for men aged 85 years.32 Based on the observational Rotterdam study, we assumed a relative risk of incident vertebral fractures of 1.8 per SD decrease of femoral neck BMD and a relative risk of 2.4 in those with (vs without) prior clinical fracture.33

The relative risk of nonvertebral nonhip fractures was assumed to be 1.34 per 1-SD decrease in femoral neck BMD based on data from the Osteoporotic Fractures in Men (MrOS) study,34 an observational study including 5362 white US men aged 65 years or older.35,36 We used unpublished MrOS data to estimate the relative risk of nonvertebral nonhip fractures in those with vs without prior clinical fracture. At the baseline MrOS examination, 17% of the white participants (913 men) reported a prior clinical fracture since age 50 years. Incident clinical fractures were assessed by self-report on questionnaires mailed every 4 months, and reported fractures were confirmed by review of radiographic reports, with 99% complete ascertainment. Through 4.9 years of follow-up, 329 nonvertebral nonhip fractures occurred. For those with vs without prior clinical fracture, the relative risk of incident nonvertebral nonhip fractures was 2.01, adjusted for age, enrollment site, and BMD.

For each starting age, the relative risks of fractures in those with vs without prior clinical fracture were further adjusted for the prevalence of prior clinical fracture to derive the risks of fractures attributable to prior clinical fracture relative to the entire male population of that same age (technical supplement available on request from corresponding author).

Relative Risk of Fracture With Drug Therapy

We assumed relative risks of 0.36 and 0.73, respectively, for incident vertebral and nonvertebral fractures during use of oral bisphosphonates vs no drug therapy, based on a meta-analysis of the 2 published prospective, randomized clinical trials of alendronate in men.37 The fracture reduction benefit was assumed to start 6 weeks after the start of therapy. After a 5-year treatment course, a gradual linear loss of fracture reduction benefit was assumed to occur over the subsequent 5 years.

Prevalence of Osteoporosis in Men With and Without Prior Fracture by Age

The prevalence of osteoporosis at the femoral neck for each screening initiation in the white male US population was estimated from the Third National Health and Nutrition Examination Survey.38 Then, the proportions of those with and without prior clinical fracture who have osteoporosis at each age were estimated, assuming an age-adjusted relative risk of 1.91 (derived from MrOS baseline data using a logistic regression model) for presence of femoral neck osteoporosis in those with (vs without) prior clinical fracture.

Direct Costs

We assumed the cost of oral bisphosphonates to be the average US wholesale price for alendronate in 2004 ($1000/y)39 and that adverse effects of bisphosphonate would generate only trivial direct medical costs. We assigned the cost of 1 physician visit ($52) for each year of bisphosphonate therapy and the cost of 1 additional bone density test after 2 years of drug therapy. The direct medical costs of acute hip, clinical vertebral, distal forearm, and other fractures (Table 1) were based on societal opportunity cost estimates, expressed in 2004 US dollars.44 The direct cost of radiographic (clinically unrecognized) vertebral fractures was assumed to be zero. We assumed the cost of a bone density test to be the mean 2007 Medicare reimbursement ($82),49 reflecting recent concerns that previous reimbursement rates were in excess of the true cost of performing and interpreting bone density tests.50

The long-term care cost for the first year after hip fracture, averaged across all hip fracture patients, was estimated from nursing home use following hip fracture compared with an age- and sex-matched control group,45 the US cost per day of long-term care,51 and the mean length of nursing home stay following hip fracture for those who were community dwelling before fracture (Table 1). Permanent long-term care in men who were community dwelling before fracture was estimated to be required for 12.2% following hip fracture, costing $7302 per year averaged across all hip fracture patients.

Indirect Costs

Lost productivity from hip, clinical vertebral, other, and distal forearm fractures, respectively, was estimated to be 0.348, 0.149, 0.127, and 0.095 years.46 Indirect costs were calculated as this proportion multiplied by the mean yearly earnings for employed white men in the United States for 2004 (stratified according to age)52 and adjusted by age-specific workforce participation rates (Table 1).53

QALYs Associated With Each Health State

Based on population-based surveys, we assumed a QALY value of 0.7 associated with the no-fracture state for elderly men.40 The disutilities for the first year following incident hip, distal forearm, and clinical vertebral fractures were derived from a Swedish prospective study of elderly men and women (Table 1).14 The assumed disutilities for the first year following “other” fractures,23 for all fractures more than 1 year after their occurrence,23 and for the post–hip and post–vertebral fracture states43 are shown in Table 1. Radiographic vertebral fractures were assumed to cause a loss of quality of life only 6 years after their occurrence because such fractures that are more than 4 to 8 years old do not appear to be associated with increased pain or limited activity.54,55 Secondary analyses were performed assuming a QALY value of 1.0 to compare estimated life-years saved with the densitometry and treatment strategy vs with no intervention.

Medication Adherence

For the base-case analysis, we assumed that only 85% of prescribed medication would be purchased and taken in the first 3 months and that this percentage would drop to 65% by the end of the first year, to 60% by the end of the second year, and to 55% by the end of the fifth (and final) year of oral bisphosphonate therapy.56 Medication costs and fracture reduction efficacy were assumed to be proportional to adherence.

Sensitivity Analyses

Univariate sensitivity analyses were performed varying discount rates, fracture rates, fracture costs, fracture disutility, the costs of bone densitometry, the offset of fracture reduction benefit following cessation of drug therapy, preventable mortality due to vertebral fracture, medication adherence, the relative risks of fractures attributable to osteoporosis or prior clinical fracture, yearly oral bisphosphonate cost, and delaying the onset of fracture reduction benefit for 7.5 months after the start of therapy. Because of uncertainty regarding the nonvertebral fracture reduction efficacy of oral bisphosphonates for men, 2-way sensitivity analyses were performed assuming reduced nonvertebral fracture efficacy, using different yearly oral bisphosphonate costs.

Probabilistic sensitivity analyses were performed using log-normal distributions of fracture direct costs44 and normal distributions of fracture rates and permanent long-term care costs following hip fracture. The distributions of the relative risks of incident fractures associated with osteoporosis, prior fracture, and oral bisphosphonate therapy were assumed to be log-normal. Uniform distributions were used to model variability in fracture disutility and indirect fracture costs. Full details of the derivation of the parameter distributions used for the probabilistic sensitivity analyses are available in an online technical supplement (on request from corresponding author). Cost-effectiveness acceptability curves were generated from these analyses.

Secondary analyses of the densitometry and follow-up treatment strategy compared with no intervention were also performed assuming treatment femoral neck T-score thresholds of −2.0 or lower and −3.0 or lower.

Model Validation

The model estimated the percentage of 50-year-old men who would have a hip fracture during their remaining lifetimes to be 6.2%, nearly identical to that estimated by Melton et al.57 The model estimated that 6.9% and 1.2%, respectively, would have 1 or more lifetime clinical vertebral and distal forearm fractures, compared with the estimates of Melton et al of 5.0% for vertebral and 2.5% for distal forearm fractures.57 However, for men aged 65 to 84 years (the age range over which treatment vs no treatment was modeled), model-predicted and actual rates, respectively, of distal forearm fractures reported from the Rochester Epidemiology Project were close to each other (46 vs 49 per 100 000 person-years). Similarly, age-adjusted actual and model-predicted clinical vertebral fractures, respectively, were 495 and 506 per 100 000 person-years.

Model Simulation Runs and Calculation of Cost-effectiveness

For the base-case analyses, we ran the model for subsets of elderly men with or without a prior clinical fracture at 5 different starting ages (65, 70, 75, 80, and 85 years) using Monte Carlo simulations. For each simulation, 50 000 men were put through each of the 2 strategies of the microsimulation model, one at a time. The incremental cost-effectiveness ratio was computed as the difference in lifetime mean costs per man divided by the difference in lifetime mean accumulated QALYs per man between the strategies. An incremental cost-effectiveness ratio represents the cost of gaining 1 QALY.

Univariate and bivariate sensitivity analyses were also run with 50 000 trials each. Probabilistic sensitivity analyses were performed with 500 simulations and 5000 trials per simulation, with a new set of values for all of the above variables randomly selected from their respective distributions for each simulation.

To estimate the proportion of men for whom clinical vertebral, hip, distal forearm, and other fractures would be prevented by the densitometry and treatment strategy, models were run with a 10-year horizon corresponding to the 5-year treatment period and gradual loss of fracture reduction benefit over the subsequent 5 years.

The estimated prevalence of femoral neck osteoporosis among men with a prior fracture ranged from 14.5% at age 65 years to 33.6% at age 85 years. Osteoporosis prevalence in the absence of a prior clinical fracture was lower, ranging from 7.6% at age 65 years to 17.6% at age 85 years. The densitometry and treatment strategy modestly reduced the absolute 10-year incidence of clinical fractures by a range of 2.1% for 65-year-old men without a prior fracture to 4.5% among 85-year-old men with a prior fracture (Figure 2).

Figure 2. Ten-Year Clinical Fracture Incidence According to Age, Prior Clinical Fracture Status, and Intervention Assignment
Graphic Jump Location

The costs per QALY gained for the densitometry and treatment strategy compared with no intervention decreased with age and were substantially lower for men with a self-reported history of clinical fracture since age 50 years. In the base-case model (Table 2), the costs per QALY gained were less than $50 000 for those with a prior clinical fracture at all ages, as well as among men aged 80 or 85 years without a prior clinical fracture. The costs per QALY gained were below $100 000 for men aged 70 years or older without a prior fracture. Among all the base-case scenarios, the maximum gain in life-years was 0.007 (2.5 days).

Table Graphic Jump LocationTable 2. Cost per QALY Gained for the Densitometry and Treatment Strategy According to Age and Prior Fracture Status
Impact of Bisphosphonate Cost and Assumed Reduction in Nonvertebral Fracture Risk

These results were sensitive to the assumed yearly cost of oral bisphosphonate therapy (Figure 3). For example, if the yearly cost of oral bisphosphonate therapy was only $500 per year, then the cost per QALY gained for 70-year-old men without a history of clinical fracture was less than $50 000, compared with $70 000 if the yearly cost of therapy was $1000. These results were also quite sensitive to the assumed nonvertebral fracture reduction benefit from bisphosphonate therapy, such that the costs per QALY gained for 80-year-old men without a history of clinical fracture would be $97 000 if nonvertebral fractures were reduced only 10% by oral bisphosphonates, compared with $46 000 in this same group if nonvertebral fractures were reduced by 27% by therapy (base model) (Figure 4). If bisphosphonate cost was only $500 per year, however, then the cost per QALY gained for 80-year-old men without prior clinical fracture would be close to $50 000 or less per year even if nonvertebral fractures were reduced only 10% by treatment.

Figure 3. Cost per QALY Gained for the Densitometry and Treatment Strategy According to Yearly Cost of Oral Bisphosphonates and Age in Men Without Prior Clinical Fracture
Graphic Jump Location

QALY indicates quality-adjusted life-year.

Figure 4. Cost per QALY Gained for the Densitometry and Treatment Strategy According to Nonvertebral Fracture Reduction Efficacy and Cost of Oral Bisphosphonates in an 80-Year-Old Man With No Prior Fracture
Graphic Jump Location

QALY indicates quality-adjusted life-year.

Other Sensitivity Analyses

Univariate sensitivity analyses showed these estimated costs per QALY gained to be quite sensitive to reasonable changes in fracture rates, fracture disutility, and the relative risks of fractures attributable to osteoporosis (Table 3) and modestly sensitive to the cost of bone densitometry. Assuming a yearly bisphosphonate cost of $1000 and a societal willingness to pay of $50 000 per QALY gained, acceptability curves generated by probabilistic sensitivity analyses showed that the densitometry and treatment strategy has only a 10% probability of being cost-effective for 70-year-old men without a prior clinical fracture but a 78% probability of being cost-effective for 75-year-old men with a prior fracture (Figure 5). These analyses show that the cost-effectiveness of the densitometry and treatment strategy is less certain for men aged 80 years without a prior fracture and 65-year-old men with a prior fracture. However, if yearly bisphosphonate costs are reduced to $500, the probabilities for the cost per QALY gained for the densitometry and treatment strategy being below $50 000 are increased to 85% and 84%, respectively, for 80-year-old men without a prior fracture and 65-year-old men with a prior fracture.

Figure 5. Cost-effectiveness Acceptability Curves: Cost per QALY Gained for the Densitometry and Treatment Strategy According to Oral Bisphosphonate Cost
Graphic Jump Location

QALY indicates quality-adjusted life-year.

Table Graphic Jump LocationTable 3. Univariate Sensitivity Analyses for an 80-Year-Old Man With No Prior Fracture

If the densitometry and treatment strategy used a T-score treatment threshold of −2.0 instead of −2.5, then the costs per QALY gained compared with no drug therapy would be higher for 80-year-old men without a prior fracture ($60 938) compared with the base case ($45 587) as well as for 65-year-old men with a prior fracture ($66 781) compared with the base case ($47 537). However, if the densitometry and treatment strategy used a T-score treatment threshold of −3.0, then the costs per QALY gained would be slightly lower for 65-year-old men with a prior fracture ($37 837) and the same for 80-year-old men without a prior fracture ($45 714) compared with the base-case scenarios.

Osteoporotic fractures are an important cause of morbidity among elderly men, and widespread bone densitometry screening programs for men older than 70 years have been recommended1,2,15 but are based on expert opinion and have not been widely adopted.19 This study provides a firm basis for developing rational clinical paradigms for the detection and treatment of men with osteoporosis.

Assuming a societal willingness to pay per QALY gained of $50 000 and current drug costs, bone densitometry followed by oral bisphosphonate therapy for those with a femoral neck T score of −2.5 or lower may be cost-effective for men aged 65 years or older with a history of clinical fracture. However, in the absence of a prior fracture or other substantial additional fracture risk factors, the densitometry and follow-up treatment strategy may be cost-effective only for men aged 80 years or older. The cost-effectiveness of the densitometry and screening strategy increases with age, even up to age 85 years, because the risk of hip and other fractures increases with age as fast or faster than mortality and because the prevalence of osteoporosis (and therefore the proportion selected for drug therapy) increases substantially with age. Universal bone densitometry for all men aged 70 years or older does not appear to be justifiable with current bisphosphonate costs, at least on grounds of cost-effectiveness. Moreover, the overall fracture burden among elderly men with osteoporosis would be affected only to a modest degree by this strategy, largely because of suboptimal medication adherence and only modest reduction of nonvertebral fractures by oral bisphosphonates.

If the societal willingness to pay per QALY is $100 000 or bisphosphonate therapy costs less than $500 per year, however, bone densitometry followed by drug therapy may be cost-effective for men aged 70 years or older, even without a prior fracture. Since alendronate will lose patent protection in the United States in 2008, the cost of oral bisphosphonate therapy in the near future may be much less than the current average US wholesale price.

Our results suggest that the cost-effectiveness of the densitometry and treatment strategy may be slightly improved by use of stricter bone density treatment thresholds. More liberal treatment thresholds expand the proportion of those eligible for drug therapy, thereby lowering the screening densitometry cost per treated person, but this is offset by the treated cohort having a lower risk of fracture. Moreover, among postmenopausal women, oral bisphosphonates may effectively reduce nonvertebral fractures only among those with a sex-specific femoral neck BMD T score of −2.5 or lower.58,59 If the fracture reduction efficacy of oral bisphosphonates is also inversely correlated with BMD in men, then the cost-effectiveness of strategies that use a more restrictive treatment BMD threshold may be even more favorable relative to strategies with more liberal treatment thresholds.

Our study is the first to assess the cost-effectiveness of widespread bone densitometry screening and subsequent drug therapy to prevent osteoporotic fracture among elderly men. We used population-based estimates of white male fracture rates, age-specific proportions of men who have osteoporosis, and direct medical costs of fractures. We used probabilistic sensitivity analyses that allowed nearly all major model parameters to vary over reasonable ranges to test the robustness of our conclusions to changes in these parameters. In contrast with virtually all previously published cost-effectiveness studies of drug therapy for osteoporosis,60 we have incorporated empirical estimates of medication nonadherence in our base-case analyses.

There are also important limitations to our study. First, these results are applicable to a treatment duration of only 5 years. Since treatment for 10 years may not reduce the risk of nonvertebral fractures more than treatment for 5 years,61 treatment for longer than 5 years may be less cost-effective. Second, these results are not applicable to treatment decisions based on BMD measured at skeletal sites other than the femoral neck, such as the lumbar spine. Third, this study is applicable only to white men residing in the United States. In particular, age-adjusted fracture rates are significantly lower among Hispanic and especially African American men compared with white US men, and hip fracture rates among Asians are lower. Fourth, our estimates of fracture disutility and fracture costs are based on studies in which a minority of the participants were men, although these studies do not indicate a significant difference in these parameters between the sexes. Fifth, there are no precise estimates of the nonvertebral fracture reduction efficacy of oral bisphosphonates among elderly men. Additional clinical trials yielding accurate estimates of nonvertebral fracture reduction with bisphosphonate therapy will allow completion of more precise modeling studies of the cost-effectiveness of oral bisphosphonate therapy. Finally, these analyses are applicable only to those with average risks based on age and prior fracture status and do not incorporate additional fracture risk factors, such as long-term systemic glucocorticoid use.

In conclusion, universal bone densitometry followed by oral bisphosphonate therapy among those found to have osteoporosis for all men aged 70 years or older regardless of fracture history or other fracture risk factors is not cost-effective using current drug costs. However, this strategy may be cost-effective for men aged 65 years or older with a prior clinical fracture and for men aged 80 years or older without a prior fracture, assuming a societal willingness to pay per QALY gained of $50 000. This densitometry and treatment strategy may also be cost-effective for white men aged 70 years or older without a prior clinical fracture if the cost of oral bisphosphonate therapy is less than $500 per year or if the societal willingness to pay per QALY gained is $100 000.

Corresponding Author: John T. Schousboe, MD, MS, Rheumatology, Park Nicollet Health Services, 3800 Park Nicollet Blvd, Minneapolis, MN 55416 (john.schousboe@parknicollet.com).

Author Contributions: Drs Schousboe and Taylor had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Schousboe, Kane.

Acquisition of data: Schousboe, Cummings, Orwoll, Melton, Ensrud.

Analysis and interpretation of data: Schousboe, Taylor, Fink, Cummings, Orwoll, Melton, Bauer, Ensrud.

Drafting of the manuscript: Schousboe.

Critical revision of the manuscript for important intellectual content: Schousboe, Taylor, Fink, Kane, Cummings, Orwoll, Melton, Bauer, Ensrud.

Statistical analysis: Schousboe, Taylor, Fink.

Obtained funding: Cummings, Orwoll, Ensrud.

Administrative, technical, or material support: Taylor, Orwoll.

Study supervision: Kane.

Financial Disclosures: Dr Schousboe reports receiving research support from Hologic Inc and serving as a consultant to Eli Lilly, Merck, and Amgen. Dr Bauer reports receiving research support from Novartis, Amgen, Procter & Gamble, and Merck. Dr Cummings reports receiving research support from Amgen, Novartis, Pfizer, Lilly, and Zelos and serving as a consultant to or receiving honoraria from Novartis, Pfizer, Lilly, and Merck. Dr Orwoll reports receiving research support from Aventis, Pfizer, Lilly, Novartis, Procter & Gamble, GlaxoSmithKline, Solvay, Zelos, and Amgen and receiving honoraria from Merck. Dr Ensrud reports receiving research support from Bionovo, Eli Lilly, and Pfizer. No other disclosures were reported.

Funding/Support: The MrOS study, which was used to derive certain model parameters, is supported by National Institutes of Health funding under the following grant numbers: National Institute of Arthritis and Musculoskeletal and Skin Diseases: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583; National Institute on Aging: U01 AG18197, U01-AG027810; and National Center for Research Resources: UL1 RR024140.

Role of the Sponsor: The funding agencies had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

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O'Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ. The prevalence of vertebral deformity in European men and women: the European Vertebral Osteoporosis Study.  J Bone Miner Res. 1996;11(7):1010-1018
PubMed   |  Link to Article
Jackson SA, Tenenhouse A, Robertson L. Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos).  Osteoporos Int. 2000;11(8):680-687
PubMed   |  Link to Article
Hasserius R, Johnell O, Nilsson BE.  et al.  Hip fracture patients have more vertebral deformities than subjects in population-based studies.  Bone. 2003;32(2):180-184
PubMed   |  Link to Article
Hasserius R, Karlsson MK, Nilsson BE, Redlund-Johnell I, Johnell O. Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study.  Osteoporos Int. 2003;14(1):61-68
PubMed   |  Link to Article
Borgström F, Zethraeus N, Johnell O.  et al.  Costs and quality of life associated with osteoporosis-related fractures in Sweden.  Osteoporos Int. 2006;17(5):637-650
PubMed   |  Link to Article
Binkley N, Bilezikian JP, Kendler DL, Leib ES, Lewiecki EM, Petak SM. Official positions of the International Society for Clinical Densitometry and executive summary of the 2005 Position Development Conference.  J Clin Densitom. 2006;9(1):4-14
PubMed   |  Link to Article
Brown JP, Josse RG.Scientific Advisory Council of the Osteoporosis Society of Canada.  2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada.  CMAJ. 2002;167(10):(suppl)  S1-S34
PubMed
Schousboe JT, Ensrud KE, Nyman JA, Melton LJ III, Kane RL. Universal bone densitometry screening combined with alendronate therapy for those diagnosed with osteoporosis is highly cost-effective for elderly women.  J Am Geriatr Soc. 2005;53(10):1697-1704
PubMed   |  Link to Article
Borgström F, Johnell O, Jonsson B, Zethraeus N, Sen SS. Cost effectiveness of alendronate for the treatment of male osteoporosis in Sweden.  Bone. 2004;34(6):1064-1071
PubMed   |  Link to Article
Feldstein AC, Nichols G, Orwoll E.  et al.  The near absence of osteoporosis treatment in older men with fractures.  Osteoporos Int. 2005;16(8):953-962
PubMed   |  Link to Article
Joakimsen RM, Fonnebo V, Sogaard AJ, Tollan A, Stormer J, Magnus JH. The Tromso study: registration of fractures, how good are self-reports, a computerized radiographic register and a discharge register?  Osteoporos Int. 2001;12(12):1001-1005
PubMed   |  Link to Article
Nevitt MC, Cummings SR, Browner WS.  et al.  The accuracy of self-report of fractures in elderly women: evidence from a prospective study.  Am J Epidemiol. 1992;135(5):490-499
PubMed
Haentjens P, Autier P, Collins J, Velkeniers B, Vanderschueren D, Boonen S. Colles fracture, spine fracture, and subsequent risk of hip fracture in men and women: a meta-analysis.  J Bone Joint Surg Am. 2003;85-A(10):1936-1943
PubMed
Kanis JA, Johnell O, Oden A.  et al.  The risk and burden of vertebral fractures in Sweden.  Osteoporos Int. 2004;15(1):20-26
PubMed   |  Link to Article
Arias E. United States life tables, 2003.  Natl Vital Stat Rep. 2006;54(14):1-40
PubMed
Kanis JA, Johansson H, Oden A, Jonsson B, Johnell O, De Laet C. How many deaths from hip fracture might be prevented [abstract]?  J Bone Miner Res. 2002;17:(suppl 1)  S146
Link to Article
Melton LJ. Excess mortality following vertebral fracture.  J Am Geriatr Soc. 2000;48(3):338-339
PubMed
Johnell O, Kanis JA, Oden A.  et al.  Mortality after osteoporotic fractures.  Osteoporos Int. 2004;15(1):38-42
PubMed   |  Link to Article
Melton LJ III, Crowson CS, O’Fallon WM. Fracture incidence in Olmsted County, Minnesota: comparison of urban with rural rates and changes in urban rates over time.  Osteoporos Int. 1999;9(1):29-37
PubMed   |  Link to Article
Melton LJ III. History of the Rochester Epidemiology Project.  Mayo Clin Proc. 1996;71(3):266-274
PubMed   |  Link to Article
Melton LJ III, Lane AW, Cooper C, Eastell R, O’Fallon WM, Riggs BL. Prevalence and incidence of vertebral deformities.  Osteoporos Int. 1993;3(3):113-119
PubMed   |  Link to Article
Johnell O, Kanis JA, Oden A.  et al.  Predictive value of BMD for hip and other fractures.  J Bone Miner Res. 2005;20(7):1185-1194
PubMed   |  Link to Article
Kanis JA, Johnell O, De Laet C.  et al.  A meta-analysis of previous fracture and subsequent fracture risk.  Bone. 2004;35(2):375-382
PubMed   |  Link to Article
van der Klift M, de Laet CE, McCloskey EV.  et al.  Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.  J Bone Miner Res. 2004;19(7):1172-1180
PubMed   |  Link to Article
Cummings SR, Cawthon PM, Ensrud KE, Cauley JA, Fink HA, Orwoll ES. BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women.  J Bone Miner Res. 2006;21(10):1550-1556
PubMed   |  Link to Article
Blank JB, Cawthon PM, Carrion-Petersen ML.  et al.  Overview of recruitment for the osteoporotic fractures in men study (MrOS).  Contemp Clin Trials. 2005;26(5):557-568
PubMed   |  Link to Article
Orwoll E, Blank JB, Barrett-Connor E.  et al.  Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study—a large observational study of the determinants of fracture in older men.  Contemp Clin Trials. 2005;26(5):569-585
PubMed   |  Link to Article
Sawka AM, Papaioannou A, Adachi JD, Gafni A, Hanley DA, Thabane L. Does alendronate reduce the risk of fracture in men? a meta-analysis incorporating prior knowledge of anti-fracture efficacy in women.  BMC Musculoskelet Disord. 2005;6:39
PubMed   |  Link to Article
Looker AC, Wahner HW, Dunn WL.  et al.  Updated data on proximal femur bone mineral levels of US adults.  Osteoporos Int. 1998;8(5):468-489
PubMed   |  Link to Article
 Drug Topics 2001 Red Book. Montvale, NJ: Medical Economics Co; 2001
Macran S, Weatherly H, Kind P. Measuring population health: a comparison of three generic health status measures.  Med Care. 2003;41(2):218-231
PubMed
Burström K, Johannesson M, Diderichsen F. Swedish population health-related quality of life results using the EQ-5D.  Qual Life Res. 2001;10(7):621-635
PubMed   |  Link to Article
Oleksik A, Lips P, Dawson A.  et al.  Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures.  J Bone Miner Res. 2000;15(7):1384-1392
PubMed   |  Link to Article
Tosteson AN, Gabriel SE, Grove MR, Moncur MM, Kneeland TS, Melton LJ III. Impact of hip and vertebral fractures on quality-adjusted life years.  Osteoporos Int. 2001;12(12):1042-1049
PubMed   |  Link to Article
Gabriel SE, Tosteson AN, Leibson CL.  et al.  Direct medical costs attributable to osteoporotic fractures.  Osteoporos Int. 2002;13(4):323-330
PubMed   |  Link to Article
Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study.  J Am Geriatr Soc. 2002;50(10):1644-1650
PubMed   |  Link to Article
Meerding WJ, Looman CW, Essink-Bot ML, Toet H, Mulder S, van Beeck EF. Distribution and determinants of health and work status in a comprehensive population of injury patients.  J Trauma. 2004;56(1):150-161
PubMed   |  Link to Article
Orwoll E, Ettinger M, Weiss S.  et al.  Alendronate for the treatment of osteoporosis in men.  N Engl J Med. 2000;343(9):604-610
PubMed   |  Link to Article
Ringe JD, Dorst A, Faber H, Ibach K. Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study.  Rheumatol Int. 2004;24(2):110-113
PubMed   |  Link to Article
Centers for Medicare and Medicaid Services.  Physician fee schedule search: 2007. http://www.cms.hhs.gov/PFSlookup/02_PFSSearch.asp. Accessed March 4, 2007
Centers for Medicare and Medicaid Services.  Five-Year Review of Work Relative Value Units Under the Physician Fee Schedule and Proposed Changeshttp://www.cms.hhs.gov/physicianfeesched/downloads/cms-1512-pn.pdf. Accessed March 8, 2007, 2007
Johnell O, Gullberg B, Kanis JA. The hospital burden of vertebral fracture in Europe: a study of national register sources.  Osteoporos Int. 1997;7(2):138-144
PubMed   |  Link to Article
Bureau of Labor Statistics, US Census Bureau.  CPS Annual Demographic Survey. http://pubdb3.census.gov/macro/032005/perinc/new05_102.htm. Accessed November 28, 2006
US Census Bureau. Workforce participation rates. http://factfinder.census.gov/home/saff/main.html?_lang=en. Accessed November 28, 2006
O’Neill TW, Cockerill W, Matthis C.  et al.  Back pain, disability, and radiographic vertebral fracture in European women: a prospective study.  Osteoporos Int. 2004;15(9):760-765
PubMed   |  Link to Article
Nevitt MC, Ettinger B, Black DM.  et al.  The association of radiographically detected vertebral fractures with back pain and function: a prospective study.  Ann Intern Med. 1998;128(10):793-800
PubMed   |  Link to Article
Huybrechts KF, Ishak KJ, Caro JJ. Assessment of compliance with osteoporosis treatment and its consequences in a managed care population.  Bone. 2006;38(6):922-928
PubMed   |  Link to Article
Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective: how many women have osteoporosis?  J Bone Miner Res. 1992;7(9):1005-1010
PubMed   |  Link to Article
Cummings SR, Black DM, Thompson DE.  et al.  Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.  JAMA. 1998;280(24):2077-2082
PubMed   |  Link to Article
McClung MR, Geusens P, Miller PD.  et al. Hip Intervention Program Study Group.  Effect of risedronate on the risk of hip fracture in elderly women.  N Engl J Med. 2001;344(5):333-340
PubMed   |  Link to Article
Schousboe JT. Cost-Effectiveness modeling research of pharmacologic therapy to prevent fractures related to osteoporosis.  Curr Rheumatol Rep. 2007;9(1):50-56
PubMed   |  Link to Article
Black DM, Schwartz AV, Ensrud KE.  et al.  Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial.  JAMA. 2006;296(24):2927-2938
PubMed   |  Link to Article

Figures

Figure 1. Markov Diagram of Health States and Possible Transitions Among Them During Each 3-Month Cycle
Graphic Jump Location

Transition to death may also occur from any state (not shown by arrows).

Figure 2. Ten-Year Clinical Fracture Incidence According to Age, Prior Clinical Fracture Status, and Intervention Assignment
Graphic Jump Location
Figure 3. Cost per QALY Gained for the Densitometry and Treatment Strategy According to Yearly Cost of Oral Bisphosphonates and Age in Men Without Prior Clinical Fracture
Graphic Jump Location

QALY indicates quality-adjusted life-year.

Figure 4. Cost per QALY Gained for the Densitometry and Treatment Strategy According to Nonvertebral Fracture Reduction Efficacy and Cost of Oral Bisphosphonates in an 80-Year-Old Man With No Prior Fracture
Graphic Jump Location

QALY indicates quality-adjusted life-year.

Figure 5. Cost-effectiveness Acceptability Curves: Cost per QALY Gained for the Densitometry and Treatment Strategy According to Oral Bisphosphonate Cost
Graphic Jump Location

QALY indicates quality-adjusted life-year.

Tables

Table Graphic Jump LocationTable 2. Cost per QALY Gained for the Densitometry and Treatment Strategy According to Age and Prior Fracture Status
Table Graphic Jump LocationTable 3. Univariate Sensitivity Analyses for an 80-Year-Old Man With No Prior Fracture

References

Olszynski WP, Shawn Davison K, Adachi JD.  et al.  Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment.  Clin Ther. 2004;26(1):15-28
PubMed   |  Link to Article
Wright VJ. Osteoporosis in men.  J Am Acad Orthop Surg. 2006;14(6):347-353
PubMed
Jones G, Nguyen T, Sambrook PN, Kelly PJ, Gilbert C, Eisman JA. Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES).  Osteoporos Int. 1994;4(5):277-282
PubMed   |  Link to Article
Mussolino ME, Looker AC, Madans JH, Langlois JA, Orwoll ES. Risk factors for hip fracture in white men: the NHANES I Epidemiologic Follow-up Study.  J Bone Miner Res. 1998;13(6):918-924
PubMed   |  Link to Article
Kellie SE, Brody JA. Sex-specific and race-specific hip fracture rates.  Am J Public Health. 1990;80(3):326-328
PubMed   |  Link to Article
Papadimitropoulos EA, Coyte PC, Josse RG, Greenwood CE. Current and projected rates of hip fracture in Canada.  CMAJ. 1997;157(10):1357-1363
PubMed
Kanis JA, Oden A, Johnell O, De Laet C, Jonsson B, Oglesby AK. The components of excess mortality after hip fracture.  Bone. 2003;32(5):468-473
PubMed   |  Link to Article
Trombetti A, Herrmann F, Hoffmeyer P, Schurch MA, Bonjour JP, Rizzoli R. Survival and potential years of life lost after hip fracture in men and age-matched women.  Osteoporos Int. 2002;13(9):731-737
PubMed   |  Link to Article
Jacobsen SJ, Goldberg J, Miles TP, Brody JA, Stiers W, Rimm AA. Race and sex differences in mortality following fracture of the hip.  Am J Public Health. 1992;82(8):1147-1150
PubMed   |  Link to Article
O'Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA, Silman AJ. The prevalence of vertebral deformity in European men and women: the European Vertebral Osteoporosis Study.  J Bone Miner Res. 1996;11(7):1010-1018
PubMed   |  Link to Article
Jackson SA, Tenenhouse A, Robertson L. Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos).  Osteoporos Int. 2000;11(8):680-687
PubMed   |  Link to Article
Hasserius R, Johnell O, Nilsson BE.  et al.  Hip fracture patients have more vertebral deformities than subjects in population-based studies.  Bone. 2003;32(2):180-184
PubMed   |  Link to Article
Hasserius R, Karlsson MK, Nilsson BE, Redlund-Johnell I, Johnell O. Prevalent vertebral deformities predict increased mortality and increased fracture rate in both men and women: a 10-year population-based study of 598 individuals from the Swedish cohort in the European Vertebral Osteoporosis Study.  Osteoporos Int. 2003;14(1):61-68
PubMed   |  Link to Article
Borgström F, Zethraeus N, Johnell O.  et al.  Costs and quality of life associated with osteoporosis-related fractures in Sweden.  Osteoporos Int. 2006;17(5):637-650
PubMed   |  Link to Article
Binkley N, Bilezikian JP, Kendler DL, Leib ES, Lewiecki EM, Petak SM. Official positions of the International Society for Clinical Densitometry and executive summary of the 2005 Position Development Conference.  J Clin Densitom. 2006;9(1):4-14
PubMed   |  Link to Article
Brown JP, Josse RG.Scientific Advisory Council of the Osteoporosis Society of Canada.  2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada.  CMAJ. 2002;167(10):(suppl)  S1-S34
PubMed
Schousboe JT, Ensrud KE, Nyman JA, Melton LJ III, Kane RL. Universal bone densitometry screening combined with alendronate therapy for those diagnosed with osteoporosis is highly cost-effective for elderly women.  J Am Geriatr Soc. 2005;53(10):1697-1704
PubMed   |  Link to Article
Borgström F, Johnell O, Jonsson B, Zethraeus N, Sen SS. Cost effectiveness of alendronate for the treatment of male osteoporosis in Sweden.  Bone. 2004;34(6):1064-1071
PubMed   |  Link to Article
Feldstein AC, Nichols G, Orwoll E.  et al.  The near absence of osteoporosis treatment in older men with fractures.  Osteoporos Int. 2005;16(8):953-962
PubMed   |  Link to Article
Joakimsen RM, Fonnebo V, Sogaard AJ, Tollan A, Stormer J, Magnus JH. The Tromso study: registration of fractures, how good are self-reports, a computerized radiographic register and a discharge register?  Osteoporos Int. 2001;12(12):1001-1005
PubMed   |  Link to Article
Nevitt MC, Cummings SR, Browner WS.  et al.  The accuracy of self-report of fractures in elderly women: evidence from a prospective study.  Am J Epidemiol. 1992;135(5):490-499
PubMed
Haentjens P, Autier P, Collins J, Velkeniers B, Vanderschueren D, Boonen S. Colles fracture, spine fracture, and subsequent risk of hip fracture in men and women: a meta-analysis.  J Bone Joint Surg Am. 2003;85-A(10):1936-1943
PubMed
Kanis JA, Johnell O, Oden A.  et al.  The risk and burden of vertebral fractures in Sweden.  Osteoporos Int. 2004;15(1):20-26
PubMed   |  Link to Article
Arias E. United States life tables, 2003.  Natl Vital Stat Rep. 2006;54(14):1-40
PubMed
Kanis JA, Johansson H, Oden A, Jonsson B, Johnell O, De Laet C. How many deaths from hip fracture might be prevented [abstract]?  J Bone Miner Res. 2002;17:(suppl 1)  S146
Link to Article
Melton LJ. Excess mortality following vertebral fracture.  J Am Geriatr Soc. 2000;48(3):338-339
PubMed
Johnell O, Kanis JA, Oden A.  et al.  Mortality after osteoporotic fractures.  Osteoporos Int. 2004;15(1):38-42
PubMed   |  Link to Article
Melton LJ III, Crowson CS, O’Fallon WM. Fracture incidence in Olmsted County, Minnesota: comparison of urban with rural rates and changes in urban rates over time.  Osteoporos Int. 1999;9(1):29-37
PubMed   |  Link to Article
Melton LJ III. History of the Rochester Epidemiology Project.  Mayo Clin Proc. 1996;71(3):266-274
PubMed   |  Link to Article
Melton LJ III, Lane AW, Cooper C, Eastell R, O’Fallon WM, Riggs BL. Prevalence and incidence of vertebral deformities.  Osteoporos Int. 1993;3(3):113-119
PubMed   |  Link to Article
Johnell O, Kanis JA, Oden A.  et al.  Predictive value of BMD for hip and other fractures.  J Bone Miner Res. 2005;20(7):1185-1194
PubMed   |  Link to Article
Kanis JA, Johnell O, De Laet C.  et al.  A meta-analysis of previous fracture and subsequent fracture risk.  Bone. 2004;35(2):375-382
PubMed   |  Link to Article
van der Klift M, de Laet CE, McCloskey EV.  et al.  Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.  J Bone Miner Res. 2004;19(7):1172-1180
PubMed   |  Link to Article
Cummings SR, Cawthon PM, Ensrud KE, Cauley JA, Fink HA, Orwoll ES. BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women.  J Bone Miner Res. 2006;21(10):1550-1556
PubMed   |  Link to Article
Blank JB, Cawthon PM, Carrion-Petersen ML.  et al.  Overview of recruitment for the osteoporotic fractures in men study (MrOS).  Contemp Clin Trials. 2005;26(5):557-568
PubMed   |  Link to Article
Orwoll E, Blank JB, Barrett-Connor E.  et al.  Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study—a large observational study of the determinants of fracture in older men.  Contemp Clin Trials. 2005;26(5):569-585
PubMed   |  Link to Article
Sawka AM, Papaioannou A, Adachi JD, Gafni A, Hanley DA, Thabane L. Does alendronate reduce the risk of fracture in men? a meta-analysis incorporating prior knowledge of anti-fracture efficacy in women.  BMC Musculoskelet Disord. 2005;6:39
PubMed   |  Link to Article
Looker AC, Wahner HW, Dunn WL.  et al.  Updated data on proximal femur bone mineral levels of US adults.  Osteoporos Int. 1998;8(5):468-489
PubMed   |  Link to Article
 Drug Topics 2001 Red Book. Montvale, NJ: Medical Economics Co; 2001
Macran S, Weatherly H, Kind P. Measuring population health: a comparison of three generic health status measures.  Med Care. 2003;41(2):218-231
PubMed
Burström K, Johannesson M, Diderichsen F. Swedish population health-related quality of life results using the EQ-5D.  Qual Life Res. 2001;10(7):621-635
PubMed   |  Link to Article
Oleksik A, Lips P, Dawson A.  et al.  Health-related quality of life in postmenopausal women with low BMD with or without prevalent vertebral fractures.  J Bone Miner Res. 2000;15(7):1384-1392
PubMed   |  Link to Article
Tosteson AN, Gabriel SE, Grove MR, Moncur MM, Kneeland TS, Melton LJ III. Impact of hip and vertebral fractures on quality-adjusted life years.  Osteoporos Int. 2001;12(12):1042-1049
PubMed   |  Link to Article
Gabriel SE, Tosteson AN, Leibson CL.  et al.  Direct medical costs attributable to osteoporotic fractures.  Osteoporos Int. 2002;13(4):323-330
PubMed   |  Link to Article
Leibson CL, Tosteson AN, Gabriel SE, Ransom JE, Melton LJ. Mortality, disability, and nursing home use for persons with and without hip fracture: a population-based study.  J Am Geriatr Soc. 2002;50(10):1644-1650
PubMed   |  Link to Article
Meerding WJ, Looman CW, Essink-Bot ML, Toet H, Mulder S, van Beeck EF. Distribution and determinants of health and work status in a comprehensive population of injury patients.  J Trauma. 2004;56(1):150-161
PubMed   |  Link to Article
Orwoll E, Ettinger M, Weiss S.  et al.  Alendronate for the treatment of osteoporosis in men.  N Engl J Med. 2000;343(9):604-610
PubMed   |  Link to Article
Ringe JD, Dorst A, Faber H, Ibach K. Alendronate treatment of established primary osteoporosis in men: 3-year results of a prospective, comparative, two-arm study.  Rheumatol Int. 2004;24(2):110-113
PubMed   |  Link to Article
Centers for Medicare and Medicaid Services.  Physician fee schedule search: 2007. http://www.cms.hhs.gov/PFSlookup/02_PFSSearch.asp. Accessed March 4, 2007
Centers for Medicare and Medicaid Services.  Five-Year Review of Work Relative Value Units Under the Physician Fee Schedule and Proposed Changeshttp://www.cms.hhs.gov/physicianfeesched/downloads/cms-1512-pn.pdf. Accessed March 8, 2007, 2007
Johnell O, Gullberg B, Kanis JA. The hospital burden of vertebral fracture in Europe: a study of national register sources.  Osteoporos Int. 1997;7(2):138-144
PubMed   |  Link to Article
Bureau of Labor Statistics, US Census Bureau.  CPS Annual Demographic Survey. http://pubdb3.census.gov/macro/032005/perinc/new05_102.htm. Accessed November 28, 2006
US Census Bureau. Workforce participation rates. http://factfinder.census.gov/home/saff/main.html?_lang=en. Accessed November 28, 2006
O’Neill TW, Cockerill W, Matthis C.  et al.  Back pain, disability, and radiographic vertebral fracture in European women: a prospective study.  Osteoporos Int. 2004;15(9):760-765
PubMed   |  Link to Article
Nevitt MC, Ettinger B, Black DM.  et al.  The association of radiographically detected vertebral fractures with back pain and function: a prospective study.  Ann Intern Med. 1998;128(10):793-800
PubMed   |  Link to Article
Huybrechts KF, Ishak KJ, Caro JJ. Assessment of compliance with osteoporosis treatment and its consequences in a managed care population.  Bone. 2006;38(6):922-928
PubMed   |  Link to Article
Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. Perspective: how many women have osteoporosis?  J Bone Miner Res. 1992;7(9):1005-1010
PubMed   |  Link to Article
Cummings SR, Black DM, Thompson DE.  et al.  Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.  JAMA. 1998;280(24):2077-2082
PubMed   |  Link to Article
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