Legal and organizational aspects of remote cardiac monitoring: the example of implantable cardioverter defibrillators.

The remote monitoring of implantable cardioverter defibrillators (ICDs) recently emerged as an attractive technological innovation that proved to be reasonably safe in partially replacing the in-clinic follow-ups of ICD patients with no or only mild symptoms. Apart from the fact that strong evidence about any additional clinical benefits and/or cost-efficiency are still awaited, legal and organizational hurdles remain in place, hampering any possibility for adoption of remote cardiac monitoring. This paper identifies a number of legal and organizational constraints which urgently need to be addressed. An elaboration of the specific juridical guidance for the interpretation and application of the relevant legislation is called for.

Using threshold values for cost per quality-adjusted life-year gained in healthcare decisions.

BACKGROUND: In many countries, the incremental cost-effectiveness ratio (ICER) is used to assess whether an intervention is worth its costs. At the same time, policy makers often feel uncomfortable with refusing reimbursement of any intervention purely on the basis of the fact that the ICER exceeds a specific threshold value. Reluctance to define a single threshold value for the ICER seems to have been stronger in social security systems than in national healthcare services systems. This study explores how basic differences between healthcare systems impact upon the potential usefulness of an ICER threshold value. METHODS: This study is a narrative review of literature about the theoretical foundations of the ICER threshold value approach and its practical relevance in different types of healthcare systems. RESULTS: A single ICER threshold value cannot be maintained, defined, or measured and should not be used as a policy-making tool. None of the solutions presented up until now to make the ICER threshold approach a valuable policy-making tool overcome the important weaknesses of the approach. CONCLUSIONS: ICERs and ICER threshold values are insufficient for assessing interventions' value for money. Rather, they should be considered as one element in the decision-making process. Complete rationalization of the decision-making process by means of quantitative decision criteria is undesirable and not feasible. Increasing transparency in the criteria used for a decision and explicitness about the relative importance of each criterion should, therefore, be the major goal.

Alendronate or alfacalcidol in glucocorticoid-induced osteoporosis.

BACKGROUND: Treatment with glucocorticoids is associated with bone loss starting soon after therapy is initiated and an increased risk of fracture. METHODS: We performed a randomized, double-placebo, double-blind clinical trial of 18 months' duration among patients with a rheumatic disease who were starting glucocorticoids at a daily dose that was equivalent to at least 7.5 mg of prednisone. A total of 201 patients were assigned to receive either alendronate (10 mg) and a placebo capsule of alfacalcidol daily or alfacalcidol (1 microg) and a placebo tablet of alendronate daily. The primary outcome was the change in bone mineral density of the lumbar spine in 18 months; the secondary outcome was the incidence of morphometric vertebral deformities. RESULTS: A total of 100 patients received alendronate, and 101 received alfacalcidol; 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1 percent in the alendronate group (95 percent confidence interval, 1.1 to 3.1 percent) and decreased by 1.9 percent in the alfacalcidol group (95 percent confidence interval, -3.1 to -0.7 percent). At 18 months, the mean difference of change in bone mineral density between the two groups was 4.0 percent (95 percent confidence interval, 2.4 to 5.5 percent). Three patients in the alendronate group had a new vertebral deformity, as compared with eight patients in the alfacalcidol group (of whom three had symptomatic vertebral fractures) (hazard ratio, 0.4; 95 percent confidence interval, 0.1 to 1.4). CONCLUSIONS: During this 18-month trial in patients with rheumatic diseases, alendronate was more effective in the prevention of glucocorticoid-induced bone loss than was alfacalcidol. (ClinicalTrials.gov number, NCT00138983 [ClinicalTrials.gov].).

Cost effectiveness of drug-eluting stents in Belgian practice: healthcare payer perspective.

BACKGROUND: There has been a steep increase in the number of percutaneous coronary intervention procedures performed for coronary heart disease since their introduction about 30 years ago. Recently, the use of drug-eluting stents (DES) compared with the original bare metal stents (BMS) has increased in many countries. OBJECTIVE: To assess the cost effectiveness of DES versus BMS in a real-world setting from the Belgian healthcare payer perspective. METHODS: We developed a decision analysis model to estimate incremental costs (year 2004 or 2007 values [depending on the underlying variable]) and effectiveness. Incremental effectiveness was calculated by combining relative benefits from published meta-analyses with real-world observations from a Belgian registry. Probabilistic modelling and sensitivity analyses were performed. The model had a 1-year time horizon. Sixteen sub groups were created based on the following characteristics: initial stent type, diabetic status, complex lesion and multi-vessel disease. Scenario analyses were performed for the influence on reinterventions and the duration of clopidogrel use. In each analysis, 1000 Monte Carlo simulations were performed. RESULTS: The incremental costs for switching from BMS to DES are substantial (approximately euro1000), while the benefits, expressed as QALYs, are extremely small (on average <0.001 QALYs gained). This led to very high incremental cost-effectiveness ratios: over euro860 000 per QALY gained in all subgroups and scenario analyses. CONCLUSION: Comparing DES with BMS, no life-years are gained and small quality-of-life improvements are achieved for short periods, resulting in a high likelihood that DES are not cost effective. When there is competition for scarce resources this should be considered when deciding on the reimbursement of this technology.

Cost-effectiveness analyses of drug eluting stents versus bare metal stents: a systematic review of the literature.

OBJECTIVES: Drug eluting stents (DES) used to treat coronary lesions reduce rates of in-stent restenosis and therefore the need for repeat revascularization compared to bare metal stents (BMS). DES, however, are considerably more expensive than BMS. We evaluated whether DES are a cost-effective alternative for BMS. METHODS: Reports of Health Technology Assessment agencies were assessed and a systematic review of economic evaluations comparing DES with BMS was performed. RESULTS: Nineteen full economic evaluations were identified. Some studies indicate that DES may be cost-effective or even cost-saving in specific patients, when used for coronary lesions with a high propensity of restenosis such as long lesions, lesions in narrow vessels, or in patients with diabetes. Other studies mention DES is not cost effective at all with ICERs of more than 200,000 Canadian dollar per QALY gained. One of the main determining factors is the influence of protocol mandated angiographic follow-up in RCTs. The risk for a re-intervention using BMS ranges from 5% to 14% in registries and is much smaller than reported in RCTs (up to 30%). As a result, the absolute reduction in repeat revascularization by DES compared to BMS is smaller in real life. Moreover, using DES instead of BMS does not increase survival or decrease myocardial infarctions. The combination of (a) a higher cost (>euro700) for DES versus BMS; (b) no life-years gained; (c) a relatively small absolute reduction in repeat procedures; and (d) a small improvement in QoL for a short period (less than 0.15 during the first month after the re-intervention), results in unfavourable cost-effectiveness ratios. CONCLUSIONS: Although several studies conclude that DES may be cost effective in large subgroups of patients, under real-world conditions, the cost-effectiveness of DES is unfavourable in comparison with BMS.

Cost-effectiveness of human papillomavirus vaccination in Belgium: do not forget about cervical cancer screening.

OBJECTIVES: The cost-effectiveness of adding a human papillomavirus (HPV) vaccination program in 12-year-old females to the recommended cervical cancer screening in Belgium is examined. Moreover, the health and economic consequences of a potential decline in screening uptake after initiation of a HPV vaccination program are investigated. METHODS: A static Markov model is developed to estimate the direct effect of vaccination on precancerous lesions and cervical cancers. RESULTS: Vaccination is estimated to avoid 20 percent of the cervical cancers occurring in a 12-year-old girls' cohort and to cost 32,665 euro per quality-adjusted life-year (QALY) gained (95 percent credibility interval [CrI]: 17,447 euro to 68,078 euro), assuming a booster injection after 10 years, a limited duration of protection and discounting costs and effects at 3 percent and 1.5 percent, respectively. Assuming lifelong protection, HPV vaccination is estimated to cost 14,382 euro (95 percent CrI: 9,238 euro to 25,644 euro) per QALY gained, while avoiding 50 percent of the cervical cancer cases. In the base-case, a 10 percent reduction in screening compliance after vaccination obliterates the effect of vaccination on cervical cancer cases avoided, whereas further declines in the level of screening compliance even turned out to be detrimental for the cohort's health, inducing a mean loss in QALYs and life-year gained compared with the situation prevaccination. CONCLUSIONS: An HPV vaccination program should only be considered if the level of screening after vaccination can be maintained.

Testing the HTA core model: experiences from two pilot projects.

OBJECTIVES: The aim of this study was to analyze and describe process and outcomes of two pilot assessments based on the HTA Core Model, discuss the applicability of the model, and explore areas of development. METHODS: Data were gathered from HTA Core Model and pilot Core HTA documents, their validation feedback, questionnaires to investigators, meeting minutes, emails, and discussions in the coordinating team meetings in the Finnish Office for Health Technology Assessment (FINOHTA). RESULTS: The elementary structure of the HTA Core Model proved useful in preparing HTAs. Clear scoping and good coordination in timing and distribution of work would probably help improve applicability and avoid duplication of work. CONCLUSIONS: The HTA Core Model can be developed into a platform that enables and encourages true HTA collaboration in terms of distribution of work and maximum utilization of a common pool of structured HTA information for national HTA reports.

Cost-effectiveness of statins in the primary prevention of cardiovascular disease: a systematic review and economic analysis for Belgium.

OBJECTIVES: 8% of total drug spending by the Belgian government goes to statins. The aim of this study is to determine the cost-effectiveness of statins for the primary prevention of cardiovascular disease (CVD) in middle-aged Belgian populations. METHODS AND RESULTS: Economic evaluations were identified in a systematic literature search and were critically appraised. Furthermore, because prices decreased drastically, a previously published model was adapted applying recent cost data from the Belgian national health insurance. Eleven full economic evaluations were identified. Nine studies compared statins with no treatment and presented heterogeneous results. If alternative interventions, such as smoking cessation or low-dose aspirin treatment were included in the analysis, statin therapy became less cost-effective. Prescribing the cheapest statin on the Belgian market (< Euro 90 medication cost per year) resulted in an incremental cost of Euro 29,173 per life-year gained (LYG) in a male high-risk group aged 60 compared to low-dose aspirin. The incremental cost in a male moderate-risk group aged 50 was Euro 87,022/LYG. Low-dose aspirin was more cost-effective ranging from Euro 3,854/LYG to Euro 29,509/LYG compared to smoking cessation therapy. Smoking cessation therapy was the most cost-effective intervention, providing savings compared to no treatment. CONCLUSIONS: In Belgium, the cost-effectiveness of statins for the primary prevention of CVD is rather elevated in comparison with low-dose aspirin, even if the cheapest statin is prescribed. From an economic point of view, prevention with low-dose aspirin is more cost-effective and may present a first choice in primary prevention. Smoking cessation, which is a dominant strategy, should be encouraged at all times.

Femoral neck BMD is a strong predictor of hip fracture susceptibility in elderly men and women because it detects cortical bone instability: the Rotterdam Study.

UNLABELLED: We studied HSA measurements in relation to hip fracture risk in 4,806 individuals (2,740 women). Hip fractures (n = 147) occurred at the same absolute levels of bone instability in both sexes. Cortical instability (propensity of thinner cortices in wide diameters to buckle) explains why hip fracture risk at different BMD levels is the same across sexes. INTRODUCTION: Despite the sexual dimorphism of bone, hip fracture risk is very similar in men and women at the same absolute BMD. We aimed to elucidate the main structural properties of bone that underlie the measured BMD and that ultimately determines the risk of hip fracture in elderly men and women. MATERIALS AND METHODS: This study is part of the Rotterdam Study (a large prospective population-based cohort) and included 147 incident hip fracture cases in 4,806 participants with DXA-derived hip structural analysis (mean follow-up, 8.6 yr). Indices compared in relation to fracture included neck width, cortical thickness, section modulus (an index of bending strength), and buckling ratio (an index of cortical bone instability). We used a mathematical model to calculate the hip fracture distribution by femoral neck BMD, BMC, bone area, and hip structure analysis (HSA) parameters (cortical thickness, section modulus narrow neck width, and buckling ratio) and compared it with prospective data from the Rotterdam Study. RESULTS: In the prospective data, hip fracture cases in both sexes had lower BMD, thinner cortices, greater bone width, lower strength, and higher instability at baseline. In fractured individuals, men had an average BMD that was 0.09 g/cm(2) higher than women (p < 0.00001), whereas no significant difference in buckling ratios was seen. Modeled fracture distribution by BMD and buckling ratio levels were in concordance to the prospective data and showed that hip fractures seem to occur at the same absolute levels of bone instability (buckling ratio) in both men and women. No significant differences were observed between the areas under the ROC curves of BMD (0.8146 in women and 0.8048 in men) and the buckling ratio (0.8161 in women and 0.7759 in men). CONCLUSIONS: The buckling ratio (an index of bone instability) portrays in both sexes the critical balance between cortical thickness and bone width. Our findings suggest that extreme thinning of cortices in expanded bones plays a key role on local susceptibility to fracture. Even though the buckling ratio does not offer additional predictive value, these findings improve our understanding of why low BMD is a good predictor of fragility fractures.

Physical activity and life expectancy with and without diabetes: life table analysis of the Framingham Heart Study.

OBJECTIVE: Physical activity is associated with a reduced risk of developing diabetes and with reduced mortality among diabetic patients. However, the effects of physical activity on the number of years lived with and without diabetes are unclear. Our aim is to calculate the differences in life expectancy with and without type 2 diabetes associated with different levels of physical activity. RESEARCH DESIGN AND METHODS: Using data from the Framingham Heart Study, we constructed multistate life tables starting at age 50 years for men and women. Transition rates by level of physical activity were derived for three transitions: nondiabetic to death, nondiabetic to diabetes, and diabetes to death. We used hazard ratios associated with different physical activity levels after adjustment for age, sex, and potential confounders. RESULTS: For men and women with moderate physical activity, life expectancy without diabetes at age 50 years was 2.3 (95% CI 1.2-3.4) years longer than for subjects in the low physical activity group. For men and women with high physical activity, these differences were 4.2 (2.9-5.5) and 4.0 (2.8-5.1) years, respectively. Life expectancy with diabetes was 0.5 (-1.0 to 0.0) and 0.6 (-1.1 to -0.1) years less for moderately active men and women compared with their sedentary counterparts. For high activity, these differences were 0.1 (-0.7 to 0.5) and 0.2 (-0.8 to 0.3) years, respectively. CONCLUSIONS: Moderately and highly active people have a longer total life expectancy and live more years free of diabetes than their sedentary counterparts but do not spend more years with diabetes.

The polypill: at what price would it become cost effective?

INTRODUCTION: A promising concept in cardiovascular disease prevention (the polypill) was introduced in 2003. Although the polypill may seem as an effective intervention, data on its costs and cost effectiveness remain unknown. The aim of this study was to determine the maximum price of the polypill for it to be a cost effective alternative in the primary prevention of cardiovascular disease. METHODS: Data on the hypothetical effects of the polypill were taken from the literature. Using data from the Framingham heart study and the Framingham offspring study, life tables were built to model the assumed benefits of the polypill. Using a third party payer perspective and a 10 years time horizon, the authors calculated what should be the maximum drug cost of the polypill for it to be cost effective (using a 20,000 euro/year of life saved threshold) in the primary prevention of cardiovascular disease among populations at different levels of absolute risk of coronary heart disease and age. RESULTS: To be cost effective among populations at levels of 10 year coronary heart disease risk over 20% (high risk), the annual cost of medication for the polypill therapy should be no more than 302 euro or 410 euro for men at age 50 and 60 years respectively. For cost effective prevention in populations at levels of coronary heart disease risk between 10% and 20% the costs should be two to three times lower. CONCLUSION: Although the polypill could theoretically be a highly effective intervention, the costs of the medication could be its caveat for implementation in the primary prevention of cardiovascular disease.

Effects of physical activity on life expectancy with cardiovascular disease.

BACKGROUND: Physical inactivity is a modifiable risk factor for cardiovascular disease. However, little is known about the effects of physical activity on life expectancy with and without cardiovascular disease. Our objective was to calculate the consequences of different physical activity levels after age 50 years on total life expectancy and life expectancy with and without cardiovascular disease. METHODS: We constructed multistate life tables using data from the Framingham Heart Study to calculate the effects of 3 levels of physical activity (low, moderate, and high) among populations older than 50 years. For the life table calculations, we used hazard ratios for 3 transitions (healthy to death, healthy to disease, and disease to death) by levels of physical activity and adjusted for age, sex, smoking, any comorbidity (cancer, left ventricular hypertrophy, arthritis, diabetes, ankle edema, or pulmonary disease), and examination at start of follow-up period. RESULTS: Moderate and high physical activity levels led to 1.3 and 3.7 years more in total life expectancy and 1.1 and 3.2 more years lived without cardiovascular disease, respectively, for men aged 50 years or older compared with those who maintained a low physical activity level. For women the differences were 1.5 and 3.5 years in total life expectancy and 1.3 and 3.3 more years lived free of cardiovascular disease, respectively. CONCLUSIONS: Avoiding a sedentary lifestyle during adulthood not only prevents cardiovascular disease independently of other risk factors but also substantially expands the total life expectancy and the cardiovascular disease-free life expectancy for men and women. This effect is already seen at moderate levels of physical activity, and the gains in cardiovascular disease-free life expectancy are twice as large at higher activity levels.

Predictive value of BMD for hip and other fractures.

UNLABELLED: The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.

Thiazide diuretics and the risk for hip fracture.

BACKGROUND: Since most hip fractures are related to osteoporosis, treating accelerated bone loss can be an important strategy to prevent hip fractures. Thiazides have been associated with reduced age-related bone loss by decreasing urinary calcium excretion. OBJECTIVE: To examine the association between dose and duration of thiazide diuretic use and the risk for hip fracture and to study the consequences of discontinuing use. DESIGN: Prospective population-based cohort study. SETTING: The Rotterdam Study. PARTICIPANTS: 7891 individuals 55 years of age and older. MEASUREMENTS: Hip fractures were reported by the general practitioners and verified by trained research assistants. Details of all dispensed drugs were available on a day-to-day basis. Exposure to thiazides was divided into 7 mutually exclusive categories: never use, current use for 1 to 42 days, current use for 43 to 365 days, current use for more than 365 days, discontinuation of use since 1 to 60 days, discontinuation of use since 61 to 120 days, and discontinuation of use since more than 120 days. RESULTS: 281 hip fractures occurred. Relative to nonuse, current use of thiazides for more than 365 days was statistically significantly associated with a lower risk for hip fracture (hazard ratio, 0.46 [95% CI, 0.21 to 0.96]). There was no clear dose dependency. This lower risk disappeared approximately 4 months after thiazide use was discontinued. CONCLUSIONS: Thiazide diuretics protect against hip fracture, but this protective effect disappears within 4 months after use is discontinued.

Osteoporosis in men and women: a story about bone mineral density thresholds and hip fracture risk.

In postmenopausal women, the T score for bone mineral density (BMD) is a well-accepted diagnostic criterion for osteoporosis. It is also used to assess fracture risk. However, it is unclear whether in elderly men similar BMD thresholds should be used. Different hypotheses have been proposed for the relation of BMD with hip fracture risk in men. In this study, we tested those hypotheses using a mathematical model and we compared the calculated results with observed prospective data from the Rotterdam study. In the model, we combined the observed femoral neck BMD distribution for men and women with previously derived hip fracture risk functions based on age and BMD. For men, we tested different hypotheses for the relation of BMD with hip fracture risk. The relation of BMD with hip fracture risk is similar in men and women (scenario 1) or the relative risk (RR) per standard deviation (SD) decrease of BMD is either larger or smaller in men than in women (scenario 2a and 2b), or, at a similar absolute fracture risk, men have a higher BMD (scenario 3). In the prospective data, men with a hip fracture had an average BMD that was 0.070 g/cm2 higher than women with a hip fracture. The calculated results from the first scenario were consistent with those data and were also consistent with the observed hip fracture incidence and the observed female-to-male (F/M) risk ratio (1.7). When the RR for each SD decrease of BMD was assumed to be either larger or smaller in men than in women (second scenario), the calculated average BMD difference in men and women became respectively smaller or larger than observed. When men would have a higher fracture risk at similar BMD levels (third scenario), the calculated total number of hip fractures increased and even exceeded that in women, with an F/M risk ratio of 0.94 in our example. In women, a larger proportion of hip fractures occurs at a T score below -2.5 than in men using the same absolute BMD threshold, but using a male-specific T score largely solves this diagnostic problem. Taken together, the average hip fracture risk in men is much lower than in women but appeared to be similar at the same BMD. Therefore, we propose the use of the same absolute BMD thresholds for decisions about interventions.

International variations in hip fracture probabilities: implications for risk assessment.

It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten-year probabilities of hip fracture were computed in men and women at 10-year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10-year risk at any age between men and women. Ten-year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15-fold range in 10-year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10-year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan [TW]], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong [HK]], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.

Risk factors for incident vertebral fractures in men and women: the Rotterdam Study.

UNLABELLED: Low BMD and prevalent vertebral fractures are known risk factors for incident vertebral fractures. In 3001 men and women from the Rotterdam Study, prevalent nonvertebral fractures, early menopause, current smoking, and walking aid use were also strong risk factors for incident vertebral fractures. INTRODUCTION: Thus far, age, low BMD, and prevalent vertebral fractures are the only well-known risk factors for incident vertebral fractures. Therefore, our aim was to investigate other potential risk factors for incident vertebral fractures in the elderly. MATERIALS AND METHODS: This study was based on the Rotterdam Study, a large prospective population-based cohort study among men and women > or =55 years of age. For 3001 subjects, spinal radiographs were obtained at baseline and again approximately 6.3 years later. These follow-up radiographs were scored for vertebral fractures using the McCloskey-Kanis method. Whenever a vertebral fracture was detected, the radiograph was compared with the baseline radiograph. If this fracture was not already present at baseline, it was considered incident. At baseline, information on potential risk factors was obtained. RESULTS: Low BMD and prevalent vertebral fractures were strong risk factors for incident vertebral fractures in both men and women (RR 2.3 [1.6-3.3] and 2.2 [0.9-5.0] for men and RR 2.1 [1.6-2.6] and 4.1 [2.5-6.7] for women, respectively). For women, age, early menopause (< or =45 years of age; RR 1.0 [1.1-3.5]), current smoking (2.1 [1.2-3.5]), and walking aid use (2.5 [1.1-5.5]) were additional independent risk factors. For men, only a history of nonvertebral fractures was a significant independent risk factor (OR 2.4 [1.2-4.8]). CONCLUSION: Apart from low BMD and prevalent vertebral fractures, prevalent nonvertebral fractures are associated with an increased incident vertebral fracture risk in men. In women, early menopause, current smoking, and walking aid use are additional independent risk factors for incident vertebral fractures.

Optimization of BMD measurements to identify high risk groups for treatment--a test analysis.

INTRODUCTION: The aim of this study was to develop a methodology to optimize the role of BMD measurements in a case finding strategy. We studied 2113 women > or = 75 years of age randomly selected from Sheffield, UK, and adjacent regions. Baseline assessment included hip BMD and clinical risk factors. Outcomes included death and fracture in women followed for 6723 person-years. MATERIALS AND METHODS: Poisson models were used to identify significant risk factors for all fractures and for death with and without BMD and the hazard functions were used to compute fracture probabilities. Women were categorized by fracture probability with and without a BMD assessment. A 10-year fracture probability threshold of 35% was taken as an intervention threshold. Discordance in categorization of risk (i.e., above or below the threshold probability) between assessment with and without BMD was examined by logistic regression as probabilities of re-classification. Age, prior fracture, use of corticosteroids, and low body mass index were identified as significant clinical risk factors. RESULTS: A total of 16.8% of women were classified as high risk based on these clinical risk factors. The average BMD in these patients was approximately 1 SD lower than in low-risk women; 21.5% of women were designated to be at high risk with the addition of BMD. Fifteen percent of all women were reclassified after adding BMD to clinical risk factors, most of whom lay near the intervention threshold. When a high probability of reclassification was accepted (without a BMD test) for high risk to low risk (p1< or = 0.8) and a low probability accepted for low to high risk (P2 < or = 0.2), BMD tests would be required in only 21% of the population. CONCLUSION: We conclude that the use of clinical risk factors can identify elderly women at high fracture risk and that such patients have a low average BMD. BMD testing is required, however, in a minority of women--a fraction that depends on the probabilities accepted for classification and the thresholds of risk chosen. These findings need to be validated in other cohorts at different ages and from different regions of the world.