1. 
 De Laet, Chris, et al.
(författare)

The impact of the use of multiple risk indicators for fracture on casefinding strategies: a mathematical approach.
 2005

Ingår i: Osteoporosis international.  : Springer.  0937941X . 14332965. ; 16:3, s. 3138

Tidskriftsartikel (refereegranskat)abstract
 The value of bone mineral density (BMD) measurements to stratify fracture probability can be enhanced in a casefinding strategy that combines BMD measurement with independent clinical risk indicators. Putative risk indicators include age and gender, BMI or weight, prior fracture, the use of corticosteroids, and possibly others. The aim of the present study was to develop a mathematical framework to quantify the impact of using combinations of risk indicators with BMD in case finding. Fracture probability can be expressed as a risk gradient, i.e. a relative risk (RR) of fracture per standard deviation (SD) change in BMD. With the addition of other continuous or categorical risk indicators a continuous distribution of risk indicators is obtained that approaches a normal distribution. It is then possible to calculate the risk of individuals compared with the average risk in the population, stratified by age and gender. A risk indicator with a gradient of fracture risk of 2 per SD identified 36% of the population as having a higher than average fracture risk. In individuals so selected, the risk was on average 1.7 times that of the general population. Where, through the combination of several risk indicators, the gradient of risk of the test increased to 4 per SD, a smaller proportion (24%) was identified as having a higher than average risk, but the average risk in this group was 3.1 times that of the population, which is a much better performance. At higher thresholds of risk, similar phenomena were found. We conclude that, whereas the change of the proportion of the population detected to be at high risk is small, the performance of a test is improved when the RR per SD is higher, indicated by the higher average risk in those identified to be at risk. Casefinding strategies that combine clinical risk indicators with BMD have increased efficiency, while having a modest impact on the number of individuals requiring treatment. Therefore, the costeffectiveness is enhanced.


2. 
 Johansson, Helena, 1981, et al.
(författare)

Optimization of BMD measurements to identify high risk groups for treatmenta test analysis.
 2004

Ingår i: Journal of bone and mineral research.  : AMBMR.  08840431 . 15234681. ; 19:6, s. 90613

Tidskriftsartikel (refereegranskat)abstract
 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 personyears. 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 10year 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 reclassification. 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 lowrisk 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 womena 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.


3. 
 Kanis, John A, et al.
(författare)

A metaanalysis of milk intake and fracture risk: low utility for case finding.
 2005

Ingår i: Osteoporosis international.  : Springer.  0937941X . 14332965. ; 16:7, s. 799804

Tidskriftsartikel (refereegranskat)abstract
 A low intake of calcium is widely considered to be a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the effect of age, gender and bone mineral density (BMD) on this risk. We studied 39,563 men and women (69% female) from six prospectively studied cohorts comprising EVOS/EPOS, CaMos, DOES, the Rotterdam study, the Sheffield study and a cohort from Gothenburg. Cohorts were followed for 152,000 personyears. The effect of calcium intake as judged by the intake of milk on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age and BMD. The results of the different studies were merged by using the weighted betacoefficients. A low intake of calcium (less than 1 glass of milk daily) was not associated with a significantly increased risk of any fracture, osteoporotic fracture or hip fracture. There was no difference in risk ratio between men and women. When both sexes were combined there was a small but nonsignificant increase in the risk of osteoporotic and of hip fracture. There was also a small increase in the risk of an osteoporotic fracture with age which was significant at the age of 80 years (RR = 1.15; 95% CI = 1.021.30) and above. The association was no longer significant after adjustment for BMD. No significant relationship was observed by age for low milk intake and hip fracture risk. We conclude that a selfreported low intake of milk is not associated with any marked increase in fracture risk and that the use of this risk indicator is of little or no value in casefinding strategies.


4. 
 Kanis, John A, et al.
(författare)

A metaanalysis of prior corticosteroid use and fracture risk.
 2004

Ingår i: Journal of bone and mineral research.  : AMBMR.  08840431 . 15234681. ; 19:6, s. 8939

Tidskriftsartikel (refereegranskat)abstract
 The relationship between use of corticosteroids and fracture risk was estimated in a metaanalysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patientyears. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.631.71, and for hip fracture 4.422.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in casefinding strategies.


5. 
 Kanis, John A, et al.
(författare)

Alcohol intake as a risk factor for fracture.
 2005

Ingår i: Osteoporosis international.  : Springer.  0937941X . 14332965. ; 16:7, s. 73742

Tidskriftsartikel (refereegranskat)abstract
 High intakes of alcohol have adverse effects on skeletal health, but evidence for the effects of moderate consumption are less secure. The aim of this study was to quantify this risk on an international basis and explore the relationship of this risk with age, sex, and bone mineral density (BMD). We studied 5,939 men and 11,032 women from three prospectively studied cohorts comprising CaMos, DOES, and the Rotterdam Study. Cohorts were followed for a total of 75,433 personyears. The effect of reported alcohol intake on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined included age and BMD. The results of the different studies were merged using weighted betacoefficients. Alcohol intake was associated with a significant increase in osteoporotic and hip fracture risk, but the effect was nonlinear. No significant increase in risk was observed at intakes of 2 units or less daily. Above this threshold, alcohol intake was associated with an increased risk of any fracture (risk ratio [RR] = 1.23; 95% CI, 1.061.43), any osteoporotic fracture (RR = 1.38; 95% CI, 1.161.65), or hip fracture (RR = 1.68; 95% CI, 1.192.36). There was no significant interaction with age, BMD, or time since baseline assessment. Risk ratios were moderately but not significantly higher in men than in women, and there was no evidence for a different threshold for effect by gender. We conclude that reported intake of alcohol confers a risk of some importance beyond that explained by BMD. The validation of this risk factor on an international basis permits its use in casefinding strategies.


6. 
 Kanis, John A, et al.
(författare)

Assessment of fracture risk.
 2005

Ingår i: Osteoporosis international.  : Springer.  0937941X . 14332965. ; 16:6, s. 5819

Tidskriftsartikel (refereegranskat)abstract
 The diagnosis of osteoporosis is based on the measurement of bone mineral density (BMD). There are a number of clinical risk factors that provide information on fracture risk over and above that given by BMD. The assessment of fracture risk thus needs to be distinguished from diagnosis to take account of the independent value of the clinical risk factors. These include age, a prior fragility fracture, a parental history of hip fracture, smoking, use of systemic corticosteroids, excess alcohol intake and rheumatoid arthritis. The independent contribution of these risk factors can be integrated by the calculation of fracture probability with or without the use of BMD. Treatment can then be offered to those identified to have a fracture probability greater than an intervention threshold.


7. 
 Kanis, John A, et al.
(författare)

Intervention thresholds for osteoporosis in men and women: a study based on data from Sweden.
 2005

Ingår i: Osteoporosis international.  : Springer.  0937941X . 14332965. ; 16:1, s. 614

Tidskriftsartikel (refereegranskat)abstract
 The aim of this study was to determine the threshold of fracture probability at which interventions became costeffective in men and women, based on data from Sweden. We modeled the effects of a treatment costing $500 per year given for 5 years that decreased the risk of all osteoporotic fractures by 35% followed by a waning of effect for a further 5 years. Sensitivity analyses included a range of effectiveness (1050%) and a range of intervention costs ($200500/year). Data on costs and risks were from Sweden. Costs included direct costs, but excluded indirect costs due to morbidity. A threshold for costeffectiveness of approximately $45,000/QALY gained was used. Cost of added years was included in a sensitivity analysis. With the base case ($500 per year; 35% efficacy) treatment in women was costeffective with a 10year hip fracture probability that ranged from 1.2% at the age of 50 years to 7.4% at the age of 80 years. Similar results were observed in men except that the threshold for costeffectiveness was higher at younger ages than in women (2.0 vs 1.2%, respectively, at the age of 50 years). Intervention thresholds were sensitive to the assumed effectiveness and intervention cost. The exclusion of osteoporotic fractures other than hip fracture significantly increased the costeffectiveness ratio because of the substantial morbidity from such other fractures, particularly at younger ages. We conclude that the inclusion of all osteoporotic fractures has a marked effect on intervention thresholds, that these vary with age, and that available treatments can be targeted costeffectively to individuals at moderately increased fracture risk.


8. 
 Johnell, Olof, et al.
(författare)

Predictive value of BMD for hip and other fractures.
 2005

Ingår i: Journal of bone and mineral research.  : AMBMR.  08840431 . 15234681. ; 20:7, s. 118594

Tidskriftsartikel (refereegranskat)abstract
 The relationship between BMD and fracture risk was estimated in a metaanalysis 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 personyears. 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 = 2.024.27) in men and by 2.88 (95% CI = 2.313.59) 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 = 1.331.51) and in women by 1.38 per SD (95% CI = 1.281.48). 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 = 1.632.71) and at a z score of 1 SD, the risk was 1.73 per SD (95% CI = 1.591.89) 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.

