FRAX-based Intervention Research Articles

FRAX-based intervention thresholds for men in the Russian Federation: Expert consensus of the Russian association on osteoporosis

According to the European guidelines for osteoporosis, the same FRAX intervention threshold is suggested for men as for women. At the same time, in the Russian Federation, according to research data, an extremely low proportion of identified men who are subject to the initiation of osteoporosis therapy. The female intervention threshold identifies only 1.1 to 4% of men for treatment. Aim – to develop and evaluate various options for the intervention threshold using the FRAX calculator for men in the Russian Federation and adopt the most acceptable intervention threshold by consensus. Material and methods. Delphi voting was conducted among 18 Russian experts who have publications and personal reports about their experience with the FRAX calculator. For discussion, 5 intervention threshold options with the corresponding rationale based on the literature reference were presented, as well as the proportion of men of different ages to be initiated in each of the options (based on several Russian population-based studies). Anonymous voting was carried out using the Delphi method with questionnaire placed in the Google form. It was proposed to evaluate all options for intervention thresholds on a 9-point Likert scale. Consensus was considered reached if the intervention threshold reached a Likert score of 7 or more points in 80% or more of the experts. The rating of each intervention threshold option was expressed as mean and standard deviations. Results. In the first round of voting, the maximum rating and percentage of agreement is reached for the 9% fixed interference threshold option based on the FRAX calculation. The rating was 7.72±1.6 points, the percentage of experts’ agreement was 88.9%. A fixed threshold of 9% determined 13–19.5% of men aged 50 years and older to be treated for osteoporosis, while their proportion increased to 26–38% at the age of 85 years and older. Conclusion. The consensus of experts of the Russian association on osteoporosis suggests initiating treatment of osteoporosis in Russian men with a 10-year probability of major osteoporotic fractures according to FRAX of 9% or higher.

Osteoporosis treatment in Austria—assessment of FRAX-based intervention thresholds for high and very high fracture risk

SummaryThe adoption of the management pathway proposed by the National Osteoporosis Guideline Group (NOGG), UK applied using the Austrian FRAX® tool in a referral population of Austrian women categorises 22–29% of women age 40 years or more eligible for treatment of whom 28–34% are classified at very high risk.PurposeThe aim of this study is to provide a reference document for the further development of existing guidelines for the management of osteoporosis in Austria, considering FRAX-based intervention thresholds for high and very high fracture risk.MethodsThe model development was based on two Austrian hospital referral cohorts. Baseline information was collected to compute the 10-year probability (using the Austrian FRAX model) of a major osteoporotic fracture (MOF) and hip fracture both with and without the inclusion of femoral neck bone mineral density (BMD). Assessment thresholds for BMD testing were defined, as well as intervention thresholds. In addition, thresholds that characterise men and women at high and very high fracture risk were established. The management pathway followed that currently recommended by the UK National Osteoporosis Guideline Group (NOGG).ResultsThe two cohorts comprised a total of 1306 women and men with a mean age of 66.7 years. Slightly more than 50% were eligible for treatment by virtue of a prior fragility fracture. In those women without a prior fracture, 22% (n = 120) were eligible for treatment based on MOF probabilities. Of these, 28% (n = 33) were found to be at very high risk. When both MOF and hip fracture probabilities were used to characterise risk, 164 women without a prior fracture were eligible for treatment (29%). Of these, 34% (n = 56) were found to be at very high risk. Fewer men without prior fracture were eligible for treatment compared with women.ConclusionThe management pathway as currently outlined is expected to reduce inequalities in patient management. The characterisation of very high risk may aid in the identification of patients suitable for treatment with osteoanabolic agents.

FRAX-based intervention thresholds for Pakistan.

The fracture risk assessment algorithm FRAX® has been recently calibrated for Pakistan, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of - 2.5. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without bone mineral density (BMD). The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤ - 2.5 was used as an intervention threshold, FRAX probabilities in women aged 50years were approximately two-fold higher than in women of the same age but with no risk factors and average BMD. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80years or more, a T-score of - 2.5 was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture, rose with age from 2.1% at the age of 40years to 17%, at the age of 90years, and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' target women at high fracture risk.

FRAX-Based Intervention Thresholds for Osteoporosis Treatment in Ukraine

Objectives Osteoporosis, in addition to its consequent fracture burden, is a common and costly condition. FRAX® is a well-established, validated, web-based tool which calculates the 10-year probability of fragility fractures. A FRAX model for Ukraine has been available since 2016 but its output has not yet been translated into intervention thresholds for the treatment of osteoporosis in Ukraine; we aimed to address this unmet need in this analysis. Methods In a referral population sample of 3790 Ukrainian women, 10-year probabilities of major osteoporotic fracture (MOF) and hip fracture separately were calculated using the Ukrainian FRAX model, with and without femoral neck bone mineral density (BMD). We used a similar approach to that first proposed by the UK National Osteoporosis Guideline Group, whereby treatment is indicated if the probability equals or exceeds that of a woman of the same age with a prior fracture. Results The MOF intervention threshold in females (the age-specific 10-year fracture probability) increased with age from 5.5% at the age of 40 years to 11% at the age of 75 years where it plateaued and then decreased slightly at age 90 (10%). Lower and upper thresholds were also defined to determine the need for BMD, if not already measured; the approach targets BMD measurements to those at or near the intervention threshold. The proportion of the referral populations eligible for treatment, based on prior fracture or similar or greater probability, ranged from 44% to 69% depending on age. The prevalence of the previous fracture rose with age, as did the proportion eligible for treatment. In contrast, the requirement for BMD testing decreased with age. Conclusions The present study describes the development and application of FRAX-based assessment guidelines in Ukraine. The thresholds can be used in the presence or absence of access to BMD and optimize the use of BMD where access is restricted.

FRAX-based intervention thresholds in eight Eurasian countries: Armenia, Belarus, Georgia, Kazakhstan, the Kyrgyz Republic, Moldova, the Russian Federation, and Uzbekistan.

The purpose of this study was to derive and compare FRAX-based intervention and BMD assessment thresholds for 8 Eurasian countries in the EVA study. The intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF), calculated without BMD, equivalent to a woman with a prior fragility fracture but no other clinical risk factors, and a body mass index (BMI) of 25.0kg/m2. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI of 25.0kg/m2, without previous fracture or other clinical risk factors. The upper assessment threshold was set at 1.2 times the IT. The age-specific intervention thresholds ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for men and women at the age of 50years and from 16 (Armenia) to 27% (Belarus) at the age of 90years. The difference between countries was most evident at younger ages and become progressively less with advancing age. For the 8 Eurasian countries, the newly established FRAX-based intervention thresholds provide an opportunity to improve the clinical detection of both men and women with a high risk of fracture and improve treatment rates.

Use of age-dependent FRAX-based intervention thresholds for Singapore

SummaryAssessment and treatment pathways based on age-specific intervention thresholds in Singapore using FRAX paths can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low risk.PurposeIntervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted a more accurate assessment of fracture risk. The aim of the present study was to explore treatment paths and characteristics of women selected for treatment in Singapore based on FRAX.MethodsThe approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Singapore. The methodology was applied to women age 50 years or more drawn from the population-based Singapore Chinese Health Study (SCHS) cohort. Missing data for the calculation of FRAX was simulated using data from Chinese cohorts from Hong Kong.ResultsIntervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.9% at the age of 50 years increasing to 32% at the age of 90 years. A total of 1927 of 29,323 women (7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 3019 women (10.3%) would be eligible for treatment on the basis of age-dependent thresholds. The mean BMD T-score of women so selected was −2.94.ConclusionProbability-based assessment of fracture risk using age-specific intervention thresholds was developed for Singapore to help guide decisions about treatment.

Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data

SummaryThis study built a micro-simulation Markov model to determine the treatment threshold of osteoporosis in postmenopausal women in Mainland China. Treatment with zoledronate is cost-effective when FRAX-based (Fracture risk assessment tool) fracture probability is over 7%.IntroductionThe purpose of this study is to estimate FRAX-based fracture probabilities in Mainland China using real-world data, at which intervention could be cost-effective.MethodsWe developed a micro-simulation Markov model to capture osteoporosis states and relevant morbidities including hip fracture, vertebral fracture, and wrist fracture. Baseline characteristics including incidences of osteoporosis and distribution of risk factors were derived from the Peking Vertebral Fracture study, the largest prospective cohort study of postmenopausal women in Mainland China. We projected incidences of fractures and deaths by age groups under two treatment scenarios: 1) no treatment, and 2) zoledronate. We also projected total quality-adjusted life-years (QALY) and total costs including fracture management and osteoporosis drugs for cost-effectiveness analysis. Cost-effective intervention thresholds were calculated based on the Chinese FRAX model.ResultsTreatment with zoledronate was cost-effective when the 10-year probability of major osteoporotic fracture based on FRAX was above 7%. The FRAX threshold increased by age from 51 to 65 years old, and decreased in elder age groups, ranging from 4% to 9%.ConclusionsUsing real-world data, our model indicated that widespread use of zoledronate was of both clinical and economic benefit among Chinese postmenopausal women. Using a FRAX-based intervention threshold of 7% with zoledronate should permit cost-effective access to therapy to patients and contribute to reducing the disease burden of osteoporosis in Mainland China.

FRAX-based intervention and assessment thresholds for osteoporosis in Iran.

The fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of - 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤ - 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80years or more, a T-score of - 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50years to 17%, at the age of 80years, and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a "fracture threshold" target women at high fracture risk.

In which patients does lumbar spine trabecular bone score (TBS) have the largest effect?

Lumbar spine TBS, a texture index derived from lumbar spine dual-energy x-ray absorptiometry (DXA) images, enhances fracture prediction. No studies to date have studied a broad range of clinical variables to determine which patients might experience the greatest benefit from the use of TBS. Using the Manitoba BMD Registry, we identified 37,176 subjects with baseline DXA, FRAX®-based fracture probability, lumbar spine TBS, and minimum 5 years of observation. Subgroups considered were based on sex, age, body mass index (BMI), prior fracture, chronic obstructive lung disease (COPD), high alcohol use, rheumatoid arthritis (RA), high glucocorticoid use, osteoporotic femoral neck T-score, number of comorbidities, diabetes, secondary osteoporosis, and prior osteoporosis treatment. Non-traumatic major osteoporotic fractures (MOF, n = 3741) and hip fractures (HF, n = 1008) were identified using population-based health services data. We analyzed baseline TBS using analysis of covariance (ANCOVA). FRAX-adjusted hazard ratios (HR) per SD reduction in TBS were estimated and tested for interactions. Categorical net reclassification improvement (NRI) was estimated using fixed FRAX-based intervention cut-offs. Adjusted baseline TBS was significantly lower (p ≤ 0.001) for women (-4.2%), osteoporotic hip T-score (-4.0%), COPD (-2.8%), diabetes (-2.6%), high alcohol use (-2.3%), prior fracture (-2.2%), glucocorticoid use (-1.5%), RA (-0.9%) and secondary osteoporosis (-0.8%), whereas recent osteoporosis therapy was associated with greater TBS (+1.5%). HRs per SD reduction in TBS for fracture prediction were larger for age < 65 vs 65+ (MOF p-interaction = 0.004, HF p-interaction < 0.001), without vs with prior fracture (MOF p-interaction = 0.003, HF p-interaction = 0.048), without vs with glucocorticoid use (HF p-interaction = 0.029), lower vs higher comorbidity score (HF p-interaction < 0.001), and without vs with osteoporosis treatment (MOF p-interaction = 0.005). NRI for using the TBS adjustment to FRAX in all subjects was 1.2% for MOF (p = 0.002) and 1.7% for HF (p = 0.016). NRI was greater in subjects age < 65 y (MOF:1.7%, HF:5.6%), no prior fracture (HF: 2.4%), non-osteoporotic T-score (HF: 3.0%), and high glucocorticoid use (MOF: 3.9%). TBS is sensitive to the effects of multiple risk factors for fracture. TBS-adjusted fracture risk assessment resulted in significant improvements for multiple subgroups.

FRAX-based intervention and assessment thresholds in seven Latin American countries.

Intervention thresholds are proposed using the Fracture Risk Assessment (FRAX) tool. We recommended their use to calculate the ten-year probability of fragility fracture (FF) in both, men and women with or without the inclusion of bone mineral density (BMD). The purpose of this study is to compute FRAX-based intervention and BMD assessment thresholds for seven Latin American countries in men and women ≥ 40years. The intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF) equivalent to a woman with a prior FF and a body mass index (BMI) equal to 25.0kg/m2 without BMD or other clinical risk factors. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI equal to 25.0kg/m2, no previous fracture and no clinical risk factors. The upper assessment threshold was set at 1.2 times the IT. For the seven LA countries, the age-specific IT varied from 1.5 to 27.5% in Argentina, 3.8 to 25.2% in Brazil, 1.6 up to 20.0% in Chile, 0.6 to 10.2% in Colombia, 0.9 up to 13.6% in Ecuador, 2.6 to 20.0% in Mexico, and 0.7 up to 22.0% in Venezuela at the age of 40 and 90years, respectively. In the LA countries, FRAX-based IT offers a substantial advance for the detection of men and women at high fracture risk, particularly in the elderly. The heterogeneity of IT between the LA countries indicates that country-specific FRAX models are appropriate rather than a global LA model.

FRAX- vs. T-score-based intervention thresholds for osteoporosis.

A FRAX® model been recently calibrated for Kuwait, but guidance is needed on how to utilise fracture probabilities in the assessment and treatment of patients. We compared age-specific fracture probabilities, equivalent to women with no clinical risk factors and a prior fragility fracture (without BMD), with the age-specific fracture probabilities associated with femoral neck T-scores of -2.5 and -1.5 SD, in line with current guidelines in Kuwait. Upper and lower assessment thresholds for BMD testing were additionally explored using FRAX. When a BMD T-score of -2.5 SD was used as an intervention threshold, FRAX probabilities of a major osteoporotic fracture in women aged 50years were approximately twofold higher than those in women of the same age but with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 83years or more, a T-score of -2.5 SD was associated with a lower probability of fracture than that of the age-matched general population with no clinical risk factors. The same phenomenon was observed from the age of 66years at a T-score of -1.5 SD. A FRAX-based intervention threshold, defined as the 10-year probability of a major osteoporotic fracture in a woman of average BMI with a previous fracture, rose with age from 4.3% at the age of 50years to 23%, at the age of 90years, and identified women at increased risk at all ages. Qualitatively comparable findings were observed in the case of hip fracture probability and in men. Intervention thresholds based on BMD alone do not optimally target women at higher fracture risk than those on age-matched individuals without clinical risk factors, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' consistently target women at higher fracture risk, irrespective of age.

Clinical Utility of Using Lumbar Spine Trabecular Bone Score to Adjust Fracture Probability: The Manitoba BMD Cohort

Decreased lumbar spine trabecular bone score (TBS), a dual-energy X-ray absorptiometry (DXA)-derived image texture measurement, is a risk factor for major osteoporotic fracture (MOF) and hip fracture (HF) independent of 10-year fracture probability estimated using FRAX. We determined how often applying the TBS adjustment to fracture probability altered treatment qualification. Using a population-based registry containing all clinical DXA results for Manitoba, Canada, we identified 34,316 women with baseline spine and hip DXA, FRAX-based fracture probability measurements (computed with femoral neck bone mineral density), lumbar spine TBS, and minimum 5 years of observation (mean 8.7 years). Population-based health services data were used to identify incident non-traumatic MOF and HF in 3503 and 945 women, respectively. Baseline MOF and HF probabilities were estimated using FRAX before and after applying the TBS adjustment. Risk recategorization was assessed using net reclassification improvement (NRI) for individual FRAX-based intervention criteria and three national clinical practice guidelines (CPGs) (US National Osteoporosis Foundation, Osteoporosis Canada, and UK National Osteoporosis Guideline Group). Overall, proportions of women reclassified with the TBS adjustment to FRAX were small (less than 5%) with more than 90% of the reclassification occurring close to the intervention threshold. For women close to an intervention cut-off reclassification, rates ranged from 9.0% to 17.9% and were <1% otherwise. There was a small but significant improvement in overall NRI for all individual FRAX-based intervention criteria (range 0.007 to 0.018) and all three national CPGs (range 0.008 to 0.011). NRI was larger in women below age 65 years (up to 0.056 for hip fracture). In summary, a small but significant improvement in MOF and HF risk assessment was found by using lumbar spine TBS to adjust FRAX probability. An improvement in risk reclassification was observed for CPGs from three different countries, with almost all of the benefit found in individuals close to an intervention threshold. © 2017 American Society for Bone and Mineral Research. © 2017 American Society for Bone and Mineral Research.

The FRAX-based Lebanese osteoporosis treatment guidelines: rationale for a hybrid model.

The FRAX risk calculator is used to guide intervention thresholds in several national osteoporosis guidelines. This study aimed to describe the approach in developing FRAX-based osteoporosis treatment guidelines in Lebanon, a country with relatively low fracture rates. We reassessed previous national guidelines combined with an evaluation of age-dependent and fixed FRAX-based intervention threshold models used in the UK, the USA, and Canada. We took into consideration the risk for major osteoporotic fractures (MOF) and the proportions of subjects considered for therapy using such thresholds, before finalizing a model for Lebanon. The new Lebanese guidelines retained the recommendation to treat individuals with fragility fracture at the hip or spine. A femoral neck T-score ≤-2.5 in subjects without fractures was dropped, since it would imply consideration of therapy for individuals with a 10-year risk for MOF of <10%, up to age 75years in women. After considering the impact of both age-dependent and fixed intervention thresholds, we chose a new hybrid algorithm, combining a fixed 10% treatment threshold until age 70years and an age-dependent threshold thereafter. The Lebanese FRAX-based hybrid model takes into consideration the risk for MOF and the proportions of subjects considered for treatment. This model avoids consideration of drug therapy in a large proportion of younger subjects at low risk for fracture and targets high risk elderly individuals. It was deemed most suitable for Lebanon and may be an option for other countries with relatively low fracture rates.

Cost-effective osteoporosis treatment thresholds in Greece.

A Greek-specific cost-effectiveness analysis determined the FRAX-based intervention thresholds. Assuming a willingness to pay of 30,000 <euro>, osteoporosis treatment is cost-effective in subjects under the age of 75 with 10-year probabilities for hip and major osteoporotic fractures of 2.5 and 10%, respectively, while for older patients, the same thresholds are raised to 5 and 15%. The purpose of this study was to determine the FRAX calculated fracture probabilities at which therapeutic intervention can be considered as cost-effective in the Greek setting. A Markov cohort model was populated with Greek data, and quality-adjusted life years (QALYs) were used to calculate the cost-effective thresholds for an annual medication cost of 733.7 <euro> by gender and age. Average FRAX-based 10-year probabilities for both major osteoporotic and hip fractures were multiplied by the model-derived relative risk at which a cost of 30,000 <euro> for each QALY gained was observed for treatment versus to no intervention. A biphasic intervention threshold model is supported by our findings. Osteoporosis treatment becomes cost-effective when absolute 10-year probabilities for hip and major osteoporotic fractures reach 2.5 and 10%, respectively, among both men and women under the age of 75. For older subjects, the proposed intervention thresholds are raised to 5 and 15% 10-year probability for hip and major osteoporotic fractures, respectively. Cost-effective osteoporosis treatment may be facilitated in Greece if FRAX algorithm is used to identify subjects with 10-year probabilities for hip and major osteoporotic fractures of 2.5 and 10%, under the age of 75, while for older patients, the relevant thresholds are 5 and 15%, respectively.

FRAX-based intervention and assessment thresholds for osteoporosis in Romania

We compared the utility of the current Romanian guidelines that recommend treatment in women with a T-score ≤-2.5 SD with a FRAX-based intervention threshold equivalent to women with a prior fragility fracture. Whereas the FRAX-based intervention threshold identified women at high fracture probability, the T-score threshold was less sensitive and decreased markedly with age. FRAX algorithm has been calibrated for Romania, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific 10-year probabilities of a major osteoporotic fracture were calculated at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of -2.5 SD, in line with Romanian guidelines. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without bone mineral density (BMD). The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤-2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50 years were twofold higher than in women of the same age with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of -2.5 SD was protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture, rose from 5.3% at the age of 50 years to 13% at the age of 80 years and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a "fracture threshold" targets women at high fracture risk irrespective of age.

Possible FRAX-based intervention thresholds for a cohort of Chinese postmenopausal women

A total of 2,266 postmenopausal Chinese women were followed for 4.5 years to determine the incidence of new fractures. The positive predictive value, negative predictive value, sensitivity and specificity of different treatment strategies were compared. Using a fixed optimal threshold calculated from receiver operating characteristics (ROC) curve had the highest sensitivity but lowest specificity. There is no specific intervention threshold based on FRAX to guide treatment for Asian populations. This prospective study sought to determine the impact of applying different intervention thresholds to a cohort of Chinese postmenopausal women. This study was part of the Hong Kong Osteoporosis Study. A total of 2,266 treatment-naïve postmenopausal women underwent clinical risk factor and BMD assessments. The subjects were followed to assess fractures. We calculated the FRAX probability of major osteoporotic fractures corresponding to women with prior fractures but no other clinical risk factors. Different treatment strategies which include treating women with prior fractures, women with age-specific FRAX probability corresponding to those with prior fractures, women with osteoporosis as well as women with FRAX probability above a fixed cut-off based on optimizing sensitivity and specificity on the ROC curve were compared. The mean age at baseline was 62.1 ± 8.5 years, and the mean follow-up time was 4.5 ± 2.8 years. One hundred six new major osteoporotic fractures were reported. An optimal (FRAX, with BMD) cut-off point of 9.95 % was identified. All strategies had negative predictive value of >90 %. Using a fixed cut-off had the highest sensitivity (62.3 %) but lowest specificity (73.5 %) and positive predictive value (10.3 %). Using a fixed cut-off would direct treatment from younger women with lower absolute risk to elderly women with higher absolute risk. Targeting only women with prior fractures is unlikely to reduce fracture burden. Other treatment strategies with higher sensitivity need to be considered but they have different shortcomings.

How to decide intervention thresholds based on FRAX in central south Chinese postmenopausal women.

The FRAX tool has been used to determine possible thresholds for therapeutic intervention; however, there are no FRAX-based intervention thresholds available for China, we proposed that the 10-year probability of major osteoporotic fracture and hip fracture of about 4.0 and 1.3 %, respectively, may be acceptable intervention thresholds for central south Chinese postmenopausal women.

Development and application of FRAX in the management of osteoporosis in Ireland

The Irish Fracture Risk Assessment (FRAX) tool is the first fracture prediction model that has been calibrated using national hip fracture incidence data and Irish mortality rates. The Irish FRAX tool can be used to identify intervention thresholds for Ireland based on the fracture probability equivalent to that of a woman with a prior fracture. The objective of the study is to describe the 10-year probability of osteoporotic fracture in men and women in Ireland by using the Irish version of the FRAX tool and to develop FRAX-based intervention thresholds. The FRAX model for Ireland was constructed from the age- and sex-stratified hip fracture incidence rates from 2008 to 2010. For other major osteoporotic fractures, incidence rates were imputed, using age- and sex-specific Swedish ratios for hip to osteoporotic fracture risks. Lifetime fracture probabilities and 10-year probabilities of a major osteoporotic fracture were calculated in women to determine potential intervention thresholds. Based on the incidence of hip fracture and mortality, the average lifetime probability of hip fracture from the age of 50 years was 7.8% in men and 18.2% in women from Ireland. Probability-based intervention threshold derived from BMD T-scores were problematic. When a BMD T-score≤-2.5 standard deviations (SD) was used as an intervention threshold, the increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T-score of -2.5 SD was protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to that of women with a previous fracture, rose with age, from 3.0% at the age of 40 years to 30% at the age of 90 years, and identified women at increased risk at all ages. The Irish FRAX tool is the first fracture prediction model that has been calibrated using national hip fracture incidence data and Irish mortality rates.

The impact of a FRAX-based intervention threshold in Turkey: the FRAX-TURK study

With the development of country-specific FRAX® tools to estimate fracture probability, guidance is required on the fracture probability at which treatment can be recommended. The aim of the present study was to determine FRAX-based intervention thresholds in men and women from Turkey and determine their population impact. Intervention thresholds for treatment and assessment thresholds for measuring BMD were devised using the strategy adopted by the National Osteoporosis Guideline Group of the UK but applied to the fracture probabilities in Turkey. The number of men and women potentially eligible for treatment was determined from the distribution of FRAX-based probabilities of a major fracture (Turkish model, version 3.6) in a representative sample of 26,394 men and women aged 50 years or more. Intervention thresholds, set at the probability equivalents of a woman with a prior fragility fracture rose with age from 7.0 % at the age of 50 years to 31 % at the age of 90 years. Approximately 8.6 % of the female Turkish population aged 50 years or more had a prior fragility fracture and would be eligible for treatment. A further 13.6 % without a prior fracture would be eligible for treatment. In contrast, the number of men aged 50 years or more eligible for treatment was 3.1 %. FRAX-based guidelines can be developed and are expected to avoid unnecessary treatment of individuals at low fracture risk and direct treatments to those at high risk. The adoption of FRAX-based intervention thresholds will demand a reappraisal of the criteria for reimbursement of interventions and health economic assessment.

Cost-effective intervention thresholds against osteoporotic fractures based on FRAX® in Switzerland

FRAX-based cost-effective intervention thresholds in the Swiss setting were determined. Assuming a willingness to pay at 2× Gross Domestic Product per capita, an intervention aimed at reducing fracture risk in women and men with a 10-year probability for a major osteoporotic fracture at or above 15% is cost-effective. The fracture risk assessment algorithm FRAX® has been recently calibrated for Switzerland. The aim of the present analysis was to determine FRAX-based fracture probabilities at which intervention becomes cost-effective. A previously developed and validated state transition Markov cohort model was populated with Swiss epidemiological and cost input parameters. Cost-effective FRAX-based intervention thresholds (cost-effectiveness approach) and the cost-effectiveness of intervention with alendronate (original molecule) in subjects with a FRAX-based fracture risk equivalent to that of a woman with a prior fragility fracture and no other risk factor (translational approach) were calculated based on the Swiss FRAX model and assuming a willingness to pay of 2 times Gross Domestic Product per capita for one Quality-adjusted Life-Year. In Swiss women and men aged 50 years and older, drug intervention aimed at decreasing fracture risk was cost-effective with a 10-year probability for a major osteoporotic fracture at or above 13.8% (range 10.8% to 15.0%) and 15.1% (range 9.9% to 19.9%), respectively. Age-dependent variations around these mean values were modest. Using the translational approach, treatment was cost-effective or cost-saving after the age 60 years in women and 55 in men who had previously sustained a fragility fracture. Using the latter approach leads to considerable underuse of the current potential for cost-effective interventions against fractures. Using a FRAX-based intervention threshold of 15% for both women and men should permit cost-effective access to therapy to patients at high fracture probability based on clinical risk factors and thereby contribute to further reduce the growing burden of osteoporotic fractures in Switzerland.