Rationale of the Spanish FRAX model in decision-making for predicting osteoporotic fractures: an update of FRIDEX cohort of Spanish women.

BACKGROUND: The FRAX® tool estimates the risk of a fragility fracture among the population and many countries have been evaluating its performance among their populations since its creation in 2007. The purpose of this study is to update the first FRIDEX cohort analysis comparing FRAX with the bone mineral density (BMD) model, and its predictive abilities. METHODS: The discriminatory ability of the FRAX was assessed using the 'area under curve' of the receiver operating characteristic (AUC-ROC). Predictive ability was assessed by comparing estimated risk fractures with incidence fractures after a 10-year follow up period. RESULTS: One thousand three hundred eight women ≥ 40 and ≤ 90 years followed up during a 10-year period. The AUC for major osteoporotic fractures using FRAX without DXA was 0.686 (95 % CI 0.630-0.742) and using FN T-score of DXA 0.714 (95 % CI 0.661-0.767). Using only the traditional parameters of DXA (FN T-score), the AUC was 0.706 (95 % CI 0.652-0.760). The AUC for hip osteoporotic fracture was 0.883 (95 % CI 0.827-0.938), 0.857 (95 % CI 0.773-0.941), and 0.814 (95 % CI 0.712-0.916) respectively. For major osteoporotic fractures, the overall predictive value using the ratio Observed fractures/Expected fractures calculated with FRAX without T-score of DXA was 2.29 and for hip fractures 2.28 and with the inclusion of the T-score 2.01 and 1.83 respectively. However, for hip fracture in women < 65 years was 1.53 and 1.24 respectively. CONCLUSIONS: The FRAX tool has been found to show a good discriminatory capacity for detecting women at high risk of fragility fracture, and is better for hip fracture than major fracture. The test of sensibility shows that it is, at least, not inferior than when using BMD model alone. The predictive capacity of FRAX tool needs some adjustment. This capacity is better for hip fracture prediction and better for women < 65 years. Further studies in Catalonia and other regions of Spain are needed to fine tune the FRAX tool's predictive capability.

Umbrales de FRAX ® para identificar personas con alto o bajo riesgo de fractura osteoporótica en población femenina española / FRAX® thresholds to identify people with high or low risk of osteoporotic fracture in Spanish female population

Fundamento y objetivo: Detectar los umbrales de la herramienta FRAX® que determinen los grupos de riesgo alto/bajo de fractura osteoporótica en la población femenina española y su valoración coste-efectiva. Pacientes y métodos: Estudio de cohortes. Ochocientas dieciséis mujeres de 40-90 años de la cohorte FRIDEX con densitometría basal, factores de riesgo de fractura y sin tratamiento para la osteoporosis en los 10 años de seguimiento. Se estratificaron en 3 grupos/niveles de riesgo de fractura principal (bajo < 10%, intermedio 10-20% y alto > 20%) según la incidencia real de fractura, y se buscaron los puntos de corte equivalentes de FRAX® basal. Resultados: Los umbrales de FRAX® basal para fractura principal fueron: riesgo bajo < 5; intermedio ≥ 5 y < 7,5 y alto ≥ 7,5. La incidencia real de fractura con estos valores fue: riesgo bajo (3,6%; IC 95% 2,2-5,9); intermedio (13,7%; IC 95%7,1-24,2), y alto (21,4%; IC 95% 12,9-33,2). La opción más coste-efectiva fue realizar una dual energy X-ray absorptiometry (DXA, «absorciometría dual de rayos X») para FRAX® ≥ 5 (riesgo intermedio y alto) para reclasificar los casos mediante FRAX® con DXA en riesgo alto/bajo. Así se seleccionarían 17,5% de las mujeres para DXA y 10% para tratamiento. Con estos umbrales calibrados de FRAX®, comparados con la estrategia tradicional basada en la DXA, se mejoran los parámetros predictivos y se reducen las DXA (82,5%), los tratamientos (35,4%) y el coste global (28,7%) para detectar al mismo número de mujeres que tuvieron fracturas. Conclusiones: La utilización de los umbrales de FRAX® identificados como alto/bajo riesgo de fractura osteoporótica en la presente calibración (modelo FRIDEX) mejorarían los parámetros predictivos en mujeres españolas y de una forma más coste-efectiva que el modelo tradicional basado en el T-score ≤ -2,5 de la DXA (AU)

Background and objective: To detect FRAX® threshold levels that identify groups of the population that are at high/low risk of osteoporotic fracture in the Spanish female population using a cost-effective assessment. Patients and methods: This is a cohort study. Eight hundred and sixteen women 40-90 years old selected from the FRIDEX cohort with densitometry and risk factors for fracture at baseline who received no treatment for osteoporosis during the 10 year follow-up period and were stratified into 3 groups/levels of fracture risk (low < 10%, 10-20% intermediate and high > 20%) according to the real fracture incidence. Results: The thresholds of FRAX® baseline for major osteoporotic fracture were: low risk < 5; intermediate ≥ 5 to < 7.5 and high ≥ 7.5. The incidence of fracture with these values was: low risk (3.6%; 95% CI 2.2-5.9), intermediate risk (13.7%; 95% CI 7.1-24.2) and high risk (21.4%; 95% CI12.9-33.2). The most cost-effective option was to refer to dual energy X-ray absorptiometry (DXA-scan) for FRAX® ≥ 5 (Intermediate and high risk) to reclassify by FRAX® with DXA-scan at high/low risk. These thresholds select 17.5% of women for DXA-scan and 10% for treatment. With these thresholds of FRAX®, compared with the strategy of opportunistic case finding isolated risk factors, would improve the predictive parameters and reduce 82.5% the DXA-scan, 35.4% osteoporosis prescriptions and 28.7% cost to detect the same number of women who suffer fractures. Conclusions: The use of FRAX ® thresholds identified as high/low risk of osteoporotic fracture in this calibration (FRIDEX model) improve predictive parameters in Spanish women and in a more cost-effective than the traditional model based on the T-score ≤ -2.5 of DXA scan (AU)

[FRAX® thresholds to identify people with high or low risk of osteoporotic fracture in Spanish female population]. / Umbrales de FRAX(®) para identificar personas con alto o bajo riesgo de fractura osteoporótica en población femenina española.

BACKGROUND AND OBJECTIVE: To detect FRAX(®) threshold levels that identify groups of the population that are at high/low risk of osteoporotic fracture in the Spanish female population using a cost-effective assessment. PATIENTS AND METHODS: This is a cohort study. Eight hundred and sixteen women 40-90 years old selected from the FRIDEX cohort with densitometry and risk factors for fracture at baseline who received no treatment for osteoporosis during the 10 year follow-up period and were stratified into 3 groups/levels of fracture risk (low<10%, 10-20% intermediate and high>20%) according to the real fracture incidence. RESULTS: The thresholds of FRAX(®) baseline for major osteoporotic fracture were: low risk<5; intermediate ≥ 5 to <7.5 and high ≥ 7.5. The incidence of fracture with these values was: low risk (3.6%; 95% CI 2.2-5.9), intermediate risk (13.7%; 95% CI 7.1-24.2) and high risk (21.4%; 95% CI12.9-33.2). The most cost-effective option was to refer to dual energy X-ray absorptiometry (DXA-scan) for FRAX(®)≥ 5 (Intermediate and high risk) to reclassify by FRAX(®) with DXA-scan at high/low risk. These thresholds select 17.5% of women for DXA-scan and 10% for treatment. With these thresholds of FRAX(®), compared with the strategy of opportunistic case finding isolated risk factors, would improve the predictive parameters and reduce 82.5% the DXA-scan, 35.4% osteoporosis prescriptions and 28.7% cost to detect the same number of women who suffer fractures. CONCLUSIONS: The use of FRAX ® thresholds identified as high/low risk of osteoporotic fracture in this calibration (FRIDEX model) improve predictive parameters in Spanish women and in a more cost-effective than the traditional model based on the T-score ≤ -2.5 of DXA scan.

FRAX® tool, the WHO algorithm to predict osteoporotic fractures: the first analysis of its discriminative and predictive ability in the Spanish FRIDEX cohort.

BACKGROUND: The WHO has recently published the FRAX® tool to determine the absolute risk of osteoporotic fracture at 10 years. This tool has not yet been validated in Spain. METHODS/DESIGN: A prospective observational study was undertaken in women in the FRIDEX cohort (Barcelona) not receiving bone active drugs at baseline. Baseline measurements: known risk factors including those of FRAX® and a DXA. Follow up data on self-reported incident major fractures (hip, spine, humerus and wrist) and verified against patient records. The calculation of absolute risk of major fracture and hip fracture was by FRAX® website. This work follows the guidelines of the STROBE initiative for cohort studies. The discriminative capacity of FRAX® was analyzed by the Area Under Curve (AUC), Receiver Operating Characteristics (ROC) and the Hosmer-Lemeshow goodness-of-fit test. The predictive capacity was determined using the ratio of observed fractures/expected fractures by FRAX® (ObsFx/ExpFx). RESULTS: The study subjects were 770 women from 40 to 90 years of age in the FRIDEX cohort. The mean age was 56.8 ± 8 years. The fractures were determined by structured telephone questionnaire and subsequent testing in medical records at 10 years. Sixty-five (8.4%) women presented major fractures (17 hip fractures). Women with fractures were older, had more previous fractures, more cases of rheumatoid arthritis and also more osteoporosis on the baseline DXA. The AUC ROC of FRAX® for major fracture without bone mineral density (BMD) was 0.693 (CI 95%; 0.622-0.763), with T-score of femoral neck (FN) 0.716 (CI 95%; 0.646-0.786), being 0.888 (CI 95%; 0.824-0.952) and 0.849 (CI 95%; 0.737-0.962), respectively for hip fracture. In the model with BMD alone was 0.661 (CI 95%; 0.583-0.739) and 0.779 (CI 95%; 0.631-0.929). In the model with age alone was 0.668 (CI 95%; 0.603-0.733) and 0.882 (CI 95%; 0.832-0.936). In both cases there are not significant differences against FRAX® model. The overall predictive value for major fracture by ObsFx/ExpFx ratio was 2.4 and 2.8 for hip fracture without BMD. With BMD was 2.2 and 2.3 respectively. Sensitivity of the four was always less than 50%. The Hosmer-Lemeshow test showed a good correlation only after calibration with ObsFx/ExpFx ratio. CONCLUSIONS: The current version of FRAX® for Spanish women without BMD analysed by the AUC ROC demonstrate a poor discriminative capacity to predict major fractures but a good discriminative capacity for hip fractures. Its predictive capacity does not adjust well because leading to underdiagnosis for both predictions major and hip fractures. Simple models based only on age or BMD alone similarly predicted that more complex FRAX® models.

Nuevas evidencias sobre la capacidad discriminativa y predictiva de la herramienta FRAX ® en la población femenina española / No disponible

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Precauciones necesarias al utilizar los umbrales predictivos de la herramienta FRAX ® en la población española para decidir la necesidad de solicitar una densitometría ósea axial / Precautions required on using the predictive thresholds of the FRAX® tool to decide the need for an axial bone density scan in the Spanish population

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Diferencias en los valores predictivos de la herramienta FRAX™ entre población española y del Reino Unido y consideraciones sobre el umbral de intervención / Differences in the predictive values of the FRAX™ tool between the Spanish and United Kingdom population and considerations about the intervention threshold

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Measuring health-related quality of life in men with osteoporosis or osteoporotic fracture.

BACKGROUND: Osteoporosis is a serious health problem that worsens the quality of life and the survival rate of individuals with this disease on account the osteoporotic fractures. Studies have long focused on women, and its presence in men has been underestimated. While many studies conducted in different countries mainly assess health-related quality of life and identify fracture risks factors in women, few data are available on a Spanish male population. METHODS/DESIGN: Observational study. STUDY POPULATION: Men ≥ 40 years of age with/without diagnosed osteoporosis and with/without osteoporotic fracture included by their family doctor. MEASUREMENTS: The relationship between customary clinical risk factors for osteoporotic fracture and health-related quality of life in a Spanish male population. A telephone questionnaire on health-related quality of life is made. STATISTICAL ANALYSIS: The association between qualitative variables will be assessed by the Chi-square test. The distribution of quantitative variables by Student's t-test. If the conditions for using this test are not met, the non-parametric Mann-Whitney's U test will be used.The validation of the results obtained by the FRAX™ tool will be performed by way of the Hosmer-Lemeshow test and by calculating the area under the Receiver Operating Characteristic (ROC) curve (AUC). All tests will be performed with a confidence intervals set at 95%. DISCUSSION: The applicability and usefulness of Health-related quality of life (HRQOL) studies are well documented in many countries. These studies allow implementing cost-effective measures in cases of a given disease and reducing the costly consequences derived therefrom. This study attempts to provide objective data on how quality of life is affected by the clinical aspects involved in osteoporosis in a Spanish male population and can be useful as well in cost utility analyses conducted by health authorities.The sample selected is not based on a high fracture risk group. Rather, it is composed of men in the general population, and accordingly comparisons should not lead to erroneous interpretations.A possible bias correction will be ensured by checking reported fractures against healthcare reports and X-rays, or by consulting health care centers as applicable.

Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX ™ tool in Spain.

BACKGROUND: Age-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years. METHODS/DESIGN: To assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations. STUDY POPULATION: Patients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors. MEASUREMENTS: At baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site. DISCUSSION: Since more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.

33% radius evaluation to assess bone mineral density in prostate cancer patients.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the standard method to assess bone mineral density (BMD). The International Society for Clinical Densitometry recommends the measurement of BMD at lumbar spine, total hip and femoral neck, but in certain circumstances the 33% radius may be the recommended area to measure BMD. The aim of this study has been to analyze whether 33% radius should be considered the recommended area to assess BMD in prostate cancer patients. METHODS: This is a retrospective study where BMD was assessed by DXA at 33% radius, lumbar spine, total hip, and femoral neck (cDXA) in 141 prostate cancer patients. Twenty-eight patients were hormone naïve while 113 were subjected to androgen suppression (AS) during the mean period of 29 months. Osteoporosis was diagnosed when T-score was lower than -2.5 and osteopenia when it ranged between -1 and -2.5. RESULTS: The osteoporosis rate was 29.8% at 33% radius, 23.4% at femoral neck, 19.9% at lumbar spine, and 12.8% at total hip. The overall osteoporosis rate at cDXA was 29.1%. Osteoporosis was detected in 52.2% at 33% radius and 36.2% at cDXA. Normal BMD was found in 17.7% at 33% radius and 34.8% at cDXA. The 33% radius was the only site where a significant increase in the osteoporosis rate was detected in patients subjected to AS compared to those hormone naïve (33 and 13.8%). CONCLUSIONS: The 33% radius seems more sensible than the central skeleton areas to detect bone mass loss in patients with prostate cancer.

Alendronate decreases the fracture risk in patients with prostate cancer on androgen-deprivation therapy and with severe osteopenia or osteoporosis.

OBJECTIVE: To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen-deprivation therapy (ADT) and with a basal T-score of >-2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture. PATIENTS AND METHODS: We selected 61 patients with prostate cancer treated with ADT; 31 were treated with oral alendronate 70 mg once-weekly and a control group of 30 were not. At baseline and 12 months we measured bone mineral density (BMD) of the lumbar spine, femoral neck and total hip by dual-energy X-ray absorptiometry. All patients had severe osteopenia or osteoporosis at baseline. The risk of femoral neck fracture was calculated at baseline and 12 months (Z-score 2.7). RESULTS: Patients treated with alendronate had a significant increase in BMD at the lumbar spine and femoral neck after 1 year of follow-up, with mean (sd) values of 1.06 (0.26) vs 1.01 (0.21) g/cm(2) at baseline (P < 0.001), and 0.75 (0.07) vs 0.73 (0.07) g/cm(2) (P = 0.03), respectively, while the control group had a significant loss of BMD at the total hip of 0.79 (0.14) vs 0.81 (0.13) g/cm(2) (P = 0.03). BMD was significantly improved at the three locations in patients treated with alendronate compared with the control group, with differences at the lumbar spine, femoral neck and total hip of 0.05 (0.07) vs 0.01 (0.10) (P = 0.001), 0.01 (0.04) vs -0.002 (0.03) (P = 0.04) and 0.01 (0.04) vs -0.01 (0.02) g/cm(2), respectively (P = 0.001). Patients treated with alendronate had a significant decrease in the fracture risk at the femoral neck, by -0.54 (1.29) (P = 0.04) after 1 year of follow-up. CONCLUSIONS: Treatment with once-weekly 70 mg alendronate significantly improved the BMD at the lumbar spine and femoral neck in patients with prostate cancer with severe osteopenia or osteoporosis and on ADT, and significantly decreased the risk of femoral neck fracture.

Prevalence of osteoporosis during long-term androgen deprivation therapy in patients with prostate cancer.

OBJECTIVES: To know the prevalence of osteoporosis in patients with prostate cancer according to the duration of androgen deprivation therapy (ADT). METHODS: Dual energy x-ray absorptiometry was used to assess the bone mineral density (BMD) at the lumbar spine, femoral neck, Ward's triangle, trochanter, and total hip in 390 patients free of bone metastases. Osteoporosis was diagnosed if a T-score of less than 2.5 was detected at any measurement site. A subset of 124 patients were hormone naive at BMD testing, and 112 had undergone ADT for 2 years, 61 for 4 years, 37 for 6 years, 35 for 8 years, and 21 for 10 years or longer. RESULTS: The osteoporosis rate was 35.4% in hormone-naive patients, 42.9% after 2 years of ADT, 49.2% after 4 years, 59.5% after 6 years, 65.7% after 8 years, and 80.6% after 10 or more years. Conversely, the rate of normal BMD decreased from 19.4% in hormone-naive patients to 17.8% after 2 years of ADT, 16.4% after 4 years, 10.8% after 6 years, 5.7% after 8 years, and 0% after 10 or more years of ADT. CONCLUSIONS: The prevalence of osteoporosis seemed high in hormone-naive patients with prostate cancer, and it increased to more than 80% after 10 years of ADT. Because of the increased risk of bone fractures in those patients, clinicians should be aware of the impact of ADT on BMD to prevent bone mass loss.

Bone mineral density changes in patients with prostate cancer during the first 2 years of androgen suppression.

PURPOSE: We characterized bone mineral density changes in patients with prostate cancer on androgen deprivation therapy during the first 2 years of uninterrupted therapy, and identified which location most reflects bone mass loss. MATERIALS AND METHODS: Using dual energy x-ray absorptiometry, bone mineral density was prospectively assessed in patients with nonmetastatic prostate cancer at the lumbar spine and femoral neck, Ward's triangle, trochanter and total hip. Measurements were performed at baseline and yearly thereafter in patients on ADT, and at baseline and 1 year in controls (age matched patients with prostate cancer, free of biochemical progression after radical prostatectomy). RESULTS: A total of 62 patients were included in the study, 31 in each group. Median age (70 and 69 years, respectively), mean Gleason score and mean baseline serum testosterone did not significantly differ. Patients receiving ADT experienced a significant bone mass loss at 12 months in all locations, ranging from 2.29% to 5.55% (p <0.001). In contrast, bone mineral density did not change significantly (0.64% to 1.68%) in patients not receiving ADT. In the 20 patients on ADT after 24 months, the second year decrease was not as severe, nor was it significant compared to first year values. The major bone mass loss occurred in Ward's triangle, with decreases of 5.55% at 12 months and 7.05% at 24 months. CONCLUSIONS: Bone mineral density decreases during the first 24 months of androgen suppression with the most relevant effect occurring in the first year. Ward's triangle is the axial skeletal site that reflects the major bone mass loss. Because the deleterious impact of long-term androgen suppression on bone mineral density is inversely related to fracture risk and indirectly related to survival in patients with prostate cancer, early diagnosis and prevention of bone mass loss are warranted in these patients.