Official Positions for FRAX® Bone Mineral Density and FRAX® Simplification: From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®

doi:10.1016/j.jocd.2011.05.017

Journal of Clinical Densitometry

Volume 14, Issue 3, July 2011, Pages 226-236

https://doi.org/10.1016/j.jocd.2011.05.017 Get rights and content

Abstract

Tools to predict fracture risk are useful for selecting patients for pharmacological therapy in order to reduce fracture risk and redirect limited healthcare resources to those who are most likely to benefit. FRAX^® is a World Health Organization fracture risk assessment algorithm for estimating the 10-year probability of hip fracture and major osteoporotic fracture. Effective application of FRAX^® in clinical practice requires a thorough understanding of its limitations as well as its utility. For some patients, FRAX^® may underestimate or overestimate fracture risk. In order to address some of the common issues encountered with the use of FRAX^® for individual patients, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundation (IOF) assigned task forces to review the medical evidence and make recommendations for optimal use of FRAX^® in clinical practice. Among the issues addressed were the use of bone mineral density (BMD) measurements at skeletal sites other than the femoral neck, the use of technologies other than dual-energy X-ray absorptiometry, the use of FRAX^® without BMD input, the use of FRAX^® to monitor treatment, and the addition of the rate of bone loss as a clinical risk factor for FRAX^®. The evidence and recommendations were presented to a panel of experts at the Joint ISCD-IOF FRAX^® Position Development Conference, resulting in the development of Joint ISCD-IOF Official Positions addressing FRAX^®-related issues.

Introduction

FRAX^® is a fracture risk assessment algorithm developed by the World Health Organization (WHO) to estimate the 10-year probability of hip fracture and major osteoporotic fracture (hip, clinical vertebral, proximal humerus, distal forearm) in untreated men and women from the age of 40 to 90 years. The input for FRAX is demographic patient information (age, sex, height, weight, and in the US only, one of 4 ethnicities) and femoral neck bone mineral density (BMD), when available. The output of FRAX can be used with clinical guidelines to aid in the selection of patients for starting pharmacological therapy to reduce fracture risk. The use of FRAX in clinical practice has raised concern that FRAX may underestimate or overestimate fracture risk in some patients, and raises the question of whether adjustments to the FRAX algorithm might improve the accuracy of fracture prediction or simplify the ease of use. To address such issues, the International Society for Clinical Densitometry (ISCD), in cooperation with the International Osteoporosis Foundation (IOF), convened the FRAX Position Development Conference (PDC) in Bucharest, Romania, on November 14, 2010. The topics considered at the PDC included the use of lumbar spine or distal 1/3 (33%) radius BMD for FRAX input as an alternative to femoral neck BMD, the use of quantitative ultrasound (QUS) of the heel instead of femoral neck BMD, and methods for simplifying the use of FRAX in clinical practice.

FRAX currently allows for the input of BMD for only the femoral neck measured by dual-energy X-ray absorptiometry (DXA), whereas the ISCD recommends that the diagnosis of osteoporosis in clinical practice be made according to the lowest DXA-measured T-score of the lumbar spine, total hip, femoral neck, or distal 1/3 (33%) radius, if measured. In some patients, the femoral neck BMD value may not be valid (e.g., structural abnormalities, surgical hardware) or measurable (e.g., the patient's weight exceeds the weight limit of the table, the patient is unable to be placed on the table due to disability), and in others the BMD at other skeletal sites, particularly the lumbar spine, may be much lower than at the femoral neck, suggesting that FRAX may underestimate fracture risk in such individuals. ISCD Official Positions were developed to address the use of lumbar spine and distal 1/3 radius BMD to predict fracture risk and whether these skeletal sites should be included in the FRAX algorithm.

FRAX is a validated tool to predict fracture risk using an input of clinical risk factors without femoral neck BMD. This is particularly useful when DXA is not available, accessible, or affordable. However, fracture risk prediction is improved when clinical risk factors are combined with BMD. In world regions where DXA measurements cannot be easily obtained, QUS is a potential alternative. QUS devices are less expensive than DXA, use no radiation, and are portable. Limitations of QUS include inability to diagnose osteoporosis with the WHO criteria, which are based on DXA-derived T-scores, and poor utility for monitoring patients treated for osteoporosis. The potential use of QUS-measured parameters of the heel for assessment of fracture risk and inclusion with FRAX was addressed at the PDC.

For the busy clinician, a simplified version of FRAX might make it more likely to be used when time and resources are limited. The utility of FRAX without BMD was evaluated, and the circumstances under which it might be appropriate to use FRAX without BMD were assessed. The evidence regarding the robustness of each of the FRAX risk factors in predicting fracture risk was evaluated, and the possibility of using fewer clinical risk factors was considered. The potential use of adding an additional risk factor, the rate of bone loss, was discussed.

All Official Positions were rated by the Expert Panel in three categories: quality of the evidence, strength of the evidence, and applicability.

Section snippets

Methodology & Data sources

Each task force subgroup performed a comprehensive review of the medical literature following PubMed searches using appropriate keywords for each topic question. Based on the findings of the reviews, preliminary Official Positions were developed and presented to the Expert Panel for consideration. All Official Positions for the 2010 PDC were rated by the Expert Panel in the following categories according to predefined criteria derived from the RAND/UCLA Appropriateness Method (RAM). Preliminary

BMD at Skeletal Sites other than Femoral Neck for FRAX Input

Questions:

a.
Can lumbar spine BMD and/or T-score be used to assess fracture risk with FRAX?
- i.
  Can lumbar spine BMD be used to assess vertebral, hip, major or any osteoporotic and any clinical fracture risk?
- ii.
  Should lumbar spine T-score be used to assess fracture risk with FRAX?
- iii.
  Should lumbar spine BMD be used to assess fracture risk with FRAX when the lumbar spine T-score is lower than the femoral neck T-score?
- iv.
  Can lumbar spine BMD be used to assess fracture risk with FRAX when femoral neck BMD cannot be measured

QUS of the Heel FRAX Input

Questions:

a.
Can QUS of the calcaneus be used to assess fracture risk with FRAX?
- vii.
  Can QUS-measured parameters (SOS, BUA, SI) of the calcaneus be used to assess vertebral, hip and any clinical fracture risk?
- viii.
  Can QUS-measured parameters (SOS, BUA, SI) of the calcaneus be used to assess major and any osteoporotic fracture risk?
- ix.
  Should QUS of the calcaneus T-score be used to assess fracture risk with current FRAX?
- x.
  Can QUS-measured parameters (SOS, BUA, SI) of the calcaneus be used to assess fracture risk with

Simplification of FRAX

Questions:

a.
How useful is FRAX without BMD?
- xii.
  What are the circumstances when it is appropriate to use FRAX without BMD?
- xiii.
  What are the circumstances when it is not appropriate to use FRAX without BMD
b.
Could a clinically useful simplified FRAX model be developed?
- xiv.
  Which of the FRAX risk factors are the strongest predictors of fracture risk?
- xv.
  Which of the FRAX risk factors are the weakest predictors of fracture risk?
- xvi.
  What is the effect of excluding the weaker FRAX risk factors on assessment of fracture risk?
- xvii.
  Is there a

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Positions of The International Society for Clinical Densitometry and Their Etiology: A Scoping Review
2023, Journal of Clinical Densitometry
The International Society for Clinical Densitometry convenes a Position Development Conference (PDC) every 2 to 3 years to make recommendations for guidelines and standards in the field of musculoskeletal measurement and assessment. The recommendations pertain to clinically relevant issues regarding the acquisition, quality control, interpretation, and reporting of measures of various aspects of musculoskeletal health. These PDCs have been meeting since 2002 and have generated 214 Adult, 26 FRAX, 41 pediatric, and 9 general nomenclature consideration positions, for a total of 290 positions. All positions are justified by detailed documents that present the background and rationale for each position. However, the linkage to these publications is not maintained by the ISCD or any other publication such that physicians cannot easily understand the etiology of the positions. Further, the wording of many positions has changed over the years after being reviewed by subsequent PDCs. This scoping review captures the references, changes, and timeline associated with each position through the 2019 PDC. It is meant to serve as a guide to clinicians and researchers for intelligent use and application of the positions.
Analysis of muscle, hip, and subcutaneous fat in osteoporosis patients with varying degrees of fracture risk using 3T Chemical Shift Encoded MRI
2020, Bone Reports
Osteoporosis (OP) is a major disease that affects 200 million people worldwide. Fatty acid metabolism plays an important role in bone health and plays an important role in bone quality and remodeling. Increased bone marrow fat quantity has been shown to be associated with a decrease in bone mineral density (BMD), which is used to predict fracture risk. Chemical-Shift Encoded magnetic resonance imaging (CSE-MRI) allows noninvasive and quantitative assessment of adipose tissues (AT). The aim of our study was to assess hip or proximal femoral bone marrow adipose tissue (BMAT), thigh muscle (MUS), and subcutaneous adipose tissue (SAT) in 128 OP subjects matched for age, BMD, weight and height with different degrees of fracture risk assessed through the FRAX score (low, moderate and high). Our results showed an increase in BMAT and in MUS in high compared to low fracture risk patients. We also assessed the relationship between fracture risk as assessed by FRAX and AT quantities. Overall, the results of this study suggest that assessment of adipose tissue via 3T CSE-MRI provides insight into the pathophysiology fracture risk by showing differences in the bone marrow and muscle fat content in subjects with similarly osteoporotic BMD as assessed by DXA, but with varying degrees of fracture risk as assessed by FRAX.
Time to Clinically Relevant Fracture Risk Scores in Postmenopausal Women
2017, American Journal of Medicine
Citation Excerpt :
Like past studies,7,8 our results do not support routine use of FRAX to identify candidates for screening in postmenopausal women aged 50 to 64 years. FRAX has been incorporated into subspecialty and clinical practice guidelines with recommended use in conjunction with bone mineral density testing.4,23 In 2011, the USPSTF recommended use of the screening-level FRAX score in postmenopausal women under age 65 but did not endorse the use of treatment-level FRAX scores in the absence of randomized controlled trial data about this treatment strategy.5
Clinical practice guidelines recommend use of fracture risk scores for screening and pharmacologic treatment decisions. The timing of occurrence of treatment-level (according to 2014 National Osteoporosis Foundation guidelines) or screening-level (according to 2011 US Preventive Services Task Force guidelines) fracture risk scores has not been estimated in postmenopausal women.
We conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores in postmenopausal women aged 50 years and older, prior to receipt of pharmacologic treatment and prior to first hip or clinical vertebral fracture.
In 54,280 postmenopausal women aged 50 to 64 years without a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of rare incidence of treatment-level scores. In 6096 women who had FRAX scores calculated with bone mineral density, the estimated unadjusted time to treatment-level FRAX ranged from 7.6 years (95% confidence interval [CI], 6.6-8.7) for those aged 65 to 69, to 5.1 years (95% CI, 3.5-7.5) for those aged 75 to 79 at baseline. Of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.
Agreement of Mexican FRAX with and without the value of bone mineral density in assessing the risk of fracture in daily clinical practice
2017, Medicina Clinica
El empleo del FRAX sin la inclusión de la densidad mineral ósea (FRAX-BMI) puede ser útil en la práctica clínica para identificar a los pacientes con riesgo elevado de fractura e informar sobre las decisiones de tratamiento, aunque su utilidad es motivo de debate. El objetivo del estudio es evaluar la concordancia entre el FRAX con y sin inclusión de la densidad mineral ósea (DMO).
Estudio trasversal que incluyó 431 mujeres entre 40-90 años sin tratamiento previo. La concordancia de la probabilidad de fractura fue evaluada mediante el coeficiente de correlación y concordancia (CCC), y mediante el método de Bland-Altman. Se empleó el índice de kappa para evaluar la concordancia entre las indicaciones de tratamiento.
La diferencia entre el riesgo de fractura osteoporótica principal (RFP) fue 1,02 ± 1,40% (IC 95% −2 a 1,90) y de −0,03 ± 0,51% (IC 95% −1,18 a 1,32) para el riesgo de fractura de cadera (RFC). Los resultados del CCC demostraron una buena concordancia, para el RFP fue de 0,879 (IC 95% 0,85-0,90), y de 0,821 (IC 95% 0,79-0,85) para el RFC. Existió una correlación moderada entre el riesgo de fractura obtenida con el FRAX-BMI y la DMO del cuello femoral, RFM (r = −0,55, p < 0,001) y RFC (r = −0,54, p < 0,001). El acuerdo entre las recomendaciones de tratamiento fue del 87% (kappa 0,61).
La buena concordancia entre el riesgo de fractura obtenido evidencia que el FRAX-BMI nos permite brindar una estimación del riesgo en la mayoría de los casos.
The use of FRAX without the inclusion of bone mineral density (FRAX-BMI) may be useful in clinical practice to identify patients at high risk of fracture and inform treatment decisions, but its usefulness is debated. The aim of the study is to evaluate the agreement between the risk of fracture calculated by FRAX with or without bone mineral density (BMD).
A cross-sectional study was conducted with 431 women (40-90 years) without treatment. The concordance of the probability of fracture was assessed by the concordance correlation coefficient (CCC), and by Bland-Altman method. The kappa index was used to evaluate the agreement between treatment indications.
The difference between the risks of a major osteoporosis fracture (MOFR) was 1.02 ± 1.40% (95% CI −2 to 1.90) and −0.03 ± 0.51% (95% CI −1.18 to 1.32) for the hip fracture risk (HFR). Agreement between MOFR and HFR FRAX scores was good (CCC 0.879, 95% CI 0.85-0.90 and CCC 0.821, 95% CI 0.79-0.85, respectively). The correlation between BMD of the femoral neck and fracture risk calculated by FRAX-BMI was a moderate, MOFR (r = −0.55, P < .001) and HFR (r = −0.54, P < .001). The agreement between the recommendations of treatment was 87% (kappa 0.61).
The good agreement between the risk of fracture obtained suggests that FRAX-BMI allows us to provide an estimate of risk in most cases.
Study of DXA-derived lateral-medial cortical bone thickness in assessing hip fracture risk
2015, Bone Reports
Citation Excerpt :
FRAX (Fracture Risk Assessment Tool) is another tool available for predicting 10-year fracture probability (RAX®: WHO Fracture Risk Assessment Tool). The tools have been demonstrated as very valuable in studying the epidemiology of osteoporosis (Kanis et al., 2011; Lewiecki et al., 2011a, 2011b; Leslie et al., 2010). But they have limited accuracy in predicting fracture risk in individual patients (Kanis et al., 2011; Marshall et al., 1996; Stone et al., 2003; Cranney et al., 2007).
The currently available clinical tools have limited accuracy in predicting hip fracture risk in individuals. We investigated the possibility of using normalized cortical bone thickness (NCBT) estimated from the patient's hip DXA (dual energy X-ray absorptiometry) as an alternative predictor of hip fracture risk. Hip fracture risk index (HFRI) derived from subject-specific DXA-based finite element model was used as a guideline in constructing the mathematical expression of NCBT. We hypothesized that if NCBT has stronger correlations with HFRI than the single risk factors such as areal BMD (aBMD), then NCBT can be a better predictor. The hypothesis was studied using 210 clinical cases, including 60 hip fracture cases, obtained from the Manitoba Bone Mineral Density Database. The results showed that, in general HFRI has much stronger correlations with NCBT than any of the single risk factors; the strongest correlation was observed at the superior side of the narrowest femoral neck with r² = 0.81 (p < 0.001), which is much higher than the correlation with femoral aBMD, r² = 0.50 (p < 0.001). The capability of aBMD, NCBT, and HFRI in discriminating the hip fracture cases from the non-fracture ones, expressed as the area under the curve with 95% confidence interval, AUC (95% CI), is respectively 0.627 (0.593–0.657), 0.714 (0.644–0.784) and 0.839 (0.787–0.892). The short-term repeatability of aBMD, NCBT, and HFRI, measured by the coefficient of variation (CV, %), was found to be in the range of (0.64–1.22), (1.93–3.41), (3.10–4.16), respectively. We thus concluded that NCBT is potentially a better predictor of hip fracture risk.
The relevance of biomaterials to the prevention and treatment of osteoporosis
2014, Acta Biomaterialia
Osteoporosis is a worldwide disease with a very high prevalence in humans older than 50. The main clinical consequences are bone fractures, which often lead to patient disability or even death. A number of commercial biomaterials are currently used to treat osteoporotic bone fractures, but most of these have not been specifically designed for that purpose. Many drug- or cell-loaded biomaterials have been proposed in research laboratories, but very few have received approval for commercial use. In order to analyze this scenario and propose alternatives to overcome it, the Spanish and European Network of Excellence for the Prevention and Treatment of Osteoporotic Fractures, “Ageing”, was created. This network integrates three communities, e.g. clinicians, materials scientists and industrial advisors, tackling the same problem from three different points of view. Keeping in mind the premise “living longer, living better”, this commentary is the result of the thoughts, proposals and conclusions obtained after one year working in the framework of this network.

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^a: Position Development Conference Members: see Appendix.

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Position Development PaperOfficial Positions for FRAX® Bone Mineral Density and FRAX® Simplification: From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®

Abstract

Introduction

Section snippets

Methodology & Data sources

BMD at Skeletal Sites other than Femoral Neck for FRAX Input

QUS of the Heel FRAX Input

Simplification of FRAX

Bone

J Clin Densitom

J Clin Densitom

J Clin Densitom

J Clin Densitom

Bone

J Clin Densitom

Bone

Semin Nucl Med

The use of clinical risk factors enhances the performance of BMD in the prediction of hip and osteoporotic fractures in men and women

Osteoporos Int

Predictive value of BMD for hip and other fractures

J Bone Miner Res

Updated data on proximal femur bone mineral levels of US adults

Osteoporos Int

Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures

BMJ

A longitudinal study of the effect of spinal degenerative disease on bone density in the elderly

J Rheumatol

Skeletal site bone mineral density heterogeneity in women and men

Osteoporos Int

Automated assessment of exclusion criteria for DXA lumbar spine scans

J Clin Densitom

Interobserver reproducibility of criteria for vertebral body exclusion

J Bone Miner Res

Exclusion of focal vertebral artifacts from spine bone densitometry and fracture prediction: a comparison of expert physicians, three computer algorithms, and the minimum vertebra

J Bone Miner Res

Effectiveness of bone density measurement for predicting osteoporotic fractures in clinical practice

J Clin Endocrinol Metab

Prediction of fracture risk in postmenopausal white women with peripheral bone densitometry: Evidence from the National Osteoporosis Risk Assessment

J Bone Miner Res

Predicting the risk of fracture at any site in the skeleton: are all bone mineral density measurement sites equally effective?

Calcif Tissue Int

Number of osteoporotic sites and fracture risk assessment: a cohort study from the Manitoba Bone Density Program

J Bone Miner Res

Single-site vs multisite bone density measurement for fracture prediction

Arch Intern Med

Spine-hip discordance and fracture risk assessment: a physician-friendly FRAX enhancement

Osteoporos Int

Does the combination of two BMD measurements improve fracture discrimination?

J Bone Miner Res

Spine-hip T-score difference predicts major osteoporotic fracture risk independent of FRAX®: A population-based report from CaMos

J Clin Densitom

Relationship between bone quantitative ultrasound and fractures: a meta-analysis

J Bone Miner Res

Position Development Paper
Official Positions for FRAX^® Bone Mineral Density and FRAX^® Simplification: From Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX^®