FRAX Calculator Research Articles

The role of the primary care physician in identifying patients at high risk of fractures in real clinical practice

BACKGROUND: The FRAX calculator is an accessible method for identifying patients at high risk of fracture. However, data on its practical use in primary health care settings are limited.
 AIM: To evaluate the correctness of calculating the 10-year fracture probability according to FRAX by primary care physicians and then analyze the impact of the results on patient routing.
 MATERIALS AND METHODS: The base of the study was the city polyclinic No. 25 of the Nevsky district of Saint Petersburg. The study included men and women aged 40 years and older.
 During 2017–2020, polyclinic doctors assessed the risk of fracture using the FRAX calculator for 11,013 people. A group of patients with significant differences (30% or more) in the obtained value of the risk of major osteoporotic fractures from the average was identified. A 10-year probability of fractures was recalculated for these patients.
 RESULTS: Major osteoporotic fracture risk scores were compared before and after recalculation. In most cases of patients (83%), the risk category did not change after recalculation. In 15% of patients changed to a higher risk. In the total group (11,013 people), errors in FRAX calculation led to an underestimation of high fracture risk in 41 patients (0.4%).
 CONCLUSIONS: The study showed that primary care physicians use the FRAX calculator correctly. The proportion of incorrect fracture risk calculations was low. Nevertheless, training of primary care physicians in the calculation and interpretation of the FRAX score is essential.

Effect of Race/Ethnicity on United States FRAX Calculations and Treatment Qualification: A Registry-Based Study.

Since 2008. the United States has had four race/ethnic fracture risk assessment tool (FRAX) calculators: White ("Caucasian"), Black, Asian, and Hispanic. The American Society for Bone and Mineral Research Task Force on Clinical Algorithms for Fracture Risk has been examining the implications of retaining race/ethnicity in the US FRAX calculators. To inform the Task Force, we computed FRAX scores according to each US calculator in 114,942 White, 485 Black, and 2816 Asian women (self-reported race/ethnicity) aged 50 years and older. We estimated treatment qualification based upon FRAX thresholds (3% for hip fracture, 20% for major osteoporotic fracture [MOF]). Finally, we examined measures for a hypothetical population-based FRAX calculator derived as the weighted mean for the US population based upon US Census Bureau statistics. With identical inputs, the highest FRAX measurements were found with the White FRAX calculator, lowest measurements with the Black calculator, and intermediate measurements for the Asian and Hispanic calculators. The percentage of women with FRAX scores exceeding the hip fracture treatment threshold was 32.0% for White, 1.9% for Black, and 19.7% for Asian women; the MOF treatment threshold was exceeded for 14.9% of White, 0.0% of Black, and 3.5% of Asian women. Disparities in treatment qualification were reduced after considering additional criteria (fracture history and dual-energy X-ray absorptiometry [DXA] T-score -2.5 or lower). When fracture risk was recalculated for non-White women using the White FRAX calculator, mean values for Asian women slightly exceeded those for White women but for Black women remained substantially below those for White women. When using a single population-based FRAX calculator, the mean probability of fracture and treatment qualification increased for non-White women across the age range. In summary, use of a single population-based FRAX calculator, rather than existing US race/ethnic FRAX calculators, will reduce differences in treatment qualification and may ultimately enhance equity and access to osteoporosis treatment. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Adjusting Trabecular Bone Score (TBS) for Level-Specific Differences Reduces FRAX®-Based Treatment Reclassification in Patients with Vertebral Exclusions: The Manitoba BMD Registry

Trabecular bone score (TBS) is a FRAX®-independent risk factor for fracture prediction. TBS values increase from cranial to caudal, with the following mean differences between TBSL1-L4 and individual lumbar vertebrae: L1 −0.093, L2 −0.008, L3 +0.055 and L4 +0.046. Excluding vertebral levels can affect FRAX-based treatment recommendations close to the intervention threshold. We examined the effect of adjusting for level-specific TBS differences in individuals with vertebral exclusions due to structural artifact on TBS-adjusted FRAX-based treatment recommendations. We identified 71,209 individuals aged ≥40 years with TBS and FRAX calculations through the Manitoba Bone Density Program. In the 24,428 individuals with vertebral exclusions, adjusting TBS using these level-specific factors agreed with TBSL1-L4 (mean difference −0.001). We compared FRAX-based treatment recommendations for TBSL1-L4 and for non-excluded vertebral levels before and after adjusting for level-specific TBS differences. Among those with baseline major osteoporotic fracture risk ≥15 %, TBS with vertebral exclusions reclassified FRAX-based treatment in 10.6 % of individuals compared with TBSL1-L4, and was reduced to 7.2 % after adjusting for level-specific differences. In 11,131 patients where L1–L2 was used for BMD reporting (the most common exclusion pattern with the largest TBS effect), treatment reclassification was reduced from 13.9 % to 2.4 %, respectively. Among individuals with baseline hip fracture risk ≥2 %, TBS vertebral exclusions reclassified 7.1 % compared with TBSL1-L4, but only 4.5 % after adjusting for level-specific differences. When L1–L2 was used for BMD reporting, treatment reclassification from hip fracture risk was reduced from 9.2 % to 5.2 %. In conclusion, TBS and TBS-adjusted FRAX-based treatment recommendations are affected by vertebral level exclusions for structural artifact. Adjusting for level-specific differences in TBS reduces reclassification in FRAX-based treatment recommendations.

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.

Role of determining trabecular bone score for appointment of osteoporotic therapy (clinical case)

Numerous studies have shown that the trabecular bone score (TBS) in patients with rheumatic diseases and especially in persons receiving glucocorticoids predicts fractures better than the bone mineral density (BMD) of the spine or the value of a 10-year probability of osteoporotic fracture according to the FRAX calculator. This article describes the role of TBS in determining the indications for prescribing anti-osteoporotic treatment on the example of a clinical case of a postmenopausal woman with a confirmed diagnosis of rheumatoid arthritis and a slight decrease in BMD.

Trabecular Bone Score Vertebral Exclusions Affect Risk Classification and Treatment Recommendations: The Manitoba Bmd Registry

Lumbar spine trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. Lumbar vertebral levels that show structural artifact are excluded from BMD measurement. TBS is relatively unaffected by degenerative artifact, and it is uncertain whether the same exclusions should be applied to TBS reporting. To gain insight into the clinical impact of vertebral exclusion on TBS, we examined the effect of lumbar vertebral exclusions in routine clinical practice on tertile-based TBS categorization and TBS adjusted FRAX-based treatment recommendations. The study population consisted of 71,209 individuals aged 40 years and older with narrow fan-beam spine DXA examinations and retrospectively-derived TBS. During BMD reporting, 34.3% of the scans had one or more vertebral exclusions for structural artifact. When TBS was derived from the same vertebral levels used for BMD reporting, using fixed L1-L4 tertile cutoffs (1.23 and 1.31 from the McCloskey meta-analysis) reclassified 17.9% to a lower and 6.5% to a higher TBS category, with 75.6% unchanged. Reclassification was reduced from 24.4% overall to 17.2% when level-specific tertile cutoffs from the software manufacturer were used. Treatment reclassification based upon FRAX major osteoporotic fracture probability occurred in 2.9% overall, but in 9.6% of those with baseline risk ≥15%. For treatment based upon FRAX hip fracture probability, reclassification occurred in 3.4% overall, but in 10.4% in those with baseline risk ≥2%. In summary, lumbar spine TBS measurements based upon vertebral levels other than L1-L4 can alter the tertile category and treatment recommendations based upon TBS-adjusted FRAX calculation, especially for those close to or exceeding the treatment cut-off. Manufacturer level-specific tertile cut-offs should be used if vertebral exclusions are applied.

FRAX calculation with and without bone mineral density for assessment of osteoporotic fracture risk in patients of rheumatic disease: a cross-sectional study.

A cross-sectional was conducted at outpatient Department of Rheumatology. Eighty-one Patients of more than 40 years of age having either sex. Diagnosed case of Rheumatic diseases were according to American College of Rheumatology (ACR) /European Alliance of Associations for Rheumatology (EULAR) criteria were included in our study. FRAX score without BMD was calculated and information was recorded in proforma. These patients were advised dual energy X-ray absorptiometry Scan and after that FRAX with BMD was calculated, after which comparison between result of two scores was made. The data were analyzed by SPSS software version 24. Effect modifiers were controlled by stratification. Post-stratification χ2 test were applied. P value less than 0.05 was considered as significant. This study consisted of 63 participants, who were assessed for osteoporotic risk fracture, with and without BMD. Data analysis revealed a significant association between the type of fracture and age (p value=0.009), previous fracture (p value=0.25), parent fractured hip (p values) and treatment with bone mineral dismissal. There was no statistically significant association seen of fractures with bone deterioration with sex, weight, height, or current smoking. FRAX may be crucial in rural areas where dual energy X-ray absorptiometry scanning is not available since it is a readily available instrument. FRAX is a useful substitute for estimating osteoporosis risk when funds are scarce. Given the possible effect it will have on healthcare costs, this is extremely pertinent.

Bone mineral density of the ultra-distal radius: are we ignoring valuable information?

Bone mineral density (BMD) measurement of a non-dominant arm is not routinely performed during dual-X-ray-absorptiometry (DXA) test, and the possible utility of ultra-distal (UDR) radius BMD is not well-studied. We evaluated in women, correlations of UDR BMD with fracture prevalence, fracture risk prediction by the fracture risk assessment tool (FRAX), and osteoporosis diagnosed by traditional sites. Women who underwent a routine DXA (including their non-dominant forearm and including UDR BMD) in a tertiary medical center were included. Risk factors relevant to FRAX calculation were assessed via a self-administered questionnaire. Spearman correlations of UDR BMD to 10-year risks of major osteoporotic and hip fractures (assessed by FRAX) were explored. The possible added value of UDR BMD in explaining prevalent osteoporotic fractures was assessed using a multivariable regression model incorporating age and traditional osteoporosis diagnosis. The study included 1245 women with a median age of 66years (interquartile range: 59-73), of whom 298 (24%) had UDR T-score ≤ - 2.5 and 154 (12%) reported prior fractures. UDR BMD was significantly negatively correlated with FRAX risk score for hip and major osteoporotic fractures (R = - 0.5 and R = - 0.41, respectively; P < 0.001). UDR T-score ≤ - 2.5 was associated with higher fracture prevalence (19% vs 10%; P < 0.001) and remained significant after adjusting for traditional BMD and age (OR 1.49, 1.01-2.19; P = 0.043). UDR BMD correlates both with prior fractures and with predicted fracture risks and might pose added value over traditional DXA sites.

Fracture liaison services creation is the key to decrease fragility fractures morbidity

Background . Fragility fractures (FF) determine main severity of medical and social consequences of osteoporosis. FF prophylaxis considers to prevent repeated fractures. For this reason special services are being created. Their principles and effectiveness require improvement and additional study. Aim . Тo highlight key role of Fracture Liaison Services (FLS) for reducing incidence of FF by means of scientific publications and own material analysis. Materials and methods . Clinical material was collected at the Artashat Medical Center (Republic of Armenia). Study included 2,332 patients aged 50–97 years, including 1,656 women (71%) and 676 men (29%) with typical FF of limb bones. First group included 765 patients treated in 2011–2013, for whom anti-osteoporotic pharmacotherapy (AP) was prescribed due to known X-ray techniques. In second group of 1567 patients the AP was prescribed based on electronic FRAX calculator in 2014–2017. Proportions of patients in two clinical groups with and without AP were compares along with proportions who had repeated low-energy bone fractures. Moreover, past 20 years scientific publications analysis dedicated to prevention of FF and role of FLS was carried out. Results . Comparative analysis revealed that patients proportion with prescribed AF based on use of FRAX calculator in second clinical group, significantly (p&lt;0.05) increased by 16.6%, while patients proportion with repeated FF significantly (p&lt;0.05) decreased by 6.5% (or 1.17 times) in relation to first group. Analysis of publications has shown high efficiency of FLS and their important role in reducing incidence of FF in general. Conclusion . Use of FRAX calculator for AP prescription allowed to achieve significant (p&lt;0.05) increase by 16.6% in proportion with prescribed specific AP, which led to significant (p&lt;0.05) decrease of patient proportion (6.5%) with repeated low-energy fractures. Analysis of scientific publications and own material confirmed key role of FLS for reducing the incidence of FF.

Fracture risk and assessment in adults with cancer.

Individuals with cancer face unique risk factors for osteoporosis and fractures. Clinicians must consider the additive effects of cancer-specific factors, including treatment-induced bone loss, and premorbid fracture risk, utilizing FRAX score and bone mineral densitometry when available. Pharmacologic therapy should be offered as per cancer-specific guidelines, when available, or local general osteoporosis guidelines informed by clinical judgment and patient preferences. Our objective was to review and summarize the epidemiologic burden of osteoporotic fracture risk and fracture risk assessment in adults with cancer, and recommended treatment thresholds for cancer treatment-induced bone loss, with specific focus on breast, prostate, thyroid, gynecological, multiple myeloma, and hematopoietic stem cell transplant.This narrative review was informed by PubMed searches to July 25, 2022, that combined terms for cancer, stem cell transplantation, fracture, bone mineral density (BMD), trabecular bone score, FRAX, Garvan nomogram or fracture risk calculator, QFracture, prediction, and risk factors. The literature informs that cancer can impact bone health in numerous ways, leading to both systemic and localized decreases in BMD. Many cancer treatments can have detrimental effects on bone health. In particular, hormone deprivation therapies for hormone-responsive cancers such as breast cancer and prostate cancer, and hematopoietic stem cell transplant for hematologic malignancies, adversely affect bone turnover, resulting in osteoporosis and fractures. Surgical treatments such as hysterectomy with bilateral salpingo-oophorectomy for gynecological cancers can also lead to deleterious effects on bone health. Radiation therapy is well documented to cause localized bone loss and fractures. Few studies have validated the use of fracture risk prediction tools in the cancer population. Guidelines on cancer-specific treatment thresholds are limited, and major knowledge gaps still exist in fracture risk and fracture risk assessment in patients with cancer.Despite the limitations of current knowledge on fracture risk assessment and treatment thresholds in patients with cancer, clinicians must consider the additive effects of bone damaging factors to which these patients are exposed and their premorbid fracture risk profile. Pharmacologic treatment should be offered as per cancer-specific guidelines when available, or per local general osteoporosis guidelines, in accordance with clinical judgment and patient preferences.

Fracture Risk Assessment and Drug Holiday in a Real-Life Setting

Purpose: Describe fracture risk assessment practices among physicians treating osteoporosis in a real-life setting. Methods:This is a retrospective cohort study in a tertiary academic center. Inclusion criteria involved adults (aged ≥18 years) who received minimum adequate therapy (bisphosphates, raloxifene, or denosumab ≥ 3 years or teriparatide ≥ 18 months). Of 1,814 charts randomly selected and reviewed, 274 patients met the inclusion criteria.Risk stratification tools included fragility fractures, Dual-energy X-ray Absorptiometry (DXA), and fracture risk assessment using the FRAX tool. Fracture risk assessment was performed before therapy initiation (N= 274) and at the time of institution of the drug holiday (N=119). High-risk patients were defined as the presence of a fragility fracture, T-score ≤-2.5, or a high-risk score by FRAX calculation. FRAX scores were independently calculated by the research team for comparison and assessment purposes. Results: Before initiation of therapy (N=274) versus upon starting a drug holiday (DH; N=119), 29.9% versus 3.4% had a history of fragility fractures (P<0.001), 58.8% versus 67.2% had a DXA scan performed (P>0.05), 10.5% versus 10.9% of physicians calculated a FRAX score (P>0.05), and 71.5% versus 66.4% were considered at high risk and eligible for therapy. A DXA scan was performed after DH in 40.2% of these patients and at least once in 95.3% of the entire cohort. Conclusion: The reporting of FRAX score in DXA scan reports may significantly increase its utilization in fracture risk assessment. We recommend comprehensive fracture risk assessment utilizing history of prevalent osteoporosis fractures, DXA assessment, and FRAX scoring.

The role and place of the FRAX calculator in initiation osteoporosis treatment: an analysis of the osteoporosis center registry

Background:The growing frequency of fractures associated with osteoporosis, the significant costs of their treatment, disability and increased mortality make it an important and urgent task to optimize the diagnosis and treatment of osteoporosis in the Russian Federation.Aim: The aim of this study was analyzed of using modern diagnostic criteria for osteoporosis by specialists when they making a clinical decision to initiate treatment for osteoporosis, including an estimate of the 10-year probability of fractures according to FRAX.Materials and methods: The study was conducted in the city consultative and diagnostic center for the prevention of osteoporosis, St. Petersburg. The register of the osteoporosis center for 2018–2021 was used to select patients for the study. Based on the analysis of registry data, a sample of 362 patients with newly diagnosed osteoporosis was obtained. In the resulting sample, the existing FRAX value was assessed on the therapeutic intervention threshold graph, all of them analyzed the primary medical documentation, as well as the available DXA densitometry data.Results: In this study, we assessed the place of FRAX 10-year risk of major osteoporotic fractures in the clinical decision of an osteoporosis specialist to start anti-osteoporosis therapy, in this case taken as the «gold standard». The study found that a positive FRAX score had a high predictive value of 100%. In contrast, the negative predictive value was very low (19.5%): a FRAX value below the intervention threshold did not guarantee a truly low fracture risk and no need to start osteoporosis treatment.Conclusion: Despite the fact that both densitometry and FRAX have significant limitations in use, and cannot identify all patients with a high risk of fractures, their combined use increases the prognostic value of the methods. FRAX technology in routine practice allows, in addition to clinical and instrumental methods for diagnosing high-risk fractures, to identify candidates for the treatment of osteoporosis, and should be used in accordance with clinical recommendations.

Fracture risk and fracture prevalence in women from outpatient osteoporosis clinic and subjects from population-based sample: A comparison between GO Study and RAC-OST-POL cohorts.

The method of recruiting the study subjects is an important element of the study design. It can have a strong influence on the results. Different recruitment schedules can give a different picture of the studied phenomenon. The aim of the study was to compare bone health in a group of female patients treated for osteoporosis with a population-based sample. A cohort of women from GO Study from 1 outpatient osteoporotic clinic (n = 1442, mean age 65.8 ±6.7 years) and population-based female sample of RAC-OST-POL Study (n = 963, mean age 65.8 ±7.5 years) were studied. Mean age did not differ between groups. Mean weight, height and body mass index (BMI) in subjects from GO Study and RAC-OST-POL Study were 69.5 ±13.1 kg, 157.8 ±6.1 cm and 27.9 ±5.1 kg/m2, and 74.2 ±13.7 kg, 156.0 ±6.0 cm and 30.5 ±5.4 kg/m2, respectively, and differed significantly (p < 0.0001 for each variable). Data on clinical risk factors for osteoporosis and fractures were collected. Bone densitometry at hip was performed using a Prodigy or Lunar DPX device (GE Healthcare, Waukesha, USA). Fracture risk was established using FRAX, Garvan and POL-RISK. Mean values of T-score for femoral neck in subjects from GO Study and RAC-OST-POL Study were -1.67 ±0.91 and -1.27 ±0.91 and differed significantly (p < 0.0001). In GO Study and RAC-OST-POL Study, there were 518 (35.9%) and 280 (29.1%) subjects with fractures, respectively. The fracture frequency was significantly higher in the GO Study group (p < 0.001). Among clinical risk factors, only rheumatoid arthritis (p < 0.0001) secondary osteoporosis (p < 0.0001) and falls (p < 0.0001) were more frequent in RAC-OST-POL Study. Fracture risk established using FRAX, Garvan and POL-RISK calculators was significantly greater in patients enrolled in the GO Study than in subjects from the RAC-OST-POL population-based sample (p < 0.0001 for each variable). Differences noted between female patients treated for osteoporosis and population-based sample, especially in regard to fracture risk, reveal a strong influence of recruitment criteria on study results in the field of bone health and osteoporosis.

The effectiveness of screening to identify patients with osteoporosis/high risk of fractures in primary health care

Background. The organization of screening for osteoporosis is an actual problem due to the need for early detection of patients with high risk of fractures and initiation of their treatment.Aim. The aim of our study was to study the effectiveness of screening for osteoporosis (high risk of fractures) in postmenopausal men and women 40 years and older.Materials and methods. Screening was performed by outpatient doctors for all people aged 40 years and older who applied for various reasons. The doctor asked standard questions included in the FRAX questionnaire.Results. In 2017– 2020, 11,013 people were screened by outpatient doctors — 31.7% of the total attached population aged 40 years and older. According to the screening results, 21.9% people were identified with a high risk of fractures. The average 10-year probability of major osteoporotic fractures in these patients (19.0±7.9%) was statistically significantly higher compared to the rest of the screened (7.6±3.3%), p=0.0001. 60% (1,450 people) of the group of individuals with an identified high risk of fractures were patients with FRAX in the area of therapeutic intervention. Among them were patients with indications of a fracture and without a history of fractures. In the remaining 40%, the high risk was determined only on the basis of the fact of a previously suffered fracture (their FRAX index was below the intervention threshold). In general, using only the FRAX calculator, 40 men and 1410 women were identified as having a high risk of fractures, which accounted for 1.3% of the male and 17.7% of the female screened population, respectively. With the simultaneous use of FRAX and anamnestic data on a previous fracture, 13.3% of men and 25.3% of women in the screening population had a high risk of fractures.Conclusion. Screening in primary health care has allowed us to identify 21.9% of the screened population of men and women aged 40 years and older (postmenopausal women) as having a high risk of fractures. Screening with simultaneous calculation of the 10-year risk of fractures according to FRAX and clarification of the presence of a history of fractures was the most effective.

Diagnosis and Treatment of Osteoporosis, an Update Bibliographic Review

Introduction: Osteoporosis is a chronic, progressive skeletal disease characterized by low bone mineral density and deterioration of bone structure. There are multiple risk factors, both modifiable and non-modifiable. The main complication is fractures, which is why it must be diagnosed early and in a timely manner. Material and methods: Fourteen articles and one book on the diagnosis and treatment of osteoporosis were chosen in order to compare the best plan to follow in these patients in the different bibliographies reviewed. Discussion: The gold standard for diagnosing osteoporosis is the measurement of bone density with the dual energy X-ray absorptiometry device, using the T-score. The use of different biomarkers is useful both for early diagnosis and for monitoring the reaction to treatment, but it is necessary to take into account that the main objective is to prevent the disease and to improve the quality of life of the patients. On the other hand, the main and early treatment consists of physical activity adapted to each patient, diet rich in calcium, magnesium and vitamins that promote bone health, the pharmacological part of the treatment has different areas that depends on the situation of each patient, considering gender such as estrogens and progestogens in postmenopausal women, tolerance to drugs such as Denosumab, and in general, bisphosphonate is used as the first line of treatment due to the increase in bone mineral density that it produces, helping to prevent fractures and improving the quality of life of each patient. Conclusion: Osteoporosis is one of the diseases that can prevent the realization of basic activities, for this disease there are different methods of diagnosis and treatment, the main objective is to detect risk factors and make an early diagnosis to avoid complications that entails, relying on tools such as the FRAX calculator and the use of biomarkers, all this to reach the conclusion of the investigation, to use the different options and tools to provide appropriate treatment, this publication being an update on the options that are available today to treat this condition.

Reverse engineering the FRAX algorithm: Clinical insights and systematic analysis of fracture risk.

The Fracture Risk Assessment Tool (FRAX) is a computational tool developed to predict the 10-year probability of hip fracture and major osteoporotic fracture based on inputs of patient characteristics, bone mineral density (BMD), and a set of seven clinical risk factors. While the FRAX tool is widely available and clinically validated, its underlying algorithm is not public. The relative contribution and necessity of each input parameter to the final FRAX score is unknown. We systematically collected hip fracture risk scores from the online FRAX calculator for osteopenic Caucasian women across 473,088 unique inputs. This dataset was used to dissect the FRAX algorithm and construct a reverse-engineered fracture risk model to assess the relative contribution of each input variable. Within the reverse-engineered model, age and T-Score were the strongest contributors to hip fracture risk, while BMI had marginal contribution. Of the clinical risk factors, parent history of fracture and ongoing glucocorticoid treatment had the largest additive effect on risk score. A generalized linear model largely recapitulated the FRAX tool with an R2 of 0.91. Observed effect sizes were then compared to a true patient population by creating a logistic regression model of the Study of Osteoporotic Fractures (SOF) cohort, which closely paralleled the effect sizes seen in the reverse-engineered fracture risk model. Analysis identified several clinically relevant observations of interest to FRAX users. The role of major osteoporotic fracture risk prediction in contributing to an indication of treatment need is very narrow, as the hip fracture risk prediction accounted for 98% of treatment indications for the SOF cohort. Removing any risk factor from the model substantially decreased its accuracy and confirmed that more parsimonious models are not ideal for fracture prediction. For women 65years and older with a previous fracture, 98% of FRAX combinations exceeded the treatment threshold, regardless of T-score or other factors. For women age 70+ with a parent history of fracture, 99% of FRAX combinations exceed the treatment threshold. Based on these analyses, we re-affirm the efficacy of the FRAX as the best tool for fracture risk assessment and provide deep insight into the interplay between risk factors.

DXA FRAX® May Differ Significantly and Substantially To Web FRAX®

Osteoporosis and the associated fractures are a major global health burden for patients, their social network and societies. Access to quality risk assessment, diagnosis and treatment is heterogeneous and inadequate around the globe. Many algorithms have been developed for deciding who to test, assessing fracture risk, when to intervene, and how to monitor the effects of interventions. FRAX® has become the dominant fracture risk assessment tool worldwide which estimates the average 10 year risk of major osteoporotic fracture risk and hip fracture, and is recommended by our global partners: ISCD and IOF. A particular attraction of the FRAX® algorithm is that on-line calculations can be made with or without DXA testing, which is particularly attractive when access to DXA is limited or non-existent. In our centre public waiting times for non-urgent DXA are up to 10 years, so reducing unnecessary testing is a laudable and overarching service goal. A recent Japanese study comparing 4 FRAX calculation tools suggested little difference exists. However in our unit we have noticed at times very different results when using the Ireland embedded DXA-FRAX® tool to the Web-FRAX® Ireland tool. 1) To Compare DXA-FRAX® to Web-FRAX® 10-year estimates for MOF and HF. 2) To Compare Web-FRAX® 10-year estimates for MOF and HF with and without DXA-measured T-scores. We used a sub-group of the DXA-HIP Cohort as previously published to gain initial insights into DXA-FRAX® to Web-FRAX® as part of a larger calibration and validation project, which has been approved by our hospitals Ethics and Research Committee. All scans are performed and reported by staff trained to ISCD standards and recommendations. At the time of reporting DXA-FRAX® scores are calculated as part of the analysis as recommended by ISCD and IOF, and more recently Web-FRAX® for Ireland has been calculated and stored with and without BMD data. All data are cleaned, merged, anonymized and stored for analysis. Summary cross-sectional data, and comparison of differences were completed using absolute and relative scales, and Bland-Altman Plots for agreement between measures. Weights were reduced to 125kg for the on-line tool and age to 90 years when values exceeded these thresholds. Data on 588 adults aged ≥40 years were available of whom 108 (18%) were men. Mean age was 67 years, BMI: 28kg/m2, 249 had a prior fracture, 64 a parental hip fracture, 40 smokers, 42 taking glucocorticoid therapy, 39 had rheumatoid arthritis, 5 were excess alcohol users while 107 had other FRAX®-listed secondary causes of osteoporosis. Mean WF femoral neck BMD T-score was -1.4. Mean MOF DXA-FRAX® was 15.3 (SD:11.1) compared to 12.6 (SD:8.5) for Web-FRAX®, while HF means were 6.7 (SD:8.4) Vs 3.8 (SD:5.5) respectively. Bland-Altman plots showed there was much greater discrepancy for men, and those with higher risk estimates. Comparisons between DXA-FRAX® and Web-FRAX® revealed similar results. Significant differences exist in results of DXA-FRAX® and Web-FRAX® for Ireland, particularly for men and those with higher risk estimates so these results should be interpreted cautiously. Reassuringly results were similar for those deemed at lower risk and for women.

Validation of the Taiwan FRAX® calculator for the prediction of fracture risk.

FRAX® is an algorithm used to calculate fracture probabilities based on clinical risk factors (CRFs) and bone mineral density (BMD). The country-specific Taiwan FRAX calculator has not been validated since its establishment in 2010. The aim of the present study is to evaluate the predictive performance of the Taiwan FRAX calculator using longitudinal fracture data. A total of 1975 subjects, aged ≧ 40years old, from Yunlin and Tianliao cohorts in Taiwan during the period 2009-2010, were identified and completely connected with the 2008-2016 National Health Insurance Research Database. During the average 6.8 ± 1.1years of follow-up, 160 incident major osteoporotic fractures (MOFs) were identified. The predictive ability assessing based on the observed to expected fractures (O/E) ratio calculated with the FRAX probability adjusted for 6.8years were 1.19 (95%CI 1.02-1.39) for MOF, and 1.07 (95%CI 0.82-1.39) for hip fractures. In the discriminative statistics, the AUC for prediction of major osteoporotic fractures using FRAX was 0.75 without and 0.77 with BMD (AUC for hip fracture was 0.75 without and 0.77 with BMD). The optimal cutoff value was 9.5% of the FRAX score with BMD for all major osteoporotic fractures, with good sensitivity (76.9%) and specificity (65.3%). For hip fractures, the optimal cutoff point for the FRAX probability with BMD was 4.0%, and the sensitivity and specificity were 74.4% and 68.3%, respectively. The Taiwan FRAX® calculator was validated to predict incident fractures preliminarily. Cutoffs are proposed for predicting fracture risk in Taiwanese individuals.

A study to predict fracture risk using bone mineral density and FRAX score in patients on chronic maintenance haemodialysis.

Introduction:Disturbances in mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and are important causes of morbidity also their diagnosis often delayed and require a spectrum of investigations. The current study attempts to predict and correlate, the fracture risk using simple tools like BMD and FRAX (Fracture Risk Assessment Tool) score in CKD patients.Methods:A cross-sectional study among 50 CKD patients age more that 40 years attending OPD (Out Patient Department) at a tertiary care Hospital in north India.Results:There is a negative correlation between BMD (NOF) and FRAX score for hip fracture risk and major osteoporotic fracture risk.Conclusion:The 10-year fracture risk in these patients, as predicted by FRAX score using FRAX (Indian) calculator, was significantly higher in CKD patients.Recommendation:FRAX can be useful tool for early screening of fracture risk in such situations for timely interventions.

Higher prevalence of metabolic bone disease (MBD) but similar fracture risk in non-alcoholic fatty liver disease (NAFLD) compared to chronic viral hepatitis

Background and Aim: A link between NAFLD and MBD has been reported. However, the main implication of MBD is fracture risk which has been largely unexplored in NAFLD. Dual energy X-ray absorptiometry, the gold standard for osteopenia and osteoporosis, is an incomplete predictor of fracture risk which is substantially influenced by clinical risk factors. Fracture risk assessment tool (FRAX) is validated for prediction of 10-year risk of major osteoporotic or hip fractures. Methods: In this ongoing cross-sectional study, we aim to compare prevalence of MBD and assess fracture risk in non-cirrhotic NAFLD with chronic viral hepatitis (CVH). Exclusion criteria include age<40 years, pregnancy, evidence of cirrhosis on imaging or liver stiffness measurement (LSM) > 12 kPa, CKD, treatment with calcium, vitamin D, tenofovir or anti-osteoporotic medications, presence of skeletal deformities or refusal to give consent. MBD, osteopenia and osteoporosis are defined as T-score <-1, -1 to -2.5 and <-2.5, respectively. Fracture risk will be estimated using the Indian FRAX calculator. Results : So far, 82 NAFLD and 99 CVH have been recruited [Hepatitis B: 19 (19.2%) Hepatitis C: 80 (80.8%)] with no difference in age or gender. NAFLD patients had significantly higher BMI and higher likelihood of T2DM, hypertension and Vitamin D insufficiency. MBD (54.9% vs 29.3%, p<0.001), osteopenia (47.6% vs 28.3%, p=0.008) and osteoporosis (7.3% vs 1%, p=0.03) were significantly more common in NAFLD. NAFLD was independently associated with MBD [aOR: 1.89 (1.04-6.1, p=0.04) after adjusting for age, gender, Vitamin D, T2DM, obesity, smoking, alcohol and LSM. However, 10-year predicted major osteoporotic [1.2% (0.7 to 11.9) vs 1.1% (0.6-10.5), p=0.54] and hip fracture risk [0.15% (0 to 3.8) vs 0.1% (0 to 2.7), p=0.63] were comparable among NAFLD and CVH. Conclusions: Although, MBD is common in NAFLD, it may not portend an increased fracture risk compared to CVH.