Higher FRAX Scores Research Articles

Higher fracture risk associates with worse cognitive performance in Mexico

AbstractBackgroundOsteoporosis is associated with an increased risk of dementia (Zhang, P. et al., 2022). The Fracture Risk Assessment Tool (FRAX) calculates the risk of hip fracture using a series of clinical variables, even in the absence of bone density knowledge. A higher FRAX scores indicates higher risk for osteoporosis. Some studies suggest that individuals with higher FRAX are also at increased risk of cognitive decline and dementia, with less evidence from low‐ and middle‐income countries (LMIC). We aim to evaluate the association between FRAX score and cognitive impairment in Mexican older adults.MethodThis is a cross‐sectional study of 500 Adults 60 years of age or older enrolled at a dementia clinic in a tertiary care hospital in México who completed baseline evaluations. We assessed the risk of hip fracture using FRAX and cognitive performance with the MMSE. Participants also received brain MRI (1.5 tesla), and a comprehensive geriatric assessment. A linear regression was performed to evaluate the association between FRAX score and cognitive impairment measured through MMSE.ResultThe sample included 295 (59%) women and 205 men (41%), with a mean age of 69±6.4 years, and a mean of 6±4.7 years of education. We excluded 1.8% of cased due to probable delirium. Among the remaining cases, 97.7% were cognitively impaired, which was classified as: mild cognitive impairment (MMSE between 24‐29, 40.8%) and dementia (MMSE < 24, 59.2%). The most prevalent diseases were hypertension (61.8%), diabetes (35.8%), and depression (23.2%). We found a negative association between the FRAX score and the MMSE score (b = ‐0.288, p = 0.001), after controlling for age, sex, and education.ConclusionA higher FRAX score was associated with a lower MMSE score in Mexican older adults, supporting an association between fracture risk and cognitive impairment. Understanding this association is important for developing integrated strategies for the prevention and management of both osteoporosis and dementia in aging populations from LMIC. Further research is warranted to elucidate the underlying mechanisms linking osteoporosis to dementia.

Prediction of Fragility Fractures and Mortality in a Cohort of Geriatric Patients.

Risk factors of refracture after fragility fractures include osteoporosis, female gender and advanced age among others. We hypothesized that the assessment of functionality, muscle health and nutrition status contribute to the risk prediction for further fractures and death. We assessed 334 patients admitted to the department of acute geriatrics for sociodemographic data, bone fragility, selected laboratory tests, body composition and data on functionality using the comprehensive geriatric assessment. Patients had follow-ups until the occurrence of further fractures or death. Dual-energy X-ray absorptiometry and pulse echo measurements were performed to assess bone mineral density. Fracture risk was assessed using the FRAX score and muscle strength according to published guidelines on sarcopenia. The mean age was 81 years (70-95), and 82.3% (275/334) were women. An incidence of 10.4% (35/334) new fragility fractures was observed within 24 months, and the mortality rate was 12.2% (41/334). A significantly higher rate of further fractures was associated with lower BMI (body mass index) (HR 0.925, CI 0.872-0.98; p = 0.009), lower parathyroid hormone levels (HR 0.986, CI 0.973-0.998; p = 0.026) and with the diagnosis of osteoporosis (HR 2.546, CI 1.192-5.438; p = 0.016). No significant associations were present in patients with previous fractures, with higher age, higher FRAX scores, sarcopenia, in women, sarcopenic obesity, frail patients, lower grip strength, lower walking speed, lower Barthel index or lower DI (density index) values. The predictive power for further fractures was 10.7% higher adding osteosarcopenia, BMI and parathyroid hormone levels to standard assessment parameters osteoporosis, age and the status of previous fractures. Mortality was significantly higher with advanced age (HR 1.101, CI 1.052-1.151; p < 0.001), in men (HR 6.464, CI 3.141-13.305; p < 0.001), in smokers (p = 0.002), higher FRAX score (HR 1.039, CI 1.009-1.070; p = 0.010), lower renal function (HR 0.987, CI 0.976-0.997; p = 0.010), lower Tinetti test scores (HR 0.943, CI 0.900-0.987; p = 0.012), lower walking speed (HR 0.084, CI 0.018-0.382; p = 0.001), lower hand grip (HR 0.876, CI 0.836-0.919; p < 0.001) and lower Barthel index scores (HR 0.984, CI 0.971-0.997; p = 0.015). In a cohort of geriatric patients, the addition of BMI, low parathyroid hormone levels and osteosarcopenia increases the predictive power for further fractures by 10.7%. These parameters are a valuable addition to the standard assessment parameters age and history of sustained fractures. Mortality is partly associated with potentially treatable functional parameters.

Analysis of the risk factors for contralateral refracture after hip fracture surgery in elderly individuals: a retrospective study

BackgroundThe risk factors for contralateral hip refracture after primary hip fracture are not fully understood; therefore, this study compared the clinical characteristics of patients with first and second hip fractures and explored and analyzed the risk factors for contralateral refracture after hip fracture in elderly individuals to provide a reference for the clinical prevention of postoperative refracture of hip fracture in elderly individuals.MethodsA retrospective study was conducted on 458 elderly patients with hip fractures who underwent surgical treatment and were discharged from our hospital from March 2016 to March 2019. The clinical data of the patients were analyzed retrospectively. Patients were divided into a case group (postoperative refracture) and a control group (no postoperative refracture) based on whether they experienced refracture within five years after surgery. The clinical data of the two groups were compared and analyzed via univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) regression analysis to identify the risk factors for refractures after hip fracture surgery in elderly patients.ResultsSixty-one patients experienced refracture, with an incidence rate of 13.3%. Age ≥ 80.5 years, female sex, poor knee joint function, FRAX score ≥ 15.5, anemia, visual impairment, osteoporosis, and Alzheimer’s disease (AD) were identified as risk factors for refracture after hip fracture surgery in elderly individuals (P < 0.05).ConclusionElderly patients with hip fractures are susceptible to refracture after surgery because of factors such as advanced age, female sex, high FRAX score, poor knee joint function, anemia, osteoporosis, visual impairment, and AD. Targeted interventions should be implemented based on the above risk factors.

Prevalence of Osteoporosis and Indications for Bone-Treatment In Older Adults Living with Frailty Enrolled in a Local Integrated Care Programme

Abstract Background Osteoporosis is estimated to affect more than 250,000 adults in Ireland, with 29.4% (€463.3 million) of the total healthcare cost attributable to osteoporosis-related fracture management, resulting in significant health and economic impact.(1,2) As such, early identification of osteoporosis and addressing associated risk factors are crucial steps in reducing osteoporosis-associated morbidity and mortality. This retrospective audit aims to assess the prevalence of osteoporosis and indications for initiating bone treatment among older adults living with frailty enrolled in the Limerick Integrated Care Programme for Older Persons (ICPOP). Methods All older adults attending ICPOP between 01/06/2023 to 29/02/2024 were included in the data collection. Data collected included patient age, gender, presence of vitamin D deficiency (&amp;lt;50), presence of osteopenia or osteoporosis via DEXA scan results, history of fragility fractures, and bone health treatment and its indication. Results A total of 310 patients (192 female, 118 male; age 70–98) attended ICPOP during the specified time period. DEXA scans identified osteopenia in 109 patients and osteoporosis in 69 patients. 86 patients experienced a history of fragility fractures, of which 30 were confirmed to have osteoporosis on DEXA. 93 patients (30.3%) displayed vitamin D deficiency, with the majority (81.7%) not previously receiving vitamin D supplementation. 151 patients were in receipt of bone treatment, of which 86 patients (56.9%) were newly commenced on bone treatment following interaction with ICPOP. The indications were osteoporosis on DEXA scan (44 patients), history of recent fragility fracture (20 patients), and high FRAX score (22 patients). Conclusion The increase in detection of risk factors and presence for osteoporosis, and initiating bone health treatment, achieved by way of an integrated care programme for older persons highlights the importance of proactive screening and timely initiation of treatment.

Application of Machine Learning Algorithms to Predict Osteoporotic Fractures in Women.

Predicting the risk of osteoporotic fractures is vital for prevention. Traditional methods such as the Fracture Risk Assessment Tool (FRAX) model use clinical factors. This study examined the predictive power of the FRAX score and machine-learning algorithms trained on FRAX parameters. We analyzed the data of 2,147 female participants from the Ansan cohort study. The FRAX parameters employed in this study included age, sex (female), height and weight, current smoking status, excessive alcohol consumption (>3 units/d of alcohol), and diagnosis of rheumatoid arthritis. Osteoporotic fracture was defined as one or more fractures of the hip, spine, or wrist during a 10-year observation period. Machine-learning algorithms, such as gradient boosting, random forest, decision tree, and logistic regression, were employed to predict osteoporotic fractures with a 70:30 training-to-test set ratio. We evaluated the area under the receiver operating characteristic curve (AUROC) scores to assess and compare the performance of these algorithms with the FRAX score. Of the 2,147 participants, 3.5% experienced osteoporotic fractures. Those with fractures were older, shorter in height, and had a higher prevalence of rheumatoid arthritis, as well as higher FRAX scores. The AUROC for the FRAX was 0.617. The machine-learning algorithms showed AUROC values of 0.662, 0.652, 0.648, and 0.637 for gradient boosting, logistic regression, decision tree, and random forest, respectively. This study highlighted the immense potential of machine-learning algorithms to improve osteoporotic fracture risk prediction in women when complete FRAX parameter information is unavailable.

Bone mass, fracture risk, and associated factors in postmenopausal women living with HIV.

The aim of this study was to assess the prevalence of low bone mass (osteopenia/osteoporosis), the factors associated with low bone mass, and the risk of fractures in Brazilian postmenopausal women living with HIV (WLH) in the Amazon region. This is a cohort study with a cross-sectional assessment at baseline conducted between March 2021 to August 2022 with 100 postmenopausal WLH undergoing antiretroviral therapy (ART) between 45 and 60 years of age and 100 age-matched HIV-negative women. Data on bone mineral density in the lumbar spine (LS) and femoral neck (FN) were collected using dual x-ray absorptiometry and the 10-year risk of hip and major osteoporotic fractures was assessed using the Fracture Risk Assessment tool (FRAX). The age of menopause onset occurred earlier in WLH ( P < 0.001). No differences in prevalence of osteoporosis and osteopenia in LS and FN were observed except for a lower T score in FN in WLH ( P = 0.039). The FRAX for major osteoporotic fracture and hip fracture were low in both groups, despite the mean of both FRAX scores was higher in WLH ( P < 0.001). Multivariate analysis showed that years since menopause onset, higher body mass index and higher FRAX major osteoporotic fracture were associated with the WLH group, while a higher frequency of physical activity was registered in the HIV-negative group. Multivariate analysis also showed that in WLH, a lower T score in FN was associated with years since menopause onset and body mass index and that the number of years since menopause onset was associated with a lower T score in the LS and a higher score in the FRAX hip fracture. Our findings show a high prevalence of low bone mass (osteopenia/osteoporosis) in Brazilian postmenopausal women from the Amazon region. Women living with HIV have higher FRAX scores than HIV-negative women and a lower T score in the FN.

THU426 Randomized Controlled Trial Comparing The Efficacy Of Teriparatide, Zoledronate And Denosumab In Postmenopausal Women With Type 2 Diabetes Mellitus At High Risk Of Fragility Fractures: 6-month Interim Analysis Of HR-pQCT Parameters

Abstract Disclosure: R. Pal: None. T.N. Prasad: None. S.K. Bhadada: None. V. Singla: None. S. Ram: None. N. Aggarwal: None. A. Kumar: None. People with type 2 diabetes (T2D) are at high-risk of fragility fractures, however, there are no randomised controlled trials (RCTs) evaluating the efficacy/safety of anti-osteoporosis drugs as a primary endpoint in T2D (1). To address this lacuna, we conducted a pilot prospective, open-labeled, blinded-end point (PROBE) RCT (CTRI/2022/02/039978) wherein consecutive postmenopausal female (≥ 50 years) with T2D (duration ≥ 5 years) were screened. Subjects with HbA1c 7-10%, eGFR &amp;gt; 45 ml/min/1.73 m2 and prior history of vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or at high-risk of fragility fractures [defined as areal bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ≤ -2.5 and high FRAX score] and without any secondary cause of osteoporosis were randomised in staggered fashion in a 1:1:1:1 ratio to receive either daily teriparatide, yearly zoledronate, biannually denosumab (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary end points were change in areal BMD and frequency of incident fractures at 18 months. The secondary end point was change in HR-pQCT parameters measured at distal radius and distal tibia (XtremeCT II, SCANCO Medical AG, Switzerland) at 6 and 18 months.Out of 412 participants who were screened, 104 subjects were randomized to any of the 4 arms. Out of these 104 subjects, 53 have completed 6 months of follow-up (teriparatide n=14, zoledronate n=14, denosumab n=15, control n=10). There were no statistically significant differences in age, HbA1c, eGFR, calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone, procollagen type I N-propeptide (PINP), C-terminal telopeptide (CTX), areal BMD, trabecular bone score (TBS), FRAX score or HR-pQCT parameters between the 4 groups at randomisation. At 6 months, there was no significant difference in HbA1c between the 4 groups; PINP and CTX rise was significantly higher in teriparatide arm compared to zoledronate, denosumab or control arms. With regard to HR-pQCT, there were no statistically significant differences in total [total volumetric BMD (vBMD), bone volume fraction], cortical (vBMD, thickness, porosity, pore diameter), or trabecular (vBMD, thickness, number, separation) bone properties at the distal radius and distal tibia between the 4 arms at 6 months of follow-up. To conclude, zoledronate, denosumab or teriparatide were unable to induce any significant microarchitectural changes than standard of care in postmenopausal women with T2D at high-risk of fragility fractures following 6 months of treatment. Longer duration of treatment and follow-up of the cohort is required to arrive at robust conclusions. Reference: (1) Pal et al., Bone fragility in type 2 diabetes mellitus: a lot left to explore. Nat Rev Endocrinol. 2022;18:651-651 Presentation: Thursday, June 15, 2023

Efficacy of zoledronate, denosumab or teriparatide in postmenopausal women with type 2 diabetes mellitus at high risk of fragility fractures: protocol of an open, blinded endpoint randomized controlled pilot trial.

People with type 2 diabetes (T2D) are at high risk of fragility fractures; however, there are no randomized controlled trials evaluating the efficacy of anti-osteoporosis drugs as a primary pre-specified endpoint in T2D. To compare the efficacy of anti-osteoporotic drugs in postmenopausal women with T2D. Prospective, randomized, open, blinded endpoint clinical pilot trial. Postmenopausal women (⩾50 years) with T2D (duration ⩾5 years), HbA1c 7-10%, eGFR ⩾45 mL/min/1.73 m2 and prior vertebral (clinical/morphometric), hip, radius, humeral fragility fracture or bone mineral density (BMD) T-score (adjusted for diabetes) at lumbar spine/femoral neck ⩽-2.5 and high FRAX score will be eligible for inclusion. Subjects with secondary causes of osteoporosis, prior exposure to bone-active therapies or history of use of glucocorticoids/pioglitazone/thiazides/canagliflozin will be excluded. Finally, eligible subjects will undergo estimation of serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, 25-hydroxyvitamin D and bone turnover markers (BTMs) (total procollagen type I N-propeptide, β-CTX) along with trabecular bone score (TBS) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of non-dominant hand and leg. After a 2-week run in phase, they will be randomized in a 1:1:1:1 ratio to receive yearly zoledronate, or biannually denosumab or daily teriparatide (in addition to standard of care, i.e., calcium 1000 mg/day and cholecalciferol 1000 IU/day) or only standard of care (control). The primary endpoints will be change in areal BMD and frequency of incident fractures at 18 months. The secondary endpoints will be change in HR-pQCT parameters, TBS and BTMs at 18 months. Adverse events will be recorded for all randomized participants. The study has been approved by the Institute Ethics Committee. Written informed consent will be obtained from each participant. The trial is expected to provide information regarding optimal anti-osteoporotic therapy in people with T2D and bone fragility. Prospectively registered in Clinical Trial Registry of India (CTRI/2022/02/039978).

Quality of Life in osteoporotic patients.

Osteoporosis is responsible for fragility fractures, which are associated with impaired quality of life (QoL) and disability. The aim of the study was to evaluate the QoL in patients affected by osteoporosis and possible determinants. One-hundred thirty-four subjects followed at the osteoprosis outpatient clinic at our institution completed the QUALEFFO-41 questionnaire for quality of life. All subjects had undergone bone densitometry measurement and the FRAX index, summarizing the risk of fragility fracture, was calculated for each of them. The QoL in these subjects and its possible determinants were investigated with univariate and multiple linear regression analysis. Subjects with osteoporosis had lower scores in the domains of physical and social function of the QUALEFFO questionnaire in comparison with subjects with normal bome mineral density. Main factors associated with impairment in QoL were high FRAX score and body mass index (BMI). Physical and social function is reduced in osteoporotic subjects. High BMI and an increased risk of fragility fracture were main determinants of impairment in the QoL in this study.

FC094: Frax is Useful Tool for Predicting All-Cause Mortality in Addition to the Risk of Fragile Fracture in Hemodialysis Patients

Abstract BACKGROUND AND AIMS The fracture risk assessment tool (FRAX®) was developed to predict the probability of fragile fractures during the next 10 years for the general population, and it is calculated by inputting risk factors of fractures such as age, gender, height, weight, fracture history, presence or absence of rheumatoid arthritis and steroid therapy. Although contents of FRAX do not include CKD as a risk factor, previous studies have shown that FRAX was useful in predicting fracture risk in maintenance dialysis patients. However, many reports are short-term observational studies targeting fracture risk. In the present study, we examined whether FRAX can be useful to predict the risk of fragile fractures and all-cause mortality in hemodialysis patients through the long-term observation. METHOD A retrospective cohort study was conducted in 273 patients aged 40 to under 90 who started hemodialysis at our hospital between March 2004 and the present and who could be followed for at least 3 years or had a fracture within 3 years. In order to assess the association between FRAX score and fragile fracture or all-cause mortality, a multivariate analysis was performed using the Cox proportional hazard model with factors related to fractures and mortality as covariates. The 10-year probability (%) of major osteoporotic fracture without bone mineral density was adopted as the FRAX score. RESULTS The average follow-up period was 6.7 years, and the average age of patients was 66 years, with women accounting for 29%. Of all 273 patients, 55 developed fragile fractures and 97 died. FRAX scores were divided into two groups (lower FRAX score and higher FRAX score) in accordance with a cut-off value of 8.2%, determined by ROC curve for fracture. Univariate analysis of factors associated with fractures revealed that higher FRAX score (8.2 or more) was a significant factor [hazard ratio (HR): 4.49 (2.59–7.85)]. Multivariate analysis conducted with significant factors in univariate analysis (mean serum albumin level, serum phosphorus level, magnesium level, C-reactive protein level and use or non-use of phosphate binder during the 3 years) as the covariates revealed that higher FRAX score was significantly associated with fractures [HR: 2.40 (1.27–4.5)]. Regarding the association between FRAX score and all-cause mortality, in univariate analysis, higher FRAX score was a significant predictive factor [HR: 4.34 (2.84–6. 64)]. In multivariate analysis adjusted with mean serum albumin level, creatinine level, magnesium level, C-reactive protein level, hemoglobin level, use or non-use of phosphate binder and calcimimetics as the covariates, higher FRAX score was found to be a significant factor of all-cause mortality [HR: 3.22 (1.97–5.22)]. CONCLUSION FRAX score was also a useful tool for predicting fractures and all-cause mortality in hemodialysis patients even in long-term analysis.

Predisposing factors for a second fragile hip fracture in a population of 1130 patients with hip fractures, treated at Oulu University Hospital in 2013–2016: a retrospective study

ObjectiveThe life-time risk of a second fragile hip fracture is 8.4%, but the risk factors that predispose to a second hip fracture remain unresolved. This study aimed to define risk factors that predisposed patients to a second hip fracture.MethodsFor this retrospective study, we retrieved clinical data on 1130 patients with fragile hip fractures (67.2% female, mean age: 79.3 years) that underwent surgery at the Oulu University Hospital in 2013–2016. These data included the fracture risk assessment score (measured with the FRAX tool), the bone-mass T-score, laboratory values, ambulatory capacity, and the time of death.ResultsIn this population, 12.4% of patients sustained a second hip fracture. The predisposing factors for a second hip fracture were: female (p = 0.016), a high FRAX score (p = 0.020), and low physical capacity (p < 0.001). The vitamin D level recommended for treating osteoporosis (i.e., vitamin D > 75 nmol/l) was observed in only 24% of patients, and 42% of patients had ionized calcium levels below the reference range. According to the level of the cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), 37% of patients did not have high bone turnover. We found a positive correlation between age and ICTP (p = 0.001). The risk of death was higher after the second hip fracture (p = 0.005), but we found no difference in age between patients with first and second hip fractures (p = 0.11).ConclusionAfter a hip fracture, a second hip fracture is a well-known risk. Nevertheless, we found that only one-third of patients with a second hip fracture had used anti-osteoporosis medication at any time previously. These findings suggested that second hip fractures were most likely to occur in patients with osteopenic T-score values, in women more often than men, and in patients with high FRAX scores and low ambulatory capacity.

Vertebral Fractures in Ireland: A Sub-analysis of the DXA HIP Project

Osteoporosis is an important global health problem resulting in fragility fractures. The vertebrae are the commonest site of fracture resulting in extreme illness burden, and having the highest associated mortality. International studies show that vertebral fractures (VF) increase in prevalence with age, similarly in men and women, but differ across different regions of the world. Ireland has one of the highest rates of hip fracture in the world but data on vertebral fractures are limited. In this study we examined the prevalence of VF and associated major risk factors, using a sample of subjects who underwent vertebral fracture assessment (VFA) performed on 2 dual-energy X-ray absorptiometry (DXA) machines. A total of 1296 subjects aged 40 years and older had a valid VFA report and DXA information available, including 254 men and 1042 women. Subjects had a mean age of 70 years, 805 (62%) had prior fractures, mean spine T-score was − 1.4 and mean total hip T-scores was − 1.2, while mean FRAX scores were 15.4% and 4.8% for major osteoporotic fracture and hip fracture, respectively. Although 95 (7%) had a known VF prior to scanning, 283 (22%) patients had at least 1 VF on their scan: 161 had 1, 61 had 2, and 61 had 3 or more. The prevalence of VF increased with age from 11.5% in those aged 40–49 years to > 33% among those aged ≥ 80 years. Both men and women with VF had significantly lower BMD at each measured site, and significantly higher FRAX scores, P < 0.01. These data suggest VF are common in high risk populations, particularly older men and women with low BMD, previous fractures, and at high risk of fracture. Urgent attention is needed to examine effective ways to identify those at risk and to reduce the burden of VF.

The association between a fracture risk tool and frailty: Geelong Osteoporosis Study

BackgroundFrailty is characterised by age-related declines in physical, psychological and social functioning. Features of frailty overlap with risk factors for fragility fractures. The aim of this study was to investigate the association between the fracture risk assessment tool (FRAX®) and frailty.MethodsIn cross-sectional analysis, frailty status was determined for participants aged 60-90 yr at 15-year follow-up of the Geelong Osteoporosis Study, using a modified Fried frailty phenotype. Using the FRAX on-line tool, scores for hip and major osteoporotic fracture (MOF) were calculated with and without bone mineral density (BMD). Using the area under Receiver Operating Characteristic (AUROC) curves, and FRAX scores calculated at the baseline visit for these participants, we investigated the association of FRAX and frailty 15 years later.ResultsForty-seven of 303 women (15.5%) and 41 of 282 men (14.5%) were frail at the 15-year visit. There was a gradient of increasing median FRAX scores from robust to frail. For example, for women, median MOF-FRAX without BMD increased from 5.9 for the robust to 7.5 for the pre-frail and 14.0 for the frail (p < 0.001). In secondary analyses, an association was observed between FRAX and frailty over 15 years, with the highest AUROC for women being 0.72 for MOF-FRAX with BMD, and for men, 0.76 hip-FRAX without BMD.ConclusionAn association was observed between FRAX and frailty where frail men and women had higher FRAX-scores compared to the other groups. Preliminary data suggest that FRAX, with or without BMD, may be useful in enhancing the information on frailty. Further research using larger datasets will be required to explore this.

SAT0482 FRAX 10-YR FRACTURE RISK IN RHEUMATOID ARTHRITIS ASSESSED WITH AND WITHOUT BONE MINERAL DENSITY – ARE WE TREATING OUR PATIENTS UNDER bDMARDs?

Background:Patients with rheumatoid arthritis (RA) have a higher risk of osteoporosis not only due to chronic inflammation status, but also due to the treatment with glucocorticoids. FRAX is a computer-based algorithm developed by the World Health Organization for estimation of the 10-year risk of a hip or major osteoporotic fracture. Inclusion of femoral neck bone mineral density (BMD) in the estimation is optional.Objectives:The study aimed to identify the RA patients under treatment with biological disease-modifying antirheumatic drug (bDMARD), who have FRAX scores, calculated with and without BMD, classified as high fracture risk and evaluate if they are receiving treatment for osteoporosis. The authors also investigated the intra-individual agreement between FRAX fracture risk calculated with and without BMD.Methods:Demographic and clinical data and BMD results from RA patients followed in a tertiary university hospital and registered in the Rheumatic Diseases Portuguese Register were used for analysis. Patients under 40 years of age at the last visit were excluded. McNemar test was applied for the identification of discordance of risk categories. The Wilcoxon test was used to characterize the intraindividual differences between paired FRAX risks with and without BMD. Correlations between pairs of variables were evaluated by the Spearman test. For independent variables Mann-Whitney test was used.Results:A total of 303 patients were included, 244 were females (80.5%) and 49 current smokers (16.2%). Mean age was 59.5 ± 9.54 years and mean disease duration 18.5 ± 10.4 years. Two hundred and twenty patients (72.4%) and 243 (80.2%) were RF and ACPA positive, respectively, and 51.5% had erosive disease. Mean disease activity score (DAS28-4V-CRP) was 3.08 ± 1.18 and mean femoral neck BMD 0.84 ± 0.12 g/cm2. One hundred and seventy nine patients (58.9%) were concomitantly treated with conventional synthetic DMARDs and 215 (70.7%) with glucocorticoids. Among all the patients, 35 (11.6%) had previous fractures and 19 (6.3%) have family history of fracture. The median 10-year risk of a major fracture and a hip fracture, calculated without BMD, was 6.0 (1.2-50) and 1.5 (0.1-39), respectively; with BMD it was 6.9 (1.3-61) and 1.7 (0-49). When FRAX score is calculated without BMD (n=303), 76 (25.1%) patients were categorized as high fracture risk. Among them, only 41 (54%) were receiving osteoporosis treatment. FRAX assessment with BMD (n=231) identified 99 (32.7%) patients with high fracture risk, 51 (51,5%) in treatment for osteoporosis. Thirty patients (21%) previously classified as low fracture risk using FRAX without BMD were recategorized as high risk (p&lt;0.001). Despite that, there was a strong correlation between fracture risks assessed with and without BMD for both major and hip fracture (r = 0.867, p &lt; 0.0001 and r = 0.728, p &lt; 0.0001, respectively). ACPA and RF positive patients did not have higher FRAX scores (including or not BMA). Patients with erosive disease had a higher 10-year probability of major fracture evaluated by FRAX when it includes BMD (p=0.041).Conclusion:It is very important to accurately assess the risk of osteoporotic fractures in RA patients to treat them properly. The authors highlight the high number of patients who are not receiving treatment according to FRAX categorization. In spite of the correlation between estimated fracture risk by FRAX with and without BMD, there is a discordance in fracture risk categorization, as one fifth of patients of low risk were reclassified as high risk. For the RA population treated with bDMARDS, our findings raise the need to request a DXA not only for patients classified as having an intermediate risk of fracture, but also for low-risk patients.Disclosure of Interests:Maria Rato: None declared, Filipe Pinheiro: None declared, Salomé Garcia: None declared, Bruno Miguel Fernandes: None declared, Sara Ganhão: None declared, Rita Gaio: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Alexandra Bernardo: None declared, Lúcia Costa: None declared

Vertebral fracture: clinical presentation and severity are linked to fracture risk factors.

Data concerning the association between risk factors of vertebral fracture and its presentation are limited. In this study, several fracture risk factors were related to the clinical and radiological presentation of vertebral fractures. The findings suggest that these factors should be considered in patient assessments. The aims of this study were to describe the prevalence of fracture risk factors in patients with vertebral fractures (VF) and to analyze their association with VF clinical presentation and severity. The study design was observational and cross-sectional. Patients were recruited between 2015 and 2018. Fracture risk factors were recorded, including bone mineral density, fracture risk assessment (FRAX) score, pain characteristics, analgesia required, and radiological features such as number, location(s), and grade of VF, affected segment, kyphosis angle, and spine deformity index (SDI). A series of 422 patients was included (mean age, 75 ± 9 years; 74% women). Single VF was present in 59%, previous fragility fracture in 39%, and osteoporosis in 52%. L1 was the most affected location (28%); 38% had grade 2 VF, and 36% had grade 3. Acute onset back pain was present in 81%. Older age, history of previous fragility fracture, body mass index ≤ 20 kg/m2, low bone mineral density, smoking habit, and high FRAX score were significantly associated with the presence of multiple VF, greater kyphosis angle, and higher SDI. Gradual onset back pain was associated with higher SDI and irradiated pain with greater kyphosis angle. Previously unpublished associations were observed between clinical and radiological characteristics of fragility VF and several fracture risk factors. The results could lead to a better understanding of the complex relationships between these risk factors and clinical presentation, and should be considered when assessing patients with VF.

Bone Health Screening and Treatment in Allogeneic Hematopoietic Stem Cell Transplant (HCT) Patients

Bone density loss is a well-recognized and common complication in allogeneic HCT recipients. Guidelines recommend screening with dual photon densitometry at 1 year post-HCT, and counseling of patients on preventative strategies along with consideration of treatment for patients at high risk for bone loss. However, osteoporosis and fragility fractures remains a major cause of morbidity, and significantly impacts the quality of life of allogeneic HCT survivors. Given the high morbidity of bone density loss in our patients, we sought to create specific guidelines, taking a more proactive approach to bone health within our program. In collaboration with the Cleveland Clinic Rheumatology department, pharmacists, and the Blood and Marrow Transplant Survivorship Program, we created specific guidelines for screening, prevention and treatment of bone loss post HCT. Given the high prevalence of older adults, pre-disposing co-morbidities and steroid use, we have initiated pre-transplant screening including Vitamin D levels and dual-energy X-ray absorptiometry (DEXA) scans on all patients during their evaluation. Patients with a history of prolonged systemic steroid use defined as ≥ 7.5 mg daily for ≥3 months are treated pre-HCT regardless of their DEXA or applied fracture risk assessment tool (FRAX) score. The DEXA and applied FRAX scores are used to determine prevention and treatment strategies for all other patients. We recommend repeat DEXA 1-year post-HCT, and recommend treatment in patients who have graft-versus-host disease requiring systemic corticosteroids (>7.5 mg prednisone equivalent for >3 months), have osteopenia or osteoporosis with a DEXA T-score of ≤ -1.0 or FRAX score (hip >3%, MOP >20%). Treatment recommendations consists of bisphosphonate therapy, yearly dosing of zolendronic acid for at least 3 years, and continuation of therapy for high risk patients (older women, vertebral fractures, low hip T-score or high FRAX score, previous major fracture, or who fracture on therapy, and continuous use of steroids). Oral bisphosphonates are considered for patients with good compliance and oral absorption. Denosumab is considered for patients with poor renal function. We provide an example of a systematic multidisciplinary approach to assess, prevent and manage bone loss in allogeneic HCT recipients. Study of patient tolerance and prevention of bone density loss in this high risk patient population with this algorithm compared to past practices is ongoing.

IMPACT OF A COLLABORATION WITH CLINICAL PHARMACISTS ON OSTEOPOROSIS TREATMENT RATES

Despite the availability of effective drugs to treat osteoporosis, many patients remain untreated and at high risk for developing a fracture. To improve treatment rates, we included clinical pharmacists in the management of patients with osteoporosis. Over 6 months, 30 days after bone mineral density (BMD) results became available to the ordering physician, all patients with an abnormal BMD were evaluated for management according to guidelines if they had not been approached for care. One of three clinical pharmacists discussed patients with the team that included an endocrinologist and a geriatrician. The team made recommendations and pharmacists followed-up by calling patients and prescribing medications. After excluding those who were already on treatment or did not have an indication, 87 patients qualified: 57 (66%) had T-score ≤-2.5, 19 (22%) had osteopenia and high FRAX score, and 11 (12%) osteopenia by BMD and a fragility fracture. After 30 days, the ordering physicians had treated 32/87 (37%) of patients with an indication: 26/57 (46%) patients with T-score ≤-2.5, 1/19 (2%) with high FRAX, and 5/11 (50%) with fractures. After the pharmacists’ intervention, an additional 33/87 (38%) patients were on treatment: 16 with T-score ≤-2.5; 14 with high FRAX, and 3 with fractures; 6 patients were unreachable, 9 declined, and 6 were referred to endocrinology for work-up. By the end of the 6-month period, 75% of patients with an indication received osteoporosis treatment. These results suggest that an osteoporosis intervention employing clinical pharmacists as part of a multidisciplinary team effectively improves osteoporosis treatment rates.

2965 Utilizing Fracture Risk Assessment Tool (FRAX) in Patients With Osteopenia Listed for Liver Transplant to Guide Treatment for Fracture Prophylaxis

INTRODUCTION: Low bone mineral density (BMD) is common in chronic liver disease and predisposes to fracture. FRAX score is a widely used web-based algorithm used to estimate fracture risk with or without dual-emission x-ray absorptiometry (DEXA). FRAX score has not been studied in patients listed for liver transplant. Aim of this study was to determine if FRAX score with DEXA is effective in patients with osteopenia listed for liver transplant to guide treatment for fracture prophylaxis. METHODS: 104 consecutive patients who were actively listed for liver transplant at Baylor St. Luke's medical center were included. Clinical and demographic patient information was collected retrospectively. FRAX scores calculated with BMD data. RESULTS: 104 patients (29 ALD, 26 HCV, 22 NASH, 27 others) were studied (mean age 56 ± 10, 59% male, 41% female, mean BMI 28 ± 5, mean MELD 17+8). All patients had bone mineral density assessed (13 [12%] were osteoporotic and 42 [40%] were osteopenic at the spine and/or hip. 4 [3.8%] had a previous osteoporotic fracture. Mean FRAX score for a 10-year probability of a hip fracture was 1.7% and a 10-year probability of a major osteoporosis-related fracture was 6.2% based on the US-adapted WHO algorithm. Among 40% osteopenic and 13% osteoporotic patients, only 3% and 8% of patients had significantly high FRAX score respectively. CONCLUSION: BMD FRAX score underestimated fracture risk in actively listed liver transplant patients. We believe this could be related to small sample size of the study and strict selection criteria for liver transplant listing. Majority of our study population was non-smoker, non-drinker and with a higher BMI. Therefore, future studies with bigger sample size would be helpful to utilize FRAX score to guide treatment in osteopenic patients for fracture prophylaxis.

FRAX is a robust predictor of baseline vertebral fractures in multiple myeloma patients.

FRAX is a commonly used tool to evaluate patient fracture risk based on individual patient models that integrate the risks associated with clinical risk factors with or without bone mineral density (BMD) at the femoral neck. Retrospectively, factors identified by the FRAX scoring algorithm were used to predict the risk for vertebral compression fractures at baseline in newly diagnosed multiple myeloma patients. The data were derived from myeloma patients enrolled in Total Therapy Protocols (TT4 & TT5) between 8/2008 and 9/2017. FRAX scores were calculated and baseline PET and MRI imaging obtained. Univariate and multivariate logistic regression analyses determined the association between FRAX components and the existence of vertebral compression fractures, both pathologic and osteoporotic. The patient population had a median age of 61 years (43-76), 37% female, and 87% white. The median major osteoporotic score (MOS) and Hip fracture scores (HFS) for TT4 patients (low-risk myeloma) were 5.6 and 0.5, respectively, while median MOS and HFS for TT5 (high risk myeloma) patients were 6.2 and 0.7, respectively. The odds ratio for fracture at diagnosis in patients with elevated MOS (>2), and HFS (>4.5) was significant OR (1.48, 95% confidence interval (1.35,1.62)) and OR (1.61, 95% confidence interval (1.42, 1.81)), respectively. In sum, an elevated baseline FRAX score was highly predictive of baseline vertebral fractures in MM patients at presentation. In addition, patients with higher FRAX scores had significantly shorter survival in the low-risk (TT4) group but this survival effect was not seen in the high-risk (TT5) group. These findings suggest that FRAX assessment of baseline fracture risk is beneficial in MM patients to identify an individual patients' risk of vertebral fracture.

Women with fracture, unidentified by FRAX, but identified by cortical porosity, have a set of characteristics that contribute to their increased fracture risk beyond high FRAX score and high cortical porosity.

The Fracture Risk Assessment Tool (FRAX) is widely used to identify individuals at increased risk for fracture. However, cortical porosity is associated with risk for fracture independent of FRAX and is reported to improve the net reclassification of fracture cases. We wanted to test the hypothesis that women with fracture who are unidentified by high FRAX score, but identified by high cortical porosity, have a set of characteristics that contribute to their fracture risk beyond high FRAX score and high cortical porosity. We quantified FRAX score with femoral neck areal bone mineral density (FN aBMD), and femoral subtrochanteric architecture, in 211 postmenopausal women aged 54-94 years with non-vertebral fractures, and 232 fracture-free controls in Tromsø, Norway, using StrAx software. Of 211 fracture cases, FRAX score > 20% identified 53 women (sensitivity 25.1% and specificity 93.5%), while cortical porosity cut-off > 80th percentile identified 61 women (sensitivity 28.9% and specificity 87.9%). The 43 (20.4%) additional fracture cases identified by high cortical porosity alone, had lower FRAX score (12.3 vs. 26.2%) than those identified by FRAX alone, they were younger, had higher FN aBMD (806 vs. 738 mg/cm2), and fewer had a prior fracture (23.3 vs. 62.9%), all p < 0.05. They had higher cortical porosity (48.7 vs. 42.1%), thinner cortices (3.75 vs. 4.12 mm), lower cortical and total volumetric BMD (942 vs. 1053 and 586 vs. 699 mg HA/cm3), larger medullary and total cross-sectional areas (245 vs. 190 and 669 vs. 593 mm2), and higher cross-sectional moment of inertia (2619 vs. 2388 cm4) all p < 0.001. When the fracture cases and controls with high cortical porosity were compared, cases had higher cortical porosity, lower cortical vBMD, lower total vBMD, smaller cortical CSA/Total CSA, larger medullary CSA and larger total CSA than controls (all p ≤ 0.05). Thus, fracture cases, unidentified by FRAX, but identified by cortical porosity, had an architecture where the positive impact of larger bone size did not offset the negative effect of thinner cortices with increased porosity. A measurement of cortical porosity may be a marker of other characteristics that capture additional fracture risk components, not captured by FRAX.