Risk Of Major Osteoporotic Fracture Research Articles

Fracture patterns in adult onset type 1 diabetes and associated risk factors – A nationwide cohort study

ObjectiveThis study aimed to determine the hazard ratios (HR) for various fracture sites and identify associated risk factors in a cohort of relatively healthy adult people with newly diagnosed type 1 diabetes (T1D). MethodsThe study utilized data from the UK Clinical Practice Research Datalink GOLD (1987–2017). Participants included people aged 20 and above with a T1D diagnosis code (n = 3281) and a new prescription for insulin. Controls without diabetes were matched based on sex, year of birth, and practice. Cox regression analysis was conducted to estimate HRs for any fracture, major osteoporotic fractures (MOFs), and peripheral fractures (lower-arm and lower-leg) in people with T1D compared to controls. Risk factors for T1D were examined and included sex, age, diabetic complications, medication usage, Charlson comorbidity index (CCI), hypoglycemia, previous fractures, falls, and alcohol consumption. Furthermore, T1D was stratified by duration of disease and presence of microvascular complications. ResultsThe proportion of any fracture was higher in T1D (10.8 %) than controls (7.3). Fully adjusted HRs for any fracture (HR: 1.43, CI95%: 1.17–1.74), MOFs (HR: 1.46, CI95%: 1.04–2.05), and lower-leg fractures (HR: 1.37, CI95%: 1.01–1.85) were statistically significantly increased in people with T1D compared to controls. The primary risk factor across all fracture sites in T1D was a previous fracture. Additional risk factors at different sites included previous falls (HR: 1.64, CI95%: 1.17–2.31), antidepressant use (HR: 1.34, CI95%: 1.02–1.76), and anxiolytic use (HR: 1.54, CI95%: 1.08–2.29) for any fracture; being female (HR: 1.65, CI95%: 1.14–2.38) for MOFs; the presence of retinopathy (HR: 1.47, CI95%: 1.02–2.11) and previous falls (HR: 2.04, CI95%: 1.16–3.59) for lower-arm and lower-leg fractures, respectively. Lipid-lowering medication use decreased the risk of MOFs (HR: 0.66, CI95%: 0.44–0.99).Stratification of T1D by disease duration showed that the relative risk of any fracture in T1D did not increase with longer diabetes duration (0–4 years: HR: 1.52, CI95%: 1.23–1.87; 5–9 years: HR: 1.30, CI95%: 0.99–1.71; <10 years: HR: 1.07, CI95%: 0.74–1.55). Similar patterns were observed for other fracture sites. Moreover, the occurrence of microvascular complications in T1D was linked to a heightened risk of fractures in comparison to controls. However, when considering the T1D cohort independently, the association was not statistically significant. ConclusionIn a cohort of relatively healthy and newly diagnosed people with T1D HRs for any fracture, MOFs, and lower-leg fractures compared to controls were increased. A previous fracture was the most consistent risk factor for a subsequent fracture, whereas retinopathy was the only diabetes related one. We postulate a potential initial fracture risk, succeeded by a subsequent risk reduction, which might potentially increase in later years due to the accumulation of complications and other factors.

A simple fragility fracture risk score for type 2 diabetes patients: a derivation, validation, comparison, and risk stratification study.

The aims of this study were to develop and validate 2 simple scores for stratification of the risks of (1) any fragility (AF) and (2) major osteoporotic fracture (MOF) in type 2 diabetes (T2D) patients; we also compared the performance of these scores with that of the Fracture Risk Assessment Tool (FRAX) and its adjustments. In this longitudinal cohort study, 1855 patients with T2D were enrolled from January 2015 to August 2019. Cox proportional hazard regression was used to model the 5-year risk of AF and MOF. These scores were internally validated using a bootstrap resampling method of 1000. During a median follow-up of 5 years, 119 (6.42%) cases of AF and 92 (4.96%) cases of MOFs were identified. Both the concordance index (C-index) and calibration plots indicated improved identification performance using the newly established scores. Furthermore, these scores also showed improved outcomes regarding the decision curve analysis (DCA) and area under the curve (AUC) compared to the widely used FRAX and its derivatives. More importantly, these scores successfully separated T2D patients into risk groups according to significant differences in fracture incidence. These novel scores enable simple and reliable fracture risk stratification in T2D patients. Future work is needed to validate these findings in external cohort(s).

Prevalence and Risk Factors of Osteoporosis in a Chinese Population: A Cross-Sectional Study in Xi'an, Shaanxi Province, China.

BACKGROUND Osteoporosis is a systemic chronic disease characterized by bone mineral density (BMD) reduction. This study aimed to assess the prevalence of osteoporosis and fracture risks in northwestern China and investigate the related anthropometric risk factors. MATERIAL AND METHODS Between July 2022 and August 2022, 1429 participants (1295 females, 134 males) with measured BMD were recruited to participate in this cross-sectional study. Data on height, weight, and T score were collected. Spearman's correlation and multiple linear regression analysis were used to investigate the relationships between various demographic factors and BMD and the 10-year risk of major osteoporotic fracture (MO) and hip fracture (HP). RESULTS The overall prevalence of osteoporosis in northwest China was 42.34%, with 44.56% in females and 20.90% in males. Age negatively affects females' T scores (r=-0.304, P<0.05), and height positively influences both sexes' T scores (r=0.059 P<0.05). Age (r=0.148, P<0.05) and height were positive predictors of MO (r=0.027, P<0.05), while weight was a negative predictor (r=-0.035, P<0.05). The conclusion for HP was consistent with that of MO, except for the T score, which was a positive predictor of HP (r=0.014, P<0.05). CONCLUSIONS The prevalence of osteoporosis in northeast China is high. The association between anthropometric parameters and osteoporosis in adults in northwest China is different between sexes.

Clinical features of osteoporosis among indigenous women of Russian and Buryat ethnicity in Trans-Baikal region

Introduction Osteoporosis (OP) is a major social and medical problem for society.The aim of research was to identify risk factors for OP and the incidence of low-energy fractures in women with OP of Russian and Buryat ethnicity in Trans-Baikal region.Materials and methods We examined 98 women with OP (50 of Russian and 48 of Buryat nationality) and 100 women without objective signs of OP, comparable by age and nationality with the main group. All women underwent a questionnaire to identify risk factors for osteoporosis and osteoporotic fractures, determination of bone mineral density (BMD) using dual-energy X-ray absorptiometry, and determination of the absolute 10-year risk of major osteoporotic fractures using the online FRAX® calculator.Results The mean age of women with OP of Russian ethnicity was 65.5 [57.0;71.0] years, of Buryat nationality – 65.3 [56.0;69.0] years. Among risk factors in female members of Russian nationality, age older than 65 years, tendency to fall and decreased creatinine clearance were found more frequently. There was an inverse association between proximal femoral BMD and risk of falls (R = -0.31, p = 0.04) and a direct correlation between family history of ОP and spinal BMD (R = 0.65, p = 0.02).Discussion Age over 65 is a significant risk factor for osteoporosis and is included in the FRAX (Fracture Risk Assessment Tool) model. Reduces creatinine clearance and a tendency to fall have been associated with the development of OP and fractures in some studies. Our findings are consistent with previous studies.Conclusion Russian women were more likely than Buryat women to have risk factors for OP, such as falls and decreased creatinine clearance. Associations were found between proximal femoral BMD and falls, spinal BMD with a family history of OP and smoking among Russian women.

Performance of FRAX in older adults with frailty: the Framingham Heart Study.

Frailty increases fracture risk. FRAX was developed to predict fractures but never validated in individuals with frailty. We aimed to compare the predictive performance of FRAX (v4.3) in individuals with and without frailty. We conducted a cohort study using the Framingham Heart Study. Frailty was defined by the Fried phenotype. Major osteoporotic fractures (MOF) were ascertained from medical records during 10-year follow-up. To evaluate discrimination and calibration of FRAX, we calculated the area-under-the-receiver-operating characteristics curves (AUC) using logistic regression models and observed-to-predicted fracture probabilities. Analyses were stratified by frailty status. Frailty was present in 550/3554 (15.5%) of participants. Participants with frailty were older (81.1 vs. 67.6years), female (68.6% vs. 55.1%), and had greater mean FRAX scores (MOF: 15.9% vs. 10.1%) than participants without frailty. During follow-up, 38 participants with frailty (6.9%) and 91 without (3.0%) had MOFs. The AUC for FRAX (without BMD) was lower in participants with frailty (0.584; 95% CI 0.504-0.663) compared to those without (0.695; 95% CI 0.649-0.741); p value = 0.02. Among participants with frailty, the AUC improved when FRAX included BMD (AUC 0.658, p value < 0.01). FRAX overestimated MOF risk, with larger overestimations in individuals without frailty. Performance of FRAX for hip fracture was similar. FRAX may have been less able to identify frail individuals at risk for fracture, as compared with individuals without frailty, unless information on BMD is available. This suggests that BMD captures features important for fracture prediction in frail persons. Future fracture prediction models should be developed among persons with frailty.

FRI679 Risks Of Incident Major Osteoporotic Fractures Following SARS-CoV-2 Infection

Abstract Disclosure: D. Lui: None. X. Xiong: None. M. Chung: None. I. Au: None. F. Lai: None. E. Wan: None. C. Chui: None. X. Li: None. F. Cheng: None. C. Cheng: None. E. Chan: None. C. Lee: None. T. Ip: None. Y. Woo: None. K. Tan: None. C. Wong: None. I. Wong: None. Objectives: Pre-clinical and small cohort studies have suggested the potential deleterious effects of SARS-CoV-2 infection on bone health. We aimed to estimate the risks of incident fractures following SARS-CoV-2 infection in a population-based cohort. Methods: This was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, proximal humerus and wrist fractures), identified by the ICD-9-CM codes 805.x, 812.x, 813.x, 814.x, 820.x. Episodes of falls were identified by the ICD-9-CM codes 781.2, 781.3, 781.99, V15.88, E880-E888. COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, comorbidities and medications. The cohort was followed up until the occurrence of outcomes, death, or 31 January 2023, whichever came first. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Results: 740,692 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (0.35% vs 0.29%; HR 1.21, 95%CI 1.14-1.29, p&amp;lt;0.001), hip fractures (0.16% vs 0.11%; HR 1.34, 95%CI 1.23-1.47, p&amp;lt;0.001), and fall (0.89% vs 0.65%; HR 1.29, 95%CI 1.24-1.34, p&amp;lt;0.001). There was also statistically non-significant increased risk of clinical vertebral (0.03% vs 0.02%; HR 1.22, 95%CI 0.99-1.50, p=0.062) and upper limb (0.14% vs 0.12%; HR 1.08, 95%CI 0.99-1.18, p=0.081) fractures. Subgroup analyses revealed no significant interaction by age (&amp;lt;60 vs ≥60 years), presence of diabetes, fracture history, and the predominant SARS-CoV-2 variant. However, the impact of SARS-CoV-2 infection on fracture and fall risks was greater among men (p-interaction&amp;lt;0.001) and unvaccinated people (p-interaction=0.015). Among COVID-19 patients, hospitalised and dexamethasone-treated ones had higher subsequent fracture and fall risks. When dividing the follow-up period into the acute phase (within 30 days after SARS-CoV-2 infection) and the post-acute phase (beyond 30 days after SARS-CoV-2 infection), the risk of major osteoporotic fractures and falls was consistently increased in the whole cohort, particularly among the older individuals (≥60 years). Conclusions: Our study demonstrated increased risk of major osteoporotic fractures following SARS-CoV-2 infection, contributed by increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors, especially older individuals, and provide appropriate preventive actions. Presentation: Friday, June 16, 2023

OR13-02 Ethnic Variation In Non-vertebral Major Osteoporotic Fractures Among US Asian/Pacific Islander Men

Abstract Disclosure: C.E. Chu: None. M. Chandra: None. N.P. Gordon: None. D.W. Zeltser: None. C. Lee: None. J.A. Darbinian: None. J.C. Lo: None. Background: Our recent characterization of hip fracture incidence among Asian/Pacific Islander (PI) adults compared Chinese, Japanese, Filipino, and South Asian adults and found that South Asian men had a higher incidence of hip fracture compared to Chinese men, but Japanese and Filipino men did not. However, published data pertaining to major osteoporotic fracture (MOF) risk remain limited. We now further examine the incidence of non-vertebral MOF among Asian/PI men, including findings by Asian subgroup. METHODS: We used data from a previously reported retrospective cohort of 188,328 Asian/PI men in an integrated healthcare delivery system who were age ≥50y during 2000-2019. Asian/PI subgroups examined included 41,862 Chinese, 45,779 Filipino, 13,322 South Asian, and 7,838 Japanese men (the four largest Asian/PI subgroups among men and women), with the remaining 79,527 Asian/PI men comprising 8,293 Vietnamese, 3,500 other Southeast Asian, 6,629 Native Hawaiian/PI (NHPI), 3,132 Korean, 451 Central Asian, and 57,522 of multiple or unspecified Asian/PI ethnicity. Incident non-vertebral MOF was defined as the first hip, humerus, or wrist fracture identified by ICD diagnosis codes during follow up to 2021. Age adjusted fracture incidence [with 95% CI] was calculated using weights from the 2010 US Census. Log-Poisson regression was used to determine fracture incidence rate ratios (IRR) with Chinese adults as reference, adjusting for age and calendar year. RESULTS: Among 188,328 Asian/PI men (aged 55.3 ± 7.8 years at entry), 1501 experienced hip (43.3%), humerus (16.3%), or wrist (37.4%) fracture, or &amp;gt;1 of these non-vertebral MOFs (3.0%) during follow-up, with mean age 71.0 ± 13.0 years at the time of incident fracture. The age-adjusted incidence of non-vertebral MOF for Asian/PI men was 1.18 [1.12-1.25] per 1000 person-years overall but varied among the major Asian/PI subgroups: 1.19 [1.08-1.29] for Chinese, 1.00 [0.88-1.12] for Filipino, 1.51 [1.28-1.77] for Japanese, and 2.01 [1.67-2.41] for South Asian men per 1000 person-years. Compared to Chinese men, the IRR for non-vertebral MOF were 0.83 [0.72-0.95] for Filipino, 1.21 [1.01-1.44] for Japanese, and 1.84 [1.54-2.20] for South Asian, and 0.89 [0.77-1.03] for all other Asian/PI men, including those with unspecified ethnicity. Conclusions: The majority of non-vertebral MOF occurred at the hip and wrist among men. When comparing fracture incidence across major Asian/PI subgroups, the largest difference in non-vertebral MOF incidence was seen among South Asian men compared to their Chinese counterparts, consistent with previous hip fracture findings. Japanese men also had somewhat higher incidence of MOF, while Filipino men had lower incidence. Future studies are needed to examine whether differences are evident in other Asian/PI subgroups and whether there are differences in clinical outcome after non-vertebral MOF fracture. Presentation: Friday, June 16, 2023

Ticagrelor was associated with lower fracture risk than clopidogrel in the dual anti-platelet regimen among patients with acute coronary syndrome treated with percutaneous coronary intervention

PurposePatients with coronary artery disease have increased fracture risks. P2Y12 inhibitors may impact fracture risks. We compared the fracture risks associated with ticagrelor and clopidogrel in dual anti-platelet therapy (DAPT).MethodsWe identified all adults who underwent first-ever percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) between 2010 and 2017 from a territory-wide PCI registry in Hong Kong. Following 1:1 propensity-score matching for baseline characteristics, patients were followed up till event occurrence, death, or 30 June 2022. Outcomes of interest were major osteoporotic fractures (MOF) identified by validated ICD-9-CM codes. Cox proportional hazards regression was used to compute the hazard ratio (HR) for MOF associated with ticagrelor versus clopidogrel use.Results3018 ticagrelor users and 3018 clopidogrel users were identified after propensity-score matching (mean age: 61.4 years; 84.1% men). Upon median follow-up of 6.5 years, 59 ticagrelor users and 119 clopidogrel users sustained MOF (annualized fracture risks: 0.34% and 0.56%, respectively). Ticagrelor use was associated with lower risks of MOF (HR 0.60, 95%CI 0.44–0.83; p = 0.002). Consistent HRs were observed for fractures over vertebrae, hip and upper limbs. Subgroup analyses showed no interaction according to age, sex, presence of diabetes, presence of chronic kidney disease and prior fracture history.ConclusionAmong adults who underwent first-ever PCI for ACS, ticagrelor use in the DAPT was associated with a lower risk of MOF compared with clopidogrel. Our results support the use of ticagrelor in the DAPT from the perspective of bone health.

Establish and validate the reliability of predictive models in bone mineral density by deep learning as examination tool for women.

Fracture risk assessment tool (FRAX) is useful in classifying the fracture risk level, and precise prediction can be achieved by estimating both clinical risk factors and bone mineral density (BMD) using dual X-ray absorptiometry (DXA). However, DXA is not frequently feasible because of its cost and accessibility. This study aimed to establish the reliability of deep learning (DL)-based alternative tools for screening patients at a high risk of fracture and osteoporosis. Participants were enrolled from the National Bone Health Screening Project of Taiwan in this cross-sectional study. First, DL-based models were built to predict the lowest T-score value in either the lumbar spine, total hip, or femoral neck and their respective BMD values. The Bland-Altman analysis was used to compare the agreement between the models and DXA. Second, the predictive model to classify patients with a high fracture risk was built according to the estimated BMD from the first step and the FRAX score without BMD. The performance of the model was compared with the classification based on FRAX with BMD. Approximately 10,827 women (mean age, 65.4 ± 9.4years) were enrolled. In the prediction of the lumbar spine BMD, total hip BMD, femoral neck BMD, and lowest T-score, the root-mean-square error (RMSE) was 0.099, 0.089, 0.076, and 0.68, respectively. The Bland-Altman analysis revealed a nonsignificant difference between the predictive models and DXA. The FRAX score with femoral neck BMD for major osteoporotic fracture risk was 9.7% ± 6.7%, whereas the risk for hip fracture was 3.3% ± 4.6%. Comparison between the classification of FRAX with and without BMD revealed the accuracy rate, positive predictive value (PPV), and negative predictive value (NPV) of 78.8%, 64.6%, and 89.9%, respectively. The area under the receiver operating characteristic curve (AUROC), accuracy rate, PPV, and NPV of the classification model were 0.913 (95% confidence interval: 0.904-0.922), 83.5%, 71.2%, and 92.2%, respectively. While FRAX with BMD could be more precise in estimating the fracture risk, DL-based models were validated to slightly reduce the number of under- and over-treated patients when no BMD measurements were available. The validated models could be used to screen for patients at a high risk of fracture and osteoporosis.

Electronic Health Records (EHRs) Can Identify Patients at High Risk of Fracture but Require Substantial Race Adjustments to Currently Available Fracture Risk Calculators.

Osteoporotic fracture prediction calculators are poorly utilized in primary care, leading to underdiagnosis and undertreatment of those at risk for fracture. The use of these calculators could be improved if predictions were automated using the electronic health record (EHR). However, this approach is not well validated in multi-ethnic populations, and it is not clear if the adjustments for race or ethnicity made by calculators are appropriate. To investigate EHR-generated fracture predictions in a multi-ethnic population. Retrospective cohort study using data from the EHR. An urban, academic medical center in Philadelphia, PA. 12,758 White, 7,844 Black, and 3,587 Hispanic patients seeking routine care from 2010 to 2018 with mean 3.8 years follow-up. None. FRAX and QFracture, two of the most used fracture prediction tools, were studied. Risk for major osteoporotic fracture (MOF) and hip fracture were calculated using data from the EHR at baseline and compared to the number of fractures that occurred during follow-up. MOF rates varied from 3.2 per 1000 patient-years in Black men to 7.6 in White women. FRAX and QFracture had similar discrimination for MOF prediction (area under the curve, AUC, 0.69 vs. 0.70, p=0.08) and for hip fracture prediction (AUC 0.77 vs 0.79, p=0.21) and were similar by race or ethnicity. FRAX had superior calibration than QFracture (calibration-in-the-large for FRAX 0.97 versus QFracture 2.02). The adjustment factors used in MOF prediction were generally accurate in Black women, but underestimated risk in Black men, Hispanic women, and Hispanic men. Single center design. Fracture predictions using only EHR inputs can discriminate between high and low risk patients, even in Black and Hispanic patients, and could help primary care physicians identify patients who need screening or treatment. However, further refinements to the calculators may better adjust for race-ethnicity.

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.

Evaluation of bone mineral density, microarchitecture, and detection of fractures on young patients living with human immunodeficiency virus: when and how to screen?

People living with the human immunodeficiency virus (PLWH) developed higher life expectancy along with chronic bone disease over the past years. Our purpose is to evaluate bone mineral density, bone microarchitecture and fractures in young PLWH and understand the disease's contribution to bone derangements and fracture risk. Eighty-one HIV-infected and 54 control young (20-50 years) male and female subjects were enrolled in this study. Methods for patient evaluation included DXA-VFA (dual energy X-rays and vertebral fracture assessment), HR-pQCT (high resolution peripheral quantitative computed tomography), biochemistry and FRAX. Fifty participants from each group completed all exams. Median age was 40 (25-49) vs. 36.5 (22-50) for the HIV and control groups, respectively (p 0.120). Ethnicity, body mass index, serum phosphorus, 25-hydroxyvitamin D, PTH and CTX were similar between groups, although ALP and OC suggested higher bone turnover in PLWH. VFA identified morphometric vertebral fractures in 12% of PLWH. PLWH had lower values for lumbar spine areal BMD and Z score, volumetric BMD, trabecular bone fraction (BV/TV) and trabecular number measured at the distal tibia by HR-pQCT; as a consequence, trabecular separation and heterogeneity were higher (all p < 0.05). The FRAX-estimated risk for hip and major osteoporotic fractures was statistically higher in PLWH (p < 0.001). Our results confirm severe bone impairment and fractures associated with HIV in young patients. Thus, we developed a screening protocol for young PLWH to detect bone fragility, reduce skeletal disease progression and morbimortality, decrease fracture risk, and increase quality of life.

Osteoporosis and Fracture Risk among Older US Asian Adults.

This review summarizes the current knowledge regarding osteoporosis and fracture among older US Asian adults. Asian adults have lower (areal) bone density than non-Hispanic White adults and thus are more likely to be diagnosed and treated for osteoporosis, despite their lower risk of hip fracture. The latter may relate to favorable characteristics in hip geometry, volumetric bone density, and bone microarchitecture; lower risk of falls; and other clinical factors. The fracture risk calculator FRAX accounts for the lower risk of hip fracture among US Asian adults. However, data on major osteoporotic fracture risk remain limited. Fracture rates also vary by Asian subgroup, which may have implications for fracture risk assessment. Furthermore, among women receiving bisphosphonate drugs, Asian race is a risk factor for atypical femur fracture, an uncommon complication associated with treatment duration. Recent clinical trial efficacy data pertaining to lower bisphosphonate doses and longer dosing intervals may be relevant for Asian adults. More research is needed to inform osteoporosis care of US Asian adults, including risk-benefit considerations and the optimal duration of bisphosphonate treatment. Greater evidence-based guidance for primary fracture prevention among US Asian adults will ensure health equity in the prevention of osteoporotic fractures.

Relationship Between Blood Monocyte-HDL Ratio and Carotid Intima Media Thickness in with Postmenopausal Women

Introduction/Background: The monocyte-to-high-density lipoprotein (HDL) ratio (MHR) and carotid intima media thickness may be used as a marker of inflammation and oxidative stres. This study is aimed to investigate the role of MHR in etiopathogenesis and to determine the association between MHR and carotid intima media thickness, fracture risk, and quality of life (QoL) in postmenopausal osteoporosis patients without comorbidities. Methodology: Sixty osteoporosis, sixty osteopenia and sixty control groups were included in the prospective study evaluating postmenapausal women. The monocyte, HDL, and MHR values of all patients were evaluated. The bone mineral density of the participants was determined using the dual energy X-ray absorptiometry device. The fracture risk was assessed using the Turkish model of the Fracture Risk Assessment Tool. The QoL was determined using the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41) scale, and carotid intima media thickness ultrasonography was used. Results: The age, body mass index, duration of menopause, monocyte, HDL, and MHR were similar in all three groups. carotid intima media thickness was higher in the osteoporosis group than in the normal group (p=0.015). A positive correlation was found between L1-4 total T score and monocytes, major osteoporotic fracture risk and physical function from QUALEFFO-41 sub-headings, MHR and QUALEFFO-41 total score (p<0.05). When all participants were evaluated, a positive correlation was found between femoral neck T score and MHR, L1-4 total T score and monocytes, while a negative correlation was found between L1-4 total T score and CIMT (p<0.05). Conclusion: Among postmenopausal women without comorbidities, MHR in the osteoporosis group was similar to that of the osteopenia and normal groups. Monocyte and MHR correlate with femoral neck T score and L1-4 total T score. CIMT was associated with a decreased L1–4 total T-score and an increased fracture risk, but not with MHR.

The associations of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as add-on to metformin with fracture risk in patients with type 2 diabetes mellitus.

To investigate whether sodium-glucose cotransporter-2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use as add-on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs). A cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first-ever prescription for a DPP-4 inhibitor or an SGLT2 inhibitor as add-on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP-4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP-4 inhibitor use. A total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP-4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP-4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91-1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64-1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age. Use of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP-4 inhibitor use.

Predictive capacity of FRAX in a spanish region with a hip fracture rate close to the national mean

BackgroundIt is known that standardized incidence rates of hip fracture vary among older people in Spain. So far, the results published on the validation of the FRAX® tool in Spain have suggested that the major osteoporotic fractures (MOFs) risk in our country is underestimated. These studies have practically been based on Spanish cohorts evaluated in Catalonia, a higher hip fracture rate area. The purpose of this study is to analyse the ability of the FRAX® in a Spanish mid-fracture rate population.MethodsStudy design: Retrospective cohort study.MeasuresMOFs: hip, humerus, wrist, spine fractures. Risk of fracture assessed by calculating odds ratios (ORs). Predictive capacity of FRAX® according to the osteoporotic fractures observed between 2009 and 2018 (ObsFr) to predicted by FRAX® without densitometry in 2009 (PredFr) ratio.Results285 participants (156 women, 54.7%) with a mean ± SD of 61.5 ± 14 years. Twenty-four people sustained 27 fractures (15 MOFs). Significant ORs were observed for an age ≥ 65 (2.92; 95% CI, 1.07–7.96), female sex (3.18; 95% CI, 1.24–8.16), rheumatoid arthritis (0.62; 95% CI, 2.03–55.55), proton pump (2.71; 95% CI, 1.20–6.09) and serotonin reuptake (2.51; 95% CI, 1.02–6.16) inhibitors. The ObsFr/PredFr ratio in women were 1.12 (95% CI, 0.95–1.29) for MOFs and 0.47 (95% CI, 0-0.94) for hip fractures. Men had a ratio of 0.57 (95% CI, 0.01–1.14) for MOF, no hip fractures were observed. The ratios for the overall group were 1.29 (95% CI, 1.12–1.48) for MOFs and 0.70 (95% CI, 0.22–1.17) for hip fractures.ConclusionsFRAX® accurately predicted MOFs in women population with a hip fracture incidence rate close to the national mean compared to previous studies conducted in higher incidence regions in Spain.

Effect of SGLT2 inhibitors versus DPP4 inhibitors on major and non-major osteoporotic fracture risks among general and high-risk type 2 diabetes patients: A nationwide retrospective cohort study

AimsTo retrospectively analyze the association of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) with a range of major and non-major fracture events, and explore heterogeneous treatment effect among high-risk patient subgroups. MethodsNewly stable SGLT2i or DPP4i users in 2017 were identified in Taiwan's National Health Insurance Research Database and followed up until a fracture occurred, loss of follow-up, death, or December 31, 2018, whichever came first. Outcomes included composite major and non-major fractures and individual components in major fractures. Cox model and restricted mean survival time (RMST) analyses were utilized to assess the treatment effect on fractures. Results21,155 propensity-score-matched SGLT2i and DPP4i users were obtained. Over 2 years, the hazard ratio and RMST difference for major fracture with SGLT2i versus DPP4i use were 0.89 (95% CI, 0.80, 1.00) and 1.51 (-0.17, 3.17) days, respectively, and those for non-major fracture with SGLT2i versus DPP4i use were 0.89 (0.81, 0.98) and 2.44 (0.47, 4.37) days, respectively. A 180-day lag time analysis for fracture outcomes showed consistent results with primary findings. A SGLT2is-associated harmful effect on major fractures (but not on non-major fractures) was observed among female patients and those with a diabetes duration of ≥ 8 years, prior fractures, and established osteoporosis. ConclusionThis study adds supporting real-world evidence for SGLT2is-associated bone safety for a wide range of fractures, which promotes the rational use of SGLT2is in routine care and highlights the importance of the close monitoring of patients with high fracture risks to maximize treatment benefits while reducing undesirable effects.

Hemoglobin Levels Improve Fracture Risk Prediction in Addition to FRAX Clinical Risk Factors and Bone Mineral Density.

Anemia and decreasing levels of hemoglobin (Hb) have previously been linked to increased fracture risk, but the added value to FRAX, the most utilized fracture prediction tool worldwide, is unknown. To investigate the association between anemia, Hb levels, bone microstructure, and risk of incident fracture and to evaluate whether Hb levels improve fracture risk prediction in addition to FRAX clinical risk factors (CRFs). A total of 2778 community-dwelling women, aged 75-80 years, and part of a prospective population-based cohort study in Sweden were included. At baseline, information on anthropometrics, CRFs, and falls was gathered, blood samples were collected, and skeletal characteristics were investigated using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. At the end of follow-up, incident fractures were retrieved from a regional x-ray archive. The median follow-up time was 6.4 years. Low Hb was associated with worse total hip and femoral neck bone mineral density (BMD), and lower tibia cortical and total volumetric BMD, and anemia was associated with increased risk of major osteoporotic fracture (MOF; hazard ratio 2.04; 95% CI 1.58-2.64). Similar results were obtained for hip fracture and any fracture, also when adjusting for CRFs. The ratio between 10-year fracture probabilities of MOF assessed in models with Hb levels included and not included ranged from 1.2 to 0.7 at the 10th and 90th percentile of Hb, respectively. Anemia and decreasing levels of Hb are associated with lower cortical BMD and incident fracture in older women. Considering Hb levels may improve the clinical evaluation of patients with osteoporosis and the assessment of fracture risk.

Validating the Fracture Risk Assessment Tool Score in a US Population-Based Study of Patients With Rheumatoid Arthritis.

The World Health Organization fracture risk assessment tool (FRAX) algorithm for risk prediction of major osteoporotic and hip fractures accounts for several risk factors, including rheumatoid arthritis (RA), since individuals with RA have an excess burden of fractures. FRAX has not been validated in population-based RA cohorts in the US. We aimed to determine the accuracy of FRAX predictions for individuals with RA in the US. This retrospective population-based cohort study included residents of Olmsted County, Minnesota, who were followed until death, migration, or last medical record review. Each patient with RA (1987 American College of Rheumatology criteria met in 1980-2007, age 40-89 years) was matched 1:1 on age and sex to an individual without RA from the same underlying population. Ten-year predictions for major osteoporotic and hip fractures were estimated using the FRAX tool. Fractures were ascertained through follow-up, truncated at 10 years. Standardized incidence ratios (SIRs) and 95% CI were calculated to compare observed and predicted fractures. The study included 662 patients with RA and 658 non-RA comparators (66.8% vs 66.9% female and a mean age of 60.6 vs 60.5 years, respectively). Among patients with RA, 76 major osteoporotic fractures and 21 hip fractures were observed during follow-up (median follow-up: 9.0 years) compared to 67.0 predicted major osteoporotic fractures (SIR 1.13, 95% CI 0.91-1.42) and 23.3 predicted hip fractures (SIR 0.90, 95% CI 0.59-1.38). The observed and predicted major osteoporotic and hip fracture risks were similar for patients with RA and non-RA comparators. The FRAX tool is an accurate method for estimating major osteoporotic and hip fracture risk in patients with RA.

#4554 FRAX® ASSOCIATION, BONE DENSITOMETRY, BIOCHEMICAL PARAMETERS OF BONE MINERAL METABOLISM AND ADVANCED CHRONIC KIDNEY DISEASE

Abstract Background and Aims Currently, there are calculation tools that predict the risk of fractures (fx), one of which is the Fracture Risk Assessment Tool (FRAX®). Patients with advanced chronic kidney disease (CKD) have a higher risk of fx than the general population and it is an independent factor for fx. However, this tool does not consider the presence or absence of CKD, where alterations in bone mineral metabolism have important clinical consequences and their prevention should be the objective of CKD control. The aim of our study is to evaluate the FRAX® tool in patients with advanced CKD and to analyze possible relationships with parameters of bone mineral metabolism. Method Observational, descriptive, retrospective study of a series of cases of patients with advanced chronic kidney disease in our center, where demographic data, FRAX® calculation, personal history of Diabetes Mellitus, etiology of CKD, personal history of fx, measurement of bone mineral densitometry by dual energy X-ray absorptiometry (DXA), estimated glomerular filtration rate (CKD-EPI), levels of serum calcium and phosphorus, vitamin D 1. 25 levels, Parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), use of phosphorus chelating treatment and vitamin D were collected. Descriptive results of continuous variables are expressed as mean and standard deviation or median and interquartile range (IQR) according to their distribution. For categorical data, frequency and percentage are reported. To analyze the impact of the variables on the event to be studied, a univariate and multivariate Cox regression model was used. Results 59 patients with advanced CKD with DXA performed within one year of the FRAX® analysis were analyzed. The median age was 66 years (IQR 22). 59.3% were male. 35.6% had a personal history of diabetes mellitus. The most frequent etiology of CKD was unknown etiology (18.6%), followed by vascular (16.9%). History of some type of fx:13.6% (3.6% vertebral). Estimated glomerular filtration rate CKD-EPI: 20.7 ml/min/1,73 m2 (IQR 7.5). 16.9% had osteoporosis of the femoral neck and 22% of the spine. DXA decreased in femoral neck 78% and in spine 59.3%. Low risk of major osteoporotic fracture according to FRAX® of 76.3% and 64.3% (without and with DXA) and elevated risk of major osteoporotic fracture according to FRAX® 5.1% and 8.5% (without and with DXA). Risk of hip fracture 25.4% and 30.5% (without and with DXA). These data are summarized in Figure 1 and Figure 2. In the multivariate analysis there is no relationship between bone mineral metabolism parameters and DXA. The results showed a negative correlation between glomerular filtration rate CKD-EPI and FRAX® hip (HR -1.7; 95% CI 1.46-9.6 p = 0.027) which would suggest an association between loss of renal function and loss of DXA. Patients with diabetes mellitus have a higher risk of fx (HR 3.7; 95% CI 1.46-9.6 p = 0.009). Conclusion In patients with advanced CKD, FRAX® index identifies patients at high fracture risk for whom active treatment for osteoporosis should be instituted. In patients with advanced chronic kidney disease, FRAX® underestimates those patients with decreased bone mass and elevated risk of osteoporosis. We did not find any association with biochemical parameters of bone mineral metabolism which could guide us in anticipating the treatment of osteoporosis. The loss of renal function accelerates the loss of bone mass, so we believe that the introduction of this variable is necessary in the equation, especially in this profile of patients.