Risk Of Major Osteoporotic Fracture Research Articles

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.

#2997 ASSESSMENT OF FRACTURE RISK IN KIDNEY TRANSPLANT RECIPIENTS BY FRAX SCORE WITHOUT BONE MINERAL DENSITY

Abstract Background and Aims Bone disease post-transplantation is a major cause of morbidity in kidney transplant (KT) recipients, with a significantly higher risk of fractures and mortality. This study investigated the added value of calculated 10-year fracture risk for major osteoporotic fracture (MOF) and hip fracture by frax score with an assessment of risk factors in KT recipients. Methods A cross-sectional study included 71 live-related KT recipients. Demographic, clinical, and laboratory data were recorded. The 10-year fracture risk for MOF and hip fracture were calculated using frax score without bone mineral density in recipients who completed at least 1 year after KT. Results The prevalence of MOF (>3% risk of fracture) was 14.1%(10 patients), MOF (<3% risk of fracture) was 85.9% (61 patients). A high hip fracture score (>3% risk of hip fracture) was in 10% (1 patient). There was a significant difference between both groups (>3%vs <3% fracture risk) in age, MOF score, hip fracture score, and serum albumin p-value were <0.00001, <0.00001, 0.000134, and 043009 respectively. The analysis of demographic data of the patients with a score (>3% fracture risk) showed that 70% were males (7 patients), 50% (5 patients) had BMI>30 and the main cause of ESRD pre-transplant was lupus nephritis and glomerulonephritis in 50% (5 patients) that exposed for long periods of immune suppression pre-transplant. In 80% (8 patients) were 1st transplant, 10% (1 patient) were 2nd transplant, and 10% (1 patient) was a combined liver-kidney transplant. The rejection episode was zero%. There was a significant difference in patients' fracture risk >3% in phosphorus pre-transplant versus post-transplant p-value 0.01. Conclusion Frax score without bone mineral density has shown a low percent of fracture risk (<3%) in most kidney transplant recipients and high scores were associated with high BMI, phosphorus, and exposure pre-transplant to immune suppression.

#5184 THE RELATIONSHIP OF BONE MINERAL DENSITY AND VITAMIN K IN RENAL TRANSPLANT PATIENTS

Abstract Background and Aims Kidney transplantation is the best treatment for end-stage renal disease (ESRD). Osteoporosis is a common health problem in kidney transplant recipients. It is known that the risk of bone fracture increases by 30% in the first 3 years after transplantation in kidney transplant recipients. Vitamin K is a cofactor involved in the activation of osteocalcin. This protein plays a role in bone mineralization. Currently, vitamin K cannot be measured directly from blood samples, and markers such as proteins induced in the absence of vitamin K (PIVKA-II) and undecarboxylated osteocalcin (ucOC) are used for indirect measurement of vitamin K. In our study, we aimed to investigate the relationship between vitamin K and osteoporosis by measuring serum PIVKA-II, ucOC and BMD in kidney transplant recipients. Method It was a cross-sectional observational study. Patients were selected from kidney transplant patients over 18 years old. A control group was formed from dialysis patients over the age of 18. For vitamin K levels, PIVKA-II and ucOC levels were measured in serum samples taken from patients. The relationship between vitamin K markers, bone mineral densitometry and the risk of major osteoporotic fracture calculated by FRAX in kidney transplant patients was evaluated. Results 68 kidney transplant patients and 20 dialysis patients followed in our clinic were included in this study. As results, it was observed the increased risk of osteoporosis in postmenopausal women patients related with decreased serum vitamin K level (r = −0.520, p = 0.047). Of the transplant group, PIVKA-II and Lumbar I-IV BMD values were statistically significant (p = 0.034, r = -0.258). PIVKA-II was found to be a risk factor for low BMD by multiple linear regression analysis in the transplant group (beta coefficient = −0.195, p = 0.037). Conclusion In our study, it has been proven that as the vitamin K level decreases in kidney transplant patients, the vertebral bone mineral density decreases while the risk of osteoporosis increases. This result shows that vitamin K replacement may have positive effects on bone metabolism.

Assessment of fracture risk among postmenopausal Sudanese women: Is the fracture risk assessment score beneficial?

Objectives: Osteoporosis leads to fragile bones with a high risk of fracture. Moreover, a bone mineral density test has low sensitivity to predict fractures. Alternatively, the World Health Organization fracture risk assessment (FRAX) tool helps improve the prediction of fractures in women even before they develop osteoporosis. This study aimed to assess the risk of developing fractures in Sudanese women using the FRAX tool by studying clinical risk factors that lead to decreased bone strength. Methods: A cross-sectional community-based study was conducted in the River Nile State, Sudan (Jan 2020–June 2020). A questionnaire comprising demographic data and clinical risk factors of fragility fracture was used to determine whether these factors met the FRAX criteria. Results: Participants were 350 postmenopausal women between the ages of 51–60 (36%), with a body mass index (BMI) >25 in 61.4%. In addition, 11% were exposed to oral glucocorticoids, and premature menopause occurred among 20.3%. The risk of major osteoporotic fracture was highest (>20%) in approximately 7% of the women, and 16.3% of them had a high risk of hip fracture (>3%). The risk for fractures increases with age, and a lower BMI is significantly associated with minimal trauma fractures. This study observed significant relationships among systemic glucocorticoid use, insulin-dependent diabetes mellitus, premature menopause, and osteoporotic fractures. All significant associations had P < 0.05. Conclusion: This study observed that multiple risk factors significantly correlated with osteoporotic fractures. Therefore, the FRAX tool is useful in 10-year fracture risk predictions.

Validation of a genome-wide polygenic score in improving fracture risk assessment beyond the FRAX tool in the Women's Health Initiative study.

Previous study has established two polygenic scores (PGSs) related to femoral neck bone mineral density (BMD) (PGS_FNBMDldpred) and total body BMD (PGS_TBBMDldpred) that are associated with fracture risk. However, these findings have not yet been externally validated in an independent cohort. This study aimed to validate the predictive performance of the two established PGSs and to investigate whether adding PGSs to the Fracture Risk Assessment Tool (FRAX) improves the predictive ability of FRAX in identifying women at high risk of major osteoporotic fracture (MOF) and hip fractures (HF). The study used the Women's Health Initiative (WHI) cohort of 9,000 postmenopausal women of European ancestry. Cox Proportional Hazard Models were used to assess the association between each PGS and MOF/HF risk. Four models were formulated to investigate the effect of adding PGSs to the FRAX risk factors: (1) Base model: FRAX risk factors; (2) Base model + PGS_FNBMDldpred; (3) Base model + PGS_TBBMDldpred; (4) Base model + metaPGS. The reclassification ability of models with PGS was further assessed using the Net Reclassification Improvement (NRI) and the Integrated discrimination improvement (IDI). The study found that the PGSs were not significantly associated with MOF or HF after adjusting for FRAX risk factors. The FRAX base model showed moderate discrimination of MOF and HF, with a C-index of 0.623 (95% CI, 0.609 to 0.641) and 0.702 (95% CI, 0.609 to 0.718), respectively. Adding PGSs to the base FRAX model did not improve the ability to discriminate MOF or HF. Reclassification analysis showed that compared to the model without PGS, the model with PGS_TBBMDldpred (1.2%, p = 0.04) and metaPGS (1.7%, p = 0.05) improve the reclassification of HF, but not MOF. The findings suggested that incorporating genetic information into the FRAX tool has minimal improvement in predicting HF risk for elderly Caucasian women. These results highlight the need for further research to identify other factors that may contribute to fracture risk in elderly Caucasian women.

Association of Insulin Resistance with Bone Mineral Density and Fracture Risk in Non-Diabetic Postmenopausal Women

Abstract There is conflicting literature evidence regarding the independent effects of insulin resistance and concomitant hyperinsulinemia on bone mineral density. In addition, it is still under debate whether the net effect is favorable or unfavorable for the fracture risk. Therefore, we conducted a cross-sectional study. Aim To assess the correlation between bone mineral density and fracture risk with insulin resistance and circulating insulin levels in non-diabetic postmenopausal women. Materials and methods The study analyzed 84 women. The mean age of the participants was 60.54 ± 7.07 years, and the mean postmenopausal period was 11.45 ± 6.62 years. A standard oral glucose tolerance test was performed with measurement of blood glucose and insulin levels at 0 and 120 min. Dual-energy X-ray absorptiometry was used to determine bone mineral density at lumbar spine and proximal femur. Fracture risk was calculated using the Fracture Risk Assessment Tool. Results We found that in non-diabetic postmenopausal women lower basal insulin levels (fasting insulin) were associated with a higher 10-year risk of major osteoporotic fracture when insulin sensitivity was preserved (HOMA-IR index < 2). Fasting insulin levels under 6.15 μIU/ml were considered high-risk regarding the fracture risk. On the other hand, higher stimulated insulin levels at 120 min (post-load insulin) were associated with a higher 10-year risk of major osteoporotic fracture at HOMA-IR index greater than 2. Stimulated insulin levels above 39.7 μIU/ml were considered high-risk regarding the fracture risk. Conclusion Our results revealed a negative relationship between stimulated insulin levels at HOMA-IR index above 2 and bone integrity in postmenopausal age. On the other hand, higher basal insulin levels at HOMA-IR index lower than 2 were associated with better parameters of postmenopausal bone health.

Heel quantitative ultrasound (QUS) predicts incident fractures independently of trabecular bone score (TBS), bone mineral density (BMD), and FRAX: the OsteoLaus Study

SummaryThis study aimed to better define the role of heel-QUS in fracture prediction. Our results showed that heel-QUS predicts fracture independently of FRAX, BMD, and TBS. This corroborates its use as a case finding/pre-screening tool in osteoporosis management.IntroductionQuantitative ultrasound (QUS) characterizes bone tissue based on the speed of sound (SOS) and broadband ultrasound attenuation (BUA). Heel-QUS predicts osteoporotic fractures independently of clinical risk factors (CRFs) and bone mineral density (BMD). We aimed to investigate whether (1) heel-QUS parameters predict major osteoporotic fractures (MOF) independently of the trabecular bone score (TBS) and (2) the change of heel-QUS parameters over 2.5 years is associated with fracture risk.MethodsOne thousand three hundred forty-five postmenopausal women from the OsteoLaus cohort were followed up for 7 years. Heel-QUS (SOS, BUA, and stiffness index (SI)), DXA (BMD and TBS), and MOF were assessed every 2.5 years. Pearson’s correlation and multivariable regression analyses were used to determine associations between QUS and DXA parameters and fracture incidence.ResultsDuring a mean follow-up of 6.7 years, 200 MOF were recorded. Fractured women were older, more treated with anti-osteoporosis medication; had lower QUS, BMD, and TBS; higher FRAX-CRF risk; and more prevalent fractures. TBS was significantly correlated with SOS (0.409) and SI (0.472). A decrease of one SD in SI, BUA or SOS increased the MOF risk by (OR(95%CI)) 1.43 (1.18–1.75), 1.19 (0.99–1.43), and 1.52 (1.26–1.84), respectively, after adjustment for FRAX-CRF, treatment, BMD, and TBS. We found no association between the change of QUS parameters in 2.5 years and incident MOF.ConclusionHeel-QUS predicts fracture independently of FRAX, BMD, and TBS. Thus, QUS represents an important case finding/pre-screening tool in osteoporosis management. The change in QUS over time was not associated with future fractures, making it inappropriate for patient monitoring.

Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and the Risk of Fracture: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Osteoporosis and hyperlipidemia are closely correlated and statins might be associated with a decreased risk of fracture. We aimed to investigate the association between proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) therapy and the risk of fracture. The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to October 22, 2022. Randomized clinical trials (RCTs) that addressed to fracture events of participants using alirocumab, evolocumab, bococizumab or inclisiran, with a follow-up of ≥ 24weeks were included. Meta-analyses were conducted to calculate the odds ratio (OR) with 95% confidence intervals (CIs) for major osteoporotic fracture, hip fracture, osteoporotic non-vertebral fracture, and total fracture. 30 trials assessing PCSK9i among 95, 911 adults were included. There were no significant associations between PCSK9i therapy and the risk of major osteoporotic fracture [OR 1.08 (95% Cl 0.87-1.34), p = 0.49], hip fracture [OR 1.05 (95% Cl 0.73-1.53), p = 0.79], osteoporotic non-vertebral fracture [OR 1.03 (95% Cl 0.80-1.32), p = 0.83], and total fracture [OR 1.03 (95% Cl 0.88-1.19), p = 0.74] over a period of 6-64months. No significant associations were detected in any of the sensitivity analyses and subgroup analyses stratified by the type of PCSK9i, follow-up duration, age, sex, sample size, and patient profile. Pooled results of our meta-analysis showed that exposure to PCSK9i was not associated with reduced risks of fracture in the short term.

FRAX Adjustment by Trabecular Bone Score with or Without Bone Mineral Density: The Manitoba BMD Registry

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a FRAX®-independent risk factor for fracture. The TBS adjustment to FRAX assumes the presence of femoral neck BMD in the calculation. However, there are many individuals in whom hip DXA cannot be acquired. Whether the TBS-adjustment would apply to FRAX probabilities calculated without BMD has not been studied. The current analysis was performed to evaluate major osteoporotic fracture (MOF) and hip fracture risk adjusted for FRAX with and without femoral neck BMD. The study cohort consisted of 71,209 individuals (89.8% female, mean age 64.0 years). During mean follow-up 8.7 years, 6743 (9.5%) individuals sustained one or more incident MOF, of which 2037 (2.9%) sustained a hip fracture. Lower TBS was significantly associated with increased fracture risk when adjusted for FRAX probabilities, with a slightly larger effect when BMD was not included. Inclusion of TBS in the risk calculation gave a small but significant increase in stratification for fracture probabilities estimated with and without BMD. Calibration plots showed very minor deviations from the line of identity, indicating overall good calibration. In conclusion, the existing equations for incorporating TBS in FRAX estimates of fracture probability work similarly when femoral neck BMD is not used in the calculation. This potentially extends the range of situations where TBS can be used clinically to those individuals in whom lumbar spine TBS is available but femoral neck BMD is not available.

Radiotherapy-related insufficiency fractures and bone mineral density: what is the connection?

Radiotherapy-related insufficiency fractures (RRIFs) represent a common, burdensome consequence of pelvic radiotherapy. Their underlying mechanisms remain unclear, and data on the effect of osteoporosis are contradictory, with limited studies assessing bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA). BMD by DXA (Hologic) scan and fracture risk following pelvic RRIF were retrospectively assessed in 39 patients (median age 68 years) at a tertiary cancer centre. Patient characteristics and treatment history are presented narratively; correlations were explored using univariate regression analyses. Additional cancer treatments included chemotherapy (n = 31), surgery (n = 20) and brachytherapy (n = 19). Median interval between initiation of radiotherapy and RRIF was 11 (7.5-20.8) and that between RRIF and DXA 3 was (1-6) months. Three patients had normal BMD, 16 had osteopenia and 16 osteoporosis, following World Health Organization classification. Four patients were <40 years at the time of DXA (all Z-scores > -2). Median 10-year risk for hip and major osteoporotic fracture was 3.1% (1.5-5.7) and 11.5% (7.1-13.8), respectively. Only 33.3% of patients had high fracture risk (hip fracture >4% and/or major osteoporotic >20%), and 31% fell above the intervention threshold per National Osteoporosis Guidelines Group (NOGG) guidance (2017). Higher BMD was predicted by lower pelvic radiotherapy dose (only in L3 and L4), concomitant chemotherapy and higher body mass index. At the time of RRIF, most patients did not have osteoporosis, some had normal BMD and overall had low fracture risk. Whilst low BMD is a probable risk factor, it is unlikely to be the main mechanism underlying RRIFs, and further studies are required to understand the predictive value of BMD.

E012 An audit examining specialist referral for osteoporosis treatment for rheumatoid arthritis patients using new NOGG (National Osteoporosis Guideline Group) Guidelines 2022

Abstract Background/Aims Major osteoporotic fractures remain an important cause of mortality and morbidity. Rheumatoid arthritis patients have significantly increased risk of fracture. New NOGG 2022 guidance recommends specialist referral for certain patients based on FRAX and other risk factors, to consider parenteral and anabolic treatment. Our aim was to assess how many rheumatoid arthritis patients would now require specialist referral. Methods We identified 38 patients with rheumatoid arthritis who had been referred for DEXA scanning in January 2022. FRAX was used to estimate fracture risk, this was then adjusted as per NOGG guidance to account for risk factors not included in FRAX. Intervention thresholds from new and old guidance were compared. Results 90% of patients were female. Average age was 63.2 years. Mean major osteoporotic fracture risk is 15.6 and mean hip fracture risk is 4.7 over 10 years. 31.6% had previous fracture, 8% had recent fracture, and 8% had vertebral fractures. 26.3% were taking steroids, 10.5% were taking high dose steroids. 5% had received parenteral treatment at time of audit. Conclusion Rheumatoid arthritis patients have an increased fracture risk and therefore require robust bone protection/fracture risk reduction. This is because of a combination of disease pathogenesis, and concurrence of fracture risk factors. Our cohort reflected this; fracture risk was high and risk factors, particularly steroid use, and previous fracture, were common. Under previous guidance, some patients would eventually be referred to a specialist at the discretion of their physician. New NOGG guidance recommends referral as first line for certain patients. When applied to this cohort, we can see that a significant number of patients would be referred to a specialist. This represents a significant shift away from oral therapies and towards consideration of specialist treatment. Under new guidance, a significant number of rheumatoid arthritis patients need specialist referral. This requires a substantial number of resources and means that parenteral therapies will have a much larger place in osteoporosis management. Disclosure A. Rauf: None. K. Moss: None.

Clinical significance of serum cystatin C-to-creatinine ratio as a surrogate marker for incident osteoporotic fracture predictions.

Detection of appropriate indicators is valuable for preventing incidental osteoporotic fractures. We statistically evaluated the significance of serum cystatin C-to-creatinine ratio (CysC/Cr) as a surrogate marker for incident major osteoporotic fractures (MOF) prediction. Eligible patients with simultaneous measurement of CysC/Cr and bone mineral density in the lumbar spine and proximal femur were selected, and their fracture histories until 5 years after baseline were observed in the retrospective area cohort data. Patients who were followed up until termination or the first osteoporotic fracture were included, and loss of follow-up or death was excluded. Candidate risk factors for osteoporotic fractures were tested for risk ratios using a cox regression analysis. Receiver operating characteristic tests were performed on factors with significantly higher risk ratios and evaluated with Kaplan-Meier survival analysis to determine the hazard ratios of the factors. A total of 175 patients of whom 28 had incident MOF, 38 men, and 137 women, were enrolled. The mean age was 70.2 years. A significantly higher risk ratio was shown in the presence of prevalent MOF, hyper fall-ability, lifestyle-related diseases, chronic kidney diseases ≥ Grade3a, and higher CysC/Cr. All parameters had cutoff indices and showed significantly higher hazard ratios. These results suggested that CysC/Cr may be a predictive marker of incident osteoporotic fractures. It might work as a screening tool for MOF risk.

The Influence of Anti-Citrullinated Polypeptide Antibodies on Bone Mineral Density Decrease and Incident Major Osteoporotic Fractures in Patients with Rheumatoid Arthritis: A Retrospective Case-Control Study

Background: Effects of anti-citrullinated polypeptide antibodies (ACPA) on the bone mineral density (BMD) reduction and incidence of major osteoporotic fractures (MOF) in patients with rheumatoid arthritis (RA) were evaluated using a retrospective longitudinal case-control study. Methods: Patients with RA who were examined using dual-energy X-ray absorptiometry and simultaneously treated for more than 5 years were recruited. BMD absolute value and Z-scores at initial measurements (baseline) and changes of these values from baseline were assessed, and associations between BMD and candidate risk factors including ACPA positivity and serum titer levels were statistically evaluated. Additional statistical evaluations of ACPA positivity in regard to the incidence of MOF were tested. Results: A total of 222 patients were included. Higher ACPA titers correlated significantly with lower BMD and Z-scores at baseline using a multivariate model (p &lt; 0.05). ACPA positivity correlated significantly with lower values and an annual decrease in the Z-score in total hip at follow-up using a univariate model (p &lt; 0.05), whereas no significant correlation was found using a multivariate model. Z-scores in the ACPA-positive group were significantly lower than those of the ACPA-negative group (p &lt; 0.05). However, ACPA-positivity demonstrated no higher risk for incident MOF. Conclusions: The presence of ACPA is a potential risk of BMD loss however weak.

Bone density and trabecular bone score to predict fractures in adults aged 20-39years: a registry-based study.

Trabecular bone score (TBS), a bone texture measurement, is associated with fracture risk independent of bone mineral density (BMD) in older adults. In adults aged 20-40years, TBS remains stable and its role in fracture risk assessment is unclear. We utilized the Manitoba Bone Density Registry to explore the relationship of fracture risk with BMD and TBS in younger adults. Women and men aged 20-39years referred for DXA testing were studied. Incident major and any fractures were captured from health records. Categories based on WHO BMD T-score classification and TBS tertile were considered using Cox regression models to estimate covariate-adjusted (including sex) hazard ratios (aHR, 95%CI) for incident fracture by category, and each SD decrement in BMD and TBS. The study included 2799 individuals (77% female, mean age 32years). Mean (SD) minimum T-score was - 0.9 (1.1) and TBS 1.355 (0.114); 7% had osteoporosis and 13% were in the lowest TBS tertile. Incident major osteoporotic fracture (MOF) and any fracture risk was elevated in those with osteopenia (aHRs 1.20/1.45) and osteoporosis (aHRs 4.60/5.16). Fracture risk was unrelated to TBS tertile. Each SD decrement in BMD was associated with increased MOF risk (aHR 1.64) and any fracture (aHR 1.71); lower TBS was unrelated to fractures. In young adults, low BMD, but not low TBS, was predictive of MOF and any fracture. Routine clinical TBS measurement is not recommended for young adults. Further study is indicated to evaluate whether TBS is beneficial in subsets of younger adults.

Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools

Screening for the primary prevention of fragility fractures among adults aged 40 years and older in primary care: systematic reviews of the effects and acceptability of screening and treatment, and the accuracy of risk prediction tools