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Background: Prevention of osteoporotic fractures remains largely insufficient, and effective means to identify patients at high, short-term fracture risk are needed. The FREM tool is available for automated case finding of men and women aged 45 years or older at high imminent (1-year) risk of osteoporotic fractures, based on administrative health data with a 15-year look-back. The aim of this study was to validate the performance of FREM, and the effect of applying a shorter look-back period. We also evaluated FREM for 5-year fracture risk prediction., Methods: Using Danish national health registers we generated consecutive general population cohorts for the years 2014 through 2018. Within each year and across the full time period we estimated the individual fracture risk scores and determined the actual occurrence of major osteoporotic fractures (MOF) and hip fractures. Risk scores were calculated with 15- and 5-year look-back periods. The discriminative ability was evaluated by area under the receiver operating curve (AUC), and negative predictive value (NPV) and positive predictive value (PPV) were estimated applying a calculated risk cut-off of 2% for MOF and 0.3% for hip fractures., Results: Applying a 15-year look-back, AUC was around 0.75-0.76 for MOF and 0.84-0.87 for hip fractures in 2014, with minor decreases in the subsequent fracture cohorts (2015 to 2018). Applying a 5-year look-back generated similar results, with only marginally lower AUC. In the 5-year risk prediction setting, AUC-values were 0.70-0.72 for MOF and 0.81-0.84 for hip fractures. Generally, PPVs were low, while NPVs were very high., Conclusion: FREM predicts the 1- and 5-year risk of MOF and hip fractures with acceptable vs excellent discriminative power, respectively, when applying both a 15- and a 5-year look-back. Hence, the FREM tool may be applied to improve identification of individuals at high imminent risk of fractures using administrative health data., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Management of osteoporosis given reduced renal function is one of the largest challenges in the bone clinic., Objectives: Identify the cut-off for renal function below which there would be no overall BMD benefit associated with bisphosphonate use. Track safety outcomes resulting in hospital encounters., Methods: Population-based, observational register-linked study of BMD trajectories in adults from the island of Funen (pop 465,000) as a function of estimated creatinine clearance (CKD-epi), treatment and adherence to oBP. One laboratory performed all the biochemical analyses for the area while all DXA scans were in a central facility. For inclusion, patients were required to have both a DXA scan and an eGFR measurement (CKD-EPI) within 1 year prior to their study index date. Medication Possession Ratio (MPR) was calculated from national data., Results: Out of 6176 incident BP users, 1789 had eGFR and DXA measurements at appropriate timepoints for the planned analysis, while this was the case for 3908 of 29,336 non-users. Users of oBPs exhibited progressively smaller gains in BMD with decreasing renal function. However, for CKD stage 3A and better, the annual change in BMD was significantly more positive than in the non-user group at similar levels of renal function. In non-users, the average annual change in BMD was negative but largely unaffected by renal function down to stage 3B. There were no new cases of acute renal injury, glomerulonephritis or dialysis. The rate of new kidney transplantation was zero in non-users and 0.26 per 1000 PY in the BP user population. Hypocalcaemia encounters did not differ significantly from that seen in non-users., Conclusions: The BMD changes observed in real-world users of oBP in this population based single-clinic are consistent with those observed in the original RCTs of alendronate. We noted a gradual decrease in the absolute gains in BMD in oBP users with decreasing renal function though there was no significant interaction - largely explained by low numbers of treated patients with poor renal function - between CKD stage and adherence driven BMD change. There were no cases of acute renal injury resulting in hospital encounters. More data is needed on the efficacy and safety of bisphosphonates in CKD stage 3B to 5 and prescribers should reconsider the low use of DXA in patients with renal function impairment now that a wider range of treatment options are available., Competing Interests: Declaration of competing interest BA: Consulting and speakers fees Amgen, UCB, Kyowa-Kirin UK. Institutional research contracts UCB and Novartis. DPA: Grants and other support from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department and open for external participants. APH: Consulting and speakers fees Amgen, UCB. Institutional research contracts Kyowa-Kirin UK and Shire. CDS, MTE, MN, KHR: None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: This observational safety study used national registers to compare the real world cardiovascular and skeletal safety of zoledronic acid (ZA) against oral bisphosphonates (oBP) and untreated population controls., Methods: Propensity score matched cohort study in Sweden and Denmark., Results: Matched cohort 1 included 8739 ZA users and 25,577 oBP users while matched cohort 2 included 8731 ZA users and 25,924 untreated subjects. In comparison to oBP users, heart failure risk was higher in ZA users, with an adjusted HR (adj) (95%CI) of 1.17 (1.04;1.32) and a higher all-cause mortality (adj HR 1.24 (1.15; 1.34)), however, there was no increased risk of cardiovascular mortality. In the comparison to untreated subjects, ZA users showed a higher risk of atrial fibrillation, adj HR 1.18 (1.05;1.32), arrhythmias adj HR 1.18 (1.06;1.31), and heart failure, adj HR 1.38 (1.24;1.54). Cardiovascular mortality was lower in ZA users (adj HR 0.87 (0.77; 0.98)) and risk of adverse skeletal outcomes was significantly higher, reflecting more severe osteoporosis in these patients. There was no association of cardiovascular risk with increasing exposure time. Sensitivity analyses produced similar findings with no substantial changes in event rates., Conclusions: We noted an increased risk of heart failure, fractures and death among ZA users compared with oral BP. The risk of cardiovascular and skeletal outcomes was higher in ZA users than in matched population controls, but there was no increase in cardiovascular mortality in ZA users compared to oral BP or untreated controls. Despite propensity score matching, it is not possible to determine with certainty whether the increased risk of cardiovascular outcomes is consistent with a true drug effect or higher baseline risk in patients who begin ZA treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: A diagnostic gap exists in the current dual photon X-ray absorptiometry (DXA) based diagnostic approach to osteoporosis. Other diagnostic devices have been developed, but no comprehensive review concerning the applicability of these diagnostic devices for population-based screening have been performed., Material and Methods: A systematic review of Embase, Medline and the Cochrane Central Register for Controlled Trials was performed for population-based studies that focused on technical methods that could either indicate bone mineral density (BMD) by DXA, substitute for DXA in prediction of fracture risk, or that could have an incremental value in fracture prediction in addition to DXA. Quality of included studies was rated by QUADAS 2., Results: Many other technical devices have been tested in a population-based setting. Five studies aiming to indicate BMD and 17 studies aiming to predict fractures were found. Overall, the latter studies had higher methodological quality. The highest number of studies was found for quantitative ultrasound (QUS). The ability to indicate BMD or predict fractures was moderate to minor for all examined devices, using reported area under the curve (AUC) of Receiver Operating Characteristic curves values as standard., Conclusions: Of the methods assessed, only QUS appears capable of perhaps replacing DXA as standalone examination in the future whilst radiographic absorptiometry could provide important information in areas with scarcity of DXA. QUS may be of added value even after DXA has been performed. Evaluation of proposed cutoff-values from population-based studies in separate population-based cohorts is still lacking for most examination devices., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To compare the power of FRAX® without bone mineral density (BMD) and simpler screening tools (OST, ORAI, OSIRIS, SCORE and age alone) in predicting fractures., Methods: This study was a prospective, population-based study performed in Denmark comprising 3614 women aged 40-90 years, who returned a questionnaire concerning items on risk factors for osteoporosis. Fracture risk was calculated using the different screening tools (FRAX®, OST, ORAI, OSIRIS and SCORE) for each woman. The women were followed using the Danish National Register registering new major osteoporotic fractures during 3 years, counting only the first fracture per person. Area under the receiver operating characteristic curve (ROC) and statistics and Harrell's index were calculated. Agreement between the tools was calculated by kappa statistics., Results: A total of 4% of the women experienced a new major osteoporotic fracture during the follow-up period. There were no differences in the area under the curve (AUC) values between FRAX® and the simpler tools; AUC values between 0.703 and 0.722 (p = 0.86). Also, Harrell's C values were very similar between the tools. Agreement between the tools was modest., Conclusion: During 3 years follow-up FRAX® did not perform better in the fracture risk prediction compared with simpler tools such as OST, ORAI, OSIRIS, SCORE or age alone in a screening scenario where BMD was not measured. These findings suggest that simpler models based on fewer risk factors, which would be easier to use in clinical practice by the GP or the patient herself, could just as well as FRAX® be used to identify women with increased risk of fracture., Summary: Comparison of FRAX® and simpler screening tools (OST, ORAI, OSIRIS, SCORE) in predicting fractures indicate that FRAX® did not perform better in fracture risk prediction compared with the simpler tools or even age alone in a screening scenario without bone mineral density assessment., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)