Access to fracture risk assessment by FRAX and linked National Osteoporosis Guideline Group (NOGG) guidance in the UK—an analysis of anonymous website activity

Purpose/Introduction In the UK, guidance on assessment of osteoporosis and fracture risk is provided by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG). We wished to determine access to this guidance by exploring website activity. Methods We undertook an analysis of FRAX and NOGG website usage for the year between 1st July 2013 and 30th June 2014 using GoogleAnalytics software. Results During this period, there was a total of 1,774,812 sessions (a user interaction with the website) on the FRAX website with 348,964 of these from UK-based users; 253,530 sessions were recorded on the NOGG website. Of the latter, two-thirds were returning visitors, with the vast majority (208,766, 82%) arising from sites within the UK. The remainder of sessions were from other countries demonstrating that some users of FRAX in other countries make use of the NOGG guidance. Of the UK-sourced sessions, the majority were from England, but the session rate (adjusted for population) was highest for Scotland. Almost all (95.7%) of the UK sessions arose from calculations being passed through from the FRAX tool (www.shef.ac.uk/FRAX) to the NOGG website, comprising FRAX calculations in patients without a BMD measurement (74.5%) or FRAX calculations with a BMD result (21.2%). National Health Service (NHS) sites were identified as the major source of visits to the NOGG website, comprising 79.9% of the identifiable visiting locations, but this is an underestimate as many sites from within the NHS are not classified as such. Conclusion The study shows that the facilitated interaction between web based fracture risk assessment and clinical guidelines is widely used in the UK. The approach could usefully be adopted in other countries for which a FRAX model is available

Overview of fracture prediction tools

The characterization of risk factors for fracture that contribute significantly to fracture risk, over and above that provided by the bone mineral density, has stimulated the development of risk assessment tools. The more adequately evaluated tools, all available online, include the FRAX® tool, the Garvan fracture risk calculator and, in the United Kingdom only, QFracture®. Differences in the input variables, output, and model construct give rise to marked differences in the computed risks from each calculator. Reasons for the differences include the derivation of fracture probability (FRAX) rather than incidence (Garvan and QFracture), limited calibration (Garvan), and inappropriate source information (QFracture). These differences need to be taken into account in the evaluation of assessment guidelines

Global impact of COVID-19 on non-communicable disease management: descriptive analysis of access to FRAX fracture risk online tool for prevention of osteoporotic fractures

Summary The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. Introduction The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). Methods The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website (www.sheffield.ac.uk/FRAX) from November 2019 to April 2020 (main analysis period February–April 2020), and the geographical source of that activity. Results Over February–April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range − 2.85 to − 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. Conclusion This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic

Spatial Interpolants

We propose Splinter, a new technique for proving properties of heap-manipulating programs that marries (1) a new separation logic-based analysis for heap reasoning with (2) an interpolation-based technique for refining heap-shape invariants with data invariants. Splinter is property directed, precise, and produces counterexample traces when a property does not hold. Using the novel notion of spatial interpolants modulo theories, Splinter can infer complex invariants over general recursive predicates, e.g., of the form all elements in a linked list are even or a binary tree is sorted. Furthermore, we treat interpolation as a black box, which gives us the freedom to encode data manipulation in any suitable theory for a given program (e.g., bit vectors, arrays, or linear arithmetic), so that our technique immediately benefits from any future advances in SMT solving and interpolation.Comment: Short version published in ESOP 201

Longer Duration of Diabetes Strongly Impacts Fracture Risk Assessment: The Manitoba BMD Cohort

Context: Type 2 diabetes is associated with a higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by the World Health Organization fracture risk assessment (FRAX) tool. Objective: The objective of the study was to examine the impact of diabetes duration on fracture risk. Methods: Using a clinical dual-energy x-ray absorptiometry registry linked with the Manitoba administrative databases, we identified all women age 40 years or older with 10 or more years of prior health care coverage undergoing hip dual-energy x-ray absorptiometry measurements (1996 –2013). Incident MOF and incident hip fractures were each studied over 7 years. Cox proportional hazards models were adjusted for FRAX (FRAX adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy, or insulin (fully adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities. Results: There were 49 098 women without and 8840 women with diabetes (31.4%10 y duration; 20.1% 5–10 y; 23.7%5 y; 24.8% new onset). In FRAX-adjusted analyses, only duration longer than 10 years was associated with a higher risk for MOF (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.30 –1.66), and this was similar in the fully adjusted models (HR 1.34, 95% CI 1.17–1.54). In contrast, a higher risk for hip fracture was seen for all durations in a dose-dependent fashion (eg, FRAX adjusted HR 2.10, 95% CI 1.71–2.59 for duration 10 y vs HR 1.32, 95% CI 1.03–1.69 for new onset). FRAX significantly underestimated the MOF risk (calibration ratio 1.24, 95% CI 1.08 –1.39) and hip fracture risk (1.93, 95% CI 1.50 –2.35) in those with a diabetes duration longer than 10 years. Conclusion: Diabetes is a FRAX-independent risk factor for MOF only in women with a long duration of diabetes, but diabetes increases hip fracture risk, regardless of duration. Those with diabetes longer than 10 years are at particularly high risk of fracture, and this elevated risk is currently underestimated by FRAX

Imminent risk of fracture after fracture

Summary The risk of major osteoporotic fracture (MOF) after a first MOF is increased over the whole duration of follow-up, but the imminent risk is even higher. If the acute increment in risk in the few years following MOF is amenable to therapeutic intervention, then immediate short-term treatments may provide worthwhile clinical dividends in a very cost-effective manner. Introduction A history of fracture is a strong risk factor for future fractures. The aim of the present study was to determine whether the predictive value of a past MOF for future MOF changed with time. Methods The study was based on a population-based cohort of 18,872 men and women born between 1907 and 1935. Fractures were documented over 510,265 person-years. An extension of Poisson regression was used to investigate the relationship between the first MOF and the second. All associations were adjusted for age and time since baseline. Results Five thousand thirty-nine individuals sustained one or more MOFs, of whom 1919 experienced a second MOF. The risk of a second MOF after a first increased by 4% for each year of age (95% CI 1.02–1.06) and was 41% higher for women than men (95% CI 1.25–1.59). The risk of a second MOF was highest immediately after the first fracture and thereafter decreased with time though remained higher than the population risk throughout follow-up. For example, 1 year after the first MOF, the risk of a second fracture was 2.7 (2.4–3.0) fold higher than the population risk. After 10 years, this risk ratio was 1.4 (1.2–1.6). The effect was more marked with increasing age. Conclusions The risk of MOF after a first MOF is increased over the whole follow-up, but the imminent risk is even higher. If the acute increment in risk in the few years following MOF is amenable to therapeutic intervention, then immediate short-term treatments may provide worthwhile clinical dividends in a very cost-effective manner, particularly in the elderly

Reassessment intervals for transition from low to high fracture risk among adults older than 50 years

Importance Fracture risk scores are used to identify individuals at high risk of major osteoporotic fracture or hip fracture for antiosteoporosis treatment. For those not meeting treatment thresholds at baseline, the optimal interval for reassessing fracture risk is uncertain. Objective To examine reassessment intervals for transition from low to high fracture risk under guidelines-defined treatment thresholds. Design, Setting, and Participants This retrospective cohort study included persons aged 50 years or older with fracture risk below treatment thresholds at baseline who had fracture risk reassessed at least 1 year later. Data were obtained from a population-based bone mineral density registry (baseline assessment during 1996-2015; reassessment to 2016) in the Province of Manitoba, Canada. Primary analysis was performed from May to June 2019. Analysis for the revision was performed in October 2019. Main Outcomes and Measures The primary outcome was time to transition from low (below the treatment threshold) to high fracture risk (treatment-qualifying risk score using osteoporosis clinical practice guidelines strategies for Canada, the United States, and the United Kingdom). Results The study population consisted of 10 564 individuals (94.1% women; mean [SD] age at baseline, 63.2 [8.2] years). At the time of reassessment (a mean [SD] interval of 5.2 [2.9] years between initial and subsequent fracture risk assessment), 690 (6.6%) had reached the fixed major osteoporotic fracture treatment threshold of 20%, 1546 (16.2%) had reached the fixed hip treatment threshold of 3%, and 932 (9.4%) had reached the age-dependent major osteoporotic fracture treatment threshold. Among those below 25% of the treatment threshold at baseline for each guideline, few (0%-3.0%) reached guidelines-defined high fracture risk at follow-up. In contrast, among those at the upper end of the scale for each guideline (75%-99% of the treatment threshold at baseline), 30.6% to 74.4% reached guidelines-defined high fracture risk. An increased number of clinical risk factors was associated with increased likelihood of reaching guidelines-defined high fracture risk (range for 3 guidelines, 17.1%-28.2%) compared with unchanged or decreased clinical risk factors (range for 3 guidelines, 3.3%-12.8%) (P < .001). Estimated time for 10% of the population to reach treatment-qualifying high fracture risk ranged from fewer than 3 years to more than 15 years. Conclusions and Relevance The findings suggest that baseline fracture risk (as a fraction of the treatment threshold) and change in clinical risk factors can identify individuals with low and high probability of guidelines-defined high fracture risk during follow-up, thereby potentially helping to inform the reassessment interval

A surrogate FRAX model for the Kyrgyz Republic

Summary The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic. Introduction The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend utilizing a surrogate FRAX model, based on the country-specific risk of death, and fracture data based on a country where fracture rates are considered to be representative of the index country. Objective This paper describes a surrogate FRAX model for the Kyrgyz Republic. Methods The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic. Results Compared with the model for Kazakhstan, the surrogate model gave somewhat higher 10-year fracture probabilities for men between 60 and 80 years of age and lower probabilities for men above the age of 80. For women the probabilities were similar up to the age of 75–80 years and then lower. There were very close correlations in fracture probabilities between the surrogate and authentic models (1.00) so that the use of the Kyrgyz model had little impact on the rank order of risk. It was estimated that 2752 hip fractures arose in 2015 in individuals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050. Conclusion The surrogate FRAX model for the Kyrgyz Republic provides the opportunity to determine fracture probability among the Kyrgyz population and help guide decisions about treatment

Epidemiology of osteoporotic fracture in Kazakhstan and development of a country specific FRAX model

Summary Retrospective and prospective population-based survey in a region of the Republic of Kazakhstan determined the incidence of fractures at the hip, proximal humerus and distal forearm. The hip fracture rates were used to create a FRAX® model to enhance fracture risk assessment in Kazakhstan. Objective This paper describes the epidemiology of osteoporotic fractures in the Republic of Kazakhstan that was used to develop a country specific FRAX® tool for fracture prediction. Methods We carried out a retrospective population-based survey in Taldykorgan in the Republic of Kazakhstan representing approximately 1% of the country’s population. Hip, forearm and humerus fractures were identified retrospectively in 2015 and 2016 from hospital registers and the trauma centre. Hip fractures were prospectively identified in 2017 from the same sources and additionally from primary care data. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Kazakhstan. Fracture probabilities were compared with those from neighbouring countries having FRAX models. Results The difference in hip fracture incidence between the retrospective and prospective survey indicated that approximately 25% of hip fracture cases did not come to hospital attention. The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 11,690 and is predicted to increase by 140% to 28,000 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures in men but not in women. Conclusion The FRAX model should enhance accuracy of determining fracture probability among the Kazakh population and help guide decisions about treatment

Epidemiology of hip fracture and the development of FRAX in Ukraine

Summary A country-specific FRAX model has been developed for the Ukraine to replace the Austrian model hitherto used. Comparison of the Austrian and Ukrainian models indicated that the former markedly overestimated fracture probability whilst correctly stratifying risk. Introduction FRAX has been used to estimate osteoporotic fracture risk since 2009. Rather than using a surrogate model, the Austrian version of FRAX was adopted for clinical practice. Since then, data have become available on hip fracture incidence in the Ukraine. Methods The incidence of hip fracture was computed from three regional estimates and used to construct a country-specific FRAX model for the Ukraine. The model characteristics were compared with those of the Austrian FRAX model, previously used in Ukraine by using all combinations of six risk factors and eight values of BMD (total number of combinations =512). Results The relationship between the probabilities of a major fracture derived from the two versions of FRAX indicated a close correlation between the two estimates (r > 0.95). The Ukrainian version, however, gave markedly lower probabilities than the Austrian model at all ages. For a major osteoporotic fracture, the median probability was lower by 25% at age 50 years and the difference increased with age. At the age of 60, 70 and 80 years, the median value was lower by 30, 53 and 65%, respectively. Similar findings were observed for men and for hip fracture. Conclusion The Ukrainian FRAX model should enhance accuracy of determining fracture probability among the Ukrainian population and help to guide decisions about treatment. The study also indicates that the use of surrogate FRAX models or models from other countries, whilst correctly stratifying risk, may markedly over or underestimate the absolute fracture probability