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

The effects of parathyroid hormone peptides on the peripheral skeleton of postmenopausal women. A systematic review.

Given current developments in anabolic therapy for bone, we wished to document the effects of the only currently available anabolic therapy, parathyroid hormone (PTH) peptides, on the peripheral skeleton of postmenopausal women. We undertook a systematic review of English articles using MEDLINE, Scopus and the Cochrane Controlled Trials Register (final update 28th March 2016). Additional studies were identified through searches of bibliographies. Studies included those comparing PTH peptides with placebo, with anti-osteoporotic treatments and in combination therapies. Participants had to be postmenopausal women and outcomes included areal or volumetric bone mineral density (BMD) and measurements of bone microarchitecture at peripheral sites, such as the forearm and tibia. Data were extracted independently and reviewed by EMcC and LMM. Data on study design were also collected for methodological risk of bias assessment. The heterogeneity between studies, regarding the drug dose and duration, and the site measured, prevented grouped meta-analysis. There were no significant differences in areal BMD between PTH peptides and placebo at peripheral skeletal sites at 12months. A decrease in aBMD occurred with PTH(1-34) (larger dose) and PTH(1-84) treatment at 18months follow-up in comparison to the placebo arms. Anti-resorptives seemed to attenuate losses of aBMD at peripheral sites when compared to PTH peptides monotherapy, likely mediated by lower cortical porosity. Finally, PTH peptides combined with bisphosphonates or denosumab attenuated peripheral BMD losses in comparison to PTH peptide monotherapy, with evidence of increased BMD at ultradistal peripheral sites when PTH(1-34) was combined with denosumab or hormone replacement therapy. This summary should act as a reference point for the comparison of new anabolic therapies, specifically in comparison to PTH(1-34)

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

Abaloparatide: an anabolic treatment to reduce fracture risk in postmenopausal women with osteoporosis

Objective Fractures due to osteoporosis represent a serious burden on patients and healthcare systems. The objective of this review is to provide an overview of the anabolic agent abaloparatide (ABL) for the treatment of postmenopausal women with osteoporosis at high risk for fracture. Methods A literature review was conducted using PubMed to identify articles focused on ABL published prior to February 10, 2020, using the search term “abaloparatide”. Results ABL, a synthetic analog of human parathyroid hormone-related protein, increased bone mineral density (BMD), improved bone microarchitecture, and increased bone strength in preclinical and clinical studies. The pivotal phase 3 trial ACTIVE and its extension (ACTIVExtend) demonstrated the efficacy of initial treatment with ABL for 18 months followed by sequential treatment with alendronate (ALN) for an additional 24 months to reduce the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and to increase BMD in postmenopausal women with osteoporosis. Discontinuations from ACTIVE were slightly more common in ABL-treated patients due to dizziness, palpitations, nausea, and headache. Post hoc analyses of ACTIVE and ACTIVExtend support the efficacy and safety of ABL in relevant subpopulations including postmenopausal women with various baseline risk factors, women ≥80 years, women with type 2 diabetes mellitus, and women with renal impairment. Conclusions ABL is an effective and well-tolerated treatment for women with postmenopausal osteoporosis at high risk for fracture. Its therapeutic effects are sustained with subsequent ALN therapy

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

Clinical utility of bone turnover markers in monitoring the withdrawal of treatment with oral bisphosphonates in postmenopausal osteoporosis

Summary Bone markers may be useful to monitor response to treatment withdrawal in osteoporosis. We used two criteria for investigating the change in BTMs after withdrawal of bisphosphonate treatment. A larger increase in BTMs was associated with greater bone loss. Bone markers may be useful in monitoring of patients taking a pause from treatment. Introduction Measurement of bone turnover markers (BTMs) may be useful to monitor offset of treatment with bisphosphonates (BP) in osteoporosis. We assessed the effect of withdrawal of BP treatment by comparing the changes in BTMs and total hip (TH) bone density (BMD). Methods We studied postmenopausal osteoporotic women who had completed a randomised study of three oral BPs. After 2 years of treatment, participants with BMD T-score > − 2.5 and in whom it was considered clinically appropriate to discontinue treatment, were invited to participate in a further 2-year observational study. Biochemical response was assessed using BTMs (CTX and PINP) with offset being defined by two criteria: (1) an increase greater than the least significant change (LSC) and (2) an increase above the reference mean value. Results Fifty women completed the study. At 48 weeks after stopping BPs, CTX was greater than the LSC for 66% of women and PINP 72%; CTX was above the reference mean for 64% of women and PINP 42%. The decrease in THBMD was greater for women with the largest increase in BTM compared to those with continued suppression (mean difference for CTX was − 2.98%, 95%CI − 4.75 to − 1.22, P < 0.001, PINP − 2.25%, 95% CI − 4.46 to − 0.032, P = 0.046). Conclusion The measurement of BTM after withdrawal of BPs is potentially useful to evaluate patients that are taking a pause from treatment. An increase in BTMs more than the LSC and/or reference mean reflects loss of treatment effect and identifies patients that are likely to have a decrease in BMD. Such changes could provide an indication for reintroduction of treatment

Contributions of clinical and technical factors to longitudinal change in trabecular bone score and bone density: a registry‐based individual‐level analysis

Lumbar spine trabecular bone score (TBS), a grey-level texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved question is whether TBS is sufficiently responsive to change over time or in response to widely used osteoporosis therapy at the individual level to serve as a useful biomarker. Using the Manitoba DXA Registry we identified 11,643 individuals age 40 years and older with two fan-beam DXA scans performed on the same instrument within 5 years (mean interval 3.2 years), of whom 6,985 (60.0%) received antiresorptive osteoporosis medication (majority oral bisphosphonate) between the scans. We examined factors that were associated with a change in lumbar spine TBS, lumbar spine BMD and total hip BMD exceeding the 95% least significant change (LSC). Change exceeding the LSC was identified in 23.0% (9.3% increase, 13.8% decrease) of lumbar spine TBS, 38.2% (22.1% increase, 16.1% decrease) lumbar spine BMD, and 42.5% (17.6% increase, 24.9% decrease) total hip BMD measurement-pairs. From regression models, the variables most strongly associated with significant change in TBS (decreasing order) were tissue thickness change, acquisition mode change, weight change and spine percent fat change. Consistent with the insensitivity of TBS to oral antiresorptive therapies, use of these agents showed very little effect on TBS change. In contrast, for both spine BMD change and total hip BMD change, osteoporosis medication use was the most significant variable, while tissue thickness change, acquisition mode change and weight change had relatively weak effects. In summary, change in spine TBS using the present algorithm appears to be strongly affected by technical factors. This suggests a limited role, if any, for using TBS change in untreated individuals or for monitoring response to anti-resorptive treatment in routine clinical practice with the current version of the TBS algorithm

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

JointCalc: A web-based personalised patient decision support tool for joint replacement

Background and purpose Health information systems (HIS) are expected to be effective and efficient in improving healthcare services, but empirical observation of HIS reveals that most perform poorly in terms of these metrics. Theoretical factors of HIS performance are widely studied, and solutions to mitigate poor performance have been proposed. In this paper we implement effective methods to eliminate some common drawbacks of HIS design and demonstrate the synergy between the methods. JointCalc, the first comprehensive patient-facing web-based decision support tool for joint replacement, is used as a case study for this purpose. Methods and results User-centred design and thorough end-user involvement are employed throughout the design and development of JointCalc. This is supported by modern software production paradigms, including continuous integration/continuous development, agile and service-oriented architecture. The adopted methods result in a user-approved application delivered well within the scope of project. Conclusion This work supports the claims of high potential efficiency of HIS. The methods identified are shown to be applicable in the production of an effective HIS whilst aiding development efficiency