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Summary: Type 1 diabetes mellitus (T1DM) is associated with a disproportionately high fracture rate despite a minimal decrease in bone mineral density. Though trabecular bone score (TBS), an indirect measure of bone architecture, is lower in adults with T1DM, the modest difference is unlikely to account for the large excess risk and calls for further exploration. Introduction: Fracture rates in type 1 diabetes mellitus (T1DM) are disproportionately high compared to the modestly low bone mineral density (BMD). Distortion of bone microarchitecture compromises bone quality in T1DM and is indirectly measured by trabecular bone score (TBS). TBS could potentially be used as a screening tool for skeletal assessment; however, there are inconsistencies in the studies evaluating TBS in T1DM. We performed this meta-analysis to address this knowledge gap. Methods: An electronic literature search was conducted using PubMed, Scopus, and Web of Science resources (all-year time span) to identify studies relating to TBS in T1DM. Cross-sectional and retrospective studies in adults with T1DM were included. TBS and BMD data were extracted for pooled analysis. Fracture risk could not be analyzed as there were insufficient studies reporting it. Result: Data from six studies were included (T1DM: n = 378 and controls: n = 286). Pooled analysis showed a significantly lower TBS [standardized mean difference (SMD) = − 0.37, 95% CI − 0.52 to − 0.21; p < 0.00001] in T1DM compared to controls. There was no difference in the lumbar spine BMD (6 studies, SMD − 0.06, 95% CI − 0.22 to 0.09; p = 0.43) and total hip BMD (6 studies, SMD − 0.17, 95% CI − 0.35 to 0.01; p = 0.06) in the case and control groups. Conclusions: Adults with T1DM have a lower TBS but similar total hip and lumbar spine BMD compared to controls. The risk attributable to the significant but limited difference in TBS falls short of explaining the large excess propensity to fragility fracture in adults with T1DM. Further studies on clarification of the mechanism and whether TBS is suited to screen for fracture risk in adults with T1DM are necessary. [ABSTRACT FROM AUTHOR]

Purpose: Trabecular bone score (TBS) is a grey-level textural measurement acquired from dual-energy X-ray absorptiometry lumbar spine images and is a validated index of bone microarchitecture. In 2015, a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) published a review of the TBS literature, concluding that TBS predicts hip and major osteoporotic fracture, at least partly independent of bone mineral density (BMD) and clinical risk factors. It was also concluded that TBS is potentially amenable to change as a result of pharmacological therapy. Further evidence on the utility of TBS has since accumulated in both primary and secondary osteoporosis, and the introduction of FRAX and BMD T-score adjustment for TBS has accelerated adoption. This position paper therefore presents a review of the updated scientific literature and provides expert consensus statements and corresponding operational guidelines for the use of TBS. Methods: An Expert Working Group was convened by the ESCEO and a systematic review of the evidence undertaken, with defined search strategies for four key topics with respect to the potential use of TBS: (1) fracture prediction in men and women; (2) initiating and monitoring treatment in postmenopausal osteoporosis; (3) fracture prediction in secondary osteoporosis; and (4) treatment monitoring in secondary osteoporosis. Statements to guide the clinical use of TBS were derived from the review and graded by consensus using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results: A total of 96 articles were reviewed and included data on the use of TBS for fracture prediction in men and women, from over 20 countries. The updated evidence shows that TBS enhances fracture risk prediction in both primary and secondary osteoporosis, and can, when taken with BMD and clinical risk factors, inform treatment initiation and the choice of antiosteoporosis treatment. Evidence also indicates that TBS provides useful adjunctive information in monitoring treatment with long-term denosumab and anabolic agents. All expert consensus statements were voted as strongly recommended. Conclusion: The addition of TBS assessment to FRAX and/or BMD enhances fracture risk prediction in primary and secondary osteoporosis, adding useful information for treatment decision-making and monitoring. The expert consensus statements provided in this paper can be used to guide the integration of TBS in clinical practice for the assessment and management of osteoporosis. An example of an operational approach is provided in the appendix. Summary: This position paper presents an up-to-date review of the evidence base, synthesised through expert consensus statements, which informs the implementation of Trabecular Bone Score in clinical practice. [ABSTRACT FROM AUTHOR]

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all‐cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient‐level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age‐ and sex‐standardized incidence rates of hip fractures, post‐hip fracture treatment (defined as the proportion of patients receiving anti‐osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all‐cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age‐ and sex‐standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8–95.4) in Brazil to 315.9 (95% CI 314.0–317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post‐hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all‐cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti‐osteoporosis medication than females, higher rates of all‐cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Summary : This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. Purpose: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. Methods: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. Results: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. Conclusions: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings. [ABSTRACT FROM AUTHOR]

Introduction: Rare bone diseases (RBDs) are a heterogenous group of disorders that are poorly understood and challenging to treat. This creates a plethora of unmet needs for people with RBDs as well as their families and care providers, including diagnostic delays, limited access to expert care, and a lack of specialized treatments. The RBD Summit, which took place across 2 days in November 2021, was a virtual meeting of 65 RBD experts from clinical, academic, and patient communities as well as the pharmaceutical industry. The first meeting of its kind, the RBD Summit aimed to facilitate dialog and information exchange between delegates to advance knowledge and awareness of RBDs and improve patient outcomes. Methods: Key challenges were discussed, and actions for overcoming them were proposed, including how obstacles to diagnosis can be overcome by (a) improving awareness of RBDs, (b) the implementation of a person-centered care pathway, and (c) how to narrow the communication gap between patients and healthcare professionals. Results: Agreed actions were categorized as short term and long term, and priorities determined. Conclusion: In this position paper, we provide an overview of key discussions from the RBD Summit, summarize the subsequent action plan, and discuss the next steps in this continued collaboration. [ABSTRACT FROM AUTHOR]

Summary: Robust data on osteoporosis in the Asia Pacific region could improve healthcare decision-making. Osteoporosis affects 10–30% of women aged 40 + , and up to 10% of men in 7 developed economies in Asia Pacific. Fractures affect 500–1000 adults aged 50 + per 100,000 person-years. Policymakers and clinicians must address this problem. Purpose: Osteoporosis and associated fractures result in considerable morbidity, loss of productivity, early mortality, and increased healthcare expenses. Many countries in the Asia Pacific (AP) region, especially middle- and higher-income economies, are faced with aging and increasingly sedentary populations. It is critical to consolidate and analyze the available information on the prevalence and incidence of the disease in these countries. Methods: We systematically reviewed articles and gray literature for Australia, China, Hong Kong, Japan, Singapore, South Korea, and Taiwan. We searched PubMed, ScienceDirect, JSTOR, Cochrane, Google Scholar, and other databases for data published 2009–2018. We included articles with prevalence or incidence estimates for adults with osteoporosis or related fractures. Results: All locations had data available, but of widely varying quantity and quality. Most estimates for osteoporosis prevalence ranged from 10 to 30% for women ages 40 and older, and up to 10% for men. Osteoporotic fracture incidence typically ranged between 500 and 1000 per 100,000 person-years among adults aged 50 and older. Both outcomes typically increased with age and were more common among women. Conclusion: Osteoporosis and associated fractures affect significant portions of the adult population in developed economies in the AP region. Governments and healthcare systems must consider how best to prevent and diagnose osteoporosis, and manage affected individuals, to reduce healthcare costs and mortality associated with fractures. [ABSTRACT FROM AUTHOR]

X‐linked hypophosphatemia (XLH) is a rare, inherited, multisystem disorder characterized by hypophosphatemia that occurs secondary to renal phosphate wasting. Mutations in PHEX gene (located at Xp22.1) in XLH alter bone mineral metabolism, resulting in diverse skeletal, dental, and other extraskeletal abnormalities that become evident in early childhood and persist into adolescence and adult life. XLH impacts physical function, mobility, and quality of life, and is associated with substantial socioeconomic burden and health care resource utilization. As the burden of illness varies with age, an appropriate transition of care from childhood and adolescence to adulthood is necessary to meet growth‐related changes and minimize long‐term sequelae of the condition. Previous XLH guidelines that encompassed transition of care have focused on Western experience. Regional differences in resource availability warrant tailoring of recommendations to the Asia‐Pacific (APAC) context. Hence, a core expert panel of 15 pediatric and adult endocrinologists from nine countries/regions across APAC convened to formulate evidence‐based recommendations for optimizing XLH care. A comprehensive literature search on PubMed using MeSH and free‐text terms relevant to predetermined clinical questions on diagnosis, multidisciplinary management, and transition of care of XLH revealed 2171 abstracts. The abstracts were reviewed independently by two authors to shortlist a final of 164 articles. A total of 92 full‐text articles were finally selected for data extraction and drafting the consensus statements. Sixteen guiding statements were developed based on review of evidence and real‐world clinical experience. The GRADE criteria were used to appraise the quality of evidence supporting the statements. Subsequently, a Delphi technique was utilized to rate the agreement on statements; 38 XLH experts (15 core, 20 additional, 3 international) from 15 countries/regions (12 APAC, 3 EU) participated in the Delphi voting to further refine the statements. Statements 1–3 cover the screening and diagnosis of pediatric and adult XLH; we have defined the clinical, imaging, biochemical, and genetic criteria and raised red flags for the presumptive and confirmatory diagnosis of XLH. Statements 4–12 tackle elements of multidisciplinary management in XLH such as therapeutic goals and options, composition of the multidisciplinary team, follow‐up assessments, required monitoring schedules, and the role of telemedicine. Treatment with active vitamin D, oral phosphate, and burosumab is discussed in terms of applicability to APAC settings. We also expound on multidisciplinary care for different age groups (children, adolescents, adults) and pregnant or lactating women. Statements 13–15 address facets of the transition from pediatric to adult care: targets and timelines, roles and responsibilities of stakeholders, and process flow. We explain the use of validated questionnaires, desirable characteristics of a transition care clinic, and important components of a transfer letter. Lastly, strategies to improve XLH education to the medical community are also elaborated in statement 16. Overall, optimized care for XLH patients requires prompt diagnosis, timely multidisciplinary care, and a seamless transfer of care through the coordinated effort of pediatric and adult health care providers, nurse practitioners, parents or caregivers, and patients. To achieve this end, we provide specific guidance for clinical practice in APAC settings. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and nonclassical manifestations, surgical and nonsurgical approaches, and natural history. To provide the most current summary of these developments, an international group, consisting of over 50 experts in these various aspects of PHPT, was convened. This paper provides the results of the task force that was assigned to review the information on the management of PHPT. For this task force on the management of PHPT, two questions were the subject of systematic reviews using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The full report addressing surgical and nonsurgical management of PHPT, utilizing the GRADE methodology, is published separately in this series. In this report, we summarize the results of that methodological review and expand them to encompass a much larger body of new knowledge that did not specifically fit the criteria of the GRADE methodology. Together, both the systematic and narrative reviews of the literature, summarized in this paper, give the most complete information available to date. A panel of experts then considered the last set of international guidelines in light of the newer data and assessed the need for their revision. This report provides the evidentiary background to the guidelines report. In that report, evidence from all task forces is synthesized into a summary statement and revised guidelines for the evaluation and management of PHPT. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Classic symptoms of primary hyperparathyroidism (PHPT) are seen in approximately 20% of patients. While features such as kidney stones and skeletal disease are often highlighted as directly related to the disease, others can be even more prevalent. For example, cognitive dysfunction and reduced quality of life are common complaints in many patients, even among those who are classified as being asymptomatic. The pathophysiology of PHPT involves the impact of excess parathyroid hormone (PTH) on calcium metabolism. Referencing putative neurocognitive issues, many animal studies have illustrated the potential roles of PTH and PTH receptors in the brain. Functional imaging and pre-and post-parathyroidectomy studies have suggested a link between the neuronal impact of elevated PTH levels on specific functional aspects of the central nervous system, such as cognition. Confounding a direct role for PTH are hypercalcemia and vitamin D deficiency, both of which could conceivably alter CNS function in PHPT. The lack of strong evidence that parathyroidectomy improves cognition in patients with PHPT raises the question as to whether parathyroid surgery should be recommended on this basis alone. This narrative review summarizes the available literature on neurocognitive function in PHPT. [ABSTRACT FROM AUTHOR]

Cinacalcet, a positive allosteric modulator of the calcium sensing receptor (CaSR) reduces parathyroid hormone (PTH) secretion by increasing the sensitivity of the CaSR on parathyroid cells. We conducted a systematic review and meta-analysis on the safety and efficacy of cinacalcet in Primary Hyperparathyroidism (PHPT). MEDLINE, Embase, BIOSIS, and the Cochrane Library were searched for published articles (from database inception to Sept 2020). All double-blind RCTs and cohort studies that reported data on the efficacy and safety of cinacalcet therapy in individuals ≥ 18 with PHPT were included. Random effect meta-analysis was performed to estimate the efficacy of cinacalcet in lowering serum calcium and PTH levels compared with placebo. 4 RCTs (177 participants) and 17 cohort studies (763 participants) were eligible for final analysis. Pooled results from the RCTs suggest that, when compared to placebo and administered for up to 28 weeks, cinacalcet normalizes serum calcium (≤ 10.3 mg/dl) in patients with PHPT [RR 20 (95% CI 6.04 – 68.52, I2 = 0%, pheterogeneity < 0·00001)]. Serum PTH levels decreased significantly after 2 weeks and up to 28 weeks after treatment with cinacalcet. In the pooled analysis of the 17 cohort studies, serum calcium levels normalized in 76% (95% CI 66% to 86%; I2 = 92%, pheterogeneity < 0·00001) of patients regardless of the duration of treatment. In most studies, PTH levels decreased by 13% to 55%. No RCT reported on BMD as a primary or secondary outcome, and no improvement in BMD was noted in the 2 non-randomized studies that reported densitometric findings. No significant difference in urinary calcium was noted with cinacalcet therapy in either the RCTs or non-randomized studies. There was no significant difference in overall adverse events (AE) (RD 0.01, 95% CI –0.07 to 0.26) compared to placebo noted in the RCTs. In the non-randomized studies, pooled weighted AE rate was 45% (95% CI 32 to 59%). Risk of bias was low in 2/4 RCTs and 6/17cohort studies; risk was intermediate in 2/4 RCTs and 8/17 cohort studies, and risk was high in 3/17 cohort studies. In PHPT, cinacalcet lowers serum calcium and PTH with greater effects on calcium than on PTH in the short term. In the doses reported, the drug is safe with tolerable side effects. These findings can help inform targeted medical therapy of PHPT in those for whom lowering the serum calcium is indicated and for whom parathyroidectomy is not an option. [ABSTRACT FROM AUTHOR]

In the Asia Pacific (AP) region, osteoporosis and its consequence of fragility fractures are not widely recognized as a major public health problem. Several challenges including underdiagnosis and undertreatment exist. The Asia Pacific Consortium on Osteoporosis (APCO) is a nonpartisan and apolitical organization comprising musculoskeletal experts and stakeholders from both private and public sectors who have united to develop tangible solutions for these substantive challenges. APCO's vision is to reduce the burden of osteoporosis and fragility fractures in the AP region. Heterogeneity in both scope and recommendations among the available clinical practice guidelines (CPGs) contribute to the large osteoporosis treatment gap in the Asia Pacific. APCO has therefore developed a pan Asia‐Oceania harmonized set of standards of care (The Framework), for the screening, diagnosis, and management of osteoporosis. First, a structured analysis of the 18 extant AP CPGs was completed. Subsequently, a prioritization of themes and agreement on fundamental principles in osteoporosis management were made through a Delphi process of consensus building. This approach, ensuring the opinions of all participating members were equally considered, was especially useful for a geographically diverse group such as APCO. It is hoped that the Framework will serve as a platform upon which new AP national CPGs can be developed and existing ones be revised. APCO is currently embarking on country‐specific engagement plans to embed the Framework in clinical practice in the AP region. This is through partnering with regulatory bodies and national guidelines development authorities, through peer‐to‐peer health care professional education and by conducting path finder audits to benchmark current osteoporosis services against the Framework standards. The principles underpinning the harmonization of guidelines in the AP region can also be utilized in other parts of the world that have similar socioeconomic diversity and heterogeneity of healthcare resources. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Summary: COVID-19 lockdowns have impacted management of chronic diseases such as osteoporosis. Adherence to the 6-monthly dosing schedule of denosumab, the parenteral anti-osteoporosis medication most often used in Singapore, was significantly reduced during the lockdown period compared to that during pre-COVID-19 times. Patients managed by endocrinologists were more likely to be adherent. Purpose: No study thus far has quantified actual adherence rates to anti-osteoporosis therapy with denosumab during COVID-19 or explored factors associated with it. We aimed to estimate the adherence rates to denosumab in Singaporean men and women during COVID-19 lockdown and to compare it with those during the pre-COVID-19 period. Method: We conducted this retrospective, electronic medical records, and pharmacy claims database study at Singapore General Hospital, the largest hospital in the country. Patients initiated on subcutaneous denosumab between August 2019 and December 2019 and were thus scheduled to receive the second dose during the COVID-19 first-wave period from February 2020 to June 2020 (lockdown group) were analyzed, as were patients initiated anytime on denosumab between September 2011 and December 2018 (pre-COVID-19 group). Data extracted from the hospital's electronic prescription platform and patients' pharmacy purchase records were matched. Adherence was defined as being punctual (with an allowable delay of up to 4 weeks) with the second dose scheduled 6 months from the 1st dose. A sensitivity analysis with an allowable delay up to 8 weeks was also performed. We compared the adherence rates between the two periods and explored factors associated with adherence. Results: A total of 768 and 1458 patients respectively during the lockdown and pre-COVID-19 periods were analyzed. The mean adherence rate during lockdown was 63.9%. The odds of being adherent during lockdown were higher if patients were managed by endocrinologists as opposed to those by other specialists [OR 2.516 (95% CI: 1.836–3.448); p < 0.001]. Adherence rates during the pre-COVID-19 period was 75.4%. Overall, the odds of being adherent to denosumab was significantly lower during lockdown than that during the pre-COVID-19 period [OR 0.525 (95% CI 0.430–0.640); p < 0.001], and odds of being adherent were higher if patients were managed by endocrinologists than if they were managed by other specialists (OR 1.765 (95% CI: 1.444–2.158; p < 0.001). Conclusion: Adherence to denosumab was significantly lower during COVID-19 lockdown than the pre-COVID-19 period. The odds of being adherent were higher in patients managed by endocrinologists. Whether healthcare providers from certain specialties spend more time counselling and educating patients about the importance of adherence to osteoporosis medications needs to be explored further. [ABSTRACT FROM AUTHOR]

X-linked hypophosphatemia (XLH) is the most prevalent form of hereditary hypophosphatemic rickets associated with phosphate wasting. However, its diagnosis is often missed, resulting in patients presenting late in the course of the disease when complications such as tertiary hyperparathyroidism and renal failure have already set in. Phosphate and calcitriol replacement, both of which have undesirable consequences of their own, have historically been the main stay of therapy. We describe the case of a 57-year-old gentleman with tertiary hyperparathyroidism, who was mislabelled as having achondroplasia for many years before we made a diagnosis of XLH in him. His XLH was found to be due to a hereto unreported deletion of entire exon 14 with partial deletions of introns 13 and 14 of the PHEX gene. Perioperative management in him was fraught with surgical and medical difficulties including an operation that was technically complicated due to his multiple anatomical deformities. Our case also highlights the critical importance of timely recognition and accurate diagnosis of XLH, as well as the long-term multidisciplinary management that is needed for this disorder. [ABSTRACT FROM AUTHOR]

Oral bisphosphonates are approved for the treatment of bone loss associated with several conditions including postmenopausal osteoporosis. Although generally well tolerated, adverse effects such as gastroesophageal reflux and oesophageal and peptic ulceration may occur. Oral mucositis and ulceration are lesser-known side effects. Proper counselling and rigorous adherence to the administration instructions are crucial. We describe a case of bisphosphonate-induced severe oral mucosal ulceration in an elderly woman that was caused by incorrect instructions and/or incorrect understanding of instructions for oral alendronate intake. [ABSTRACT FROM AUTHOR]

Background: Whether the sensitivity of Deep Learning (DL) models to screen chest radiographs (CXR) for CoVID-19 can approximate that of radiologists, so that they can be adopted and used if real-time review of CXRs by radiologists is not possible, has not been explored before. Objective: To evaluate the diagnostic performance of a doctor-trained DL model (Svita_DL8) to screen for COVID-19 on CXR, and to compare the performance of the DL model with that of expert radiologists. Materials and Methods: We used a pre-trained convolutional neural network to develop a publicly available online DL model to evaluate CXR examinations saved in.jpeg or.png format. The initial model was subsequently curated and trained by an internist and a radiologist using 1062 chest radiographs to classify a submitted CXR as either normal, COVID-19, or a non-COVID-19 abnormal. For validation, we collected a separate set of 430 CXR examinations from numerous publicly available datasets from 10 different countries, case presentations, and two hospital repositories. These examinations were assessed for COVID-19 by the DL model and by two independent radiologists. Diagnostic performance was compared between the model and the radiologists and the correlation coefficient calculated. Results: For detecting COVID-19 on CXR, our DL model demonstrated sensitivity of 91.5%, specificity of 55.3%, PPV 60.9%, NPV 77.9%, accuracy 70.1%, and AUC 0.73 (95% CI: 0.86, 0.95). There was a significant correlation (r = 0.617, P = 0.000) between the results of the DL model and the radiologists' interpretations. The sensitivity of the radiologists is 96% and their overall diagnostic accuracy is 90% in this study. Conclusions: The DL model demonstrated high sensitivity for detecting COVID-19 on CXR. Clinical Impact: The doctor trained DL tool Svita_DL8 can be used in resource-constrained settings to quickly triage patients with suspected COVID-19 for further in-depth review and testing. [ABSTRACT FROM AUTHOR]

This paper introduces a new HEp‐2 cell classification model under two phases. In the initial phase, the input image is segmented using the morphological operations (opening and closing), and the segmented image is given for Convolutional Neural Network (CNN) classifier that gives the classified output. In the second phase, the given input is processed under (i) segmentation process (ii) Feature Extraction, and (iii) Classification. From the segmented images; the features like Gray level co‐occurrence Matrix TGLCM) and Gray level Run Length Matrix (GLRM) are extracted. After extracting the features, they are subjected to a classification process, where Neural Network (NN) is used. Finally, the mean of both classified output (first phase and second phase) is considered to be the final classified output. As the main contribution, to enhance the classification accuracy, the hidden neurons of both classifiers (CNN and NN) are optimally chosen during the classification process. To make this possible, this paper aims to propose a new Randomized Update based Grey Wolf Optimization (RP‐GWO) algorithm. Finally, the performance of the implemented approach is compared over other conventional approaches and its superiority is proven with respect to certain measures. [ABSTRACT FROM AUTHOR]

This paper introduces a new HEp-2 cell classification model under two phases. In the initial phase, the input image is segmented using the morphological operations (opening and closing), and the segmented image is given for Convolutional Neural Network (CNN) classifier that gives the classified output. In the second phase, the given input is processed under (i) segmentation process (ii) Feature Extraction, and (iii) Classification. From the segmented images; the features like Gray level co-occurrence Matrix TGLCM) and Gray level Run Length Matrix (GLRM) are extracted. After extracting the features, they are subjected to a classification process, where Neural Network (NN) is used. Finally, the mean of both classified output (first phase and second phase) is considered to be the final classified output. As the main contribution, to enhance the classification accuracy, the hidden neurons of both classifiers (CNN and NN) are optimally chosen during the classification process. To make this possible, this paper aims to propose a new Randomized Update based Grey Wolf Optimization (RP-GWO) algorithm. Finally, the performance of the implemented approach is compared over other conventional approaches and its superiority is proven with respect to certain measures. [ABSTRACT FROM AUTHOR]

Summary: Assessment and treatment pathways based on age-specific intervention thresholds in Singapore using FRAX paths can be used to identify patients at high risk of fracture and avoid unnecessary treatment in those at low risk. Purpose: Intervention thresholds for the treatment of osteoporosis have been based historically on the measurement of bone mineral density. The development of FRAX® has permitted a more accurate assessment of fracture risk. The aim of the present study was to explore treatment paths and characteristics of women selected for treatment in Singapore based on FRAX. Methods: The approach to the setting of intervention and assessment thresholds used the methodology adopted by the National Osteoporosis Guideline Group for FRAX-based guidelines in the UK but based on the epidemiology of fracture and death in Singapore. The methodology was applied to women age 50 years or more drawn from the population-based Singapore Chinese Health Study (SCHS) cohort. Missing data for the calculation of FRAX was simulated using data from Chinese cohorts from Hong Kong. Results: Intervention thresholds expressed as a 10-year probability of a major osteoporotic fracture ranged from 2.9% at the age of 50 years increasing to 32% at the age of 90 years. A total of 1927 of 29,323 women (7%) had a prior fragility fracture and would be eligible for treatment for this reason. An additional 3019 women (10.3%) would be eligible for treatment on the basis of age-dependent thresholds. The mean BMD T-score of women so selected was −2.94. Conclusion: Probability-based assessment of fracture risk using age-specific intervention thresholds was developed for Singapore to help guide decisions about treatment. [ABSTRACT FROM AUTHOR]

Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject. [ABSTRACT FROM AUTHOR]

Adequate calcium intake during childhood is necessary to achieve optimal peak bone mass and this has the potential by increasing bone reserves, to modulate the rate of age-associated bone loss. However, data regarding the efficacy of calcium obtained either through the diet or in the form of medicinal supplementation, for prevention of bone loss and osteoporotic fractures in the elderly is conflicting. Calcium alone is unlikely to be of benefit for this purpose though the co-administration of calcium and vitamin D may have modest fracture risk benefits. Supplemental calcium with or without vitamin D has recently come into the spotlight after the publication of the findings from a controversial randomized controlled trial that associated calcium supplementation with an increased risk of myocardial infarction. Since then, multiple studies have explored this potential link. The data remains conflicting and the potential mechanistic link if any exists, remains elusive. This review examines the relationship between supplemental calcium intake and skeletal and cardiovascular health in the aging individual through an appraisal of studies done on the subject in the last three decades. It also briefly details some of the studies evaluating fractional absorption of calcium in the elderly and the rationale behind the current recommended dietary allowances of calcium. [ABSTRACT FROM AUTHOR]

Diabetes be it type 1 or type 2 is associated with an increased risk of fragility fractures. The mechanisms underlying this increased risk are just being elucidated. Anti-diabetes medications are crucial for maintaining glucose control and for preventing micro- and macrovascular complications in diabetes. However, they may modulate fracture risk in diabetes in different ways. Thiazolidinediones have demonstrated an unfavorable effect on the skeleton, while metformin and sulfonylureas may have a neutral if not beneficial effect on bone. The use of insulin has been associated with an increased risk of fragility fractures though it is not clear whether it is due to direct influence of insulin or whether it is mediated through hypoglycemia and increased falls risk. The overall effect of incretin mimetics appears to be beneficial; however, this has to be elucidated further. The bone effects of pramlintide, a synthetic analog of amylin, have not been explored fully. Finally, issues regarding bone safety of SGLT2 (sodium-dependent glucose transporter 2) inhibitors, the newest anti-diabetic medications on the market are of concern. The purpose of this review is to provide a comprehensive overview of the effect of these medications on bone metabolism and the studies exploring the risk or lack thereof of these medications on bone loss and fragility fractures. [ABSTRACT FROM AUTHOR]

Introduction: Whether parathyroidectomy is more beneficial to renal function when compared to medical therapy or observation in primary hyperparathyroidism (PHPT) is unclear. Neither has this premise been explored in non-Caucasian populations. The estimated glomerular filtration rate (eGFR) threshold below which parathyroid hormone (PTH) levels rise if at all in PHPT has also not been established. We determined if surgery was superior to medical therapy and observation in a multi-ethnic Asian patient population with PHPT and whether there was an eGFR threshold below which PTH levels further increased in them. Methods: Retrospective evaluation of patients with PHPT. Results: There were 68.6% Chinese, 17.4% Malays, 10.7% Indians, and 3.3% Eurasians. The median (interquartile range) follow-up was 18.0 months (4.5-46.8). At last follow-up, eGFR in the surgical (80 ± 30 ml/min) was higher than the medical (52 ± 32 ml/min) or observation groups (48 ± 33 ml/min); P < 0.01. This difference persisted after adjusting for age, gender, ethnicity, pre-intervention eGFR levels, nephrolithiasis, serum calcium, phosphate, urinary calcium, and duration of follow-up; P = 0.035. There was no definite eGFR level below which PTH values rose. Conclusion: Our study provides compelling evidence that in PHPT, surgery may be associated with a better renal outcome compared to medical management or observation. This has to be confirmed through prospective randomized controlled trials and the reasons for this finding have to be elucidated through functional and histological measures. The finding in our study of a lack of a specific eGFR threshold below which PTH levels further rose challenges the concept of a fixed renal threshold for secondary elevations of PTH in PHPT. [ABSTRACT FROM AUTHOR]

A fragility fracture signals the potential for the occurrence of a subsequent fracture, and it often represents the first opportunity for care of osteoporosis. It is now well accepted knowledge that fracture liaison services can close or, at the very least, narrow the care gap that exists in the management of these sentinel events in patients with osteoporosis. The challenge, however, lies in translating this knowledge into practice and to implement these programs in health care systems with varied infrastructure and delivery practices operating in varied geographical environments. A review of a functioning model of care in an open health system in an Asian country and a short account of the problems encountered and the lessons learned during the course of its implementation are provided. [ABSTRACT FROM AUTHOR]

Introduction Osteoporosis is a condition characterized by low bone mass and micro-architectural deterioration of the bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. APCO Framework of Clinical Standards of Care: An Innovative Initiative to Improve Osteoporosis Care The Asia-Pacific Consortium on Osteoporosis (APCO) comprises 39 osteoporosis experts from 19 countries and regions spanning the entire Asia-Pacific region (www.apcobonehealth.org). [Extracted from the article]

Summary: The prevalence of secondary contributors to osteoporosis in our population of SE Asian patients is high. Though various low thresholds Z score values have been proposed as suggestive of a high likelihood of secondary osteoporosis, they appear to have only limited discriminatory value in identifying a secondary cause. Introduction: Many patients with osteoporosis have significant secondary contributors towards their bone loss. The sensitivity and diagnostic utility of using Z score thresholds to screen for secondary osteoporosis have not yet been convincingly demonstrated nor has there been any previous attempt to estimate the prevalence of secondary osteoporosis in South East Asia. We aimed to study the prevalence of commonly recognized contributors and to determine the discriminatory ability of Z score thresholds in screening for them in Singaporean men and post-menopausal women with osteoporosis. Method: Three hundred thirty-two consecutive patients seen at the osteoporosis clinic of the largest hospital in Singapore were evaluated. The frequencies of the different contributors were determined and sensitivities, specificities, and positive and negative predictive values (PPV and NPV) of pre-specified Z score cut-off values calculated. Results: Vitamin D deficiency was present in 18.5% of the patients, hyperthyroidism in 10.11%, primary hyperparathyroidism in 1%, secondary hyperparathyroidism in 6%, hypercalciuria in 21.63%, glucocorticoid use in 8.43%, and hypogonadism in 9.4% of males. A Z score value of <−1 had a sensitivity of 71.7 % and NPV of 66.2 % in identifying the presence of a secondary contributor in post-menopausal women. The sensitivity and NPV of a similar threshold in men was 59.1 and 40 %, respectively. ROC curves used to investigate various Z score diagnostic thresholds for sensitivity and specificity showed that they provided poor predictive value for the presence of secondary osteoporosis. Conclusion: Secondary contributors are common in our patients with osteoporosis. Z score diagnostic thresholds have only limited value in discriminating between primary and secondary osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: This survey investigated osteoporosis management practices in the Asia-Pacific region. While access to anti-osteoporotic medication is reasonable, screening for secondary contributors is performed insufficiently. FRAX® is well-known, but not used by many physicians. High costs of medication and unawareness about the disease are the biggest barriers to osteoporosis care. Purpose: Osteoporosis is an increasing burden amongst countries of the Asia-Pacific. The fracture risk assessment tool FRAX® has recently been introduced in some Asian countries. This study aimed to identify attitudes about osteoporosis management in general and the utilization of FRAX® in particular amongst physicians in the Asia-Pacific region. Methods: A 26-item questionnaire was distributed to the participants of the first Asian regional osteoporosis meeting of the IOF in 2010. In total, 247 valid questionnaires representing 17 countries from the Asia-Pacific region were analyzed. Results: Most physicians make use of bone densitometry devices (94 %) and have access to at least one type of anti-osteoporotic medication (100 %). Central dual-energy X-ray absorptiometry was the most accessible device (87 %). Oral bisphosphonates were the only medication that was available to health care professionals in all surveyed Asia-Pacific countries. Seventy-six percent were aware of FRAX®; however, among these only 62 % used it. The main reason for not using FRAX® was the lack of country-specific models (46 %). Screening for secondary osteoporosis was performed by 36 % of the respondents. The high costs of medication and lack of awareness amongst physicians and patients about the disease were perceived as the most important barriers to osteoporosis care. Conclusion: More FRAX® models should be established and implemented into the local guidelines. The necessity of screening for secondary contributors to osteoporosis should be emphasized, as easily treatable causes might be identified. To further improve osteoporosis diagnosis and treatment, the awareness of osteoporosis among doctors as well as patients needs to be raised. [ABSTRACT FROM AUTHOR]

Background: Falls are common in frail older adults and often result in injuries and hospitalisation. The Nintendo® Wii™ is an easily available exercise modality in the community which has been shown to improve lower limb strength and balance. However, not much is known on the effectiveness of the Nintendo® Wii™ to improve fall efficacy and reduce falls in a moderately frail older adult. Fall efficacy is the measure of fear of falling in performing various daily activities. Fear contributes to avoidance of activities and functional decline.Methods: This randomised active-control trial is a comparison between the Nintendo WiiActive programme against standard gym-based rehabilitation of the older population. Eighty subjects aged above 60, fallers and non-fallers, will be recruited from the hospital outpatient clinic. The primary outcome measure is the Modified Falls Efficacy Scale and the secondary outcome measures are self-reported falls, quadriceps strength, walking agility, dynamic balance and quality of life assessments.Discussions: The study is the first randomised control trial using the Nintendo Wii as a rehabilitation modality investigating a change in fall efficacy and self-reported falls. Longitudinally, the study will investigate if the interventions can successfully reduce falls and analyse the cost-effectiveness of the programme. [ABSTRACT FROM AUTHOR]

Examines the role of adinopectin, a bioactive protein secreted by the adipocyte tissue, in diabetes. Structure of monomeric adinopectin; Model for assembly of adinopectin complexes; Mode of action; Metabolic roles.

This article provides some recommendations on managing diabetes during air travel. Overseas travel poses special problems for people with diabetes, especially those on insulin. However, the fear of dealing with medications and acute complications should not prevent people with diabetes from traveling, whether for work or recreation. A British study in 1993 clearly demonstrated that most physicians, including diabetologists, are uncertain about how to adjust insulin doses for patients who travel across several time zones. Ideally, patients who are planning overseas travel should schedule an office visit with their health care provider at least four to six weeks before departure so as to assess their patients' current level of diabetes control, to give specific advice regarding diabetes management and prevention of acute complications. Patients should obtain a travel itinerary showing departure and arrival times, durations of flights, and time differences between the points of embarkation and disembarkation. It is also helpful to find out beforehand the serving time of meals. All medications and supplies should be carried by the patient. Insulin is stable under normal conditions at airport terminals and passenger security check points and when passing through X-ray machines.

Osteoporosis is the most prevalent metabolic bone disease in the United States. Although the disease has historically been reported mostly in white women, it can affect individuals of both sexes and all ethnic groups. The presence of osteoporosis related to diabetes is not well acknowledged and the impact of osteoporosis in a diabetic patient is often not considered. Routine screening or initiation of preventive medications for osteoporosis in all patients with type 1 or type 2 diabetes is not recommended at the present time. However, in all patients with diabetes, besides optimal glycemic control, general recommendations regarding adequate dietary calcium intake, regular exercise, and avoidance of other potential risk factors such as smoking should be given. In patients who have positive risk factors for osteoporosis, or in those who present with fractures, evaluation of bone density should be done and respective preventive or therapeutic interventions should be applied. [ABSTRACT FROM AUTHOR]

Gastrointestinal disorders are common in patients with diabetes mellitus. As many as 75% of patients visiting diabetes clinics will report significant gastrointestinal (GI) symptoms. The symptom complex experienced may vary widely. Many patients go undiagnosed and undertreated. Patients with a history of retinopathy, nephropathy, or neuropathy should be presumed to have GI abnormalities until proven otherwise. The workup should start with a thorough patient history and appropriate laboratory, radiographic, and GI testing. In addition to pharmacologic therapy, glycemic control and dietary manipulation play an important role in managing GI disorders in people with diabetes. [ABSTRACT FROM AUTHOR]

Objective: To assess the effects of adjunctive treatment with pramlintide, an analog of the beta-cell hormone amylin, on 24-h glucose fluctuations and postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion (CSII).Research Design and Methods: In this study, 18 patients (16 of whom could be evaluated) with type 1 diabetes (age 44 +/- 11 years, HbA(1c) 8.2 +/- 1.3% [mean +/- SD]) were given mealtime injections of 30 micro g pramlintide t.i.d. for 4 weeks in addition to their preexisting CSII regimen (16 lispro, 2 regular insulin). Mealtime insulin boluses were reduced by a minimum of 10% during the first 3 days, and re-adjusted thereafter based on clinical judgment. At weeks 0 (baseline), 4 (on treatment), and 6 (2 weeks off treatment), 24-h interstitial glucose concentrations were measured using a continuous glucose monitoring system (CGMS), and postprandial plasma glucose, glucagon, and triglyceride concentrations were measured in response to a standardized test meal.Results: At baseline, patients had excessive 24-h glucose fluctuations, with 59% of the CGMS measurements >140 mg/dl, 13% <80 mg/dl, and only 28% in the euglycemic range (80-140 mg/dl). After 4 weeks on pramlintide, measurements in the hyperglycemic range declined to 48% and measurements within the euglycemic range increased to 37%. This shift from the hyperglycemic to the euglycemic range occurred with a concomitant 17% reduction in mealtime insulin dosages and without relevant increases in measurements below the euglycemic range (15%) or any severe hypoglycemic events. After 4 weeks on pramlintide, postprandial glucose, glucagon, and triglyceride excursions were reduced by approximately 86, approximately 87, and approximately 72%, respectively (incremental areas under the curve, all P < 0.05 vs. baseline). At week 6 (off treatment), the 24-h glucose profile and postprandial glucose, glucagon, and triglyceride excursions approached pretreatment values.Conclusions: In this study, the addition of pramlintide to insulin therapy reduced excessive 24-h glucose fluctuations as well as postprandial glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes intensively treated with insulin pumps. [ABSTRACT FROM AUTHOR]

The evolution of trabecular bone score (TBS) and bone mineral density (BMD) over the first 5 years after renal transplantation was prospectively evaluated in 164 patients. Dual energy X‐ray absorptiometry (DXA) scans were performed at 0, 6, 12, 24, and 60 months. Cumulative steroid dose, serum 25(OH)D, calcium, parathyroid hormone, and total ALP levels at these time points were checked. Incident fractures were identified from X‐rays/vertebral fracture assessments. Mean (SD) age, TBS, and lumbar spine BMD at baseline were 47.11 (9.53), 1.424 (0.097), and 0.935 (0.183) gm/cm2, respectively. Baseline TBS was lower in tertiary 1.38 (0.07) vs secondary hyperparathyroidism 1.43 (0.01) vs post‐parathyroidectomy 1.46 (0.11); P = .035. Trabecular bone score and BMD significantly decreased from baseline‐>6 months, changes after that at consecutive time points were non‐significant. 11% had incident fractures during the follow‐up period, majority being metatarsal with no vertebral or hip fractures noted. This first prospective evaluation of TBS and BMD evolution at multiple time points over 5 years suggest that microarchitectural and bone density deteriorations post‐renal transplantation stabilize after 6 months. Stabilization of these parameters could partially account for the absence of major fractures noted in this Asian population. Possible genetic and ethnic differences in fracture risk between Asian and Caucasian renal transplant patients have to be explored through large population‐based studies. [ABSTRACT FROM AUTHOR]

Summary: This paper revised the fixed intervention thresholds (ITs) based on the Sri Lankan fracture risk assessment tool (FRAX) published in 2013 and introduced new ITs, hybrid and two-tier, aiming to help clinicians in the management of postmenopausal osteoporosis. The hybrid and two-tier ITs have a better discriminatory power than age-dependent and revised fixed ITs.Introduction: This study revised the Sri Lankan FRAX®-based intervention thresholds (ITs) previously published in 2013.Method: Age-dependent ITs were estimated, from 50-80 years with 5-year intervals, using a Sri Lankan FRAX® algorithm for a woman with a BMI of 24.8 kg/m2 and history of prior fragility fracture without other clinical risk factors. Data of 653 postmenopausal women were used in estimating fixed, hybrid, and two-tier ITs. ITs were determined using the ROC curve and partial Youden index. New ITs were validated using data of 356 postmenopausal women who underwent DXA and 62 women who had a recent fragility fracture. Women in the two groups (n = 653 and n = 356) came from the Southern Province and had undergone DXA in our state-owned tertiary care hospital as a part of their routine clinical assessment.Results: The mean (SD) age and BMI of the subjects (n = 653) were 62 (8) years and 24.8 (1.2) kg/m2, respectively. Age-dependent ITs of major osteoporotic fracture risk (MOFR) and hip fracture risk (HFR) ranged from 2.7 to 18% and from 0.4 to 7.1%. The best fixed ITs for women aged 50-80 years were 9% for MOFR and 3% for HFR. In the hybrid method, MOFR of 6% and HFR of 2% were found appropriate for women aged < 70 years. These were combined with age-dependent ITs for women aged 70 years and above. In the two-tier system, two sets of ITs were calculated (ITs of MOFR/HFR for women aged < 70 years and ≥ 70 years were 6%/2% and 12%/5%, respectively). When age-dependent ITs were considered the reference standard, sensitivities of the fixed, hybrid, and two-tier ITs were 0.63, 0.73, and 0.74, respectively. The specificities were 0.76, 0.86, and 0.80 in the same order. Sensitivities of the age-dependent, fixed, hybrid, and two-tier ITs in identifying a woman with an incident fracture were 26%, 48%, 61%, and 61%, respectively.Conclusions: The new fixed MOFR is slightly lower than the previous value and hybrid and two-tier ITs perform better than age-dependent and fixed ITs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article by E. Mann and colleagues related to hip fracture incidences in the Austrian population of those aged 50 and over.