Trabecular bone score in adults with type 1 diabetes: a meta-analysis.

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.

Impact of pheochromocytoma or paraganglioma on bone metabolism: A systemic review and meta-analysis.

INTRODUCTION: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap. METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP). RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery. CONCLUSION: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

Improving care pathways for people living with rare bone diseases (RBDs): outcomes from the first RBD Summit.

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.

Prevalence of osteoporosis and incidence of related fractures in developed economies in the Asia Pacific region: a systematic review.

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.

Update on the clinical use of trabecular bone score (TBS) in the management of osteoporosis: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), and the International Osteoporosis Foundation (IOF) under the auspices of WHO Collaborating Center for Epidemiology of Musculoskeletal Health and Aging.

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. 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.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

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.

Adherence to dosing schedule of denosumab therapy for osteoporosis during COVID-19 lockdown: an electronic medical record and pharmacy claims database study from Asia.

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.

The efficacy and safety of cinacalcet in primary hyperparathyroidism: a systematic review and meta-analysis of randomized controlled trials and cohort studies.

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.

Cognitive deficits in primary hyperparathyroidism - what we know and what we do not know: A narrative review.

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.

Parathyroid allotransplantation to treat post-thyroidectomy hypoparathyroidism: A review of case studies.

OBJECTIVE: Symptomatic long-term hypoparathyroidism following thyroid surgery requires an alternative and permanent therapy that would effectively restore parathyroid function and eliminate the need for substitution drug therapy. The aim of this study was to systematically review the literature on the efficacy and safety of parathyroid allotransplantation to treat post-operative hypoparathyroidism. METHODS: MEDLINE, Embase, BIOSIS and the Cochrane Library were searched for published articles (from inception of each database to September 30, 2018). A total of 9 studies comprising 146 patients (177 allotransplantations) with post thyroidectomy hypoparathyroidism were identified. RESULTS: Parathyroid tissues used for allotransplant were cultured parathyroid cells, cryopreserved parathyroid cells and encapsulated microspheres. Post-transplant immunosuppression was only reported in three studies, mainly with oral prednisolone for 2 weeks to 6 months. Mean graft survival following allotransplantation was 47% (95% CI 24%-71%) when patients were followed-up to 6 months and 41% (95% CI 2.3%-80%) at 12 months. There was significant unexplained heterogeneity observed between studies in both these groups (I2 > 50%). Parathyroid hormone (PTH) levels, and serum calcium levels post intervention was not reported in all studies, but available evidence suggests the levels remains higher (PTH level around 12 pg/ml; Ca level around 8 mg/dl) post-allotransplantation for up to 24 months. CONCLUSIONS: Long-term benefit and harms of allotransplantation is still unclear due to the clinical and statistical heterogeneity observed among the studies. Therefore, conduct of a well-designed controlled clinical trial in the immediate future on allotransplantation is of paramount importance.

Addressing bone quality and bone density after renal transplantation: A prospective evaluation of the evolution of trabecular bone score and bone mineral density over the first 5 years following renal transplantation in Asian patients.

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.

Supplemental calcium intake in the aging individual: implications on skeletal and cardiovascular health.

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.

Diabetes Drug Effects on the Skeleton.

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.

Fracture Risk Assessment in Clinical Practice: Why Do It? What to Do It With?

Fracture is the outcome of concern in osteoporosis, and fracture reduction is the primary goal of osteoporosis treatment. Fracture risk assessment is a critical component in osteoporosis management. The earlier approach of deciding on whether to treat solely based on bone mineral density (BMD) T-scores has been supplanted by employing the concept of absolute risk over medium time periods and more encompassing integration of clinical risk factors with or without BMD into robust fracture risk assessment tools. Fracture risk estimation allows for identifying high-risk patient groups not only at a health system and population-based level and thereby allowing allocation of financial resources to the people most at risk, but also at an individual level for the clinician to involve the patient in shared decision-making processes for treatment. The process of fracture risk assessment involves several steps including performing a thorough history and physical examination, assessing BMD, doing radiological assessment for vertebral fractures, and laboratory evaluation to rule out secondary contributors to osteoporosis. The data thus obtained can be input into any one of several fracture risk assessment tools that are now available. The decision on which tool to use can be made on the background of country-specific guidelines, although it is imperative that the physician be aware of the limitations inherent to whichever tool is chosen. This article aims to provide a brief overview of why fracture risk estimation is important and the methods that can be employed for it by the physician in clinical practice.

AXIAL BMD IN DIABETIC AND NONDIABETIC SOUTHEAST ASIANS WITH HIP FRACTURES: DO RACE AND BODY MASS INDEX MATTER?

OBJECTIVE: Obesity is less prevalent in Asian subjects with type 2 diabetes mellitus (T2DM) in contrast to Caucasians. Whether higher axial bone mineral density (BMD) often reported in T2DM is independent of body mass index (BMI) has not been clearly shown. BMD characterization in T2DM patients with hip fractures has also not been performed. We compared the BMD of Asian diabetic and nondiabetic patients with new hip fractures and explored how BMD was influenced by BMI. METHODS: We included 255 diabetic and 148 nondiabetic patients. BMD adjusted for age; BMI; race; sex; renal function; and use of statins, proton pump inhibitors, steroids, anticonvulsants, and calcium and/or vitamin D supplements were compared between the groups. We were particularly interested in the BMD comparison between underweight diabetics and nondiabetics with hip fractures. RESULTS: The presence of T2DM was associated with higher BMD (g/cm(2)) at the femoral neck (0.527 ± 0.103 vs. 0.491 ± 0.102, P<.01) and lumbar spine [LS] (0.798 ± 0.147 vs. 0.723 ± 0.156, P<.01). This association persisted after adjustment for multiple confounding variables including BMI. The age-, BMI-, and sex-adjusted LS BMD was higher in underweight (BMI <18.5 kg/m(2)) diabetics compared to similar weight nondiabetics (0.733 ± 0.126 vs. 0.649 ± 0.131 g/cm(2), P = .014). CONCLUSION: T2DM is independently associated with higher axial BMD in patients with new hip fractures. The finding of higher BMD even in underweight diabetics with hip fractures compared to their nondiabetic counterparts suggests that higher BMD in subjects with T2DM is not due to higher BMI. ABBREVIATIONS: BMD = bone mineral density BMI = body mass index CV = coefficient of variation DXA = dual-energy X-ray absorptiometry HbA1c = glycated hemoglobin IGF-1 = insulin growth factor-1 LS = lumbar spine 25(OH)D = 25-hydroxyvitamin D T2DM = type 2 diabetes mellitus.

Dropping the Ball and Falling Off the Care Wagon. Factors Correlating With Nonadherence to Secondary Fracture Prevention Programs.

Health care systems and hospitals in several countries have implemented Fracture Liaison Services (FLSs). Success rates of FLSs with regard to osteoporosis assessment and treatment, fracture reduction, and adherence to osteoporosis medications have been reported by several groups including ours. A significant drop-out rate among patients in these programs may occur. This has not been evaluated before. We explored the factors correlating with nonadherence among a multiethnic population of patients in the FLS at our institution, the largest tertiary teaching hospital in South East Asia. Our secondary objective was to explore whether patients who defaulted follow-up visits continued to be compliant with medications. A retrospective analysis of our FLS's computerized database was performed. Of 938 patients followed up more than 2 years, 237 defaulted at various time points. A significant percentage of patients who dropped out of the program opined that it was because the follow-up visits were too time consuming. Non-Chinese patients were more likely than Chinese (adjusted hazard ratio [aHR] = 1.98, 1.33-2.94), patients with primary school education and below were more likely than those with secondary school and above education (aHR = 1.65, 1.11-2.45) and those with nonvertebral and/or multiple fractures were more likely than those with spine fractures (aHR = 1.38, 1.06-1.81) to be nonadherent. A fraction of patients who defaulted continued to fill osteoporosis medication prescriptions. Median medication possession ratio among the patients who defaulted was 12.3% (interquartile range: 4.1%-36.7%) at 2 years. Persistence ranged from 15.1% to 20.8% and from 1.9% to 7.5% at 1 and 2 years, respectively after defaulting from the program. Our study, which to the best of our knowledge is the first of its kind, provides insight into the factors correlating with nonadherence to FLSs. Knowledge of the challenges faced by patients may be of help to health care providers interested in developing FLSs.

The effect of four loading intravitreal aflibercept injections on macular fluid in treatment-naïve neovascular age-related macular degeneration.

PURPOSE: To evaluate the effect of four versus three loading aflibercept injections on macular fluid resolution and visual acuity (VA) in exudative neovascular AMD (nAMD). METHODS: Multicentre, retrospective cohort study of treatment naïve nAMD eyes undergoing 3 versus 4 loading doses of aflibercept. Change in VA and fluid resolution on optical coherence tomography (OCT), were evaluated at 8 weeks post loading. The primary outcome was proportion of patients with no intraretinal (IRF) and/or subretinal (SRF) fluid at central 1 mm and whole macula at 8 weeks after loading. Data were summarised with mean ± SD for continuous variables, and n (%) for categorical variables. RESULTS: Data from 995 patients was analysed (355 patients - 4 loading doses and 640-3 loading doses). At 8 weeks post 4 loading doses proportion of eyes with neither IRF nor SRF, no IRF and no SRF were 62.8%, 88.7% and 79.2% at fovea versus 56.1%, 87.9% and 69.9% in the whole macula, respectively. Fluid resolution at both fovea and macula were significantly higher in eyes with 4 loading injections versus 3 (p = 0.0001). The mean VA change was +4.0 (±11.3) and +5.4(±13.3) letters for 3 and 4 loading doses groups (p = 0.09). CONCLUSION: Four loading dose injections of aflibercept results in higher proportion of eyes with total fluid resolution in the central subfield and total macular scan when compared to those receiving 3 loading dose injections at 8 weeks post loading phase. However, the better drying effect of 4th loading dose does not translate into better short-term VA outcomes.

Evidence-Based Guideline for the management of osteoporosis in men.

Historically, osteoporosis has been viewed as a disease of women, with research, trials of interventions and guidelines predominantly focused as such. It is apparent, however, that this condition causes a substantial health burden in men also, and that its assessment and management must ultimately be addressed across both sexes. In this article, an international multidisciplinary working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases presents GRADE-assessed recommendations for the diagnosis, monitoring and treatment of osteoporosis in men. The recommendations are based on a comprehensive review of the latest research related to diagnostic and screening approaches for osteoporosis and its associated high fracture risk in men, covering disease burden, appropriate interpretation of bone densitometry (including the use of a female reference database for densitometric diagnosis in men) and absolute fracture risk, thresholds for treatment, and interventions that can be used therapeutically and their health economic evaluation. Future work should specifically address the efficacy of anti-osteoporosis medications, including denosumab and bone-forming therapies.