Follow-up Bone Mineral Density Testing: 2023 Official Positions of the International Society for Clinical Densitometry.

Dual-energy X-ray absorptiometry (DXA) is the gold standard method for measuring bone mineral density (BMD) which is most strongly associated with fracture risk. BMD is therefore the basis for the World Health Organization's densitometric definition of osteoporosis. The International Society for Clinical Densitometry (ISCD) promotes best densitometry practices and its official positions reflect critical review of current evidence by domain experts. This document reports new official positions regarding follow-up DXA examinations based on a systematic review of literature published through December 2022. Adoption of official positions requires consensus agreement from an expert panel following a modified RAND protocol. Unless explicitly altered by the new position statements, prior ISCD official positions remain in force. This update reflects increased consideration of the clinical context prompting repeat examination. Follow-up DXA should be performed with pre-defined objectives when the results would have an impact on patient management. Testing intervals should be individualized according to the patient's age, sex, fracture risk and treatment history. Incident fractures and therapeutic approach are key considerations. Appropriately ordered and interpreted follow-up DXA examinations support diagnostic and therapeutic decision making, thereby contributing to excellent clinical care. Future research should address the complementary roles of clinical findings, imaging and laboratory testing to guide management.

Executive Summary of the 2023 Adult Position Development Conference of the International Society for Clinical Densitometry: DXA Reporting, Follow-up BMD Testing and Trabecular Bone Score Application and Reporting.

After 15 months of preparation by task force chairs and teams, ISCD's 9th Position Development Conference (PDC) convened in Northbrook, IL, USA on March 28th and 29th, 2023 to approve new ISCD Official Positions in the topic areas of DXA Reporting, Follow-up BMD Testing and TBS Application and Reporting. Three teams of participants work to bring the PDC to fruition: the Steering Committee, Task Forces and Chairs, and the Expert Panel. To reach agreement on draft Official Positions, the PDC follows a scripted process with the UCLA/RAND Appropriateness Method (UCLA/RAM) as its foundation. Multiple rounds of data review, public debate and voting resulted in 32 new or modified Official Positions. Six companion position papers are also published along with this Executive Summary, serving as the detailed substantiation for the Official Positions. This Executive Summary reviews the personnel groups, activities and products of the 2023 PDC, with the entirety of the updated 2023 Official Positions presented in Appendix A. New Official Positions are highlighted in bold.

Persistent Bilateral Atypical Femoral Fractures in an Antiresorptive-Naïve Singaporean Chinese Patient with Graves' Disease.

Atypical femoral fractures (AFFs) are rare adverse effects of bisphosphonate therapy. We report an unusual case of bilateral diaphyseal AFFs in an antiresorptive-naïve Singaporean Chinese female with Graves' disease. She presented with complete right AFF requiring surgical fixation, and persistent left incomplete AFF for over four years. Femoral bowing, varus femoral geometry, and ethnic influence likely contributed to the AFFs' formation. This case may provide insights into the pathogenesis of AFFs in high-risk Asian populations.

Proton-pump inhibitor use amongst patients with severe hypomagnesemia.

Introduction: Long-term proton pump inhibitor (PPI) use has been associated with hypomagnesemia. It is unknown how frequently PPI use is implicated in patients with severe hypomagnesemia, and its clinical course or risk factors. Methods: All patients with severe hypomagnesemia from 2013 to 2016 in a tertiary center were assessed for likelihood of PPI-related hypomagnesemia using Naranjo algorithm, and we described the clinical course. The clinical characteristics of each case of PPI-related severe hypomagnesemia was compared with three controls on long-term PPI without hypomagnesemia, to assess for risk factors of developing severe hypomagnesemia. Results: Amongst 53,149 patients with serum magnesium measurements, 360 patients had severe hypomagnesemia (<0.4 mmol/L). 189 of 360 (52.5%) patients had at least possible PPI-related hypomagnesemia (128 possible, 59 probable, two definite). 49 of 189 (24.7%) patients had no other etiology for hypomagnesemia. PPI was stopped in 43 (22.8%) patients. Seventy (37.0%) patients had no indication for long-term PPI use. Hypomagnesemia resolved in most patients after supplementation, but recurrence was higher in patients who continued PPI, 69.7% versus 35.7%, p = 0.009. On multivariate analysis, risk factors for hypomagnesemia were female gender (OR 1.73; 95% CI: 1.17-2.57), diabetes mellitus (OR, 4.62; 95% CI: 3.05-7.00), low BMI (OR, 0.90; 95% CI: 0.86-0.94), high-dose PPI (OR, 1.96; 95% CI: 1.29-2.98), renal impairment (OR, 3.85; 95% CI: 2.58-5.75), and diuretic use (OR, 1.68; 95% CI: 1.09-2.61). Conclusion: In patients with severe hypomagnesemia, clinicians should consider the possibility of PPI-related hypomagnesemia and re-examine the indication for continued PPI use, or consider a lower dose.

Telecarers improve osteoporosis treatment and compliance rates in secondary osteoporosis prevention for elderly hip fracture patients.

Introduction: A significant treatment gap has been observed in patients with osteoporosis. Our previous audit found a 31.5% rate of anti-osteoporosis medication initiation after fragility fractures at one year. We piloted the use of telecarers to monitor osteoporosis treatment and compliance. Methods: From January 2017 to January 2018, all hip fracture patients at Changi General Hospital, Singapore, were automatically enrolled into the Health Management Unit valued care hip fracture programme. Telecarer calls were scheduled at discharge, 3, 6 and 12 months. We assessed the acceptability, completion and treatment rates of patients enrolled in this programme. Results: A total of 537 patients with a hip fracture were enrolled in the telecarer programme over one year. Their average age was 79.8 ± 8.23 years, and 63.1% of them were female. A total of 341 patients completed 12 months of follow-up, of which 251 (73.6%) patients were on treatment at 12 months. The most common cause of lack of initiation of secondary osteoporosis treatment was patient or family rejection (34.4%), followed by physician failure to prescribe (24.4%) and renal impairment (24.4%). 16.7% of patients were deemed to have advanced dementia with a life-limiting illness and were, thus, deemed unsuitable for treatment. Conclusion: Telecarers may be a useful adjunct in the monitoring of osteoporosis treatment after hip fractures in an elderly population. The main limitations are patient or family rejection and physician inertia. Further studies should focus on a combination of interventions for both patients and physicians to increase awareness of secondary fracture prevention.

Treatment of Primary Aldosteronism and Reversal of Renin Suppression Improves Left Ventricular Systolic Function.

Introduction: Primary aldosteronism (PA) is associated with increased risk of cardiovascular events. However, treatment of PA has not been shown to improve left ventricular (LV) systolic function using the conventional assessment with LV ejection fraction (LVEF). We aim to use speckle-tracking echocardiography to assess for improvement in subclinical systolic function after treatment of PA. Methods: We prospectively recruited 57 patients with PA, who underwent 24-h ambulatory blood pressure (BP) measurements and echocardiography, including global longitudinal strain (GLS) assessment of left ventricle, at baseline and 12 months post-treatment. Results: At baseline, GLS was low in 14 of 50 (28.0%) patients. On multivariable analysis, GLS was associated with diastolic BP (P = 0.038) and glomerular filtration rate (P = 0.026). GLS improved post-surgery by -2.3, 95% CI: -3.9 to -0.6, P = 0.010, and post-medications by -1.3, 95% CI: -2.6 to 0.03, P = 0.089, whereas there were no changes in LVEF in either group. Improvement in GLS was independently correlated with baseline GLS (P < 0.001) and increase in plasma renin activity (P = 0.007). Patients with post-treatment plasma renin activity ≥1 ng/ml/h had improvements in GLS (P = 0.0019), whereas patients with persistently suppressed renin had no improvement. Post-adrenalectomy, there were also improvements in LV mass index (P = 0.012), left atrial volume index (P = 0.002), and mitral E/e' (P = 0.006), whereas it was not statistically significant in patients treated with medications. Conclusion: Treatment of hyperaldosteronism is effective in improving subclinical LV systolic dysfunction. Elevation of renin levels after treatment, which reflects adequate reversal of sodium overload state, is associated with better systolic function after treatment. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03174847.

Incidence of Atypical Femoral Fracture and Its Mortality in a Single Center in Singapore.

Bisphosphonates (BP) are the most commonly prescribed effective form of osteoporosis treatment with adverse effects associated with prolonged use such as atypical femoral fractures (AFF). Asians have an elevated risk of AFF at 5 to 6 times those of whites and Hispanics. In this study, we characterize factors associated with AFF and its mortality in a single center in Singapore. We conducted a cohort study of subjects older than 50 years admitted to Changi General Hospital (CGH), Singapore, with fragility subtrochanteric femoral fractures from 2009 to 2015. Using the ASBMR 2014 criteria, fractures are classified into atypical and typical subtrochanteric femoral fractures. CGH uses a nationalized electronic health record that allows review of information on patients' demographics, clinical history and previous investigations. Mortality was assessed as of December 31, 2019. Between 2009 and 2015, there were 3097 hip fractures, of which 393 were subtrochanteric femoral fractures and 69 were classified as AFF by ASBMR 2014 criteria. A total of 52.2% of AFF occurred with BP exposure of median duration 56.5 (28 to 66) months. Multivariate regression showed that BP exposure was associated with the highest risk of AFF (odds ratio [OR] = 6.65 [2.35-18.9]). AFF patients had higher 5-year survival (0.85 versus 0.62, p = 0.001) compared with typical subtrochanteric fracture patients. However, after adjusting for variables, the type of subtrochanteric femoral fractures were no longer significantly associated with progression to death, whereas older age, higher mean Charlson comorbidity score, and Malay ethnicity were the strongest predictors of death. AFF constitutes a small proportion of hip and femoral fractures with prolonged BP use being the highest risk factor for its development. There is no evidence of increased mortality or morbidity in patients with AFF compared with the typical subtrochanteric fracture. The fear of AFF should not impede treatment of typical osteoporotic fractures in this population. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Improvement in quality of life and psychological symptoms after treatment for primary aldosteronism: Asian Cohort Study.

BACKGROUND: In addition to increased cardiovascular risk, patients with primary aldosteronism (PA) also suffer from impaired health-related quality of life (HRQoL) and psychological symptoms. We assessed for changes in HRQoL and depressive symptoms in a cohort of Asian patients with PA, after surgical and medical therapy. METHODS: Thirty-four patients with PA were prospectively recruited and completed questionnaires from 2017 to 2020. HRQoL was assessed using RAND-36 and EQ-5D-3L, and depressive symptoms were assessed using Beck Depression Inventory (BDI-II) at baseline, 6 months, and 1 year post-treatment. RESULTS: At 1 year post-treatment, significant improvement was observed in both physical and mental summative scores of RAND-36, +3.65, P = 0.023, and +3.41, P = 0.033, respectively, as well as four subscale domains (physical functioning, bodily pain, role emotional, and mental health). Significant improvement was also seen in EQ-5D dimension of anxiety/depression at 1 year post-treatment. Patients treated with surgery (n = 21) had significant improvement in EQ-5D index score post-treatment and better EQ-5D outcomes compared to the medical group (n = 13) at 1 year post-treatment. 37.9, 41.6 and 58.6% of patients had symptoms in the cognitive, affective and somatic domains of BDI-II, respectively. There was a significant improvement in the affective domain of BDI-II at 1 year post-treatment. CONCLUSION: Both surgical and medical therapy improve HRQoL and psychological symptoms in patients with PA, with surgery providing better outcomes. This highlights the importance of early diagnosis, accurate subtyping and appropriate treatment of PA.

Effects of water stably-enriched with oxygen as a novel method of tissue oxygenation on mitochondrial function, and as adjuvant therapy for type 2 diabetes in a randomized placebo-controlled trial.

BACKGROUND: Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans. METHODS: We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water. RESULTS: ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo. CONCLUSIONS: ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.

Outcomes in unilateral primary aldosteronism after surgical or medical therapy.

CONTEXT: Studies find surgery superior to medications in the treatment of primary aldosteronism (PA). It would be ideal to compare surgical and medical therapy in patients with unilateral PA only, who have the option between these treatment modalities. However, this is challenging as most patients with unilateral PA on adrenal vein sampling (AVS) undergo surgery. OBJECTIVE: To compare outcomes of surgery and medications in patients with confirmed or likely unilateral PA. DESIGN: Retrospective cohort study of 274 patients with PA managed at two referral centres from 2000 to 2019. PATIENTS: 154 patients identified with unilateral PA using AVS and a validated clinical prediction model were treated with surgical (n = 86) or medical (n = 68) therapy. MEASUREMENTS: Primary outcome was a composite incident cardiovascular event comprising acute myocardial infarction, coronary revascularization, stroke, atrial fibrillation or congestive cardiac failure. Secondary outcomes were clinical and biochemical control. RESULTS: Cardiovascular outcomes were comparable, with the surgery group having an adjusted hazard ratio of 0.93 (95% CI: 0.32-2.67), p = .89. Both treatments improved clinical and biochemical control, but surgery resulted in better systolic blood pressure, 133.0 ± 11.7 mmHg versus 137.9 ± 14.6 mmHg, p = .02, and lower defined daily dosages of antihypertensive medications, 1.0 (IQR 0.0-2.0) versus 2.6 (IQR 0.8-4.3), p < .001. In addition, 12 of 86 patients in the surgery group failed medical therapy before opting for surgery. CONCLUSION: In patients with unilateral PA who can tolerate medications, medical therapy improves clinical and biochemical control, and may offer similar cardiovascular protection. However, surgery reduces pill burden, may cure hypertension and is recommended for unilateral PA.

Bone mineral density and trabecular bone score in elderly type 2 diabetes Southeast Asian patients with severe osteoporotic hip fractures.

INTRODUCTION: Studies show trabecular bone score (TBS) may provide information regarding bone quality independent of bone mineral density (BMD) in type 2 diabetes (DM2) patients. We analyzed our Southeast Asian severe osteoporotic hip fracture patients to study these differences. METHODS: We conducted a retrospective cross-sectional analysis of subjects admitted to Changi General Hospital, Singapore with severe osteoporotic hip fractures from 2014-2017 who had BMD performed. Electronic records were reviewed and subjects were classified as having diabetes according to the WHO 2019 criteria. DM2 patients were classified according to their HbA1c into well controlled (HbA1c < 7%) and poorly controlled (HbA1c ≥ 7%) DM2. RESULTS: Elderly patients with hip fractures present with average femur neck T scores at the osteoporotic range, however those with DM2 had higher BMD and TBS values compared to non DM2 patients. These differences were statistically significant in elderly women-poorly controlled elderly DM2 women with hip fracture had the highest total hip T-score (-2.57 ± 0.86) vs (-2.76 ± 0.96) in well controlled DM2 and (-3.09 ± 1.01) in non DM2 women with hip fracture, p < 0.001. In contrast, TBS scores were lower in poorly controlled DM2 women with hip fracture compared to well controlled DM2 women with hip fracture (1.22 ± 0.11) vs (1.24 ± 0.09), but these were still significantly higher compared to non DM2 women with hip fracture (1.19 ± 0.10), p < 0.001. In elderly men with hip fractures, univariate analysis showed no statistically significant differences in TBS or hip or LS BMD between those with poorly controlled DM2, well controlled DM2 and non DM2. The differences in TBS and BMD remained significant in all DM2 women with hip fractures even after adjustments for potential confounders. Differences in TBS and BMD in poorly controlled DM2 men with hip fractures only became significant after accounting for potential confounders. However, upon inclusion of LS BMD into the multivariate model these differences were attenuated and remained significant only between elderly women with well controlled DM2 and non DM2 women with hip fractures. CONCLUSIONS: Elderly patients with DM2 and severe osteoporosis present with hip fractures at a higher BMD and TBS values compared to non DM2 patients. These differences were significant after adjustment for confounders in all DM2 women and poorly controlled DM2 men with hip fractures, TBS differences were attenuated with the inclusion LS BMD. Further studies are needed to ascertain differences in BMD and TBS in older Southeast Asian DM2 patients with variable glycemic control and severe osteoporosis.

Dual-energy X-ray absorptiometry bone densitometry and pitfalls in the assessment of osteoporosis: a primer for the practicing clinician.

A guide to the clinician on the use of dual-energy x-ray absorptiometry bone densitometry for the management of osteoporosis and the importance of recognizing its pitfalls. PURPOSE: Osteoporosis is a major risk factor for severe fractures in the aging population worldwide, posing a serious public health issue. Dual-energy X-ray absorptiometry (DXA) is and remains the main tool for screening of osteoporosis and monitoring of osteoporosis treatment through quantitative measurement of bone mineral density (BMD). Employing DXA to measure BMD is not without pitfalls. We set out to analyze and classify the potential pitfalls of DXA acquisitions and BMD measurements encountered in clinical practice in our institution. METHODS: Technical inaccuracies and discrepancies in BMD interpretation in the history of our department were analyzed and classified into different categories of pitfalls. RESULTS: We found that major pitfalls of BMD acquisition and interpretation using DXA can be classified into technical, patient, and interpretive factors. These are illustrated with case examples. CONCLUSION: Good technical understanding of BMD measurements using DXA and recognition of potential pitfalls allow for greater technical and interpretive accuracy, which together hopefully increases the precision of osteoporosis management when practiced in accordance with established clinical guidelines.

A Case Report of Mixed Osteomalacia and Low Bone Density from Vitamin D Deficiency as a Cause of Bilateral Tibial Stress Fractures in a Young Male Military Recruit from Singapore.

Despite being a tropical country, vitamin D deficiency is common in Singapore. All young Singaporean males between the age of 18 and 21 years have to undergo mandatory military service. Stress fractures occur in military recruits, and risk factors include a sudden increase in physical activity and vitamin D deficiency. We report the bone histomorphometry findings from a case of bilateral tibial stress fractures in an 18-year-old military recruit who had vitamin D deficiency. The histomorphometry showed a mixed osteomalacia and osteoporosis pattern. This case is unique as it shows that stress fractures from a marching exercise can occur in apparently healthy well young man with vitamin D deficiency despite living in a tropical country.

Effect of multidisciplinary intensive targeted care in improving diabetes mellitus outcomes: a randomized controlled pilot study - the Integrated Diabetes Education, Awareness and Lifestyle modification in Singapore (IDEALS) Program.

BACKGROUND: There is a global pandemic of type 2 diabetes mellitus (T2DM), especially in Asia. Singapore has a prevalence of T2DM at 10.5%, which is higher than the world average of 8.8%. Multiple studies have shown that multidisciplinary, team-based, coordinated care has been associated with improved measures of quality care and reduced healthcare utilization. Patients with poor glycemic control and nephropathy are at the highest risk of developing cardiovascular complications and renal failure. In this study, we aimed to investigate the impact of intensive multidisciplinary diabetes mellitus care with patient empowerment versus routine clinical care on the rate of progression of micro and macrovascular complications and peripheral atherosclerotic burden, as measured by changes in femoral intima-media thickness (IMT) in patients with persistently elevated HbA1c and nephropathy. METHODS: The study is a single-center randomized controlled trial (RCT) with two study arms - intensive diabetes mellitus care versus routine clinical care. Patients in the intensive arm will receive care from a multidisciplinary team consisting of an endocrinologist, diabetes nurse educator, dietitian, renal pharmacist and medical social worker for counselling. In addition, patients will be provided with tools for self-care empowerment such as glucometers, blood pressure monitors and android tablets to facilitate care, monitoring and education. Patients in the routine clinical care arm will receive standard clinical care. Follow up (FU) will be for 3 years. Primary outcomes include cardiovascular events, rate of progression of nephropathy and development of end-stage renal disease. Secondary endpoints include the proportions of patients with documented improved control of cardiovascular risk factors (HbA1c, blood pressure, low density lipoprotein-C (LDL-C), reduction in body weight), frequency of hypoglycemia, hospitalization days and changes in femoral IMT. We will also examine the prevalence of peripheral atherosclerosis and the predictive value and usability of lower extremity arterial ultrasound to predict cardio-cerebrovascular events, amputation and peripheral intervention. DISCUSSION: Diabetes mellitus carries significant healthcare costs. Patients with poor glycemic control and nephropathy are at highest risk of developing cardiovascular complications and renal failure. Intensive diabetes mellitus care with patient empowerment may lead to sustained glycemic control, reduction of clinical complications and progression of nephropathy, and incidence of cardiovascular complications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03413215 . Registered on 29 January 2019.

Cross-sectional survey of biosimilar insulin utilization in Asia: The Joint Asia Diabetes Evaluation Program.

AIMS/INTRODUCTION: Biosimilar insulin can reduce treatment costs, although the extent of its use is largely unknown. We examined biosimilar insulin use and its associations with the quality of glycemic control using the Joint Asia Diabetes Evaluation register. MATERIALS AND METHODS: We carried out a cross-sectional analysis in 81,531 patients with type 1 and type 2 diabetes enrolled into the Joint Asia Diabetes Evaluation Program from 2007 to 2014. All insulin related terms are extracted from the Joint Asia Diabetes Evaluation portal, and compared clinical profiles between biosimilar and originator insulin users. Multivariate analysis was performed to assess the association of biosimilar insulin compared with originator insulin with dosage, glycated hemoglobin and hypoglycemia events. RESULTS: Amongst 81,531 patients, 20.5% (n = 16,738) were insulin-treated. In four countries with high use of biosimilar insulin, 4.7% (n = 719) of insulin users (n = 10,197) were treated with biosimilar insulin (India n = 507, 70.3%; the Philippines n = 90, 12.5%; China n = 62, 8.6%; Vietnam n = 60, 8.3%). Biosimilar insulin users were younger and had higher body mass index, glycated hemoglobin, insulin dosage and more frequent hypoglycemia than originator insulin users. These associations were non-significant after adjustment for confounders. Only age, college education, diabetes education, lipid control, physical activity and history of cardiovascular complications were independently associated with these quality measures. CONCLUSIONS: Biosimilar insulin use is not uncommon in Asia. Data exclusion due to incomplete capturing of brand names suggests possibly higher use. The multiple determinants of the quality of glycemic control call for establishment of prospective cohorts and diabetes registers to monitor the safety and efficacy of different brands of biosimilar insulin and their impacts on clinical outcomes.

High prevalence of missed opportunities for secondary fracture prevention in a regional general hospital setting in Singapore.

This study aims at assessing the gap in secondary fracture prevention at a regional general hospital setting in Singapore. Male patients have significantly lower rate of being investigated and treated for osteoporosis than their female counterparts. Vitamin D deficiency is prevalent in our population. PURPOSE: Secondary fracture prevention services are not routine in Singapore; we seek to assess the treatment gap that exists in the lack of diagnosis and treatment of osteoporosis in fragility fracture patients. METHODS: We performed a retrospective analysis of all admissions for fragility fractures between December 2013 and December 2014. Demographic data, rates of BMD performance, serum vitamin D investigation and calcium and vitamin D supplementation as well as antiresorptive initiation 1 year post admission were analysed. RESULTS: There were 125 fragility fractures in patients below 65 and 615 fractures in older patients. There was a slightly higher proportion of males in the younger population, whereas females predominated in the older population. Median vitamin D levels were low in both younger (19.1 µg/L) and older (22.0 µg/L) groups, but supplementation was lower in younger patients (4.8 versus 16.6%, p = 0.003). Rate of BMD performance was lower in younger patients (34.4 versus 64.6%, p < 0.01); there was a significant difference of BMD performance between male and female patients in the younger population (19.1 versus 52.8%, p < 0.01) which was not present in the older age group. Antiresportive initiation was significantly lower in the younger age group versus older (10.4 versus 31.5%, p < 0.01); male patients in the younger and older age groups had significantly lower antiresorptive initiation rate compared to the females. CONCLUSION: There is a significant treatment gap in diagnosis and treatment of osteoporosis in fragility fracture patients in a regional hospital setting in Singapore. Male osteoporosis remains inadequately investigated and treated in both age groups.

PILL Series. Vitamin D deficiency.

Vitamin D deficiency is common and may contribute to osteopenia, osteoporosis and falls risk in the elderly. Screening for vitamin D deficiency is important in high-risk patients, especially for patients who suffered minimal trauma fractures. Vitamin D deficiency should be treated according to the severity of the deficiency. In high-risk adults, follow-up serum 25-hydroxyvitamin D concentration should be measured 3-4 months after initiating maintenance therapy to confirm that the target level has been achieved. All patients should maintain a calcium intake of at least 1,000 mg for women aged ≤ 50 years and men ≤ 70 years, and 1,300 mg for women > 50 years and men > 70 years.

Low testosterone levels as an independent predictor of mortality in men with chronic liver disease.

OBJECTIVE: To examine the prevalence and prognostic implications of low serum testosterone levels in men with chronic liver disease. DESIGN: We conducted an observational study at a tertiary referral centre. PATIENTS AND MEASUREMENTS: Baseline serum testosterone was measured in 171 men presenting to the Victorian Liver Transplant Unit for liver transplant evaluation. Patients were followed up to liver transplant or death. RESULTS: Sixty-one per cent of men had a low total testosterone level (TT, <10 nm), and 90% of men had a low calculated free testosterone level (cFT, <230 pm). During the available observation time (median 8 months, interquartile range 4-14 months), 56 men (33%) died and 63 (37%) received a liver transplant. Fifty-two (30%) survived without a transplant. Median time to death was 8 months (range 2-13) and to liver transplant was 8 months (4-14). Baseline low TT and cFT levels both (P < 0·0001) predicted mortality. Moreover, in a Cox proportional hazard model, both low total (P = 0·02) and free testosterone (P = 0·007) levels remained predictive of death independently of established prognostic factors, such as the model for end-stage liver disease (MELD) score and serum sodium levels. A decrease in TT by 1 nm and in cFT by 10 pm was associated with an 8% increase in mortality. CONCLUSIONS: Low testosterone levels are common in men with severe liver disease and predict mortality independent of MELD, the standard score used to prioritize the allocation of liver transplants.

Failure of functional imaging with gallium-68-DOTA-D-Phe1-Tyr3-octreotide positron emission tomography to localize the site of ectopic adrenocorticotropic hormone secretion: a case report.

INTRODUCTION: The diagnostic efficacy of biochemical and imaging modalities for investigating the causes of Cushing's syndrome are limited. We report a case demonstrating the limitations of these modalities, especially the inability of functional imaging to help localize the site of ectopic adrenocorticotropic hormone secretion. CASE PRESENTATION: A 37-year-old Arabian woman presented with 12 months of progressive Cushing's syndrome-like symptoms. Biochemical evaluation confirmed adrenocorticotropic hormone -dependent Cushing's syndrome. However, the anatomical site of her excess adrenocorticotropic hormone secretion was not clearly delineated by further investigations. Magnetic resonance imaging of our patient's pituitary gland failed to demonstrate the presence of an adenoma. Spiral computed tomography of her chest only revealed the presence of a non-specific 7 mm lesion in her left inferobasal lung segment. Functional imaging, including a positron emission tomography scan using 18-fluorodeoxyglucose and gallium-68-DOTA-D-Phe1-Tyr3-octreotide, also failed to show increased metabolic activity in the lung lesion or in her pituitary gland. Our patient was commenced on medical treatment with ketoconazole and metyrapone to control the clinical features associated with her excess cortisol secretion. Despite initial normalization of her urinary free cortisol excretion rate, levels began to rise eight months after commencement of medical treatment. Repeated imaging of her pituitary gland, chest and pelvis again failed to clearly localize a source of her excess adrenocorticotropic hormone secretion. The bronchial nodule was stable in size on serial imaging and repeatedly reported as having a nonspecific appearance of a small granuloma or lymph node. We re-explored the treatment options and endorsed our patient's favored choice of resection of the bronchial nodule, especially given that her symptoms of cortisol excess were difficult to control and refractory. Subsequently, our patient had the bronchial nodule resected. The histological appearance of the lesion was consistent with that of a carcinoid tumor and immunohistochemical analysis revealed that the tumor stained strongly positive for adrenocorticotropic hormone. Furthermore, removal of the lung lesion resulted in a normalization of our patient's 24-hour urinary free cortisol excretion rate and resolution of her symptoms and signs of hypercortisolemia. CONCLUSION: This case report demonstrates the complexities and challenges in diagnosing the causes of adrenocorticotropic hormone -dependent Cushing's syndrome. Functional imaging may not always localize the site of ectopic adrenocorticotropic hormone secretion.