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Context: Although bone loss is a recognized consequence of premature ovarian insufficiency (POI), the impact on skeletal muscle health is less well-defined., Objective: To compare muscle mass and function parameters between women with POI and controls., Methods: Cross-sectional study from a tertiary health network and community between 2017 and 2023. Participants were women aged 20 to 40 years with POI associated with Turner syndrome (TS; n = 11) and spontaneous normal karyotype POI (s-POI; n = 7) compared with age- and body mass index (BMI)-matched controls (n = 45)., Results: All women with POI (mean age 28.70 ± 5.58) were using hormone therapy. Appendicular lean mass (ALM)/total fat mass and ALM/ BMI was lower in the POI group. Height-adjusted muscle mass parameters did not differ between groups. Compared with controls, women with TS and s-POI had lower muscle strength (TS 19.72 ± 4.89; s-POI 22.73 ± 5.35; controls 28.67 ± 5.65 kg; P < .001) and muscle quality (TS 11.09 ± 2.06; s-POI 10.89 ± 2.01; controls 14.10 ± 1.99 kg/kg; P < .001). Higher C-reactive protein levels, higher depression scores, and lower sex-steroid and physical activity levels were observed in women with POI ( P < .05). Creatinine/cystatin C ratio, insulin-like growth factor-1, and transthyretin did not differ between groups., Conclusion: Despite hormone therapy usage, women with POI exhibited compromised muscle parameters compared with age-matched controls. Potential contributory factors were identified. Further research is required to clarify pathophysiology and inform management strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism., Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions., Results: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended., Conclusions: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism., (© 2021 John Wiley & Sons Ltd.)

Despite well-defined criteria for radiographic diagnosis of atypical femur fractures (AFFs), missed and delayed diagnosis is common. An AFF diagnostic software could provide timely AFF detection to prevent progression of incomplete or development of contralateral AFFs. In this study, we investigated the ability for an artificial intelligence (AI)-based application, using deep learning models (DLMs), particularly convolutional neural networks (CNNs), to detect AFFs from femoral radiographs. A labelled Australian dataset of pre-operative complete AFF (cAFF), incomplete AFF (iAFF), typical femoral shaft fracture (TFF), and non-fractured femoral (NFF) X-ray images in anterior-posterior view were used for training (N = 213, 49, 394, 1359, respectively). An AFFnet model was developed using a pretrained (ImageNet dataset) ResNet-50 backbone, and a novel Box Attention Guide (BAG) module to guide the model's scanning patterns to enhance its learning. All images were used to train and internally test the model using a 5-fold cross validation approach, and further validated by an external dataset. External validation of the model's performance was conducted on a Sweden dataset comprising 733 TFF and 290 AFF images. Precision, sensitivity, specificity, F1-score and AUC were measured and compared between AFFnet and a global approach with ResNet-50. Excellent diagnostic performance was recorded in both models (all AUC >0.97), however AFFnet recorded lower number of prediction errors, and improved sensitivity, F1-score and precision compared to ResNet-50 in both internal and external testing. Sensitivity in the detection of iAFF was higher for AFFnet than ResNet-50 (82 % vs 56 %). In conclusion, AFFnet achieved excellent diagnostic performance on internal and external validation, which was superior to a pre-existing model. Accurate AI-based AFF diagnostic software has the potential to improve AFF diagnosis, reduce radiologist error, and allow urgent intervention, thus improving patient outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter R Ebeling reports financial support was provided by National Health & Medical Research Council. Peter R Ebeling reports a relationship with Amgen Inc., Sanofi, Alexion, Kyowa-Kirin that includes: funding grants. Senior author Peter R Ebeling is the Editor in Chief of Bone If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To study the prevalence of osteoporosis, falls and fractures in adults with ischaemic stroke., Methods: Observational cohort study of adults aged ≥ 50 years admitted with ischaemic stroke over a 12-month period were invited to participate in a telephone interview one-year post-stroke to ascertain falls and fracture. A Fracture Risk After Ischaemic Stroke (FRAC-stroke) score was calculated., Results: Of the 1267 patients admitted to the stroke unit between 1 January 2020 and 31 December 2020, 624 had a modified Rankin Score documented. Of these, 316 adults ≥ 50 years had ischaemic stroke and 131 consented to a telephone interview. Mean age was 72.4 ± 10.7 years and 36.6% were female. 34 patients (25.9%) had a FRAC-stroke score of ≥ 15, equating to ≥ 5% risk of fracture in the year following stroke. Eleven (8.4%) patients (6 female) had a minimal trauma fracture in the 12 months post-stroke. There was a significant difference in patients experiencing falls pre- and post-stroke (19.8% vs 31.3%, p = 0.04). FRAC-stroke score was higher in those who had a fracture post stroke compared those who did not (20.4 vs 8.9, p < 0.001). Receiver operating characteristic analysis found an area under the curve of 0.867 for FRAC-stroke score (95% CI 0.785-0.949, p < 0.005). The optimal cutoff value for FRAC-stroke score predicting fracture was 12 with a sensitivity of 90.9% and specificity of 70%., Conclusion: The FRAC-stroke score is a simple clinical tool that can be used to identify patients at high risk of fracture post-stroke who would most benefit from osteoporosis therapy. Stroke is a risk factor for fracture due to immobilisation, vitamin D deficiency and increased falls risk. This study found that a simple bedside tool, the FRAC-stroke score, can predict fracture after ischaemic stroke. This will allow clinicians to plan treatment of osteoporosis prior to discharge from a stroke unit., (© 2024. Crown.)

Objectives: To explore delayed puberty in cerebral palsy (CP) and to test the acceptability of an interventional puberty induction algorithm., Methods: A two phase cohort study in children and adolescents diagnosed with CP who have delayed puberty. Phase 1: Retrospective review of clinical records and interviews with patients who have been treated with sex-steroids and Phase 2: Prospective interventional trial of pubertal induction with a proposed algorithm of transdermal testosterone (males) or oestrogen (females). Phase 1 examined experiences with sex-steroid treatment. Phase 2 collected data on height adjusted bone mineral density (BMAD), fractures, adverse effects, mobility and quality of life over two years during the induction., Results: Phase 1, treatment was well tolerated in 11/20 treated with sex-steroids; phase 2, using the proposed induction algorithm, 7/10 treated reached Tanner stage 3 by nine months. One participant reached Tanner stage 5 in 24 months. Mean change in BMAD Z-scores was +0.27 % (SD 0.002) in those who could be scanned by dual-energy X-ray absorptiometry (DXA)., Conclusions: Delayed puberty may be diagnosed late. Treatment was beneficial and well tolerated, suggesting all patients with severe pubertal delay or arrest should be considered for sex hormone supplementation., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Women with premature ovarian insufficiency (POI) lack oestrogen, which is a key determinant of bone growth, epiphyseal closure, and bone tissue organisation. Although dual-energy X-ray absorptiometry (DXA)-derived areal bone mineral density (BMD) remains the gold standard for fracture risk evaluation, it does not fully characterise the skeletal abnormalities present in these women. Hence, we aimed to assess hip/femur anatomy, strength, and geometry and femoral alignment using advanced hip analysis (AHA)., Methods: We conducted a cross-sectional, case-control study including 89 women with spontaneous normal karyotype POI (s-POI) or iatrogenic POI (i-POI), aged 20-50 years compared with 89 age- and body mass index (BMI)-matched population-based female controls. Hip anatomy, strength, geometrical parameters, and femur alignment were measured using hip DXA images and Lunar AHA software. Femoral orientation angle (FOA) was quantified as the overall orientation of the femur with respect to the axis of the forces transmitted from the upper body., Results: The median age of POI diagnosis was 35 (18-40) years; the mean POI duration at the time of DXA was 2.07 (range 0-13) years, and 84% of POI women received oestrogen therapy. Areal BMD at all sites was significantly lower in the POI group (all P < .05). Indices of compressive and bending strength were lower in women with POI compared with controls, specifically the cross-sectional area (CSA, mm2) and section modulus (SM, mm3) (139.30 ± 29.08 vs 157.29 ± 22.26, P < .001 and 665.21 ± 129.54 vs 575.53 ± 150.88, P < .001, respectively). The FOA was smaller (124.99 ± 3.18) in women with POI as compared with controls (128.04 ± 3.80; P < .001) at baseline and after adjusting for height and femoral neck BMD., Conclusion: Alongside lower BMD at multiple sites, the femora of women with POI demonstrate reduced strength and a misalignment with forces transmitted from the upper body. Further research is needed to establish the role of these newly identified features and their role in fracture risk prediction in this population., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Objective: To formulate clinical consensus recommendations on the presentation, assessment, and management of primary hyperparathyroidism (PHPT) in adults., Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing nine key questions., Results: PHPT is a biochemical diagnosis. Serum calcium should be measured in patients with suggestive symptoms, reduced bone mineral density or minimal trauma fractures, and in those with renal stones. Other indications are detailed in the manuscript. In patients with hypercalcaemia, intact parathyroid hormone, 25-hydroxy vitamin D, phosphate, and renal function should be measured. In established PHPT, assessment of bone mineral density, vertebral fractures, urinary tract calculi/nephrocalcinosis and quantification of urinary calcium excretion is warranted. Parathyroidectomy is the only definitive treatment and is warranted for all symptomatic patients and should be considered for asymptomatic patients without contraindications to surgery and with >10 years life expectancy. In patients who do not undergo surgery, we recommend annual evaluation for disease progression. Where the diagnosis is not clear or the risk-benefit ratio is not obvious, multidisciplinary discussion and formulation of a consensus management plan is appropriate. Genetic testing for familial hyperparathyroidism is recommended in selected patients., Conclusions: These clinical consensus recommendations were developed to provide clinicians with contemporary guidance on the assessment and management of PHPT in adults. It is anticipated that improved health outcomes for individuals and the population will be achieved at a decreased cost to the community., (© 2021 John Wiley & Sons Ltd.)

Objectives: Low skeletal muscle index (SMI) is common in inflammatory bowel disease (IBD) but has an uncertain relationship with active intestinal inflammation. This study evaluated body composition by whole-body dual-energy X-ray absorptiometry (DXA) in patients with IBD and healthy controls to enable the value of formal body composition analysis to be judged., Methods: Patients with IBD and sex/age-matched controls prospectively underwent full body composition assessment by DXA, assessment by BMI, eating questionnaires and handgrip strength. Disease activity was assessed by faecal calprotectin (active ≥150 µg/g). A cohort undergoing biologic induction therapy were assessed at baseline and after ≥13 weeks., Results: Total fat mass was higher in 54 patients with IBD (56% Crohn's disease, 61% male) than in 30 controls (median 25.1 vs. 18.7 kg, P  = 0.042). DXA offered little more than BMI. Low SMI was more common than in controls (15% vs. 0%, P  = 0.027). A normal BMI was seen in many patients with low SMI and handgrip strength was a poor marker of change in SMI. Body composition was similar in 28 patients with active vs. 22 with inactive disease. However, SMI increased specifically by 9.7% ( P  = 0.004) and BMI by 6.4% ( P  = 0.012) in 9 responders to therapy., Conclusion: DXA identifies many patients with reduced SMI who are not detected by standard methodologies. While disease activity is not associated with low SMI, resolution of inflammation leads to improved SMI. The potential for recognition of such patients to influence therapeutic decisions underlines the need for DXA assessment in clinical practice., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Disturbance of skeletal muscle mass has clinically important implications in patients with inflammatory bowel disease (IBD), but accurate quantification requires radiation-intense techniques., Aims: We aimed to compare point-of-care muscle assessments and their change with therapy with those using reference-standard whole-body dual energy X-ray absorptiometry (DXA)., Methods: Adult patients with IBD and healthy controls underwent prospective assessment of muscularity by ultrasound of the dominant arm and both thighs, bioelectrical impedance analysis (BIA), anthropometric measurements, and DXA. Patients with active IBD were assessed again ≥13 weeks after initiating biologic induction therapy., Results: In 54 patients with IBD and 30 controls, all muscle assessments correlated significantly with DXA-derived skeletal muscle index (SMI). In IBD, ultrasound of the arm and legs had the best agreement with DXA-derived SMI (mean difference 0 kg/m 2 , 95% limits of agreement -1.3 to 1.3), while BIA overestimated DXA-derived SMI by 1.07 (-0.16 to +2.30) kg/m 2 . In 17 patients who underwent biologic therapy, the percentage change in DXA-derived SMI correlated significantly with the percentage change in all other muscle assessment techniques. Responders (n = 9) increased SMI from baseline to follow-up when derived from DXA (mean 7.8-8.5 kg/m 2 , p = 0.004), ultrasound of the arm and legs (300-343 cm 2 , p = 0.021) and BIA (9.2-9.6 kg/m 2 , p = 0.011)., Conclusions: Ultrasound of the arm and legs out-performed other point-of-care methods in its accuracy of measuring muscle mass. All methods, except mid-arm circumference, were responsive to therapy-induced change. Ultrasound is the preferred non-invasive test for measuring muscle mass in patients with IBD., (© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Based on the current paradigm, a healthy bone is one with adequate mass without microarchitectural decay. However, these two features may not be sufficient to ensure that a bone is healthy. In addition, components must be correctly assembled and aligned. This ensures " the right amount of bone, at the right place " and thus, an optimal cohesion or interplay between constituents. Disorganization may be an independent contributor to bone abnormalities including fragility fractures. Indeed, many bone diseases may be characterized by the presence of disorganized bone, including osteogenesis imperfecta, hypophosphatasia, and atypical femur fractures (AFFs). Despite its likely importance, currently, there are no tools to quantify disorganization in vivo. We address this unmet need by describing a novel method for quantifying bone disorganization from X-ray images. Disorganization is quantified as variations in the orientation of bone components in relation to a target reference point. True disorganization created by disarranging (misplacing) pixels within the bone served as "gold standard." To further validate the method in clinical settings, we compared disorganization in three groups of femurs: (i) femurs of women with AFFs ( n  = 9); (ii) fracture-free femurs contralateral to AFFs ( n  = 9); and (iii) fracture-free femurs from controls ( n  = 25). There was excellent agreement between measured disorganization and "gold standard," with R 2 values ranging from 0.84 to 0.99. Precision error ranged from 1.72% to 4.69%. Disorganization produced by abnormalities associated with AFFs was accurately captured. Disorganization level was lowest in fracture-free control femurs, higher in fracture-free contralateral femurs to AFFs, and highest in femurs with AFFs (all p  < 0.0001). Quantification of disorganization, a novel biomarker, may provide novel insights into the pathogenesis of metabolic bone diseases beyond that provided by bone mineral density (BMD) or microarchitecture. We provide evidence that measurement of disorganization is likely to help identify patients at risk for fractures, especially in those poorly explained by BMD or microarchitecture such as AFFs. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Objective: Patients with end-stage kidney disease (ESKD) caused by type 1 diabetes mellitus (T1DM) have a heightened fracture risk. Bone mineral density (BMD) may predict fracture less accurately in ESKD than in patients with chronic kidney disease (CKD) stages 1-3b or the general population. Alternate, readily available imaging modalities are needed to improve ESKD fracture risk assessment. This study aimed to assess dual-energy X-ray absorptiometry (DXA)-derived BMD, the trabecular bone score (TBS) and advanced hip analysis parameters in patients with ESKD due to T1DM and to compare their results with those of patients with ESKD from other causes., Methods: We compared the DXA-derived TBS, hip cortical thickness (CT) and femoral neck (FN) buckling ratio (BR), an index of FN stability, of patients with T1DM and ESKD undergoing simultaneous pancreas kidney transplantation, patients with ESKD from other causes receiving kidney transplants and population reference ranges., Results: Of 227 patients with ESKD, 28% had T1DM and 65% were male. Compared with other ESKD patients, patients with T1DM were younger (42 ± 7.7 vs 51 ± 13.8 years), had shorter dialysis duration (24.4 ± 21 vs 42.6 ± 40 months), had higher HbA1c (7.9 ± 1.57% vs 5.4 ± 0.95%) and had lower BMI (25 ± 6 vs 27 ± 5 kg/m2). They had lower spine, hip and UD radius BMD Z-scores (all P ≤ 0.001), TBS (1.33 ± 0.12 vs 1.36 ± 0.12; P = 0.05), CT at the FN (P = 0.03), calcar (P = 0.006) and shaft (P < 0.001) and higher BR (10.1±7.1 vs 7.7±4; P = 0.006). All ESKD parameters were lower than population-based reference ranges (P < 0.001). Adjusting for age, sex, dialysis vintage and weight, prevalent vertebral fractures in patients with T1DM and ESKD were associated with higher BR (odds ratio (OR): 3.27 (95% CI: 1.19-8.92), P = 0.002) and lower FN CT (OR: 3.70 (95% CI: 1.13-12.50))., Conclusion: Patients with ESKD and T1DM have reduced TBS, reduced CT and increased BR compared with other ESKD patients. Prospective study of these parameters is warranted to determine their utility in fracture risk prediction and management., Significance Statement: Patients with ESKD and T1DM have an elevated fracture risk due to decreased bone strength. As an adjunct to BMD, evaluating dual-energy X-ray absorptiometry parameters that incorporate structural change may have greater value in patients with ESKD and T1DM than in the general population. In this study, patients with ESKD due to T1DM had lower BMD, lower trabecular bone scores, more severe loss of CT and higher BR than other patients with ESKD and people from the general population. Both lower CT and higher BR were associated with prevalent vertebral fractures in patients with T1DM and ESKD. Changes to these parameters should be evaluated for incident fracture prediction.

Background: Low bone density (BMD) and fractures commonly affect women with premature ovarian insufficiency (POI). However, bone microarchitecture and body composition data are lacking., Objective: To assess and characterise musculoskeletal phenotype and effects of oestrogen replacement therapy (ERT) in women with POI., Method: Cross-sectional and longitudinal studies of 60 normal karyotype women with POI, aged 20-40 years, from 2005-2018. Dual x-ray absorptiometry (DXA)-derived spinal (LS) and femoral neck (FN) BMD, trabecular bone score (TBS), appendicular lean mass (ALM), total fat mass (TFM), and fracture prevalence were compared with 60 age-, and BMI-matched population-based controls. Longitudinal changes in bone and body composition variables and ERT effects were analysed using linear mixed models over a median duration of 6 years., Results: Women with POI were subdivided into spontaneous (s)-POI (n=25) and iatrogenic (i)-POI (n=35). Median(range) age of POI diagnosis was 34 (10-40) years with baseline DXA performed at median 1(0-13) year post-diagnosis. ERT was used by 82% women (similar for both POI groups). FN-BMD were lowest in s-POI (p<0.002). Low TBS was more common in s-POI [(44%), p=0.03], versus other groups. LS-BMD and ALM were lower in both s-POI and i-POI groups than controls (p<0.05). Fracture prevalence was not significantly different: 20% (s-POI), 17% (i-POI), and 8% (controls) (p=0.26). Longitudinal analysis of 23 POI women showed regular ERT was associated with ALM increment of 127.05 g/year (p<0.001) and protected against bone loss. However, ERT interruption was associated with annual reductions in FN BMD and TBS of 0.020g/cm 2 and 0.0070 (p<0.05), respectively., Conclusion: Deficits in BMD, trabecular microarchitecture, and lean mass were present in women with POI. However, regular ERT protected against declines in bone variables, with an increase in ALM. Assessment of skeletal and muscle health, and advocating ERT adherence, is essential in POI to optimise musculoskeletal outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Samad, Nguyen, Hashimura, Pasco, Kotowicz, Strauss, Ebeling, Milat and Vincent.)

Objective: Glucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture-risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals., Design: A narrative review is presented, following a systematic search of the literature from 2000 to 2021., Results: Our current appreciation of glucocorticoid-induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood., Conclusion: Through this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults., (© 2021 John Wiley & Sons Ltd.)

Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, > 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged < 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ -2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoporosis in premenopausal women and men younger than 50 years is challenging to diagnose and treat. There are many barriers to optimal management of osteoporosis in younger adults, further enhanced by a limited research focus on this cohort. Herein we describe dilemmas commonly encountered in diagnosis, investigation, and management of osteoporosis in younger adults. We also provide a suggested framework, based on the limited available evidence and supported by clinical experience, for the diagnosis, assessment, and management of osteoporosis in this cohort. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: MH has no conflicts of interest or disclosures to declare. AC has received research support from Eli Lilly and Amgen. PRE has received research funding form Amgen, Eli‐Lilly, and Alexion, and honoraria from Amgen. FM has no conflicts of interest or disclosures to declare., (© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Introduction: Bone mineral density, measured by dual X-ray absorptiometry (DXA), is the gold standard for diagnosis of osteoporosis. The utility of DXA relies on the accuracy of scan acquisition, interpretation of data, and the adequacy of reports. The International Society for Clinical Densitometry (ISCD) has published guidelines regarding minimum reporting guidelines. This study assessed whether DXA reports for patients receiving care at an academic teaching hospital adhere to these reporting standards, and determine whether differences exist depending on patient factors and the imaging service., Methods: Patients aged ≥18 years, receiving care at specialist outpatient clinics between January 1, 2018 and December 31, 2019, with a DXA report available, were eligible for inclusion. DXA reports were manually reviewed for adherence to ISCD guidelines, with each criterion scored as one point, giving a total score of 14 for baseline DXA scans and 18 for repeat DXA scans. The score was then converted to a percentage., Results: Of 459 DXA scans included, 214 were performed internally at our hospital and 245 performed at 23 external imaging services. Mean (SD) patient age was 60 (16.3) years, and 75.8% were female. The overall median (IQR) report score was 57.1% (42.9, 82.4). ISCD criteria with the lowest scores were recommendation and timing of future DXA scans (included in 1.1% of reports) and investigation for secondary causes of osteoporosis (included in 1.2% of reports). Reports performed internally had significantly higher scores than those performed externally, after adjusting for age, sex, indication, and type of scan (incidence rate ratio 1.83, 95% confidence interval 1.77, 1.89). Baseline DXA reports had slightly higher scores than repeat DXA scans, and, among external imaging services, rural services had higher scores than metropolitan services., Conclusion: This study, the largest comprehensive evaluation of DXA reports, highlights significant deficiencies and variation in report standards between imaging services. This has potential implications for osteoporosis diagnosis and management., (Copyright © 2020 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

This study evaluated mediators of fracture risk in postmenopausal women with type 1 (T1D) and type 2 diabetes (T2D), over a 15-year follow-up period. This study provides evidence that the increased fracture risk in women with T1D or T2D is partially explained by falls. Furthermore, a shorter reproductive lifespan in women with T1D contributes modestly to fracture risk in this cohort., Purpose: Skeletal fragility is associated with diabetes mellitus, while limited estrogen exposure during the reproductive years also predisposes to lower bone mass and higher fracture risk. We aimed to determine osteoporosis diagnosis, fall and fracture rates in women with type 1 (T1D) and type 2 (T2D) diabetes mellitus, and explore mediators of the diabetes-fracture relationship., Methods: Prospective observational data drawn from the Australian Longitudinal Study in Women's Health (ALSWH) from 1996 to 2010. Women were randomly selected from the national health insurance database. Standardized data collection occurred at six survey time points, with main outcome measures being self-reported osteoporosis, incident fracture, falls, and reproductive lifespan. Mediation analyses were performed to elucidate relevant intermediaries in the diabetes-fracture relationship., Results: Exactly 11,313 women were included at baseline (T1D, n = 107; T2D, n = 333; controls, n = 10,873). A total of 885 new cases of osteoporosis and 1099 incident fractures were reported over 15 years. Women with T1D or T2D reported more falls and fall-related injuries; additionally, women with T1D had a shorter reproductive lifespan. While fracture risk was increased in women with diabetes (T1D: OR 2.28, 95% CI 1.53-3.40; T2D: OR 2.40, 95% CI 1.90-3.03), compared with controls, adjustment for falls attenuated the risk of fracture by 10% and 6% in T1D and T2D, respectively. In women with T1D, reproductive lifespan modestly attenuated fracture risk by 4%., Conclusion: Women with T1D and T2D have an increased risk of fracture, which may be partially explained by increased falls, and to a lesser extent by shorter reproductive lifespan, in T1D.

Background: Patients with end-stage kidney disease (ESKD) have higher fracture rates and post-fracture mortality than the general population, but bone mineral density by dual-energy X-ray absorptiometry (DXA) is less predictive of fracture in this patient group. Bone biopsy and high-resolution imaging indicate that cortical thickness (CT) is reduced and cortical porosity is increased in ESKD. The aim of this study was to assess cortical parameters using DXA in patients with ESKD. It was hypothesized that these parameters would show deterioration and be associated with fracture., Methods: Using advanced hip analysis, normal age-related ranges were determined from 752 female and 861 male femur scans and were compared with scans of 226 patients with ESKD at the time of transplantation., Results: Compared with controls, female patients had lower mean±SD CT (mms) at the femoral neck (FN) (2.59 ± 1.42 versus 5.23 ± 1.85), calcar (3.46 ± 1.07 versus 5.09 ± 1.30) and shaft (4.42 ± 1.21 versus 7.44 ± 2.07; P < 0.001 for each), and buckling ratios were higher (8.21 ± 4.6 versus 3.63 ± 1.42; P < 0.001), indicating greater FN instability. All findings were similar for men. Prevalent fracture was documented in 28.8% of patients; 12.4% vertebral only, 8.4% non-vertebral only and 8% vertebral plus non-vertebral. In adjusted models, each 1 SD reduction in FN CT and increase in the buckling ratio was associated with a respective 1.73 (1.22-2.46)- and 1.82 (1.49-2.86)-fold increase in the risk of prevalent vertebral fracture., Conclusions: In patients with ESKD, DXA-derived cortical parameters are markedly abnormal compared with age- and sex-matched controls. These parameters should be assessed for incident fracture prediction and targeting treatment., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Type 1 diabetes (T1D) is associated with reproductive dysfunction, particularly in the setting of poor metabolic control. Improvements in contemporary management ameliorate these problems, albeit at the cost of increased exogenous insulin and rising obesity, with emerging reproductive implications., Objective: To evaluate changes in body mass index (BMI) and the relationship between obesity, menstrual irregularity and polycystic ovary syndrome (PCOS) in young women with T1D, compared with controls., Methods: Longitudinal observational study using data from the Australian Longitudinal Study in Women's Health of the cohort born in 1989-95, from 2013 to 2015. Three questionnaires administered at baseline and yearly intervals were used to evaluate self-reported menstrual irregularity, PCOS and BMI., Results: Overall, 15 926 women were included at baseline (T1D, n = 115; controls, n = 15 811). 61 women with T1D and 8332 controls remained at Year 2. Median BMI was higher in women with type 1 diabetes (25.5 vs 22.9 kg/m 2 , P < .001), where over half were overweight or obese (54.4% vs 32.9%, P < .001). Median BMI increased by 1.11 and 0.45 kg/m 2 , in the T1D and control groups, respectively. T1D was independently associated with an increased risk of menstrual irregularity (RR 1.22, 95% CI 1.02-1.46) and PCOS (RR 2.41, 95% CI 1.70-3.42). Obesity conferred a 4-fold increased risk of PCOS, compared to those with normal BMI (RR 3.93, 95% CI 3.51-4.42)., Conclusions: Obesity is prevalent amongst women with T1D and may be a key contributor to the higher risk of menstrual irregularity and PCOS in this cohort, representing an important opportunity for prevention and intervention., (© 2020 John Wiley & Sons Ltd.)

Accelerated bone loss and muscle decline coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This article is the first of a two-part review which describes estrogen signaling in muscle and its role in musculoskeletal health and disease. Current evidence regarding the utility of available diagnostic tests and therapeutic options is also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In addition to bone loss, muscle decay and dysfunction is now increasingly recognized. Nevertheless, there is a paucity of validated tools to assess muscle parameters. There is a growing need to acknowledge bone-muscle codependence to design new therapies which target both muscle and bone, resulting in improved physical performance and reduced morbidity and mortality. More high-quality research and international collaborations are needed to address the deficiencies in our understanding and management of musculoskeletal health in women with POI., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Accelerated bone loss and muscle loss coexist in women with premature ovarian insufficiency (POI), but there are significant gaps in our understanding of musculoskeletal health in POI. This review describes estrogen signaling in bone and its role in skeletal health and disease. Possible mechanisms contributing to bone loss in different forms of POI and current evidence regarding the utility of available diagnostic tests and therapeutic options are also discussed. A literature review from January 2000 to March 2020 was conducted to identify relevant studies. Women with POI experience significant deterioration in musculoskeletal health due to the loss of protective effects of estrogen. In bone, loss of bone mineral density (BMD) and compromised bone quality result in increased fracture risk; however, tools to assess bone quality such as trabecular bone score (TBS) need to be validated in this population. Timely initiation of HRT is recommended to minimize the deleterious effects of estrogen deficiency on bone in the absence of contraindications; however, the ideal estrogen replacement regimen remains unknown. POI is associated with compromised bone health, regardless of the etiology. Ongoing research is warranted to refine our management strategies to preserve bone health in women with POI., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Asian race, younger age, higher body mass index (BMI) and antiresorptive drugs have all been associated with atypical femur fractures (AFFs). This increased risk of AFF in Asians is important as by 2050, >50% of hip fractures globally will occur in Asia, with an increased demand for antiresorptive drugs being likely. It is also currently unclear whether AFF risk is increased in all Asian subgroups. We therefore aimed to identify the incidence of AFFs in an Australian tertiary hospital, the contribution of ethnic origin to AFF risk, and determine other clinical risk factors for AFF. From January 1, 2009 to December 31, 2017, 97 AFFs (82 complete and 15 incomplete) occurred in 71 individuals in the overall study population of 204,358. Patients with AFF were more likely to be female (88.7% vs 69.1%, p < 0.001) and younger [median (IQR): 74(52-92) years vs 83(75-88) years, p < 0.001] than the "typical" femur fracture group (n = 3330). The cumulative incidence rate of AFF was 4.2 per 100,000 person-years, far lower than for any ICD-10 AM coded "typical" femur fracture (202.9 per 100,000 person-years). Asians were 3.4 (95%CI, 2.1-5.6) times more likely to sustain an AFF than non-Asians, the highest incidence being in those from South East Asian countries (16.6 per 100,000 person years), suggesting differences in risk between Asian countries. In the nested case-control study, bisphosphonate use was an independent association with AFF development. We conclude Asian ethnicity is an important association with AFF in this large Australian cohort., Competing Interests: Declaration of competing interest PRE: has received research funding or honoraria from Amgen, Eli-Lilly and Theramex. AJV has received research funding or honoraria from Amgen. RZ has received research funding or honoraria from Amgen, MSD, Servier, GENZYME & AKP. He is a Director of StraxCorp Pty Ltd. All other authors state they do not have other conflicts of interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To determine whether geographic variation exists in osteoporosis knowledge, management, and barriers to care in the setting of premature ovarian insufficiency (POI), among general practitioners (GPs) and women with POI., Methods: Australian GPs completed an online questionnaire regarding osteoporosis knowledge, barriers to care and educational preferences for managing osteoporosis in POI. Women with POI/early menopause (EM) completed an online questionnaire regarding osteoporosis knowledge, risk factors and health beliefs. Clinicians and consumers in metropolitan areas were compared to those in rural areas., Results: Of 688 GP respondents, 62.2% practised in major capital cities, 13.1% in major regional cities, 7.8% in regional centres, 8.7% in rural areas and 8.1% in remote areas. Mean ± SD osteoporosis knowledge score was 9.1 ± 1.5/13, with no difference by location. Forty-one percent of GPs reported barriers to care which varied by location. Of 316 women with POI/EM, 61.1% lived in metropolitan, 22.5% in regional, 11.7% in rural and 4.4% in remote locations. The mean osteoporosis knowledge score was 8.2 ± 3.1/20, with lower scores in women living in rural and remote versus metropolitan locations (difference - 1.3; 95% CI - 2.3, - 0.25; p = 0.02). Women in rural areas were less likely to use vitamin D supplements and more likely to have a family history of osteoporosis (both p < 0.05)., Conclusions: GP knowledge gaps and specific, location-dependent care barriers for osteoporosis in POI were identified. Geographic differences in osteoporosis knowledge and risk factors exist in women with POI/EM. These factors require consideration when designing programs to improve bone health in POI.

Context: Cerebral palsy (CP) is a motor disorder affecting movement, muscle tone and posture due to damage to the foetal or infant brain. The subsequent lack of ambulation, nutritional deficiencies, anticonvulsant use and hormonal deficiencies have been implicated in the low bone mass associated with this condition., Objective: To assess changes in areal bone mineral density (aBMD) during adolescence and young adulthood in individuals with CP. The effect of ambulation, nutrition, hypogonadism on longitudinal changes in aBMD is also examined., Design: Retrospective longitudinal study., Setting and Participants: Forty-five subjects with CP who had longitudinal dual-energy X-ray absorptiometry (DXA) scans at a single tertiary hospital between 2006 and 2018., Results: Mean age at first DXA was 19.4 years (range: 10-36 years), 57.8% were male and 80% were nonambulatory. The mean Z-scores at baseline were <-2.0 at all sites - lumbar spine (LS), femoral neck (FN), total hip (TH) and total body (TB). The median change in aBMD was +1.2%-1.9% per year in all subjects but in those <20 years of age, the median change was 4%-8% per year. Z-scores across all sites remained stable over time. Reduced functional state as measured by the gross motor functional classification scale (GMFCS) had a small negative effect on aBMD over time., Conclusion: In adolescents with CP, low bone mass was evident from the baseline DXA. However, significant bone accrual occurred during the second decade, followed by bone maintenance in young adulthood. Future studies should focus on optimizing bone health from early childhood., (© 2019 John Wiley & Sons Ltd.)

Background: Osteoporosis is a key concern of women with premature ovarian insufficiency (POI) but there are gaps in clinicians' knowledge of bone health., Objectives: 1) To systematically evaluate the quality of clinical practice guidelines (CPGs) related to POI and bone health; 2) to formulate a management algorithm., Methods: Systematic search for English-language clinical practice guidelines (CPGs) from August 2012 to August 2017 (PROSPERO registration number CRD42017075143). Four reviewers independently evaluated the methodological quality of included CPGs using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument (comprising 23 items across 6 domains) using the My AGREE PLUS platform. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). Individual domain and total percentage scores were calculated for each CPG. Data from high-scoring CPGs were extracted and summarised to develop the algorithm, with subsequent refinement via expert and end-user clinician feedback., Results: The systematic search yielded 16 CPGs for appraisal. ICC values were 0.71 (good) to 0.95 (very good). The quality of the CPGs was appraised as "high" in 4 cases, "average" in 8 and "low" in 4. High-quality CPGs had mean total scores of 82-96%. Recommendations from high-quality CPGs were summarised into 6 categories: screening; risk factors; initial assessment; diagnosis; subsequent assessment; and management. Only "management" had recommendations (moderate-quality to low-quality evidence) from all four high-quality CPGs. Limitations are reflected in the algorithm., Conclusions: Most CPGs regarding bone health and POI are of average to poor quality. High-quality CPGs have evidence limitations and recommendation gaps indicating the need for further research., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Osteoporosis associated with premature ovarian insufficiency (POI) and early menopause (EM) is a major concern for women. We aimed to (a) identify information and knowledge gaps and behaviours regarding bone health in women with POI/EM and (b) co-design an osteoporosis fact sheet., Design: Mixed-methods study: survey of women and online resource appraisals to develop and refine, using semi-structured interviews, an osteoporosis fact sheet., Patients: Women with POI/EM (menopause before ages 40 and 45 years respectively)., Measurements: Demographics, comorbidities, information needs, calcium intake, exercise, osteoporosis knowledge (OKAT), beliefs and self-efficacy, DISCERN appraisal (validated scales)., Analysis: descriptive statistics, logistic regression and thematic analysis of interviews., Results: Median age of survey respondents (n = 316) was 54(IQR47-63) years, median age of menopause was 40(IQR38-43) years, and osteoporosis diagnosis was reported in 19%. Most reported inadequate dietary calcium intake (99%) and exercise (65%). Median OKAT score 8 [IQR6-10]/19 indicated knowledge gaps regarding risk factors and treatment options. Adjusting for age and education, OKAT predicted calcium intake (OR 1.126 [CI 1.035-1.225]; P = 0.006) and screening (OR 1.186 [CI 1.077-1.305]; P = 0.001); beliefs predicted screening (OR 1.027 [CI 1.004-1.050]; P = 0.019); and self-efficacy predicted calcium intake (OR1.040 (CI 1.013-1.069); P = 0.003] and exercise (OR 1.117 [CI 1.077-1.160]; P < 0.001). Current online resources have deficiencies. Five themes identified from two interview rounds (n = 10/ round) were as follows: content, emotional response, design, perceived usefulness and clinical considerations. The final fact sheet was considered acceptable and useful in addressing knowledge gaps, promoting information-seeking, impacting behaviours and facilitating healthcare discussions., Conclusion: A co-designed fact sheet is acceptable and addresses identified osteoporosis knowledge gaps in women with POI/EM., (© 2019 John Wiley & Sons Ltd.)

Introduction: Representatives appointed by relevant Australian medical societies used a systematic approach for adaptation of guidelines (ADAPTE) to formulate clinical consensus recommendations on assessment and management of bone health in women with oestrogen receptor-positive early breast cancer receiving endocrine therapy. The current evidence suggests that women receiving adjuvant aromatase inhibitors and pre-menopausal woman treated with tamoxifen have accelerated bone loss and that women receiving adjuvant aromatase inhibitors have increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven anti-fracture benefit in post-menopausal women receiving aromatase inhibitors for hormone receptor-positive breast cancer., Main Recommendations: Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density measurement, with monitoring based on risk factors. Weight-bearing exercise and vitamin D and calcium sufficiency are recommended routinely. Anti-resorptive treatment is indicated in women with prevalent or incident clinical or morphometric fragility fractures, and should be considered in women with a T score (or Z score in women aged < 50 years) of < - 2.0 at any site, or if annual bone loss is ≥ 5%, considering baseline bone mineral density and other fracture risk factors. Duration of anti-resorptive treatment can be individualised based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with anti-resorptive treatments are low., Changes in Management as Result of the Position Statement: Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimised by non-pharmacological intervention and, where indicated, anti-resorptive treatment, in an individualised, multidisciplinary approach., (© 2019 AMPCo Pty Ltd.)

The metabolic abnormalities affecting bone in the setting of chronic kidney disease (CKD) are complex with overlapping and interacting aetiologies and have challenging diagnostic and management strategies. Disturbances in calcium, phosphate, fibroblast growth factor 23, parathyroid hormone concentrations and vitamin D deficiency are commonly encountered and contribute to the clinical syndromes of bone disorders in CKD, including hyperparathyroidism, osteomalacia, osteoporosis and adynamic bone disease. Mineral and bone abnormalities may also persist or arise de novo post-renal transplantation. The Kidney Disease Improving Global Outcomes organisation describes these mineral metabolism derangements and skeletal abnormalities as 'CKD Mineral and Bone Disorder'. Patients with this disorder have an increased risk of fracture, cardiovascular events and overall increased mortality. In light of the recently updated 2017 guidelines from the Kidney Disease Improving Global Outcomes, we present a clinical case-based discussion to highlight the complexities of investigating and managing the bone health of patients with CKD with a focus on these updates., (© 2018 Royal Australasian College of Physicians.)

Purpose of Review: Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD., Methods: EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3-5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools., Recent Findings: Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21-3.38) and femoral neck (SMD 3.29; 95% CI 3.21-3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.

Context: Bone fragility in cerebral palsy (CP) is secondary to a complex interplay of functional, hormonal, and nutritional factors that affect bone remodelling. A greater understanding of bone microarchitectural changes seen in CP should assist therapeutic decision making., Objective: To examine the relationship between trabecular bone score (TBS), BMD and fractures in adults with CP; the influence of clinical factors and body composition on bone microarchitecture were explored., Design: Retrospective cross-sectional study., Setting and Participants: 43 adults (25 male) with CP of median age 25 years (interquartile range 21.4-33.9) who had evaluable dual-energy X-ray absorptiometry imaging of the lumbar spine from a single tertiary hospital between 2005-March 2018., Results: 24/43 (55.8%) of patients had TBS values indicating intermediate or high risk of fracture (<1.31). TBS correlated with areal BMD at the lumbar spine, femoral neck and total body. TBS was significantly associated with arm and leg lean mass, with adjustment for age, gender and height (adjusted R 2  = 0.18, p = 0.042 for arm lean mass; adjusted R 2  = 0.19, p = 0.036 for leg lean mass). There was no difference in TBS when patients were grouped by fracture status, anticonvulsant use, gonadal status or use of PEG feeding. TBS was lower in non-ambulatory patients compared with ambulatory patients (1.28 vs 1.37, p = 0.019)., Conclusions: Abnormal bone microarchitecture, as measured by TBS, was seen in >50% of young adults with CP. TBS correlated with both areal BMD and appendicular lean mass. Maintaining muscle function is likely to be important for bone health in young adults with CP and needs to be confirmed in further studies., (Copyright © 2018. Published by Elsevier Inc.)

Context: Turner syndrome (TS) is associated with short stature, gonadal failure, and fractures. Spinal trabecular bone score (TBS) is a novel bone imaging modality that has not been evaluated in TS., Objective: To evaluate TBS in TS and its association with bone mineral density (BMD), prevalent fracture, and risk factors., Design and Setting: Longitudinal study of TS from a single tertiary hospital between 2006 and 2017., Patients or Other Participants: Fifty-eight subjects with TS aged 20 to 49 years who underwent dual-energy X-ray absorptiometry (DXA)., Main Outcome Measures: TBS, DXA parameters, and prevalent fractures were investigated., Results: Normal, partially degraded, and degraded TBSs were observed in 39 (67%), 15 (26%), and four (7%) subjects, respectively. High rates of prescribed estrogen replacement therapy (ERT) with stable TBS and BMD were observed during follow-up. TBS was positively correlated with spine and femoral neck (FN) BMD and Z-scores (all P < 0.05) and negatively correlated with age (-0.004 per year; P = 0.014) and delay in ERT initiation in women with primary amenorrhea (-0.010 per year; P < 0.001). Fractures were present in 17 (31%) subjects. Low TBS had a significantly higher area under the receiver operator curve for predicting prevalent fracture than low bone mass at either the spine or FN (P < 0.05). Subjects with no history of fracture were more likely to have a normal TBS (P = 0.023)., Conclusions: BMD and TBS can be preserved with early initiation and continued use of ERT. TBS may provide additional fracture risk prediction to standard DXA parameters in TS and needs to be validated in larger prospective studies.

To formulate clinical consensus recommendations on bone health assessment and management of women with oestrogen receptor-positive early breast cancer receiving endocrine therapy, representatives appointed by relevant Australian Medical Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing 5 key questions. Women receiving adjuvant aromatase inhibitors and the subset of premenopausal woman treated with tamoxifen have accelerated bone loss and increased fracture risk. Both bisphosphonates and denosumab prevent bone loss; additionally, denosumab has proven antifracture benefit. Women considering endocrine therapy need fracture risk assessment, including clinical risk factors, biochemistry and bone mineral density (BMD) measurement, with monitoring based on risk factors. Weight-bearing exercise, vitamin D and calcium sufficiency are recommended routinely. Antiresorptive treatment should be considered in women with prevalent or incident clinical or morphometric fractures, a T-score (or Z-scores in women <50 years) of <-2.0 at any site, or if annual bone loss is ≥5%, considering baseline BMD and other fracture risk factors. Duration of antiresorptive treatment can be individualized based on absolute fracture risk. Relative to their skeletal benefits, risks of adverse events with antiresorptive treatments are low. Skeletal health should be considered in the decision-making process regarding choice and duration of endocrine therapy. Before and during endocrine therapy, skeletal health should be assessed regularly, optimized by nonpharmacological intervention and where indicated antiresorptive treatment, in an individualized, multidisciplinary approach. Clinical trials are needed to better delineate long-term fracture risks of adjuvant endocrine therapy and to determine the efficacy of interventions designed to minimize these risks., (© 2018 John Wiley & Sons Ltd.)

Background: Type 1 diabetes mellitus (T1DM) is associated with skeletal fragility. While previous meta-analyses have demonstrated an increased risk of fracture in individuals with T1DM, little is known about fracture risk in T1DM, in the absence of age-related confounders., Aims: To determine the risk of fracture in young and middle-aged adults with T1DM aged 18-50 years old., Design: Systematic review and meta-analysis., Data Sources: Ovid MEDLINE, PubMed, EMBASE, EBM reviews and relevant conference abstracts., Study Inclusion Criteria: Studies of adults aged between 18-50 years with type 1 diabetes mellitus, with reported fracture outcomes., Primary Outcomes: Incident or prevalent fracture., Results: Six studies were included in the meta-analysis. A total of 1724 fractures occurred in 35 925 patients with T1DM and 48 253 fractures occurred in 2 455 016 controls. RR for all fractures was 1.88 (95% CI 1.52-2.32, P < .001). Fifty-six hip fractures occurred among 34 707 patients with T1DM and 594 hip fractures occurred in 2 295 177 controls. The RR of hip fractures was 4.40 (95% CI 2.58-7.50, P < .001). Females and males with T1DM had a RR of 5.79 (95% CI 3.55-9.44, P < .001) and 3.67 (95% CI 2.10-6.41, P < .001), respectively., Conclusions: In the absence of age-related comorbidities, fracture risk remains significantly elevated in young and middle-aged adults with T1DM. Younger age does not mitigate against hip fracture risk in T1DM, and health professionals need to be aware of this risk. Further studies are needed to evaluate the mechanisms of fracture in T1DM., (© 2018 John Wiley & Sons Ltd.)

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Progressive chronic kidney disease (CKD) confers a marked increase in risk for vascular calcification, cardiovascular disease, fracture and mortality, with likely contributing factors including dysregulated bone metabolism and mineral homeostasis. In general population studies, increased vascular calcification is directly related to mortality and inversely related to bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). In patients with CKD, abnormalities in turnover, mineralization and bone volume reduce the ability of DXA to predict fracture. The trabecular bone score (TBS) obtained from lumbar spine DXA images, provides a surrogate measure of microarchitectural integrity not captured by BMD. This study aimed to examine the association of the TBS to prevalent abdominal aortic calcification (AAC) in patients with CKD receiving dialysis., Methods: We performed a cross-sectional study of dialysis patients awaiting transplantation. All patients underwent laboratory testing, lateral spinal radiographs including the abdominal aorta, DXA imaging and TBS assessment. AAC scores were determined using the Kauppila method. Correlations and linear regression models were used to determine predictors of AAC scores., Results: 146 patients (60% male, mean age 48 ± 13 years) were included, of whom 49% had prevalent calcification with an AAC score ≥ 1. Of those with calcification, the mean AAC score was 7 ± 5.5 and 42 patients had scores ≥ 6, considered to indicate severe AAC. TBS values corresponding to intermediate or high risk for fracture (<1.31) were present in 35% of patients. TBS values correlated inversely to AAC scores (β = -0.206, p = 0.013) and remained significant in multivariable linear regression, adjusting for age, BMI and time on dialysis (-0.160, p = 0.031). There was no significant correlation of AAC scores to any BMD parameter., Conclusion: There is a high prevalence of AAC in relatively young dialysis patients awaiting transplantation and their AAC scores are inversely related to the TBS but not to DXA-derived BMD parameters. In patients with CKD on dialysis, TBS assessment reflects microarchitectural abnormalities of bone not captured by DXA. The inverse relationship of TBS to vascular calcification may provide insights into bone-vascular interactions in CKD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The association between type 1 diabetes mellitus (T1DM) and bone health has garnered interest over the years. Fracture risk is known to be increased in individuals with T1DM, although bone health assessment is not often performed in the clinical setting. We describe the case of a 21-year-old male with longstanding T1DM with multilevel vertebral fractures on imaging, after presenting with acute back pain without apparent trauma. Dual-energy X-ray absorptiometry (DXA) revealed significantly reduced bone mineral density at the lumbar spine and femoral neck. Extensive investigations for other secondary or genetic causes of osteoporosis were unremarkable, apart from moderate vitamin D deficiency. High-resolution peripheral quantitative computed tomography and bone biospy revealed significant alterations of trabecular bone microarchitecture. It later transpired that the patient had sustained vertebral fractures secondary to unrecognised nocturnal hypoglycaemic seizures. Intravenous zoledronic acid was administered for secondary fracture prevention. Despite anti-resorptive therapy, the patient sustained a new vertebral fracture after experiencing another hypoglycaemic seizure in his sleep. Bone health in T1DM is complex and not well understood. There are significant challenges in the assessment and management of osteoporosis in T1DM, particularly in young adults, where fracture prediction tools have not been validated. Clinicians should be aware of hypoglycaemia as a significant risk factor for fracture in patients with T1DM., Learning Points: Type 1 diabetes mellitus (T1DM) is a secondary cause of osteoporosis, characterised by reduced bone mass and disturbed bone microarchitecture.Hypoglycaemic seizures generate sufficient compression forces along the thoracic column and can cause fractures in individuals with compromised bone quality.Unrecognised hypoglycaemic seizures should be considered in patients with T1DM presenting with fractures without a history of trauma.Patients with T1DM have increased fracture risk and risk factors should be addressed. Evaluation of bone microarchitecture may provide further insights into mechanisms of fracture in T1DM.Further research is needed to guide the optimal screening and management of bone health in patients with T1DM.

Atypical femoral fractures (AFFs) are uncommon and have been associated particularly with long-term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate-naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand-searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders ( gene ): osteogenesis imperfecta ( COL1A1/COL1A2 ), pycnodysostosis ( CTSK ), hypophosphatasia ( ALPL ), X-linked osteoporosis ( PLS3 ), osteopetrosis, X-linked hypophosphatemia ( PHEX ), and osteoporosis pseudoglioma syndrome ( LRP5 ). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate-naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X-linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole-exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the GGPS1 gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted ALPL gene sequencing, an ALPL heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in ALPL . Targeted sequencing of ALPL , COL1A1 , COL1A2 , and SOX9 genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs. A large multicenter collaborative study of well-phenotyped AFF cases and controls is needed to understand the role of genetics in this uncommon condition., (© 2017 The Authors published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.)