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Background: Benign prostatic hypertrophy increases with age and can result in substantially decreased quality of life for older men. Surgery is often required to control symptoms. It has been hypothesized that long-term administration of a nonamplifiable pure androgen might decrease prostate growth, thereby decreasing or delaying the need for surgical intervention. Objective: To test the hypothesis that dihydrotestosterone (DHT), a nonamplifiable and nonaromatizable pure androgen, reduces late-life prostate growth in middle-aged men. Design: Randomized, placebo-controlled, parallel-group trial. (Australian New Zealand Clinical Trials Registry number: ACTRN12605000358640) SETTING: Ambulatory care research center. Participants: Healthy men (n = 114) older than 50 years without known prostate disease. Intervention: Transdermal DHT (70 mg) or placebo gel daily for 2 years. Measurements: Prostate volume was measured by ultrasonography; bone mineral density (BMD) and body composition were measured by dual-energy x-ray absorptiometry; and blood samples and questionnaires were collected every 6 months, with data analyzed by mixed-model analysis for repeated measures. Results: Over 24 months, there was an increase in total (29% [95% CI, 23% to 34%]) and central (75% [CI, 64% to 86%]; P < 0.01) prostate volume and serum prostate-specific antigen level (15% [CI, 6% to 24%]) with time on study, but DHT had no effect (P > 0.2). Dihydrotestosterone treatment decreased spinal BMD (1.4% [CI, 0.6% to 2.3%]; P < 0.001) at 24 months but not hip BMD (P > 0.2) and increased serum aminoterminal propeptide of type I procollagen in the second year of the study compared with placebo. Dihydrotestosterone increased serum DHT levels and its metabolites (5α-androstane-3α,17β-diol and 5α-androstane-3β,17β-diol) and suppressed serum testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels. Dihydrotestosterone increased hemoglobin levels (7% [CI, 5% to 9%]), serum creatinine levels (9% [CI, 5% to 11%]), and lean mass (2.4% [CI, 1.6% to 3.1%) but decreased fat mass (5.2% [CI, 2.6% to 7.7%]) (P <0.001 for all). Protocol-specific discontinuations due to DHT were asymptomatic increased hematocrit (n = 8), which resolved after stopping treatment, and increased prostate-specific antigen levels (n = 3; none with prostate cancer) in the DHT group. No serious adverse effects due to DHT occurred. Limitation: Negative findings on prostate growth cannot exclude adverse effects on the natural history of prostate cancer. Conclusion: Dihydrotestosterone treatment for 24 months has no beneficial or adverse effect on prostate growth but causes a decrease in spinal but not hip BMD. These findings have important implications for the wider use of nonsteroidal pure androgens in older men. Primary Funding Source: BHR Pharma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Endogenous glucocorticoids (GCs) modulate numerous biologic systems involved in the initiation and maintenance of arthritis. Bone cells play a critical role in the progression of arthritis, and some of the effects of GCs on inflammation may be mediated via these cells. The aim of this study was to investigate the impact of osteoblast-targeted disruption of GC signaling on joint inflammation, cartilage damage, and bone metabolism in the K/BxN mouse serum transfer model of autoimmune arthritis. METHODS: Intracellular GC signaling was disrupted in osteoblasts through transgenic overexpression of 11beta-hydroxysteroid dehydrogenase type 2 under the control of a type I collagen promoter. Arthritis was induced in 5-week-old male transgenic mice and their wild-type (WT) littermates, and paw swelling was assessed daily until the mice were killed. The mice were examined by histology, histomorphometry, and microfocal computed tomography, and serum was analyzed for cytokines, adrenocorticotropic hormone, and corticosterone. RESULTS: Acute arthritis developed in both transgenic and WT mice treated with K/BxN mouse serum. However, the arthritis and local inflammatory activity were significantly attenuated in transgenic mice, as judged by clinical and histologic indices of inflammation and cartilage damage. Bone turnover and bone volume remained unchanged in arthritic transgenic mice, while WT mice exhibited stimulated bone resorption, suppressed osteoblast activity, and significantly reduced bone volume, compatible with the known effects of active inflammation on bone. Circulating levels of proinflammatory cytokines tended to be lower in arthritic transgenic mice than in control transgenic mice. CONCLUSION: Disruption of GC signaling in osteoblasts significantly attenuates K/BxN mouse serum-induced autoimmune arthritis in mice. These data suggest that osteoblasts modulate the immune-mediated inflammatory response via a GC-dependent pathway. [ABSTRACT FROM AUTHOR]

Background: Osteoporotic fractures signal severely compromised bone strength and are associated with a greatly increased risk of refracture. Despite the availability of effective and safe medications that reduce fracture risk, 70-80% of patients are inadequately investigated or treated for osteoporosis following an initial fracture, constituting a significant 'osteoporosis care gap'. Optimal methods of bridging this gap with primary care at the forefront of secondary fracture prevention remain undetermined. This protocol describes a cluster randomised controlled trial to evaluate the effectiveness of a novel integrated model of secondary fracture prevention and management in primary care., Methods: The cluster randomised controlled trial involves multiple branches of a community-based radiology provider (CRP), a hospital-based secondary fracture prevention program (SFPP) and numerous primary care practices in metropolitan Sydney that refer to either the CRP or SFPP. Using natural language processing tools, patients diagnosed with a potential osteoporotic fracture will be identified by automatically screening radiology reports generated at the CRP or SFPP. The primary care practices that these patients attend will be randomised (1:1) to either the intervention or usual care. The intervention consists of (i) electronic and fax alerts informing the practice/primary care physician that their patient has been diagnosed with a potential osteoporotic fracture; (ii) provision of osteoporosis management guidelines and (iii) follow-up surveys at 4 weeks and 6 months. Practices in the usual care (control) group will receive no alerts and provide usual care. The primary outcome is the proportion of patients undergoing a bone density scan and/or filling a prescription for osteo-protective pharmacotherapy within 3 months of the initial diagnostic imaging report. Secondary outcomes are the proportion of patients: (i) undergoing an osteoporosis-related blood test within 3 months of the initial diagnostic imaging report; (ii) initiated on a chronic disease management plan within 3 months of the diagnostic report, and (iii) filling a second prescription for osteo-protective pharmacotherapy within 9 months post initial diagnostic imaging report. Outcomes will be obtained through de-identified linked data from Medical Benefits Schedule and Pharmaceutical Benefits Scheme held by the Australian Institute of Health and Welfare., Discussion: This is the first randomised trial to integrate case-detection of potential osteoporotic fractures in a hospital and community setting with direct alerts to the patient's primary care provider. This study will determine whether such an intervention is effective in improving investigation and/or treatment rates of osteoporosis in patients with a potential osteoporotic fracture., Trial Registration: This study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000658617p., (© 2024. The Author(s).)

A male of East Asian background in his 30s presented to the emergency department with acute onset global muscle weakness, elevated creatine kinase, profound hypokalaemia and hyperthyroidism. A diagnosis of thyrotoxic periodic paralysis was made and the myopathy resolved promptly with potassium replacement. However, 3 months after being commenced on carbimazole for hyperthyroidism, the patient developed myalgias without weakness associated with an elevated creatine kinase. The myositis panel was negative, while a muscle biopsy showed nonspecific, mild myopathic changes with minimal lymphocytic inflammation. As a change in therapy from carbimazole to propylthiouracil resulted in prompt symptom improvement and normalisation of serum creatine kinase levels, a presumptive diagnosis of carbimazole-induced myositis was made. Genetic testing for hereditary skeletal muscle channelopathies did not identify any gene of interest., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The global burden of osteoporosis continues to rise with an ageing population. Untreated osteoporotic fractures not only heighten the risk of subsequent fractures but are associated with excess mortality. Although primary care guidelines consistently stress the importance of secondary fracture prevention, fewer than 20% of patients are appropriately treated for osteoporosis following an initial osteoporotic fracture. This worldwide phenomenon is known as the osteoporosis care gap. This literature review examines the barriers to secondary fracture prevention in primary care and evaluates the effectiveness of targeted primary care interventions. Common themes emerged from the majority of qualitative studies, including a need for improved communication between the hospital team and primary care, better defined responsibilities and osteoporosis-directed education for the primary care physicians. Quantitative studies demonstrated that most targeted, intensive interventions aimed at educating patients and their primary care physician about osteoporosis treatment significantly increased rates of investigation and treatment. Greater uptake of models of secondary fracture prevention in primary care is urgently needed to address the osteoporosis care gap., (© 2024. The Author(s).)

Glucocorticoids are steroid hormones, secreted by the adrenals to regulate a range of metabolic, immunologic, and homeostatic functions. Due to their potent anti-inflammatory effects, synthetic glucocorticoids are widely used to treat inflammatory disorders. However, their use especially at high doses and over the long-term is associated with several unwanted side effects that compromises their intended use (e.g. glucocorticoid-induced osteoporosis and/or diabetes, myopathy, and skin atrophy). Both endogenous and synthetic glucocorticoids exert their effects through the glucocorticoid receptor, a transcription factor present in nearly all nucleated cells. Glucocorticoid receptor knockout mouse models have proved to be valuable tools in understanding how glucocorticoids contribute to skeletal health and disease. These models, described in this review, have helped to establish that the effects of glucocorticoids on the skeleton are multifaceted, cell specific and concentration dependent. Intriguingly, while endogenous glucocorticoids are essential for bone formation, high-dose exogenous glucocorticoids may induce bone loss. Additionally, the actions of endogenous glucocorticoids vary greatly depending on the disease microenvironment. For example, endogenous glucocorticoids have predominately beneficial anti-inflammatory effects in rheumatoid arthritis, but detrimental actions in osteoarthritis by driving cartilage loss and abnormal bone formation. Studies in tissue-specific knockout models provide important insights that will aid the development of new glucocorticoid therapeutics that can specifically target certain cell types to minimise unwanted effects from current glucocorticoid therapy.

Objectives: To project how many minimal trauma fractures could be averted in Australia by expanding the number and changing the operational characteristics of fracture liaison services (FLS)., Study Design: System dynamics modelling., Setting, Participants: People aged 50 years or more who present to hospitals with minimal trauma fractures, Australia, 2020-31., Main Outcome Measures: Numbers of all minimal trauma fractures and of hip fractures averted by increasing the FLS number (from 29 to 58 or 100), patient screening rate (from 30% to 60%), and capacity for accepting new patients (from 40 to 80 per service per month), and reducing the proportion of eligible patients who do not attend FLS (from 30% to 15%); cost per fracture averted., Results: Our model projected a total of 2 441 320 minimal trauma fractures (258 680 hip fractures; 2 182 640 non-hip fractures) in people aged 50 years or older during 2020-31, including 1 211 646 second or later fractures. Increasing the FLS number to 100 averted a projected 5405 fractures (0.22%; $39 510 per fracture averted); doubling FLS capacity averted a projected 3674 fractures (0.15%; $35 835 per fracture averted). Our model projected that neither doubling the screening rate nor reducing by half the proportion of eligible patients who did not attend FLS alone would reduce the number of fractures. Increasing the FLS number to 100, the screening rate to 60%, and capacity to 80 new patients per service per month would together avert a projected 13 672 fractures (0.56%) at a cost of $42 828 per fracture averted., Conclusion: Our modelling indicates that increasing the number of hospital-based FLS and changing key operational characteristics would achieve only moderate reductions in the number of minimal trauma fractures among people aged 50 years or more, and the cost would be relatively high. Alternatives to specialist-led, hospital-based FLS should be explored., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Introduction: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment., Methods: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB., Results: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups., Conclusions: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB., Trial Registration Number: ISRCTN11616770., Competing Interests: Competing interests: DS reports receiving honoraria from GE Healthcare outside the submitted work; OC reports receiving lecture fees from Nordic Pharma and financial support for attending conferences from Abbvie, outside the submitted work; GH reports funding from the Royal Osteoporosis Society to her institution and honoraria from Amgen and UCB outside the submitted work; JT reports funding to his institution from the Wellcome trust and Medical Research Council, outside the submitted work and that he is chair of the Royal Osteoporosis Society Research and Innovation grant assessment panel; SYM report receiving lecture fees from Janssen Pharmaceuticals outside the submitted work; RC reports funding to her institution from Kyowa Kirin and Amgen outside the submitted work; WDF reports funding to his institution from Novartis, Takeda, NPS Pharma, Sanofi, Amolyt and Entera-Bio Pharma outside the submitted work and donation of assay materials and evaluation kits from Abbot Diagnostics outside the submitted work; NG reports receiving honoraria from Amgen, UCB, Lilly and Gedeon Richter and support from UCB for attending conferences outside the submitted work; MJS reports funding to his institution from Amgen and Allergen outside the submitted work and funding from the National Health and Medical Research Council of Australia to his institution outside the submitted work; MKK reports funding to his institution from the Medical Research Futures Fund; GM is a member of the Scientific Advisory Board of Osteoporosis Australia; SHR reports funding to his institution from Kyowa Kirin, UCB, the Paget’s Association and the Royal Osteoporosis Society outside the submitted work. The other authors have no interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Diet is associated with major adverse cardiovascular events (MACE)., Objective: We evaluated the associations between empirically derived dietary patterns and MACE., Design: Prospective cohort study., Setting: The Concord Health and Ageing in Men Project, Sydney, Australia., Participants: 539 community-dwelling older Australian men aged 75 years and older., Methods: Men underwent dietary assessment using a validated dietitian-administered diet history questionnaire. Cox regression analyses were conducted between MACE and the three dietary patterns identified from factor analysis. Five-point MACE comprised of all-cause mortality, myocardial infarction (MI), congestive cardiac failure (CCF), coronary revascularisation, and/or ischaemic stroke. Four-point MACE included the four endpoints of MI, CCF, coronary revascularisation, and/or ischaemic stroke, and excluded all-cause mortality., Results: At a median of 5.3 (IQR 4.6-6.3) years of follow-up, the incidences were: five-point MACE 31.2% (n = 168); four-point MACE excluding all-cause mortality 17.8% (n = 96); all-cause mortality 20.1% (n = 111); CCF 11.3% (n = 61); MI 3.7% (n = 20); stroke 3.2% (n = 17); and coronary revascularisation 3.1% (n = 15). In fully adjusted analyses, compared to the bottom tertile, the middle tertile of 'vegetables-legumes-seafood' dietary pattern was associated with reduced five-point MACE (HR 0.67 [95% CI: 0.45, 0.99, P = .047]), and CCF (HR 0.31 [95% CI: 0.15, 0.65, P = .002]), whilst the middle tertile of 'wholegrains-milk-other fruits' dietary pattern was associated with increased five-point MACE (HR 1.78 [95% CI: 1.17, 2.70, P = .007]), four-point MACE (HR 1.92 [95% CI: 1.12, 3.30, P = .018]), and CCF (HR 2.33 [95% CI: 1.17, 4.65, P = .016]). For the 'discretionary-starchy vegetables-processed meats' dietary pattern, a higher score was associated with increased five-point MACE (HR 1.33 [95% CI: 1.09, 1.62, P = .004]), and all-cause mortality (HR 1.63 [95% CI: 1.26, 2.12, P < .001]), and compared to the bottom tertile, the top tertile was associated with increased all-cause mortality (HR 2.26 [95% CI: 1.27, 4.00, P = .005])., Conclusion: Older men may benefit from consuming a 'vegetables-legumes-seafood' dietary pattern rather than 'discretionary-starchy vegetables-processed meats' and 'wholegrains-milk-other fruits' dietary patterns for the prevention of MACE., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: Diet may be associated with frailty., Objective: We aimed to evaluate the associations between empirically derived dietary patterns and frailty in older men., Design: Prospective cohort study., Setting: The Concord Health and Ageing in Men Project, Sydney, Australia., Participants: 785 community-dwelling older Australian men aged 75 years and older., Methods: Men underwent dietary assessment using a validated dietitian-administered diet history questionnaire. Factor analysis identified three dietary patterns. Multinomial logistic regression was conducted between frailty and dietary patterns for cross-sectional analyses and longitudinal analyses over a 3-year follow-up. Frailty was defined by the Fried frailty phenotype., Results: Of the 785 men, pre-frailty was prevalent in 47.1% (n = 370), and frailty in 8.3% (n = 65). In fully adjusted cross-sectional analyses, the top tertile and a higher 'vegetables-legumes-seafood' dietary pattern score were associated with reduced prevalence of frailty (OR 0.34 [95% CI: 0.12, 0.93, P = .036]) and OR 0.50 [95% CI: 0.30, 0.83, P = .007] respectively). The top tertile of the 'discretionary-starchy vegetables-processed meats' dietary pattern was also associated cross-sectionally with increased prevalence of pre-frailty (OR 1.75 [95% CI: 1.08, 2.83, P = .022]). Of the 296 robust men in fully adjusted longitudinal analyses, the incidence of pre-frailty was 52.4% (n = 155), and frailty was 5.4% (n = 16) over a 3-year follow-up. The middle tertile of the 'vegetables-legumes-seafood' dietary pattern had a non-significant trend towards reduced incident pre-frailty (OR 0.52 [95% CI: 0.27, 1.00, P = .050])., Conclusion: Consumption of a 'vegetables-legumes-seafood' dietary pattern appears to be less favoured by frail older men., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: We examined associations between intra-generational social mobility (reflected in life-course socioeconomic trajectories) and mortality, among older men., Methods: Data came from a prospective Australian community-based cohort of older men. Social mobility was defined by socioeconomic indicators from three points in the life-course: educational attainment (late adolescence-early adulthood), occupation (mid-life), and current sources of income (older age). We defined indicators of social mobility trajectory (6 categories; reflecting the direction of social mobility) and social mobility status (2 categories; mobile or non-mobile). We used Cox regression to examine associations with mortality, adjusting for age, country of birth, and living arrangement., Results: We followed 1568 men (mean age 76.8, SD 5.4) for a mean duration of 9.1 years, with 797 deaths recorded. Moving upward was the predominant social mobility trajectory (36.0%), followed by mixed trajectories (25.1%), downward (15.1%), stable low (12.2%), stable high (7.6%), and stable middle (4.0%). Men with downward (Hazard ratio 1.58, 95% CI 1.13 to 2.19) and stable low socioeconomic trajectories (1.77, 1.25 to 2.50) had higher mortality risks than men with stable high socioeconomic trajectories, while men with upward trajectories had similar risks to those with stable high trajectories. 76.2% of the participants were classified as having mobile status; no associations were evident between binary social mobility status and mortality., Discussions: These findings suggest cumulative and persistent exposure to disadvantaged socioeconomic conditions across the life-course, rather than social mobility, is associated with increased mortality. For each stage of the life-course, addressing socioeconomic disadvantage may reduce inequities in mortality., Competing Interests: The authors report no conflict of interest., (© 2023 The Authors.)

The global burden of osteoporosis and osteoporotic fractures will increase significantly as we enter a rapidly aging population. Osteoporotic fractures lead to increased morbidity, mortality, and risk of subsequent fractures if left untreated. However, studies have shown that the majority of patients who suffer an osteoporotic fracture are not investigated or treated for osteoporosis, leading to an inexcusable "osteoporosis care gap." Systematic and coordinated models of care in secondary fracture prevention known as fracture liaison services (FLS) have been established to streamline and improve the care of patients with osteoporotic fractures, and employ core principles of identification, investigation, and initiation of treatment. Our approach to the multifaceted care of secondary fracture prevention at a hospital-based FLS is illustrated through several case vignettes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objectives: The aims of this study were to assess oral health-related quality of life (OHRQoL) in a cohort of older Australian men and explore the association between their general health conditions, socio-demographic factors and OHRQoL., Methods: The Concord Health and Ageing in Men Project (CHAMP) is a cohort study of the health of a representative sample of Australian men, initiated in 2005-2006 with an initial sample of 1705 men 70 years or over. Participants completed a self-administered health and socio-demographic questionnaire and attended an interview and clinical assessment at baseline and each of three follow-up assessments. Information on oral health and responses to the Oral Health Impact Profile (OHIP-14) were collected in the 4th follow-up in which 778 men completed the OHIP-14 questionnaire and 614 men had a dental assessment. The prevalence of oral health impact was defined as a response of fairly often or very often to one or more of the OHIP-14 questions. Mean OHIP-14 scores were calculated for the 14 questions and used as the dependent variable in the regression analyses. Zero-inflated Poisson regression was used to estimate prevalence rate ratios (PRR)., Results: Only 10% of men presented oral health impacts. In multivariate regression modelling, being born in Italy/Greece (PRR: 2.16, 95% CI: 1.93-2.42) or in other countries (PRR: 2.12, 95% CI: 1.89-2.38), having poor self-rated general health (PRR: 1.38, 95% CI: 1.24-1.53), having poor mental wellbeing (PRR: 1.14, 95% CI: 1.04-1.24), having ≥6 depressive symptoms (PRR: 1.18, 95% CI: 1.05-1.32), being a current smoker (PRR: 1.34, 95% CI: 1.06-1.70) and having more decayed tooth surfaces (PRR:1.01, 95% CI: 1.00-1.02) were associated with higher impact scores., Conclusions: Overall, older Australian men exhibit good oral health-related quality of life. The inter-relationship between perceptions of general health and well-being, health and oral health variables and social background supports policy objectives of closer integration of general health and oral health services for older Australian men., (© 2022 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Introduction: Previous studies have demonstrated positive correlations between computed tomography (CT) attenuation of lumbar spine vertebrae and their bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DEXA). However, these studies were performed using a standard 120 kilovoltage peak (kVp) setting. As radiation attenuation in mineralised tissues varies by the tube voltage applied, we determined the diagnostic accuracy of CT attenuation at identifying individuals with low BMD at different kVp settings., Methods: Single centre retrospective study of adults who had CT and DEXA scans within 6 months of each other. CT scans were performed at either 100 kVp, 120 kVp or dual energy (80 kVp/140 kVp). Attenuation was measured in axial cross-sections of L1-4 vertebrae and correlated with the results of DEXA. Receiver operated characteristic (ROC) curves were generated to determine diagnostic cut-off thresholds., Results: Analysis included 268 subjects (169 females; mean age: 70, range: 20-94 years). CT attenuation values at L1 or mean L1-4 correlated positively with DEXA-derived T-scores. At L1, the optimal Hounsfield units (HU) thresholds for predicting DEXA T-scores of -2.5 or less at 100 kVp, 120 kVp and dual-energy scans were <170, <128 and <164, with corresponding AUCs of 0.925, 0.814 and 0.743 respectively. For mean L1-4, the HU thresholds were <173, <134 and <151, with corresponding AUCs of 0.933, 0.824 and 0.707 respectively., Conclusion: CT attenuation thresholds differ depending on the tube voltage used. We provide voltage-specific, probability-optimised thresholds for the identification of persons likely to have low BMD on DEXA scanning., (© 2023 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Objective: Disruption of endogenous glucocorticoid signalling in bone cells attenuates osteoarthritis (OA) in aged mice, however, the role of endogenous glucocorticoids in chondrocytes is unknown. Here, we investigated whether deletion of the glucocorticoid receptor, specifically in chondrocytes, also alters OA progression., Design: Knee OA was induced by surgical destabilisation of the medial meniscus (DMM) in male 22-week-old tamoxifen-inducible glucocorticoid receptor knockout (chGRKO) mice and their wild-type (WT) littermates (n = 7-9/group). Mice were harvested 2, 4, 8 and 16 weeks after surgery to examine the spatiotemporal changes in molecular, cellular, and histological characteristics., Results: At all time points following DMM, cartilage damage was significantly attenuated in chGRKO compared to WT mice. Two weeks after DMM, WT mice exhibited increased chondrocyte and synoviocyte hypoxia inducible factor (HIF)-2α expression resulting in extensive synovial activation characterised by synovial thickening and increased interleukin-1 beta expression. At 2 and 4 weeks after DMM, WT mice displayed pronounced chondrocyte senescence and elevated catabolic signalling (reduced Yes-associated protein 1 (YAP1) and increased matrix metalloprotease [MMP]-13 expression). Contrastingly, at 2 weeks after DMM, HIF-2α expression and synovial activation were much less pronounced in chGRKO than in WT mice. Furthermore, chondrocyte YAP1 and MMP-13 expression, as well as chondrocyte senescence were similar in chGRKO-DMM mice and sham-operated controls., Conclusion: Endogenous glucocorticoid signalling in chondrocytes promotes synovial activation, chondrocyte senescence and cartilage degradation by upregulation of catabolic signalling through HIF-2α in murine posttraumatic OA. These findings indicate that inhibition of glucocorticoid signalling early after injury may present a promising way to slow osteoarthritic cartilage degeneration., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Disruption of glucocorticoid (GC) signaling in osteoblasts results in a marked attenuation of acute antibody-induced arthritis. The role of endogenous GCs in chronic inflammatory arthritis is however not fully understood. Here, we investigated the impact of endogenous GC signaling in osteoblasts on inflammation and bone integrity under chronic inflammatory arthritis by inactivating osteoblastic GC signaling in a long-term K/BxN serum transfer-induced induced arthritis (STIA) model., Methods: Intracellular GC signaling in osteoblasts was disrupted by transgenic (tg) overexpression of 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2). Inflammatory arthritis was induced in 5-week-old male tg mice and their wild type (WT) littermates by intraperitoneal (i.p.) injection of K/BxN serum while controls (CTRLs) received phosphate-buffered saline (PBS). In a first cohort, K/BxN STIA was allowed to abate until  the endpoint of 42 days (STIA). To mimic rheumatic flares, a second cohort was additionally injected on days 14 and 28 with K/BxN serum (STIA boost ). Arthritis severity was assessed daily by clinical scoring and ankle size measurements. Ankle joints were assessed histopathologically. Systemic effects of inflammation on long bone metabolism were analyzed in proximal tibiae by micro-computed tomography (μCT) and histomorphometry., Results: Acute arthritis developed in both tg and WT mice (STIA and STIA boost ) and peaked around day 8. While WT STIA and tg STIA mice showed a steady decline of inflammation until day 42, WT STIA boost and tg STIA boost mice exhibited an arthritic phenotype over a period of 42 days. Clinical arthritis severity did not differ significantly between WT and tg mice, neither in the STIA nor in the STIA boost cohorts. Correspondingly, histological indices of inflammation, cartilage damage, and bone erosion showed no significant difference between WT and tg mice on day 42. Histomorphometry revealed an increased bone turnover in tg CTRL and tg STIA boost compared to WT CTRL and WT STIA boost animals, respectively., Conclusions: In contrast to the previously reported modulating effects of endogenous GC signaling in osteoblasts during acute K/BxN STIA, this effect seems to perish during the chronic inflammatory and resolution phase. These findings indicate that endogenous GC signaling in osteoblasts may mainly be relevant during acute and subacute inflammatory processes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Summary: We report the case of a 69-year-old female with systemic mastocytosis, diagnosed based on widespread pigmented papules and macules, elevated serum tryptase levels and confirmatory skin and bone marrow biopsy, on a background of osteoporosis. A CT demonstrated multiple sclerotic lesions within lumbar vertebral bodies, sacrum and ileum, with surrounding osteolysis but no obvious compression fractures. She was treated with the RANK-L inhibitor denosumab, resulting in significant bone mineral density gain over the following 5 years. However, her serum tryptase levels gradually increased during this period despite treatment with the multikinase inhibitor, midostaurin. It is thus conceivable that her rapid increase in bone mineral density may be partly contributed by a predominance of pro-osteoblastic mediators released by abnormal mast cells, suggestive of more advanced disease. This case highlights the complexities of systemic mastocytosis-related bone disease and the interplay of numerous mediators contributing to a phenotype of both increased bone resorption and formation., Learning Points: Systemic mastocytosis is a neoplastic disease of mast cells characterized by abnormal proliferation and accumulation in the skin and other organs. It is most frequently associated with the somatic gain-of-function KIT D816V mutation. Systemic mastocytosis should be suspected in patients presenting with not only cutaneous symptoms suggestive of mast cell degranulation such as anaphylaxis, flushing or urticaria but also unexplained osteoporosis and gastrointestinal and constitutional symptoms. The prevalence of osteoporosis in systemic mastocytosis is high. Mast cell activation leads to the secretion of numerous chemical mediators which either promote or inhibit osteoclastic and/or osteoblastic activity, with the balance usually in favour of increased bone resorption. However, in advanced diseases with high mast cell burden, mast-cell-derived cytokines and mediators may promote osteoblastic activity, leading to osteosclerosis and apparent increases in bone mineral density. Treatment of osteoporosis in systemic mastocytosis involves antiresorptive therapy with bisphosphonates and more recently, denosumab. There are limited data on the role of osteoanabolic agents.

Background: Nutritional intake can influence major adverse cardiovascular events (MACE). Dietary iron is found in two forms: haem-iron (HI) only found in animal sources and non-haem iron (NHI) present mostly in plant sources., Objective: We evaluated the associations between dietary iron intakes with MACE and iron status biomarkers., Design: Prospective cohort study., Setting: The Concord Health and Ageing in Men Project, Sydney, Australia., Participants: 539 community-dwelling older Australian men aged 75 years and older., Methods: Men underwent nutritional assessment using a validated diet history questionnaire. Entries were converted to food groups and nutrients. The dietary calculation was used to derive HI and NHI intakes from total iron intakes. Analyses of iron intakes with iron status biomarkers were conducted using linear regression, and with MACE and individual endpoints were conducted using Cox regression. Five-point MACE comprised of all-cause mortality, myocardial infarction (MI), congestive cardiac failure (CCF), coronary revascularisation, and/or ischaemic stroke. Four-point MACE included the four endpoints of MI, CCF, coronary revascularisation, and/or ischaemic stroke, and excluded all-cause mortality., Results: At a median of 5.3 (4.6 - 6.3) years follow-up, the incidences were: 31.2% (n = 168) five-point MACE, 17.8% (n = 96) four-point MACE excluding all-cause mortality, 20.1% (n = 111) all-cause mortality, 11.3% (n = 61) CCF, and 3.1% (n = 15) coronary revascularisation. In adjusted analyses, higher HI intake (per 1mg increment) was associated with increased five-point MACE (HR: 1.45 [95% CI: 1.16, 1.80, P = .001]), four-point MACE excluding all-cause mortality (HR: 1.64 [95% CI: 1.26, 2.15, P <.001]), all-cause mortality (HR: 1.51 [95% CI: 1.15, 1.99, P = .003]), CCF (HR: 2.08 [95% CI: 1.45, 2.98, P <.001]), and coronary revascularisation (HR: 1.89 [95% CI: 1.15, 3.10, P = .012]). Compared with the bottom tertile of NHI intake, the middle tertile of NHI intake was associated with reduced risk of all-cause mortality (HR: 0.56 [95% CI: 0.33, 0.96, P = .035]). Total iron intake was not associated with MACE and individual endpoints. Dietary iron intakes were not associated with serum iron and haemoglobin., Conclusion: Higher haem iron intake was independently associated with increased risks of five-point MACE, four-point MACE excluding all-cause mortality, all-cause mortality, CCF, and coronary revascularisation in older men over 5 years., Competing Interests: The authors declare no conflicts of interest.

Objective: This healthcare improvement initiative was designed to increase inpatient osteoporosis treatment after hip fracture., Methods: A new protocol was developed by Geriatric Medicine and Endocrinology departments at a tertiary care hospital in Sydney. Its aim was to standardize assessment and treatment of osteoporosis in patients admitted with hip fracture. Eligible inpatients would receive intravenous zoledronic acid during their admission. A 6-month sample of hip fracture patients admitted after the protocol's implementation was compared to a group admitted before. Data collected included demographics, biochemistry, treatment rates, adverse effects, and admission survival., Results: There was a considerable increase in osteoporosis treatment after introducing the protocol. Before the protocol's introduction, none of 36 eligible patients received treatment. After the intervention 79% (23 out of 29) of eligible patients were treated.All treated patients had renal function and serum calcium levels checked post-infusion with no adverse outcomes. Eight patients developed flu-like symptoms within 24 h of the infusion. There were no instances of arrhythmias, ocular inflammation, or death. The cost per patient treated was AUD $87., Conclusion: Adopting a standardized protocol for osteoporosis treatment in patients admitted for hip fracture was effective in improving treatment rates whilst being relatively safe and inexpensive., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 The Authors. Aging Medicine published by Beijing Hospital and John Wiley & Sons Australia, Ltd.)

Background: Data in the Offspring Framingham Osteoporosis Study (FOS) suggested that higher intake of dietary fiber was modestly protective against loss of bone mineral density at the femoral neck in men but not in women., Aim: To examine the relationship of fiber intake with risk of hip fractures in men., Methods: We included 367 men from the FOS Original cohort, 1730 men from the FOS Offspring cohort, and 782 men from the Concord Health and Ageing in Men Project (CHAMP) in the analysis. Incident fractures were defined as medically confirmed first occurrence of osteoporotic fractures at the proximal femur. Fiber intake was estimated via a validated food frequency questionnaire (FFQ) or diet history. Cox proportional hazards models were applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A random-effects model was used to estimate the pooled relative risk in meta-analysis., Results: Seventy-two incident hip fractures were identified, of which 24 occurred in the FOS Original cohort [mean (SD): age 75.3 (5.1) years; follow-up time: 8.5 (6.2) years; dietary fiber: 19 (8) (g/d)], 19 in the FOS Offspring cohort [58.8 (9.8) years; 11.0 (5.9) years; 19 (8) (g/d)], and 29 in CHAMP [81.4 (4.5) years; 5.2 (1.5) years; 28 (10) (g/d)]. We did not find significant associations within each cohort between fiber intake and risk of hip fractures. The pooled HR (95% CI) was 0.80 (0.39, 1.66) comparing energy-adjusted dietary fiber at tertile 3 vs. tertile 1 (I 2 = 0, p = 0.56)., Conclusion: These data suggested that dietary fiber was not associated with risk of incident hip fractures in men.

Importance: Among older adults, there is limited and inconsistent evidence on the association between socioeconomic position (SEP) and elective and nonelective hospitalization., Objective: To evaluate the association between SEP and all-cause and cause-specific elective and nonelective hospitalization and hospital length of stay among older men., Design, Setting, and Participants: This population-based, prospective cohort study used data from the Concord Health and Aging in Men Project (CHAMP). CHAMP recruited 1705 men aged 70 years or older between January 28, 2005, and June 4, 2007, in Sydney, Australia. Data were analyzed from February 1 to September 30, 2021., Exposures: Indicators of SEP, including education (university degree certificate, diploma or no postschool qualifications), occupation (professionals and managers; small employers and self-employed; or lower clerical, service, sales workers, skilled, and unskilled workers), and source of income (other sources of income than government pension, reliance on government pensions and other sources of income, or reliant solely on a government pension), and a cumulative SEP score (tertiles) as SEP indicators; 3-level variables present high, intermediate, and low SEP., Main Outcomes and Measures: All-cause and cause-specific elective and nonelective hospitalizations, number of hospitalizations, and length of stay were the study outcomes, ascertained through data linkage. Associations were quantified using competing-risks survival regression and negative binomial regression., Results: A total of 1566 men (mean [SD] age, 76.8 [5.4] years) were included. During a mean (SD) 9.07 (3.53) years of follow-up, 1067 men had at least 1 elective hospitalization, and 1255 men had at least 1 nonelective hospitalization. No associations were found between SEP and elective hospitalizations. Being in the lowest tertile for educational level (subhazard ratio [SHR], 1.32; 95% CI, 1.11-1.58), occupational position (SHR, 1.30; 95% CI, 1.12-1.50), sources of income (SHR, 1.33; 95% CI, 1.17-1.52), and cumulative SEP tertile groups (SHR, 1.45; 95% CI, 1.24-1.68) were all associated with having at least 1 nonelective hospitalization compared with those in the highest tertiles. Significant associations were found between being in the lowest SEP groups and increased numbers and longer length of stay of nonelective hospitalizations., Conclusions and Relevance: In this prospective cohort study, low SEP was inversely associated with nonelective hospitalizations but not elective hospitalization in older men in Australia. These findings point to the existence of socioeconomic inequalities in health care use, indicative of a need to take action to reduce these inequalities.

We assessed two electronic search tools that screen medical records for documented fractures. Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. A hybrid tool combining the methodology of both tools is likely to improve the identification of those with osteoporosis., Purpose: Most patients who suffer a minimal trauma fracture remain undiagnosed, placing them at high risk of refracture. Case finding can be improved by electronic search tools that screen medical records for documented fractures. Here, we assessed the efficacy of two new programs, AES and XRAIT, in identifying patients with minimal trauma fracture., Methods: Each tool was applied to search the electronic medical record and/or radiology reports at two tertiary hospitals in Sydney, Australia, from 1 July to 31 December 2018. Samples of the extracted reports were then manually reviewed to determine the sensitivity of each program in detecting minimal trauma fractures., Results: At the two centers, AES detected 872 and 1364 cases, whereas XRAIT identified 1414 and 2180 patients with fractures, respectively. The true positive rate for "any fracture" was similar for both instruments (77-88%). However, the ability to detect "minimal trauma fractures" differed between programs and centers (53-75% accuracy), with each tool identifying separate subsets of patients. Concordance between both tools was less than half of the combined total number of minimal trauma fractures (43-45%). Considering the total number of minimal trauma fractures detected by both tools combined, AES correctly identified 52-55% of cases while XRAIT identified 88-93% of cases., Conclusion: Both programs reliably identified patients with any fracture but missed individuals with minimal trauma fracture to different degrees. Hybrid tools combining the methodology of XRAIT and AES are likely to improve the identification of patients who require investigation and treatment for osteoporosis., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background & Aims: Mediterranean dietary patterns may exert favourable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet as well as its components, with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men., Methods: Seven hundred ninety-four (794) community-dwelling men with mean age 81.1 ± 4.5 years, who participated in the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP) were included in the cross-sectional analysis, and 616 attended follow-up three years later. Adherence to Mediterranean diet was assessed using MEDI-LITE (literature-derived Mediterranean diet) score which was obtained using a validated diet history questionnaire. Twenty-four evaluable circulating cytokines were analyzed using Bio-Plex Pro Human Cytokine 27-plex Assay kit. Appendicular lean mass (ALM) and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA). Three-year changes in gait speed and hand grip strength were assessed by walking a 6-m course and using a dynamometer respectively and analyzed using linear mixed-effects models. Incident falls over three years were determined through telephone interviews every four months. Multivariable linear regression was utilized to determine the cross-sectional associations between MEDI-LITE scores and circulating cytokines, bone mineral density, ALM, and ALM BMI . Linear mixed-effects models were performed to estimate associations between MEDI-LITE scores and three-year change in hand grip strength and gait speed while negative binomial regression was applied to estimate associations between MEDI-LITE scores and three-year incident falls as well as associations between each MEDI-LITE component and three-year incident falls. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing., Results: A higher MEDI-LITE score, indicating greater adherence to Mediterranean diet, was associated with higher appendicular lean mass adjusted for body mass index (ALM BMI ) (β: 0.004 kg; 95% CI: 0.000, 0.008), and lower incident falls rates (IRR: 0.94; 95% CI: 0.89, 0.99). Higher consumption of monounsaturated fatty acids (IRR: 0.76; 95% CI: 0.59, 0.98) and monounsaturated fatty acids to saturated fatty acids ratio (IRR: 0.72; 95% CI: 0.57, 0.90) were associated with 24%, and 28% lower falls risk in older men respectively. MEDI-LITE scores were not associated with BMD or physical function parameters., Conclusions: Adherence to a Mediterranean diet is associated with higher ALM BMI , and fewer falls in community-dwelling older men. Monounsaturated and saturated fatty acids were the most important contributors to the association between Mediterranean diet and falls risk., Competing Interests: Conflict of Interest All other authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)