Publications by authors named "Eugene Mc Closkey"

FRAX, a risk calculator that provides individualized 10-year probabilities of hip and major osteoporotic fracture, has been widely used for fracture risk assessment since its launch in 2008. It is now incorporated into very many guidelines worldwide to inform osteoporosis management. In this review, we explore the development of FRAX and how it enhances fracture risk prediction as compared to use of bone mineral density alone, as well as approaches to utilizing FRAX in determining intervention and assessment thresholds.

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Mild cognitive impairment, dementia and osteoporosis are common diseases of ageing and, with the increasingly ageing global population, are increasing in prevalence. These conditions are closely associated, with shared risk factors, common underlying biological mechanisms and potential direct causal pathways. In this review, the epidemiological and mechanistic links between mild cognitive impairment, dementia and skeletal health are explored.

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Importance: Fragility fractures are often defined as those that occur after a certain age (eg, 40-50 years). Whether fractures occurring in early adulthood are equally associated with future fractures is unclear.

Objective: To examine whether the age at which a prior fracture occurred is associated with future fracture risk.

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Article Synopsis
  • - The guidelines update the International Osteoporosis Foundation's (IOF) 20-year-old position paper on bone markers, reflecting advancements in bone biology and disorders.
  • - The authors introduce a new classification called Bone Status Indices (BSI) to replace outdated terms like bone turnover markers and metabolic markers for better clarity.
  • - The proposal includes standardized nomenclature, abbreviations, and measurement units for these indices to ensure consistency in the study and treatment of bone health.
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Unlabelled: Sequential romosozumab-to-alendronate or sequential teriparatide-to-alendronate can be a cost-effective treatment option for postmenopausal women at very high risk of fracture.

Purpose: To estimate the 10-year probability of a major osteoporotic fracture (MOF) at which sequential treatment with romosozumab or teriparatide followed by alendronate, compared with alendronate alone, becomes cost-effective in a UK setting.

Methods: A microsimulation model with a Markov structure was used to simulate fractures, costs, and quality-adjusted life years (QALYs), in women receiving sequential treatment with either romosozumab or teriparatide followed by alendronate, compared with alendronate alone.

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Importance: The Fracture Risk Assessment Tool (FRAX) is a fracture risk prediction tool for 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Whether FRAX is useful in individuals with cancer is uncertain.

Objective: To determine the performance of FRAX for predicting incident fractures in individuals with cancer.

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Article Synopsis
  • Paget's disease of bone (PDB) makes bones grow and change shape in a messy way, which can lead to problems like pain, deafness, and broken bones.
  • A study with 168 people found that about 73% of them had musculoskeletal pain, mainly because of osteoarthritis in joints away from the PDB affected areas.
  • The research showed that pain was more common in older folks and women, and highlighted the need to check each person's pain to treat it correctly.
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Purpose Of Review: This review aims to consolidate recent observations regarding extra-osseous roles of the RANK-RANKL-OPG axis, primarily within skeletal muscle.

Recent Findings: Preclinical efforts to decipher a common signalling pathway that links the synchronous decline in bone and muscle health in ageing and disease disclosed a potential role of the RANK-RANKL-OPG axis in skeletal muscle. Evidence suggests RANKL inhibition benefits skeletal muscle function, mass, fibre-type switching, calcium homeostasis and reduces fall incidence.

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Unlabelled: Insulin resistance, defined as an impaired biological response to insulin stimulation in target tissues, arises most frequently in the presence of central obesity. Although obesity is generally associated with increased bone mass, recent data challenge this view and, if complicated by T2DM, obese patients are at high risk for fragility fractures. IR may play a key role in this increased fracture risk through effects on bone quality rather than bone quantity.

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Background: People with coeliac disease (CD) are at increased risk of osteoporosis and fractures. Currently, baseline dual-energy X-ray absorptiometry (DXA) is recommended for all patients with newly diagnosed CD. We aimed to determine the prevalence of osteoporosis and the clinical utility of the Fracture Risk Assessment Tool (FRAX) in predicting major osteoporotic fractures (MOF) in patients with biopsy-proven CD.

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Unlabelled: Associations between different sarcopenia definitions and the risk of injurious falls were investigated in 75-80-year-old women in the Swedish SUPERB cohort. Only sarcopenia according to the Sarcopenia Definitions and Outcomes Consortium (SDOC) definition was associated with incident injurious falls with and without fractures in older women.

Purpose: To investigate the association between three commonly used sarcopenia definitions and the risk of injurious falls in a population of older Swedish women.

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Article Synopsis
  • * The authors advocate for keeping ethnic and race-specific FRAX models in the US, suggesting they should be based on updated data related to fracture and death risks.
  • * The position opposing fixed bone mineral density thresholds is supported by the International Osteoporosis Foundation (IOF) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), emphasizing the need for equity in fracture risk assessment.
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  • - The International Osteoporosis Foundation (IOF) has published a position paper addressing partnerships with scientists from countries involved in armed conflicts.
  • - A commission within the IOF has assessed and recommended guidelines for such collaborations to ensure ethical considerations are met.
  • - The IOF Board has unanimously adopted these findings and recommendations, emphasizing a commitment to responsible engagement in scientific partnerships.
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Background: Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.

Aim: We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.

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Purpose Of Review: The assessment of fracture risk is playing an ever-increasing role in osteoporosis clinical management and informing international guidelines for osteoporosis. FRAX, a fracture risk calculator that provides individualized 10-year probabilities of hip and major osteoporotic fracture, has been widely used since 2008. In this review, we recap the development and limitations of intervention thresholds and the role of absolute fracture risk.

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Article Synopsis
  • - The study aims to create a consensus in the Asia-Pacific region on long-term management and sequential therapy for osteoporosis, focusing on effective fracture prevention through individualized treatment strategies.
  • - A panel of experts analyzed current literature and expert opinions, resulting in 12 key recommendations, such as using anabolic agents for high fracture risk patients and switching to antiresorptive agents post-anabolic therapy if needed.
  • - The findings offer a cost-effective framework for osteoporosis management, emphasizing shared decision-making and integration of local healthcare systems to enhance patient care in the Asia-Pacific region.
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Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018.

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Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites.

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Article Synopsis
  • Osteoporosis has traditionally been seen as a women's disease, but recent evidence highlights its significant impact on men, necessitating more balanced research and guidelines for both genders.
  • An international working group has developed GRADE-assessed recommendations focusing on diagnosing, monitoring, and treating osteoporosis in men, based on a thorough review of current research.
  • Key areas of focus include understanding bone densitometry interpretations, treatment thresholds, and evaluating the economic impact of interventions, while future research needs to explore the effectiveness of various osteoporosis medications.
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The purpose of this study was to investigate the prevalence of three sarcopenia definitions and their associations with fracture risk in older Swedish women when adjusted for fracture risk assessment (FRAX)-based risk factors; 2,883 women with a mean age of 77.8 years were included. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC; low handgrip strength [kg] and gait speed (m/s)), revised European Working Group on Sarcopenia in Older People (EWGSOP2; low appendicular lean mass index, appendicular lean mass [ALM]/height; kg/m2], and hand grip strength [kg]), and Asian Working Group for Sarcopenia (AWGS; low ALM (kg), and hand grip strength [kg]) definitions.

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Context: The addition of androgen receptor signalling inhibitors (ARSIs) to standard androgen deprivation therapy (ADT) has improved survival outcomes in patients with advanced prostate cancer (PCa). Advanced PCa patients have a higher incidence of osteoporosis, compounded by rapid bone density loss upon commencement of ADT resulting in an increased fracture risk. The effect of treatment intensification with ARSIs on fall and fracture risk is unclear.

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  • A meta-analysis of data from 46 cohorts found that individuals who reported falling in the past year had an increased risk of fractures, highlighting falls as an important factor for fracture risk assessment.
  • Previous falls were correlated with a significant rise in fracture risks for both men and women, with hazard ratios indicating that the risk is greater for men.
  • The study suggests that falls should be included in the FRAX® algorithm, which currently does not consider this important risk factor for osteoporotic fractures.
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  • Osteoporosis is diagnosed using bone mineral density (BMD) measured by DXA, but other skeletal factors also impact bone strength and fracture risk.
  • Lumbar spine texture analysis (TBS) enhances fracture prediction beyond BMD and can be used to refine fracture risk assessments, particularly for patients aged 40 and older who are nearing treatment thresholds.
  • Recommendations include using TBS from L1-L4 vertebrae for adjusted FRAX calculations and noting that TBS changes may not be useful with current methods, although future updates to the algorithm may improve its effectiveness.
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Objectives: FRAX uses clinical risk factors, with or without BMD, to calculate 10-year fracture risk. RA is a risk factor for osteoporotic fracture and a FRAX input variable. FRAX predates the current era of RA treatment.

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