Key insights into antiresorptive drug use and osteonecrosis in osteoporotic patients undergoing tooth extractions: A clinical and CBCT assessment.

This study investigates the effects of antiresorptive drugs and risk factors for medication-related osteonecrosis of the jaws in osteoporotic patients undergoing tooth extraction. Among the findings, antiresorptive-treated patients had thicker lamina dura and longer healing times. Additionally, corticosteroid intake and multi-rooted teeth carried a higher osteonecrosis risk. Bone sequestrum indicated osteonecrosis. PURPOSE: To describe the effects of antiresorptive drugs (ARD) in the maxilla and mandible and risk factors for medication-related osteonecrosis of the jaws (MRONJ) in osteoporotic patients undergoing tooth extractions using clinical data and cone beam computed tomography (CBCT). METHODS: This retrospective cohort study collected clinical and CBCT data from 176 patients. The study group (n = 78; 224 extractions) received ARD treatment, underwent tooth extraction, and had a pre-operative CBCT. Additionally, age-, sex-, and tooth-matched controls were selected (n = 98; 227 extractions). Radiographic examinations were performed independently by three calibrated examiners. Statistical analysis included Chi-square, Fisher's exact, Mann-Whitney U, and t-tests to contrast clinical and radiographic data between study and control, MRONJ + and MRONJ - , and bisphosphonate and denosumab patients/sites. Significance was set at p ≤ 0.05. RESULTS: From the study group, 4 patients (5%) and 5 sites (2%) developed MRONJ after tooth extraction. ARD-treated patients exhibited significantly more thickening of the lamina dura and a longer average mucosal healing time (4.4 weeks) than controls (2.6 weeks). In the study group, MRONJ risk significantly increased with corticosteroid intake and in multi-rooted teeth. No significant differences between bisphosphonates and denosumab use were seen in the tomographic features (p > 0.05). Lastly, bone sequestrum was exclusively observed in osteoporotic patients, who exhibited post-operative exposed bone or histological evidence of osteonecrosis. CONCLUSION: Osteoporotic patients under ARD may exhibit thickening of the lamina dura and prolonged post-operative healing. Among these patients, multi-rooted teeth are at higher risk for MRONJ than single-rooted teeth. Sequester formation is a radiographic indicator of osteonecrosis.

Semi-automatic proximal humeral trabecular bone density assessment tool: technique application and clinical validation.

PURPOSE: This study aimed to apply a newly developed semi-automatic phantom-less QCT (PL-QCT) to measure proximal humerus trabecular bone density based on chest CT and verify its accuracy and precision. METHODS: Subcutaneous fat of the shoulder joint and trapezius muscle were used as calibration references for PL-QCT BMD measurement. A self-developed algorithm based on a convolution map was utilized in PL-QCT for semi-automatic BMD measurements. CT values of ROIs used in PL-QCT measurements were directly used for phantom-based quantitative computed tomography (PB-QCT) BMD assessment. The study included 376 proximal humerus for comparison between PB-QCT and PL-QCT. Two sports medicine doctors measured the proximal humerus with PB-QCT and PL-QCT without knowing each other's results. Among them, 100 proximal humerus were included in the inter-operative and intra-operative BMD measurements for evaluating the repeatability and reproducibility of PL-QCT and PB-QCT. RESULTS: A total of 188 patients with 376 shoulders were involved in this study. The consistency analysis indicated that the average bias between proximal humerus BMDs measured by PB-QCT and PL-QCT was 1.0 mg/cc (agreement range - 9.4 to 11.4; P > 0.05, no significant difference). Regression analysis between PB-QCT and PL-QCT indicated a good correlation (R-square is 0.9723). Short-term repeatability and reproducibility of proximal humerus BMDs measured by PB-QCT (CV: 5.10% and 3.41%) were slightly better than those of PL-QCT (CV: 6.17% and 5.64%). CONCLUSIONS: We evaluated the bone quality of the proximal humeral using chest CT through the semi-automatic PL-QCT system for the first time. Comparison between it and PB-QCT indicated that it could be a reliable shoulder BMD assessment tool with acceptable accuracy and precision. This study developed and verify a semi-automatic PL-QCT for assessment of proximal humeral bone density based on CT to assist in the assessment of proximal humeral osteoporosis and development of individualized treatment plans for shoulders.

Automated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning.

Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = -0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.

Assessment of the Methods Used to Develop Vitamin D and Calcium Recommendations-A Systematic Review of Bone Health Guidelines.

BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.

Bone Mineral Density: Clinical Relevance and Quantitative Assessment.

Bone mineral density (BMD) measurement by dual-energy x-ray absorptiometry (DXA) is an internationally accepted standard-of-care screening tool used to assess fragility-fracture risk. Society guidelines have recommended which populations may benefit from DXA screening and the use of the fracture risk assessment tool (FRAX) to guide decisions regarding pharmacologic treatment for osteoporosis. According to the U.S. National Osteoporosis Foundation guidelines, postmenopausal women and men at least 50 y old with osteopenic BMD warrant pharmacologic treatment if they have a FRAX-calculated 10-y probability of at least 3% for hip fracture or at least 20% for major osteoporotic fracture. Patients with osteoporosis defined by a clinical event, namely a fragility fracture, or with an osteoporotic BMD should also be treated. Patients who are treated for osteoporosis should be monitored regularly to track expected gains in BMD by serial DXA scans. With some drug therapies, BMD targets can be reached whereby further improvements in BMD are not associated with further reductions in fracture risk. Although reaching this target might suggest a stopping point for therapy, the reversibility of most treatments for osteoporosis, except for the bisphosphonates, has dampened enthusiasm for this approach. In the case of denosumab, it is now apparent that stopping therapy at any point can lead to an increase in multiple-fracture risk. For patients who do not respond to antiosteoporosis pharmacologic therapy with an improvement in BMD, or who have an incident fragility fracture on therapy, secondary causes of osteoporosis or non-compliance with medical therapy should be considered.

Overview of Skeletal Repair (Fracture Healing and Its Assessment).

The study of postnatal skeletal repair is of immense clinical interest. Optimal repair of skeletal tissue is necessary in all varieties of elective and reparative orthopedic surgical treatments. However, the repair of fractures is unique in this context in that fractures are one of the most common traumas that humans experience and are the end-point manifestation of osteoporosis, the most common chronic disease of aging. In the first part of this introduction the basic biology of fracture healing is presented. The second part discusses the primary methodological approaches that are used to examine repair of skeletal hard tissue and specific considerations for choosing among and implementing these approaches.

Updates in epidemiology, pathophysiology and management strategies of glucocorticoid-induced osteoporosis.

INTRODUCTION: Endogenous or exogenous (corticosteroid-induced) glucocorticoids (GCs) excess represents, together with diabetes, the most common cause of secondary osteoporosis. AREAS COVERED: We present a comprehensive overview about the pathophysiology, clinical management and treatment of GCs induced osteoporosis (GIOP). According to PRISMA guidelines, a literature search identifying articles about bone and GCs was done. EXPERT OPINION: Despite the progress over the years and the increase in therapeutic options, there still are controversial issues about the management of GIOP. These mainly include the failure of BMD or FRAX to completely account for the rapid increase in fracture risk of most GC-treated patients, the understanding about the independent contribution on bone fragility of the underlying disease requiring GCs therapy, and the necessity of clearer information about the anti-fracture efficacy and long term-safety of most therapeutic options. Moreover, there are no specific indications for the management of bone fragility in endogenous hypercortisolism. Notwithstanding the above limitations there is a general consensus to recommend an assessment of fracture risk in all individuals >40 years committed to receive (or continuing) high dose (>7.5 mg of prednisone equivalent) GCs for ≥3 months and in all patients with fragility fracture history.

Assessment of the effect of pulsed electromagnetic field application on the healing of bone defects in rats with heparin-induced osteoporosis.

Osteoporosis is a systemic skeletal disease characterized by an increase in bone fragility and fracture risk due to low bone mass and deterioration of bone tissue. Application of pulsed electromagnetic fields (PEMF), a non-invasive method with a low complication risk, is known to stimulate bone formation. The present study examines the histomorphometric and biochemical effects of PEMF application on the healing of bone defects in rats with heparin-induced secondary osteoporosis. Briefly, 12-month-old male Sprague-Dawley rats were examined in a prospective, randomized, single-blind study. Osteoporosis was induced by administering a daily dose of 2 IU/g heparin for 33 days. Bone defects were created on the right femur on Day 35. PEMF of an average intensity of 0.8 ± 0.2 mT and a frequency of 7.3 Hz, was applied for 1 h/day, for 28 days following surgery. Bone healing was evaluated by histomorphometric and biochemical analyses. The heparin + PEMF group displayed the largest amount of new bone area (P = .002) and the lowest mean CTx on Day 63 (P = .05). This study demonstrates that heparin administration leads to bone loss and osteoporosis, whereas the application of PEMF decreases this effect.

Osteoporosis epidemiology using international cohorts.

PURPOSE OF REVIEW: The field of osteoporosis research has been active for the past 20 years and has allowed significant advancement in the management of osteoporosis. This review will give an overview of the latest data from international cohorts that relate to current and recent osteoporosis research. RECENT FINDINGS: The clinical diagnosis of osteoporosis relies heavily on bone mineral density (BMD) measured at femoral neck or spine and although BMD has excellent predictive value for future fractures, fracture risk assessment has evolved over the years, resulting in the birth of fracture prediction tools. Fracture risk factors not currently featured in these tools are being considered for inclusion, including imminent risk fracture following a sentinel fracture, number of falls, and previous vertebral fractures. Data from groups with comorbidities such as chronic obstructive pulmonary disease are helping us understand how to best manage patients with multiple comorbidities. Finally, the prevalence of vertebral fracture in the older general population and other selected populations has been explored, alongside the global burden of osteoporosis and its consequences. SUMMARY: Our understanding of osteoporosis continues to expand, but knowledge gaps remain.

Quantitative assessment of acetabular bone defects: A study of 50 computed tomography data sets.

OBJECTIVES: Acetabular bone defect quantification and classification is still challenging. The objectives of this study were to suggest and define parameters for the quantification of acetabular bone defects, to analyze 50 bone defects and to present the results and correlations between the defined parameters. METHODS: The analysis was based on CT-data of pelvises with acetabular bone defects and their reconstruction via a statistical shape model. Based on this data, bone volume loss and new bone formation were analyzed in four sectors (cranial roof, anterior column, posterior column, and medial wall). In addition, ovality of the acetabulum, lateral center-edge angle, implant migration, and presence of wall defects were analyzed and correlations between the different parameters were assessed. RESULTS: Bone volume loss was found in all sectors and was multidirectional in most cases. Highest relative bone volume loss was found in the medial wall with median and [25, 75]-percentile values of 72.8 [50.6, 95.0] %. Ovality, given as the length to width ratio of the acetabulum, was 1.3 [1.1, 1.4] with a maximum of 2.0, which indicated an oval shape of the defect acetabulum. Lateral center-edge angle was 30.4° [21.5°, 40.4°], which indicated a wide range of roof coverage in the defect acetabulum. Total implant migration was 25.3 [14.8, 32.7] mm, whereby cranial was the most common direction. 49/50 cases showed a wall defect in at least one sector. It was observed that implant migration in cranial direction was associated with relative bone volume loss in cranial roof (R = 0.74) and ovality (R = 0.67). CONCLUSION: Within this study, 50 pelvises with acetabular bone defects were successfully analyzed using six parameters. This could provide the basis for a novel classification concept which would represent a quantitative, objective, unambiguous, and reproducible classification approach for acetabular bone defects.

Osteoporosis in patients with dementia is associated with high morbidity and mortality: Findings from a single orthogeriatric unit.

BACKGROUND AND OBJECTIVES: Osteoporosis and dementia are common and associated with a high healthcare burden. The aim of this paper was to assess the impact of dementia on treatment, morbidity and mortality in osteoporosis. METHOD: Data were collected on 502 prospective orthogeriatric admissions for fracture. Fisher's exact chi-square was used to compare treatment stratified by dementia status. RESULTS: Of the 502 patients, 281 (56%) had osteoporosis, 226 (45%) had dementia,  and 156 (31%) had dementia and osteoporosis diagnosed before they sustained fractures. Patients with dementia were more likely to have osteoporosis but less likely to be receiving treatment. Although there was a significant improvement in discharge versus admission rates of osteoporosis treatment, those with dementia were less likely to be treated with antiresorptive therapy (36%, compared with 59%, P <0.001) or combined therapy (32%, compared with 56%, P <0.001) and had double the 90-day mortality (17.3%, compared with 9.6%) and six times the 30-day mortality (6.4%, compared with 1.6%). DISCUSSION: Patients with dementia and osteoporosis have a higher risk of recurrent fractures and mortality. Prevention may be the key strategy.

Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study.

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. INTRODUCTION: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. METHODS: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. RESULTS: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. CONCLUSIONS: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.

Assessment of Muscle Function and Physical Performance in Daily Clinical Practice : A position paper endorsed by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test-retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

Healthcare Resource Utilization and Direct Medical Costs for Patients With Osteoporotic Fractures in China.

OBJECTIVES: To estimate annual healthcare resource utilization and direct medical costs for patients with osteoporotic fractures in China. METHODS: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2008-2011). Included patients were 50 years or older with one or more diagnoses of osteoporotic fractures between 2009 and 2010. The annual healthcare resource utilization and direct medical costs were estimated. Regression model was applied to identify factors associated with the direct medical costs. RESULTS: A total of 5941 patients were included (mean age, 65.9 years; women, 62.1%; retired, 88.2%). During the 12 months after a fracture, the annual mean all-cause cost was $2549 per patient. Osteoporosis-related costs accounted for 53.8% of the total costs; 92.0% of these costs were for inpatient services. For osteoporosis-related health services, 33.2% of the patients experienced at least 1 hospitalization, with a mean cost of $3010 per admission; 83.2% of the patients experienced at least 1 outpatient visit, with a mean cost of $18 per visit during the 12-month follow-up period. The regression model revealed that osteoporosis-related costs tended to increase with age, and patients with hip, vertebral, lower leg, and multiple fractures were more likely to have higher costs. CONCLUSIONS: Costs for patients with osteoporotic fractures were considerable in China, driven mainly by osteoporosis-related hospitalizations. Efforts focused on reducing the utilization of inpatient services by lowering the fracture risks may lighten the economic burden of osteoporotic fractures in China.

Cost-Effectiveness of Osteoporosis Screening Using Biomechanical Computed Tomography for Patients With a Previous Abdominal CT.

Osteoporosis screening rates by DXA are low (9.5% women, 1.7% men) in the US Medicare population aged 65 years and older. Addressing this care gap, we estimated the benefits of a validated osteoporosis diagnostic test suitable for patients age 65 years and older with an abdominal computed tomography (CT) scan taken for any indication but without a recent DXA. Our analysis assessed a hypothetical cohort of 1000 such patients in a given year, and followed them for 5 years. Separately for each sex, we used Markov modeling to compare two mutually exclusive scenarios: (i) utilizing the CT scans, perform one-time "biomechanical computed tomography" (BCT) analysis to identify high-risk patients on the basis of both femoral strength and hip BMD T-scores; (ii) ignore the CT scan, and rely instead on usual care, consisting of future annual DXA screening at typical Medicare rates. For patients with findings indicative of osteoporosis, 50% underwent 2 years of treatment with alendronate. We found that BCT provided greater clinical benefit at lower cost for both sexes than usual care. In our base case, compared to usual care, BCT prevented hip fractures over a 5-year window (3.1 per 1000 women; 1.9 per 1000 men) and increased quality-adjusted life years (2.95 per 1000 women; 1.48 per 1000 men). Efficacy and savings increased further for higher-risk patient pools, greater treatment adherence, and longer treatment duration. When the sensitivity and specificity of BCT were set to those for DXA, the prevented hip fractures versus usual care remained high (2.7 per 1000 women; 1.5 per 1000 men), indicating the importance of high screening rates on clinical efficacy. Therefore, for patients with a previously taken abdominal CT and without a recent DXA, osteoporosis screening using biomechanical computed tomography may be a cost-effective alternative to current usual care. © 2019 American Society for Bone and Mineral Research.

Osteoporosis is inversely associated with arterial stiffness in the elderly: An investigation using the Osteoporosis Self-assessment Tool for Asians index in an elderly Chinese cohort.

Although the association of arterial stiffness and osteoporosis has been reported, the relation of arterial stiffness with risk of osteoporosis and bone fracture is not established. The authors investigated the correlation between arterial stiffness (brachial-ankle pulse wave velocity [baPWV]), including a cutoff value, and risk of osteoporosis as assessed by the Osteoporosis Self-assessment Tool for Asia (OSTA) index in 129 elderly Chinese community-dwelling individuals (age 83.2 ± 12.8 years, 63 females). OSTA was negatively correlated with baPWV (r = -0.326, P = 0.023) after adjusting for confounding factors such as gender, body mass index, low-density lipoprotein, triglycerides, estimated glomerular filtration rate, absence or presence of diabetes, absence or presence of hypertension, and uric acid. baPWV was an independent factor for changes in OSTA (ß = -0.001, P = 0.002). ROC curve analysis confirmed association between baPWV and OSTA index (AUC = 0.742 [CI: 0.660, 0.824]; P < 0.001) with a baPWV cutoff value of 1676 cm/s (sensitivity, 80.7%; specificity, 60%) for prediction of high OSTA index. The study showed a significant correlation between OSTA index and baPWV, suggesting a potential predictive value of baPWV in elderly patient at high risk of osteoporosis.

Current and Emerging Diagnostic Imaging-Based Techniques for Assessment of Osteoporosis and Fracture Risk.

Osteoporosis is a metabolic bone disorder characterized by low bone mass, degradation of bone microarchitecture, and susceptibility to fracture. It is a growing major health concern across the world, especially in the elderly population. Osteoporosis can cause hip or spinal fractures that may lead to high morbidity and socio-economic burden. Therefore, there is a need for early diagnosis of osteoporosis and prediction of fragility fracture risk. In this review, state of the art and recent advances in imaging techniques for diagnosis of osteoporosis and fracture risk assessment have been explored. Segmentation methods used to segment the regions of interest and texture analysis methods used for classification of healthy and osteoporotic subjects are also presented. Furthermore, challenges posed by the current diagnostic tools have been studied and feasible solutions to circumvent the limitations are discussed. Early diagnosis of osteoporosis and prediction of fracture risk require the development of highly precise and accurate low-cost diagnostic techniques that would help the elderly population in low economies.

Behavioural and objective vestibular assessment in persons with osteoporosis and osteopenia: a preliminary investigation / Behavioural and objective vestibular assessment in persons with osteoporosis and osteopenia: a preliminary investigation

Abstract Introduction: Calcium is vital for the functioning of the inner ear hair cells as well as for the neurotransmitter release that triggers the generation of a nerve impulse. A reduction in calcium level could therefore impair the peripheric vestibular functioning. However, the outcome of balance assessment has rarely been explored in cases with osteopenia and osteoporosis, the medical conditions associated with reduction in calcium levels. Objective: The present study aimed to investigate the impact of osteopenia and osteoporosis on the outcomes of behavioural and objective vestibular assessment tests. Methods: The study included 12 individuals each in the healthy control group and osteopenia group, and 11 individuals were included in the osteoporosis group. The groups were divided based on the findings of bone mineral density. All the participants underwent behavioural tests (Fukuda stepping, tandem gait and subjective visual vertical) and objective assessment using cervical and ocular vestibular evoked myogenic potentials. Results: A significantly higher proportion of the individuals in the two clinical groups' demonstrated abnormal results on the behavioural balance assessment tests (p < 0.05) than the control group. However, there was no significant difference in latencies or amplitude of cervical vestibular evoked myogenic potential and oVEMP between the groups. The proportion of individuals with absence of ocular vestibular evoked myogenic potential was significantly higher in the osteoporosis group than the other two groups (p < 0.05). Conclusion: The findings of the present study confirm the presence of balance-related deficits in individuals with osteopenia and osteoporosis. Hence the clinical evaluations should include balance assessment as a mandatory aspect of the overall audiological assessment of individuals with osteopenia and osteoporosis.

Resumo: Introdução: O cálcio é vital para o funcionamento das células ciliadas, assim como para a liberação dos neurotransmissores que desencadeiam um impulso nervoso. Uma redução nos níveis de cálcio poderia, portanto, prejudicar o funcionamento vestibular periférico. No entanto, a avaliação do equilíbrio tem sido raramente explorada em casos de osteopenia e osteoporose, condições médicas associadas à redução dos níveis de cálcio. Objetivo: O presente estudo teve como objetivo investigar o impacto da osteopenia e da osteoporose nos resultados dos testes de avaliação comportamental e vestibular objetiva. Método: O estudo incluiu 12 indivíduos nos grupos controle e grupo de osteopenia e 11 indivíduos no grupo da osteoporose. Os grupos foram divididos com base nos achados da densidade mineral óssea. Todos os participantes foram submetidos a testes comportamentais (Prova dos Passos de Fukuda, Marcha em tandem e Vertical Visual Subjetiva) e à avaliação objetiva com o uso de potenciais evocados miogênicos vestibulares cervical e ocular (cVEMP e oVEMP). Resultados: Uma proporção significativamente maior de indivíduos nos dois grupos com condições clínicas mostrou resultados anormais nos testes de avaliação comportamental e do equilíbrio (p < 0,05) do que o grupo controle. Embora não tenha havido diferença significativa nas latências ou na amplitude de cVEMP e oVEMP entre os grupos, a proporção de indivíduos com ausência de oVEMP foi significativamente maior no grupo da osteoporose do que nos outros dois grupos (p < 0,05). Conclusão: Os resultados do presente estudo demonstram a presença de déficits de equilíbrio em indivíduos com osteopenia e osteoporose. Assim, as avaliações clínicas gerais e audiológicas de indivíduos com osteopenia e osteoporose deveriam incluir a avaliação do equilíbrio como um aspecto obrigatório.

The role of illness burden in theory of mind performance among older adults.

Background/Study Context: Theory of Mind (ToM) reflects the ability to reason about mental states in order to understand and predict behavior. Research has identified links between increased pulse pressure, a measure of vascular health, and reduced cognitive ToM in older adults. However, the relationships between other vascular and nonvascular conditions and reduced ToM are unknown. We examined (1) illnesses as predictors of cognitive and affective ToM and (2) neurocognitive mediators of illness burden and ToM. METHODS: We used hierarchical regression and mediation to investigate the effects of vascular illness burden (hypertension, Type 2 diabetes, high cholesterol, and high pulse pressure) and nonvascular illness burden (osteoporosis, osteoarthritis, rheumatoid arthritis, and thyroid dysfunction) on cognitive and affective ToM in N = 86 community-dwelling older adults (59 females; 27 males, M age = 71.74 years). RESULTS: Vascular illness burden emerged as a significant predictor of older adults' cognitive ToM (R2 = .43, p < .001), and this relationship was mediated by executive functioning. Nonvascular illness burden did not predict cognitive nor affective ToM in this sample. CONCLUSION: Our findings highlight the specific importance of considering vascular health as a risk factor for declines in ToM in later life. Further elucidation of the associations between health, neurocognition, and ToM will be valuable in developing effective interventions for older adults given the high prevalence of vascular illness in later life.

Assessment of the genetic and clinical determinants of fracture risk: genome wide association and mendelian randomisation study.

OBJECTIVES: To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. DESIGN: Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. SETTING: 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. PARTICIPANTS: A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. RESULTS: Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10-68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture. CONCLUSIONS: This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.