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Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40-70%), nonvertebral (by 25-40%) and hip fractures (by 40-53%) in postmenopausal women with osteoporosis. Due to the risk of rare side-effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well-proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk-based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long-term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone-building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long-term fracture prevention and should be the golden standard of future osteoporosis treatment., (© 2019 The Association for the Publication of the Journal of Internal Medicine.)

Background: The importance of the gut microbiome for bone metabolism in mice has recently been demonstrated, but no studies are available in humans. Lactobacillus reuteri ATCCPTA 6475 (L. reuteri 6475) has been reported to increase bone mineral density (BMD) in mice but its effect on the human skeleton is unknown. The objective of this trial was to investigate if L. reuteri 6475 affects bone loss in older women with low BMD., Methods: In this double-blind, placebo-controlled study, women from the population who were 75 to 80 years old and had low BMD were randomized to orally receive 10 10 colony-forming units of L. reuteri 6475 daily or placebo. The predefined primary end-point was relative change after 12 months in tibia total volumetric BMD (vBMD)., Results: Ninety women were included and 70 completed the study. L. reuteri 6475 reduced loss of total vBMD compared to placebo both in the intention-to-treat (ITT) analysis [-0.83% (95% confidence interval [CI], -1.47 to -0.19%) vs. -1.85% (95% CI, -2.64 to -1.07%); mean difference 1.02% (95% CI, 0.02-2.03)] and per protocol analysis [-0.93% (95% CI, -1.45 to -0.40) vs. -1.86% (95% CI, -2.35 to -1.36); mean difference 0.93% (95% CI, 0.21-1.65)]. In general, similar but smaller effects were observed in the secondary bone variable outcomes, but these differences did not reach statistical significance in the ITT population. Adverse events did not differ between groups., Conclusions: Supplementation with L. reuteri 6475 should be further explored as a novel approach to prevent age-associated bone loss and osteoporosis., (© 2018 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: There is high evidence for secondary prevention of fractures, including hip fracture, with alendronate treatment, but alendronate's efficacy to prevent hip fractures in the oldest-old (≥80 years old), the population with the highest fracture risk, has not been studied., Objective: To investigate whether alendronate treatment amongst the oldest-old with prior fracture was related to decreased hip fracture rate and sustained safety., Methods: Using a national database of men and women undergoing a fall risk assessment at a Swedish healthcare facility, we identified 90 795 patients who were 80 years or older and had a prior fracture. Propensity score matching (four to one) was then used to identify 7844 controls to 1961 alendronate-treated patients. The risk of incident hip fracture was investigated with Cox models and the interaction between age and treatment was investigated using an interaction term., Results: The case and control groups were well balanced in regard to age, sex, anthropometrics and comorbidity. Alendronate treatment was associated with a decreased risk of hip fracture in crude (hazard ratio (HR) 0.62 (0.49-0.79), P < 0.001) and multivariable models (HR 0.66 (0.51-0.86), P < 0.01). Alendronate was related to reduced mortality risk (HR 0.88 (0.82-0.95) but increased risk of mild upper gastrointestinal symptoms (UGI) (HR 1.58 (1.12-2.24). The alendronate association did not change with age for hip fractures or mild UGI., Conclusion: In old patients with prior fracture, alendronate treatment reduces the risk of hip fracture with sustained safety, indicating that this treatment should be considered in these high-risk patients., (© 2017 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual-energy X-ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength., Objective: To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD)., Methods: From an ongoing population-based study, we identified 46 women with a prevalent X-ray-verified hip fracture and 361 control subjects without any fractures. aBMD was measured with DXA. High-resolution peripheral quantitative computed tomography was used to measure bone microstructure at the standard (ultradistal) site and at 14% (distal) of the tibial length., Results: Women with a previous hip fracture had lower aBMD at the femoral neck (-11.8%) and total hip (-14.6%) as well as higher cortical porosity at the ultradistal (32.1%) and distal (29.3%) tibia compared with controls. In multivariable logistic regression analysis, with adjustment for covariates (age, height, weight, smoking, calcium intake, physical activity, walk time, oral glucocorticoids, parental hip fracture, rheumatoid arthritis, previous fall, current bisphosphonate treatment and femoral neck aBMD), cortical porosity at the ultradistal [odds ratio per standard deviation increase (95% confidence interval) 2.61 (1.77-3.85)] and distal [1.57 (1.12-2.20)] sites was associated with prevalent hip fracture., Conclusion: Cortical porosity was associated with prevalent hip fracture in older women independently of femoral neck aBMD and clinical risk factors., (© 2017 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Bone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported., Objective: To investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men., Methods: A population-based cohort of 444 elderly men (mean ± SD age 80.2 ± 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay., Results: Mean cortical porosity at the distal tibia was 14.7% higher (12.5 ± 4.3% vs. 10.9 ± 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L -1 ) or insufficiency [25-49 nmol L -1 , in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L -1 )], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized β = -0.110, R 2 = 1.1%, P = 0.024), area (β = 0.123, R 2 = 1.4%, P = 0.007) and cortical volumetric BMD (β = 0.125, R 2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck (β = 0.102, R 2 = 0.9%, P = 0.04)., Conclusion: Serum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry., (© 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: It has been suggested that osteoblasts are involved in the regulation of haematopoietic stem cells. Whether osteocalcin, which is derived from osteoblasts and is metabolically active, influences blood haemoglobin (Hb) levels is not known., Objective: To determine whether plasma osteocalcin is a determinant of Hb in elderly men., Methods: A total of 993 men (mean age 75.3 ± 3.2 years) participated in the population-based MrOS (osteoporotic fractures in men) study. Plasma osteocalcin concentration was evaluated in relation to Hb and adjustments were made for potential confounders (i.e. age, body mass index, erythropoietin, total oestradiol, fasting insulin, adiponectin, ferritin and cystatin C)., Results: Hb correlated (age adjusted) negatively with osteocalcin in the total study group (r = -0.12, P < 0.001) as well as in the subgroup of nondiabetic men (r = -0.16, P < 0.001). In nondiabetic men with higher osteocalcin levels, it was more likely that Hb would be in the lowest quartile (odds ratio per SD decrease in osteocalcin 1.32, 95% confidence interval 1.13-1.53). Quartiles of Hb were negatively associated (age adjusted) with osteocalcin (P < 0.001). Anaemic men (47/812) (Hb <130 g L(-1) ) had significantly higher mean osteocalcin levels than nonanaemic men (33.9 vs. 27.1 μg L(-1) , P < 0.001). In multiple stepwise linear regression analyses (adjusted for age, body mass index, total oestradiol, adiponectin, erythropoietin, fasting insulin, cystatin C, leptin, ferritin and holotranscobalamin), osteocalcin was an independent predictor of Hb concentration in nondiabetic men (P < 0.05)., Conclusions: These data add further support to the evidence indicating that the bone-specific protein osteocalcin has several endocrine functions targeting the pancreas, testes, adipocytes, brain. An additional novel finding is that osteocalcin may also have a paracrine function as a regulator of haematopoiesis., (© 2016 The Association for the Publication of the Journal of Internal Medicine.)

Objectives: Blood haemoglobin (Hb) concentration declines in elderly men, whilst the level of the adipocyte-derived protein adiponectin increases with age. The association between erythropoiesis and adiponectin in elderly men is unclear. The aim of this study was to determine whether adipokines such as adiponectin and leptin are associated with anaemia and Hb concentration in elderly community-dwelling men., Design and Setting: The Gothenburg part of the population-based Swedish Osteoporotic Fractures in Men (MrOS) cohort (n = 1010; median age 75.3 years, range 69-81)., Main Outcome Measures: We investigated the associations between levels of adiponectin and Hb before and after adjusting for potential confounders [i.e. age, body composition, erythropoietin (EPO), total oestradiol, leptin, cystatin C and iron and B vitamin status]., Results: In these elderly men, age was negatively associated with Hb (r = -0.12, P < 0.001) and positively associated with adiponectin level (r = 0.13, P < 0.001). In age-adjusted partial correlations, Hb and adiponectin levels were negatively correlated (r = -0.20, P < 0.001); this association remained significant after multivariable adjustment for age, body composition, EPO, fasting insulin, sex hormones, leptin and ferritin. Age-adjusted mean adiponectin concentrations were significantly higher in anaemic men (66/1005; Hb <130 g L(-1) ) compared to nonanaemic men (14.0 vs. 11.7 μg mL(-1) , P < 0.05). In multivariate analysis, adiponectin together with EPO, total oestradiol, insulin, albumin, transferrin saturation, HDL cholesterol, cystatin C, total body fat mass and free thyroxine, but not leptin, explained 35% of the variation in Hb level. These results remained essentially unchanged after exclusion of men with diabetes., Conclusions: Serum adiponectin, but not leptin, was negatively and independently associated with Hb. This finding suggests a possible role of adiponectin in the age-related decline in Hb level observed in apparently healthy elderly men., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

The global trend towards increased longevity has resulted in ageing populations and a rise in diseases or conditions that primarily affect older persons. One such condition is osteoporosis (fragile or porous bones), which causes an increased fracture risk. Vertebral and hip fractures lead to increased morbidity and mortality and result in enormous healthcare costs. Here, we review the evolution of the diagnosis of osteoporosis. In an attempt to separate patients with normal bones from those with osteoporosis and to define the osteoporosis diagnosis, multiple factors and characteristics have been considered. These include pathology and histology of the disease, the endocrine regulation of bone metabolism, bone mineral density (BMD), fracture type or trauma severity, risk models for fracture prediction, and thresholds for pharmacological intervention. The femoral neck BMD -2.5 SDs cut-off for the diagnosis of osteoporosis is arbitrarily chosen, and there is no evidence to support the notion that fracture location (except vertebral fractures) or severity is useful to discriminate osteoporotic from normal bones. Fracture risk models (including factors unrelated to bone) dissociate bone strength from the diagnosis, and treatment thresholds are often based on health-economic considerations rather than bone properties. Vertebral fractures are a primary feature of osteoporosis, characterized by decreased bone mass, strength and quality, and a high risk of another such fracture that can be considerably reduced by treatment. We believe that the 2001 definition of osteoporosis by the National Institutes of Health Consensus Development Panel on Osteoporosis is still valid and useful: 'Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture'., (© 2015 The Association for the Publication of the Journal of Internal Medicine.)

Aim: To report a literature study of leadership for learning in clinical practice in the United Kingdom. Background Previous research in the United Kingdom showed that the ward sister was central to creating a positive learning environment for student nurses. Since the 1990s, the ward mentor has emerged as the key to student nurses' learning in the United Kingdom., Methods: A literature study of new leadership roles and their influence on student nurse learning (restricted to the United Kingdom) which includes an analysis of ten qualitative interviews with stakeholders in higher education in the United Kingdom undertaken as part of the literature study., Results: Learning in clinical placements is led by practice teaching roles such as mentors, clinical practice facilitators and practice educators rather than new leadership roles. However, workforce changes in clinical placements has restricted the opportunities for trained nurses to role model caring activities for student nurses and university based lecturers are increasingly distant from clinical practice., Conclusions and Implications for Practice: Leadership for learning in clinical practice poses three unresolved questions for nurse managers, practitioners and educators - what is nursing, what should student nurses learn and from whom?, Implications for Nursing Management: Leadership for student nurse learning has passed to new learning and teaching roles with Trusts and away from nursing managers. This has implications for workforce planning and role modelling within the profession.

Objectives: Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor alpha (ORalpha) gene and in the transforming growth factor beta (TGF-beta1) gene were related to the presence of AS in postmenopausal women., Design: Case-control study., Subjects and Methods: Relationships were tested between polymorphisms in the ORalpha gene defined by the restriction enzymes PvuII and XbaI, and in the TGF-beta1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age- and sex-matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 +/- 1.2 years., Results: In the postmenopausal patients and age-matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13-10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF-beta1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68-12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low-density lipoprotein cholesterol (LDL) (P = 0.04)., Conclusions: We have demonstrated that the PvuII polymorphism in the ORalpha gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels.

This paper is based mainly on archival research. It is focused on letters from Florence Nightingale to one of her favourites, Rachel Williams, the reforming 19th century matron of St Mary's Hospital, Paddington, who established the nurse training school in 1877. Discussion centres on Miss Nightingale's mentoring of Miss Williams, both in terms of personal/pastoral and more objective management advice. The discussion is then related to current theories of mentoring in nurse management. It would appear that Nightingale and modern mentors follow the same main precept of 'having the best interests of the mentored person at heart'. Differences relate more to style of expression than to the basic principles of mentorship.

Aim: The intention is to highlight key issues related to research by nurse and midwifery teachers., Background: The debate centres on the 'culture change' facing teachers from traditional colleges moving to universities where a more formal research requirement prevails., Origins of Information: Data were drawn from selected official reports and other literature informing the introductory discussion. Emerging themes were discussed by 25 nurse and midwife teachers at Forresterhill College, Aberdeen in March 1996 and their views were recorded and analysed., Data Analysis: Selected documents and discussion records were reviewed, using a thematic approach., Key Issues: Main themes concerned nursing as art and science, balance between multidisciplinary and unidisciplinary research and ring-fencing nursing research funds., Conclusions: Anxieties among teachers centred on the increased research requirement in universities with possible neglect of teaching excellence.

A historical overview of nurse leadership in the late 19th and late 20th centuries is presented, supported by relevant material from the literature. The 19th century material revealed the following main themes: emphasis on practical and domestic aspects of management; prominent input of religious ideals and social conscience and, autocratic and feminized style of leadership. The main themes in the contemporary literature examined were: role models in history, dysfunctional leadership styles, importance of knowledge, gender as an influencing factor on nurse leadership and threats to the autonomy of nurse leaders. It was concluded that formal nurse professionalization has progressed steadily during the past hundred years with associated evolution of nurse leaders to fit in with contemporary needs. It is hoped that future policies for nursing will encourage decision-making nearer the 'bed-side', more resource-driven care and value-based leadership.

An increased emphasis on quality assurance in the National Health Service (NHS) became evident in the literature related to health following the Government's White Paper, "Working for Patients" (1989) and the Patients' Charter (1991). The latter included specific quality standards to which purchasers and providers of health care made a commitment. This review of published and un-published (grey) literature concentrates on patient views about outpatient services in British hospitals, with special emphasis on the role of nurses. Findings indicate central emphasis on easily measurable factors, such as waiting times in outpatient departments and comparative neglect of more qualitative aspects, which may be of greater importance to patients. Specific attention has been given to exploring the role of nurses working in the outpatient department, which appears to be under-researched, based on this selective literature review.

The results of a national survey of hospital patients as they relate to nursing are presented. A brief review of the literature locates the study in the context of developments in nursing quality assurance, examining, in particular, conceptual issues of how the nursing process may be measured, and the role of the nursing profession in quality assurance. Results of the study identify a number of problems with the process of nursing care, including pain management, discharge planning and physical care, with wide variation between hospitals on many issues. The implications of these results for managers of nursing are discussed.

Early nursing reforms in the 19th century are usually associated with Nightingale, although later emphasis has been placed on similar movements in the Poor Law sector. Extension of nursing influence over decision-making in terms of nursing practice and education is charted, using examples from 19th century Minutes of hospital committees and more recent experience based mainly on the observations made by one of the writers, who had substantial input into steering the hospital through the stages prior to achieving National Health Service (NHS) Trust status. The significance of nurse executive power following the 1990s NHS reforms is highlighted and means of extending the use of this authority are explored.