Bisphosphonates for post-menopausal osteoporosis: are they all the same?

The primary goal of treatment for post-menopausal osteoporosis (PMO) is reduction in fracture risk. Therefore, clinicians must recommend therapies that are safe and have proven anti-fracture efficacy. Bisphosphonates have long been established as first-line therapy for osteoporosis and several of these drugs significantly reduce osteoporotic fracture risk. However, choosing among different bisphosphonates can represent a difficult clinical decision. This review outlines the pharmacology of various bisphosphonates, discusses how their pharmacological characteristics affect their efficacy, and summarizes clinical safety and efficacy data. Clinical trial data and the opinions of expert bodies suggest that alendronate, risedronate, ibandronate and zoledronic acid all provide fracture protection for patients with PMO. However, there are differences among these agents. For example, all four agents have demonstrated efficacy in preventing vertebral fractures, but only zoledronic acid and risedronate significantly reduce non-vertebral fracture risk in pivotal trials. Moreover, reduction in hip fracture risk has only been established for alendronate, risedronate and zoledronic acid. Current data suggest that ibandronate and zoledronic acid have the most persistent antifracture effect. Bisphosphonates have been associated with a number of side effects, the evidence for which is summarized in this review. The most pertinent of these when choosing a bisphosphonate for a particular patient are the well-documented associations between gastrointestinal adverse events and oral administration, and between acute phase reactions and intravenous administration. Ultimately, selection of a specific bisphosphonate for treatment of PMO should be based on efficacy, risk profile, cost-effectiveness and patient preferenc

Prevalence of vertebral fracture in oldest old nursing home residents

Summary: We evaluated vertebral fracture prevalence using DXA-based vertebral fracture assessment and its influence on the Fracture Risk Assessment (FRAX) tool-determined 10-year fracture probability in a cohort of oldest old nursing home residents. More than one third of the subjects had prevalent vertebral fracture and 50% osteoporosis. Probably in relation with the prevailing influence of age and medical history of fracture, adding these information into FRAX did not markedly modify fracture probability. Introduction: Oldest old nursing home residents are at very high risk of fracture. The prevalence of vertebral fracture in this specific population and its influence on fracture probability using the FRAX tool are not known. Methods: Using a mobile DXA osteodensitometer, we studied the prevalence of vertebral fracture, as assessed by vertebral fracture assessment program, of osteoporosis and of sarcopenia in 151 nursing home residents. Ten-year fracture probability was calculated using appropriately calibrated FRAX tool. Results: Vertebral fractures were detected in 36% of oldest old nursing home residents (mean age, 85.9 ± 0.6years). The prevalence of osteoporosis and sarcopenia was 52% and 22%, respectively. Ten-year fracture probability as assessed by FRAX tool was 27% and 15% for major fracture and hip fracture, respectively. Adding BMD or VFA values did not significantly modify it. Conclusion: In oldest old nursing home residents, osteoporosis and vertebral fracture were frequently detected. Ten-year fracture probability appeared to be mainly determined by age and clinical risk factors obtained by medical history, rather than by BMD or vertebral fractur

Reducing Stigma toward the Transgender Community: An Evaluation of a Humanizing and Perspective-Taking Intervention

Transgender (TG) individuals, or those whose gender identities, expressions and/or behaviors differ from their biological sex (Kirk & Kulkarni, 2006) feel there is a pervasive pattern of discrimination and prejudice directed toward them (Lombardi et al., 2001). In comparison to their heterosexual peers, LGBT youth and emerging adults are at increased risk for a host of adverse outcomes including: suicide, depression, harassment, and victimization (IOM, 2011). Stigma has been characterized as encompassing several components: labeling, making an association between the label and a negative stereotype, separating those who are different as an “out-group” and discriminating. In a recent analysis of the transgender experience, Hill (2002) described three key constructs that can be used to understand negative emotions and behaviors toward transgender individuals: transphobia – an emotional disgust toward gender non-conforming individuals; genderism – a belief that gender non-conforming individuals are pathological or disordered; gender bashing – assault or harassment of gender non-conforming individuals. Recent work on minority stress posits a distal-proximal model of stress in which a person identifies with and makes proximal, distal social attitudes that can have negative effects on their psychological well-being (Meyer, 2003). Thus, stigmatized attitudes and behaviors not only have the potential to contribute to violence or discriminatory behavior but also have a direct impact on the psychological health of the target individual. Thus, the question of how to change negative attitudes and behaviors toward TG individuals is paramount. Researchers have sought to develop interventions aimed at reducing stigma with three basic strategies identified: protest, education and contact (Corrigan & Penn, 1999). However, to date only two such strategies have garnered empirical support: contact and education. In relation to mental illness, education strategies have received limited support (Holmes et al., 1999; see Luty et al., 2007 for an exception). In contrast, contact-based interventions yield the most dramatic changes in attitudes and behaviors; contact involving media depictions have also been demonstrated to yield positive attitude change. Comparing traditional diagnosis-centered teaching about mental illness to a humanizing approach that required students to write a first-person narrative about suffering from a mental illness, Mann and Himelein (2008) found that attitudes changed only when students were required to adopt the perspective of a mentally ill individual. In their recent meta-analysis, Pettigrew and Tropp (2006) demonstrated that contact reduces prejudice and is particularly effective when it occurs under favorable conditions (e.g., conditions of equality, cooperation, and institutional support). While a wealth of research has supported the contact hypothesis related to changing negative attitudes toward ethnic minorities, the mentally ill, the homeless, gays/lesbians and other stigmatized groups, there have been a limited number of studies evaluating associations between contact and attitudes toward the TG community (Harvey, 2002; Hill & Willoughby, 2005) and no controlled studies to evaluate the efficacy of such methods. The current study extends work evaluating anti-stigma interventions to the TG community and seeks to evaluate whether attitude change will differ between participants receiving basic education about the transgender community and those who are educated about TG through media depictions of TG families and are asked to engage in a perspective-taking task. We hypothesize that participants in the humanizing condition who view a documentary and write a first-person narrative of transgender experiences will show a more significant change in transphobia, genderist attitudes and desire for social distance across time relative to participants in the education-only condition signaling less stigmatized and prejudicial attitudes at post-test. Hodson (2011) recently examined the existing contact literature and found that, consistent with Pettigrew’s (1998) focus on individual differences, intergroup contact was effective (and perhaps even more effective) among individuals who were intolerant and cognitively rigid. Religious fundamentalism has been associated with anti-homosexual sentiment (Fulton et al., 1999). Whether religiosity is similarly associated with negative attitudes toward TG individuals will be explored. Whether religiosity and prior contact with the LGBTQ community will moderate intervention outcomes will also be explored

Osteoporosis therapy: an example of putting evidence-based medicine into clinical practice

A major aim of evidence-based medicine is to assist clinical decision-making by providing the most current and reliable medical information. Systematic reviews and meta-analyses are important tools in this process. Systematic reviews identify and compile relevant evidence, while meta-analyses summarize and quantify the results of such reviews. Results from meta-analyses are, at present, the main source of summary evidence for the efficacy of treatments for a specific condition. They are important tools for helping to choose among treatment options, although they cannot be used to directly compare the magnitude of the effect of various therapies. However, the methods used and the consequent clinical value of the results, may be poorly understood by clinicians, who may therefore not take full advantage of the evidence. Recently, a panel of experts in osteoporosis and evidence-based medicine applied rigorous, validated, scientific standards to produce a systematic review and meta-analysis of randomized controlled trials of anti-resorptive agents used to treat osteoporosis. They found that, although several agents reduced the risk of vertebral fracture, only two, alendronate and risedronate, demonstrated convincing evidence for both non-vertebral and vertebral fracture risk reductions. The clinical implication of these results is that there are important differences in anti-fracture efficacy among currently available agents. In the absence of evidence from head-to-head clinical trials and because of the systematic nature and methodological rigor of the analyses, these data provide important information for clinical decision-makin

PTH improves titanium implant fixation more than pamidronate or renutrition in osteopenic rats chronically fed a low protein diet

Summary : We evaluated the effects of parathyroid hormone (PTH), pamidronate, or renutrition on osseointegration of titanium implants in the proximal tibia of rats subject to prolonged low-protein diets. PTH improved mechanical fixation, microarchitecture, and increased pull-out strength. Pamidronate or renutrition had lesser effects. PTH can thus improve implant osseointegration in protein-malnourished rats. Introduction: Protein malnutrition impairs implant osseointegration in rats. PTH and pamidronate prevent deleterious effects of protein restriction introduced just prior to implantation. Whether these treatments improve osseointegration after chronic protein deprivation, i.e., in osteopenic bone at time of implantation, is unknown. We evaluated effects of PTH, pamidronate, or renutrition on resistance to pull-out of titanium rods implanted into the rat tibiae following isocaloric low-protein intake. Methods: Forty-one adult female rats received normal or isocaloric low-protein diets. Six weeks later, implants were surgically inserted into proximal tibiae. Following implantation, rats on low-protein diets were treated with PTH (1-34), pamidronate, saline vehicle, or normal protein diets, for another 8weeks. Tibiae were removed for micro-computerised tomographic morphometry and evaluation of pull-out strength. Results: Pull-out strength decreased in rats on isocaloric low-protein diets compared with normal protein group (−33.4%). PTH increased pull-out strength in low-protein group, even compared to controls from the normal protein group. PTH and pamidronate increased bone volume/tissue volume, bone-to-implant contact, and trabecular thickness, whilst trabecular separation was reduced, with a shift to more plate-like bone surrounding the implants. Conclusions: PTH reversed the deleterious effects of long-term protein undernutrition on mechanical fixation and bone microarchitecture and improved implant osseointegration more than pamidronate or renutrition, likely through changes to structure model inde

Overvoltages in DC Urban Light Railway Systems: Statistical Analysis and Possible Causes

In DC light railway systems the equipment in the power substations and certain devices along the lines are protected against lightning overvoltages thanks to surge arresters. This paper analyses the overvoltages occurring on the tram network of Torino, Italy to discover the causes that brought to the explosion of several surge arresters in the past years. The cause is found to be the regenerative breaking of a particular type of vehicles, in conditions of low load in the system. The benefits of regenerative breaking are discussed in the light of the possible problems introduced. Finally, possible solutions are proposed

Heritable and nutritional influences on bone mineral mass

Osteoporosis is the net result of the maximal amount of bone mineral mass achieved by the end of pubertal growth (peak bone mass) minus post-menopausal and elderly bone losses. Peak bone mineral mass is determined from early childhood by both heritable and environmental factors. Recent developments in the molecular epidemiology of osteoporosis have shown the interest, but also the limitations, of specific molecular markers, such as the vitamin D receptor gene polymorphisms Bsm 1 and Fok 1, to explain bone mineral density differences across the population. Importantly, however, interactions between VDR gene polymorphisms and environmental factors, particularly dietary calcium, have provided new insights into the complex determination of bone mineral mas

Ant Colony System for a Dynamic Vehicle Routing Problem

An aboundant literature on vehicle routing problems is available. However, most of the work deals with static problems, where all data are known in advance, i.e. before the optimization has started. The technological advances of the last few years give rise to a new class of problems, namely the dynamic vehicle routing problems, where new orders are received as time progresses and must be dynamically incorporated into an evolving schedule. In this paper a dynamic vehicle routing problem is examined and a solving strategy, based on the Ant Colony System paradigm, is proposed. Some new public domain benchmark problems are defined, and the algorithm we propose is tested on them. Finally, the method we present is applied to a realistic case study, set up in the city of Lugano (Switzerland