Osteoporosis from genes to phenotypes

Osteoporosis is a leading public health problem in our rapidly growing, aging population. It is a systemic skeletal disease characterized by reduced bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Family and twin studies have shown that osteoporosis and its associated phenotypes are under strong genetic control. In addition, it has been shown than not one major locus is responsible of the susceptibility to develop osteoporosis; instead, diverse genetic and environmental factors involved with the disease have confi rmed its complex multifactorial nature

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the drug development process and a molecular redefinition of skeletal disease can help overcoming current shortcomings in pharmaceutical research, including failed attempts and appalling costs. This review summarizes the achievements of genetic studies in the bone field and their application to clinical care, illustrating the imminent advent of the genomic medicine era

Novel antibacterial bioactive glass nanocomposite functionalized with tetracycline hydrochloride

To prevent the high frequency of wound infections, anti-bacterial agents can be loaded onto composites. In the present study, the antibiotic tetracycline hydrochloride (TC)was incorporated, for the first time, in collagen type I membranes coated with nano-sized SiO2-CaOP2O5 bioactive glass (n-BG) obtained by a sol-gel chemical route. Collagen membranes coated with n-BG were immersed in simulated body fluid (SBF) containing 0.25, 0.75 or 1.25 mg mL−1 of TC for 48 h at 37∘C following a coprecipitation method. The antibiotic was released in distilledwater at 37∘C for up to 72 h. The antibacterial activity of the composites was evaluated in vitro by the inhibition zone test and plate count method. Two different Staphylococcus aureus strains, S. aureus ATCC29213 and S. aureus ATCC25923, were exposed to the biomaterials. The results showed that the incorporation but not the release of TC was dependent on the initial concentration of TC in SBF. The biomaterials inhibited S. aureus growth, although the efficacy was similar for all the concentrations. The results allow us to conclude that the new composite could have potential in the prevention of wound infections.Fil: Rivadeneira, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; ArgentinaFil: Luz, Gisela M.. Universidade Do Minho; PortugalFil: Audisio, Marcela Carina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones Para la Industria Química. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones Para la Industria Química; ArgentinaFil: Mano, Joao F.. Universidade Do Minho; PortugalFil: Gorustovich Alonso, Alejandro Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long". Universidad de Buenos Aires. Facultad de Ingeniería. Instituto de Tecnologías y Ciencias de la Ingeniería "Hilario Fernández Long"; Argentin

Using Mendelian Randomization to Decipher Mechanisms of Bone Disease

Purpose of Review: This review summarizes the basic principles of Mendelian randomization (MR) and provides evidence for the causal effect of multiple modifiable factors on bone outcomes. Recent Findings: Several studies using MR approach have provided support for the causal effect of obesity on bone mineral density (BMD). Strikingly, studies have failed to prove a causal association between elevated 25(OH) D concentrations and higher BMD in community-dwelling individuals. Summary: The MR approach has been successfully used to evaluate multiple factors related to bone mineral density variation and/or fracture risk. The MR approach avoids some of the classical observational study limitations and provides more robust causal evidence, ensuring bigger success of the clinical trials. The selection of interventions based on genetic evidence could have a substantial impact on clinical practice

Metodología para la implementación de Intranets

Aplicación intranet FICARedes de computadores.- Internet.- Intranet.- Protocolos TCP/IP.- Estructura Interna.- Capa Física.- Capa de enlace.- Estructura del DNS de internet.- Categorías básicas de grupos de dominios de internet.- World wide web (WWW).- Servidor web.- Correo Electrónico.- Historia del correo electrónico.- Protocolos utilizados en el correo electrónico.- Seguridad.- Peligros y modos de ataque.- Técnicas de defensa- Formación de un equipo ejecutor.- Nivelación de criterios.- Elección de la plataforma.- Costos.- Mantenimiento

The contribution of hip geometry to the prediction of hip osteoarthritis

SummaryObjectiveTo determine how well measures of hip geometry can predict radiological incident hip osteoarthritis (HOA) compared to well known clinical risk factors.DesignThe study population is part of the Rotterdam Study, a prospective population-based cohort. Baseline pelvic radiographs were used to measure hip geometry by two methods: Statistical Shape Models (SSM) and predefined geometry parameters (PGPs). Incident HOA (Kellgren and Lawrence (KL) ≥ 2) was assessed in 688 participants after 6.5 years without radiographic HOA at baseline. The ability to predict HOA was quantified using the area under the Receiver Operating Characteristics (ROC) curve (AUC).ResultsComparison of the two methods showed that both contain information that is not captured by the other method. At 6.5 years follow-up 132 hips had incident HOA. Five PGPs (Wiberg angle, Neck Width (NW), Pelvic Width (PW), Hip Axis Length (HAL) and Triangular Index (TI)) and two SSM (modes 5 and 9) were significant predictors of HOA (P = 0.007). Hip geometry added 7% to the prediction obtained by clinical risk factors (AUC = 0.67 (geometry), 0.66 (gender, age, Body Mass Index (BMI)) and combining both: AUC = 0.73, respectively). Mode 12 (associated with position of the femoral head in acetabulum) and Wiberg angle were predictors of HOA in participants without radiological signs at baseline (KL = 0). Although the strength of the prediction decreased for all variables at a longer follow-up, the contribution of hip geometry was still significant (P = 0.01).ConclusionsHip geometry has a moderate ability to predict HOA in participants with and without initial signs of osteoarthritis (OA), similar to and largely independent of the predictive value of clinical risk factors

Recent advances in the genetics of fractures in osteoporosis

Genetic susceptibility, together with old age, female sex, and low bone mineral density (BMD) are amongst the strongest determinants of fracture risk. Tmost recent large-scale genome-wide association study (GWAS) meta-analysis has yielded fifteen loci. This review focuses on the advances in the research of genetic determinants of fracture risk. We first discuss the genetic architecture of fracture risk, touching upon different methods and overall findings. We then discuss in a second paragraph the most recent advances in the field and focus on the genetics of fracture risk and also of other endophenotypes closely related to fracture risk such as bone mineral density (BMD). Application of state-of-the-art methodology such as Mendelian randzation in fracture GWAS are reviewed. The final part of this review touches upon potential future directions in genetic research of osteoporotic fractures

Evaluation of the Arthritis Foundation’s Camine Con Gusto Program for Hispanic Adults With Arthritis

INTRODUCTION: Camine Con Gusto (CCG) is the Hispanic version of an evidence-based walking program for people with arthritis. This study examined CCG outcomes, feasibility, tolerability, safety, and acceptability and potential tailoring. METHOD: A pre and post 6-week evaluation was conducted in Hispanic people with arthritis. Outcomes included pain, stiffness, fatigue, functional capacity, helplessness, and self-efficacy. A formative evaluation with program participants and key stakeholders explored program tailoring. RESULTS: Participants' mean age was 46.9 years, 44.4% had a high school degree or less, 2.5% were born in United States, 60.1% spoke only Spanish, and 74.7% were female. Moderate effect sizes were found: 0.50 for pain, 0.75 for fatigue, 0.49 for stiffness, 0.33 for function, 0.26 for helplessness, and 0.24 for self-efficacy. There were 285 participants recruited with an 82% 6-week retention (feasibility), no adverse events were reported (safety), and 98% reported program satisfaction (acceptability). Recommended adaptations included simpler language, more pictures and content addressing nutrition and chronic conditions, shortened materials, and inclusion of motivational strategies. CONCLUSION: CCG showed improvement in outcomes in Hispanic individuals comparable to those noted in non-Hispanic White and Black individuals with arthritis