Summary
Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, ...the clinician should reassess the adherence to the treatment and also other potential issues with the drug.
Introduction
Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients.
Methods
The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis.
Results
Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%.
Conclusions
If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.
Summary
This paper provides a framework for the development of national guidelines for the management of glucocorticoid-induced osteoporosis in men and women aged 18 years and over in whom oral ...glucocorticoid therapy is considered for 3 months or longer.
Introduction
The need for updated guidelines for Europe and other parts of the world was recognised by the International Osteoporosis Foundation and the European Calcified Tissue Society, which set up a joint Guideline Working Group at the end of 2010.
Methods and results
The epidemiology of GIO is reviewed. Assessment of risk used a fracture probability-based approach, and intervention thresholds were based on 10-year probabilities using FRAX. The efficacy of intervention was assessed by a systematic review.
Conclusions
Guidance for glucocorticoid-induced osteoporosis is updated in the light of new treatments and methods of assessment. National guidelines derived from this resource need to be tailored within the national healthcare framework of each country.
Plant breeding has been very successful in developing improved varieties using conventional tools and
methodologies. Nowadays, the availability of genomic tools and resources is leading to a new ...revolution of plant
breeding, as they facilitate the study of the genotype and its relationship with the phenotype, in particular for complex
traits. Next Generation Sequencing (NGS) technologies are allowing the mass sequencing of genomes and transcriptomes,
which is producing a vast array of genomic information. The analysis of NGS data by means of bioinformatics
developments allows discovering new genes and regulatory sequences and their positions, and makes available large
collections of molecular markers. Genome-wide expression studies provide breeders with an understanding of the
molecular basis of complex traits. Genomic approaches include TILLING and EcoTILLING, which make possible to
screen mutant and germplasm collections for allelic variants in target genes. Re-sequencing of genomes is very useful for
the genome-wide discovery of markers amenable for high-throughput genotyping platforms, like SSRs and SNPs, or the
construction of high density genetic maps. All these tools and resources facilitate studying the genetic diversity, which is
important for germplasm management, enhancement and use. Also, they allow the identification of markers linked to
genes and QTLs, using a diversity of techniques like bulked segregant analysis (BSA), fine genetic mapping, or
association mapping. These new markers are used for marker assisted selection, including marker assisted backcross
selection, ‘breeding by design’, or new strategies, like genomic selection. In conclusion, advances in genomics are
providing breeders with new tools and methodologies that allow a great leap forward in plant breeding, including the
‘superdomestication’ of crops and the genetic dissection and breeding for complex traits.
The liquid-crystal dimer 1'',7''-bis(4-cyanobiphenyl-4'-yl)heptane (CB7CB) exhibits two liquid-crystalline mesophases on cooling from the isotropic phase. The high-temperature phase is nematic; the ...identification and characterization of the other liquid-crystal phase is reported in this paper. It is concluded that the low-temperature mesophase of CB7CB is a new type of uniaxial nematic phase having a nonuniform director distribution composed of twist-bend deformations. The techniques of small-angle x-ray scattering, modulated differential scanning calorimetry, and dielectric spectroscopy have been applied to establish the nature of the nematic-nematic phase transition and the structural features of the twist-bend nematic phase. In addition, magnetic resonance studies (electron-spin resonance and (2)H nuclear magnetic resonance) have been used to investigate the orientational order and director distribution in the liquid-crystalline phases of CB7CB. The synthesis of a specifically deuterated sample of CB7CB is reported, and measurements showed a bifurcation of the quadrupolar splitting on entering the low-temperature mesophase from the high-temperature nematic phase. This splitting could be interpreted in terms of the chirality of the twist-bend structure of the director. Calculations using an atomistic model and the surface interaction potential with Monte Carlo sampling have been carried out to determine the conformational distribution and predict dielectric and elastic properties in the nematic phase. The former are in agreement with experimental measurements, while the latter are consistent with the formation of a twist-bend nematic phase.
Summary
Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is ...urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions.
Introduction
Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication.
Methods
A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken.
Results
Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it.
Conclusion
These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.
Summary
Network meta-analysis techniques (meta-analysis, adjusted indirect comparison, and mixed treatment comparison MTC) allow for treatment comparisons in the absence of head-to-head trials. In ...this study, conditional estimates of relative treatment efficacy derived through these techniques show important differences in the fracture risk reduction profiles of marketed pharmacologic therapies for postmenopausal osteoporosis.
Introduction
This study illustrates how network meta-analysis techniques (meta-analysis, adjusted indirect comparison, and MTC) can provide comparisons of the relative efficacy of postmenopausal osteoporosis therapies in the absence of comprehensive head-to-head trials.
Methods
Source articles were identified in MEDLINE; EMBASE; Cochrane Central Register of Controlled Trials (CENTRAL) via Wiley Interscience; and Cumulative Index to Nursing and Allied Health Literature (CINAHL) between April 28, 2009 and November 4, 2009. Two reviewers identified English-language articles reporting randomized controlled trials (RCTs) with on-label dosing of marketed osteoporosis agents and fracture endpoints. Trial design, population characteristics, intervention and comparator, fracture outcomes, and adverse events were abstracted for analysis. Primary analyses included data from RCTs with fracture endpoints. Sensitivity analyses also included studies with fractures reported through adverse event reports. Meta-analysis compared fracture outcomes for pharmacological therapies vs. placebo (fixed and random effects models); adjusted indirect comparisons and MTC assessed fracture risk in postmenopausal women treated with denosumab vs. other agents.
Results
Using data from 34 studies, random effects meta-analysis showed that all agents except etidronate significantly reduced the risk of new vertebral fractures compared with placebo; denosumab, risedronate, and zoledronic acid significantly reduced the risk for nonvertebral and hip fracture, while alendronate, strontium ranelate, and teriparatide significantly reduced the risk for nonvertebral fractures. MTC showed denosumab to be more effective than strontium ranelate, raloxifene, alendronate, and risedronate in preventing new vertebral fractures.
Conclusions
The conditional estimates of relative treatment efficacy indicate that there are important differences in fracture risk reduction profiles for marketed pharmacological therapies for postmenopausal osteoporosis.
This trial evaluated the feasibility and efficacy of the infusion of mesenchymal stem cells expanded using human serum for the treatment of refractory acute or chronic graft-versus-host disease. ...Twenty-eight expansions were started. In 22, a minimum of more than 1 x 10⁶ mesenchymal stem cells/kg were obtained after a median of 26 days; this threshold was not obtained in the remaining cases. Ten patients received cells for the treatment of refractory or relapsed acute graft-versus-host disease and 8 for chronic disease. One patient treated for acute graft-versus-host disease obtained a complete response, 6 had a partial response and 3 did not respond. One of the chronic patients achieved complete remision, 3 a partial response, and 4 did not respond. The current study supports the use of this approach in less heavily treated patients for both acute and chronic graft-versus-host disease. The trial has been registered at ClinicalTrials.gov: identifier NCT00447460.
Biomaterials and scaffolds for Tissue Engineering are widely used for an effective healing and regeneration. However, the implantation of these scaffolds causes an innate immune response in which the ...macrophage polarization from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype is crucial to avoid chronic inflammation. Recent studies have showed that the use of bioactive ions such as cobalt (Co
), copper (Cu
) and magnesium (Mg
) could improve tissue regeneration, although there is limited evidence on their effect on the macrophage response. Therefore, we investigated the immunomodulatory potential of Co
, Cu
and Mg
in macrophage polarization. Our results indicate that Mg
and concentrations of Cu
lower than 10 μM promoted the expression of M2 related genes. However, higher concentrations of Cu
and Co
(100 μM) stimulated pro-inflammatory marker expression, indicating a concentration dependent effect of these ions. Furthermore, Mg
were able to decrease M1 marker expression in presence of a mild pro-inflammatory stimulus, showing that Mg
can be used to modulate the inflammatory response, even though their application can be limited in a strong pro-inflammatory environment.
Summary
Type 2 diabetes mellitus (T2DM) is associated with an excess risk of fractures and overall mortality. This study compared hip fracture and post-hip fracture mortality in T2DM and non-diabetic ...subjects. The salient findings are that subjects in T2DM are at higher risk of dying after suffering a hip fracture.
Introduction
Previous research suggests that individuals with T2DM are at an excess risk of both fractures and overall mortality, but their combined effect is unknown. Using multi-state cohort analyses, we estimate the association between T2DM and the transition to hip fracture, post-hip fracture mortality, and hip fracture–free all-cause death.
Methods
Population-based cohort from Catalonia, Spain, including all individuals aged 65 to 80 years with a recorded diagnosis of T2DM on 1 January 2006; and non-T2DM matched (up to 2:1) by year of birth, gender, and primary care practice.
Results
A total of 44,802 T2DM and 81,233 matched controls (53% women, mean age 72 years old) were followed for a median of 8 years: 23,818 died without fracturing and 3317 broke a hip, of whom 838 subsequently died. Adjusted HRs for hip fracture–free mortality were 1.32 (95% CI 1.28 to 1.37) for men and 1.72 (95% CI 1.65 to 1.79) for women. HRs for hip fracture were 1.24 (95% CI 1.08 to 1.43) and 1.48 (95% CI 1.36 to 1.60), whilst HRs for post-hip fracture mortality were 1.28 (95% CI 1.02 to 1.60) and 1.57 (95% CI 1.31 to 1.88) in men and women, respectively.
Conclusion
T2DM individuals are at increased risk of hip fracture, post-hip fracture mortality, and hip fracture–free death. After adjustment, T2DM men were at a 28% higher risk of dying after suffering a hip fracture and women had 57% excess risk of post-hip fracture mortality.
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