ABSTRACT The compromised regenerative capacity of diabetic bone defects remains a critical clinical challenge, with pathological alterations in the bone marrow microenvironment emerging as key contributors. While mechanical signals within the marrow niche critically regulate bone regeneration, how diabetic matrix abnormalities impair bone marrow‐derived mesenchymal stem cells (BMSCs) function remains unclear. Herein, it is revealed that diabetes induces a characteristic hyperviscous state in bone marrow extracellular matrix (ECM). Through comparative mechanobiological analyses, it is demonstrated that diabetic BMSCs exhibit amplified mechanosensitivity to ECM viscosity via transient receptor potential vanilloid 2 (TRPV2) activation. This mechanotransduction cascade triggers calcium influx, which activates CaMKII and subsequently phosphorylates cofilin, thereby shifting the G‐/F‐actin equilibrium toward perinuclear F‐actin disassembly. The cytoskeletal remodeling induces nuclear envelope deformation through regulation of Lamin A/C, driving spatial rearrangement of chromatin architecture. Mechanistically, these physical nuclear changes promote perinuclear heterochromatin accumulation and enhance H3K9me3 repressive histone modification, ultimately suppressing osteogenic transcriptional programs. Importantly, TRPV2 inhibition rescued both chromatin accessibility and osteogenic potential in diabetic BMSCs. This findings establish a novel mechano‐pathological axis where diabetic ECM hyperviscosity propagates mechanical signals from cytoskeleton to chromatin through TRPV2 activation, proposing mechanomodulation as a promising therapeutic strategy for diabetic osteopathy.
<b>Background</b>: Low peak bone mass (PBM) is a major contributor to later osteoporosis risk. This study sought to understand young people’s knowledge of factors associated with bone health. <b>Methods</b>: Young people in Aotearoa New Zealand were approached. Eight focus groups (26 participants in total, aged 11 to 17 years) were conducted using a semi-structured approach with open-ended questions and prompts. Transcripts were thematically coded using an inductive content analysis approach. <b>Results</b>: Knowledge of factors associated with good bone health was limited. There was a general awareness of the positive and negative impacts of many lifestyle behaviours on health generally, but not specifically PBM. Dairy intake was commonly mentioned as being beneficial for bone health. Some participants reported potential benefits of sport, but most did not know that weight bearing activity specifically was beneficial. <b>Conclusions</b>: Knowledge of osteoporosis and lifestyle factors that impact PBM was limited. Educational interventions involving promotion of bone health knowledge and supporting weight bearing physical activity in adolescents may be an important contributor to public health strategies.
<b>Background/Objectives:</b> Semiquantitative grading of the vertebral body (SQ) is an easy screening method for vertebral body deformation. The validity of SQ as a risk factor and screening tool for incident osteoporotic fractures in the vertebral body (OF) was investigated using retrospective case-control data. <b>Methods:</b> Outpatients with osteoporosis who were followed up for ≥2 years as patients with osteoporosis were recruited. All of them were tested using X-ray images of the lateral thoracolumbar view and other tests at baseline. Patients were classified according to the SQ grade, and potential risk factors were compared for each SQ group. Cox regression analyses were conducted on the incident OFs. Statistical differences in the possible risk factors among the groups and the likelihood of incident OFs in the variables were examined. After propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) for confounding factors, the possibility of incident OFs was compared between the SQ grade groups. <b>Results</b>: In the crude dataset, the probability of incident OF in SQ Grade 3 was significantly higher than in other grade groups. Using a Cox regression analysis in multivariate mode, SQ grade was the only statistically significant factor for incident OF. However, no significant differences were observed between PSM and IPTW. <b>Conclusions</b>: These results suggest that the SQ classification was inappropriate for predicting incident OFs. However, the grading showed a significantly higher risk than that available for screening.
Diabetes mellitus, characterized by enduring hyperglycemia, precipitates oxidative stress, engendering a spectrum of complications, notably increased bone vulnerability. The genesis of reactive oxygen species (ROS), a byproduct of oxygen metabolism, instigates oxidative detriment and impairs bone metabolism in diabetic conditions. This review delves into the mechanisms of ROS generation and its impact on bone homeostasis within the context of diabetes. Furthermore, the review summarizes the cutting-edge progress in the development of ROS-neutralizing biomaterials tailored for the amelioration of diabetic osteopathy. These biomaterials are engineered to modulate ROS dynamics, thereby mitigating inflammatory responses and facilitating bone repair. Additionally, the challenges and therapeutic prospects of ROS-targeted biomaterials in clinical application of diabetic bone disease treatment is addressed.
Zian Shabbir, Layla Mazdeyasnan, Naila Iqbal
et al.
Immunology is an important component of the medical curriculum. It provides a foundation for understanding the cellular and molecular processes by which the body protects itself from external substances and the immunological responses that contribute to the development of many illnesses. The inclusion of immunology in an osteopathic medical curriculum is essential to understanding the body’s defense systems as well as the alignment of osteopathic concepts with immunology. By encompassing innate and adaptive immunity, immunology reflects the interconnectedness of the body’s systems and the foundation for self-regulation inherent in osteopathy. A problem facing medical educators is determining how to facilitate students’ learning of immunological concepts in a way that will help them retain and apply the material throughout their clinical years and beyond. This paper aims to provide an immunology education framework designed to effectively integrate immunology topics across the preclinical courses of an osteopathic medical curriculum. Drawing insights from an extensive review of the literature and current medical curricula, we propose an integrative curriculum model that broadly incorporates fundamental concepts of immunology across multiple disciplines and systems-based courses horizontally as well as vertically over the preclinical years using clinical presentations and laboratory findings and further connecting them to osteopathic principles. This integrative curriculum will augment medical students’ understanding of immunology, making them better able to connect core concepts with clinical applications and enhance their application of immunological concepts in osteopathic patient care in alignment with the NBOME guidelines. Using the proposed integrative medical curriculum may better prepare medical students for providing holistic medical care and guidance to their future patients.
Julia Luca, Samantha McCarthy, Thomas Parmentier
et al.
BackgroundCanine epilepsy is a chronic common neurologic condition where seizures may be underreported. Electroencephalography (EEG) is the patient-side test providing an objective diagnostic criterion for seizures and epilepsy. Despite this, EEG is thought to be rarely used in veterinary neurology.ObjectivesThis survey study aims to better understand the current canine EEG usage and techniques and barriers in veterinary neurology.MethodsThe online Qualtrics link was distributed via listserv to members of the American College of Veterinary Internal Medicine (ACVIM) Neurology Specialty and the European College of Veterinary Neurology (ECVN), reaching at least 517 veterinary neurology specialists and trainees worldwide.ResultsThe survey received a 35% response rate, for a total of 180 participant responses. Fewer than 50% of veterinary neurologists are currently performing EEG and it is performed infrequently. The most common indication was to determine a discrete event diagnosis. Other reasons included monitoring treatment, determining brain death, identifying the type of seizure or epilepsy, localizing foci, sleep disorders, for research purposes, and post-op brain surgery monitorization. Most respondents interpreted their own EEGs. Clinical barriers to the performance of EEG in dogs were mainly equipment availability, insufficient cases, and financial costs to clients.ConclusionThis survey provides an update on EEG usage and techniques for dogs, identifying commonalities of technique and areas for development as a potential basis for harmonization of canine EEG techniques. A validated and standardized canine EEG protocol is hoped to improve the diagnosis and treatment of canine epilepsy.
Aim: to perform structural and functional analysis of the activity of reparative osteogenesis processes at pre- and postmenopausal women with diabetes mellitus (DM).Materials and Methods. There were enrolled 142 pre- and postmenopausal patients with type I and type II diabetes mellitus type (DM-1 and DM-2) as well as 43 females in control group. Subjects taking medicines acting on bone metabolism comorbid with chronic diseases were excluded from the study. All patients underwent Dual-energy X-ray Absorptiometry (DXA) to assess bone mineral density (BMD, T-score). Serum markers of bone remodeling (alkaline phosphatase, ALP; procollagen type I N propeptide, PINP; beta-Cross laps, b-CTx), metabolic and hormone parameters (glycated hemoglobin, parathyroid hormone, calcitonin, vitamin D, electrolytes) were also measured.Results. A positive correlation was found between the duration of DM-1 and DM-2 and b-CTx level (DM-1: г = 0.349, р = 0.08; DM-2: г = 0.214, р = 0.04). A negative correlation was found between the lumbar spine T-score and the duration of diabetes (DM-1: r = -0.568, p = 0.001; DM-2: r = -0.267, p = 0.04). A statistically significant correlation was found between the lumbar spine T-score and b-CTx levels (DM-1: r = -0.452, p = 0.002; DM-2: r = -0.357, p = 0.09).Conclusion. The results of current study suggest that reparative osteogenesis in patients with post-menopausal DM-1 vs. DM-2 and the control group was moderately increased. In patients with DM-2, a less pronounced change in BMD was determined in parallel with inconsistent bone remodeling processes, which casts doubt on the ability of DXA to predict fractures in these patients. Such changes contribute to decreased bone quality, which distinguishes diabetic osteopathy from traditional menopausal osteoporosis manifested mainly by low BMD.
La pleitrofina (PTN) en un péptido implicado en el desarrollo y el mantenimiento del tejido óseo, y con importantes funciones en los procesos inflamatorios. Sin embargo, la deleción de la PTN en modelos murinos no produce un deterioro óseo significativo, sin que hasta la fecha se hayan estudiado los mecanismos que compensan su perdida. Con este estudio quisimos comprobar cómo afecta la deleción de PTN y la inflamación aguda a la expresión de factores óseos. Para ello empleamos ratones hembra de tres meses deficientes para la PTN (PTNKo) a las que indujimos una inflamación aguda por administración de lipopolisacárido (LPS). Se aislaron las vértebras y las tibias para poder medir la expresión de genes y realizar un recuento de osteocitos. En cultivos celulares comprobamos si la PTN podía proteger a células MC3T3 (osteoblásticas) y MLOY4 (osteocitos) de la inducción de muerte celular producida por etopósido. Nuestros resultados muestran que la expresión de osteocalcina está incrementada en las vértebras de los ratones PTNKo, y que la inflamación produjo el incremento de expresión de podaplanina (E11), conexina 43 (Cox43) y el péptido relacionado con la parathormona (PTHrP) en los ratones PTNKo tratados con LPS. La administración de PTN redujo de manera significativa la muerte inducida por etopósido en cultivos de células MC3T3 y MLOY4. En conclusión, la deficiencia de PTN indujo un aumento de la expresión de OCN, y la inflamación aguda produjo la sobrexpresión de E11, PTHrP, y Cox43 en ratones PTNKo. La PTN aumentó la viabilidad de células osteblásticas y osteocitos frente al tratamiento con etopósido.
The mandibular cranial osteopathy (MCO) is a degenerative, osteopetrotic, self-limiting, non-neoplastic bone disorder, with no sexual predilection, which rarely affects dogs in the pre-pubertal stage. The most predisposed breeds are the Terries featured in the West Highland Terrier. The clinical signs are variable depending on the altered bones and degree of involvement. Among the most common are fever, mouth opening pain, jaw enlargement, hyporexia and sialorrhea. The bones of the skull are the most damaged, especially the mandibular, temporomandibular joints and tympanic sounds. The diagnosis of this condition is based on the clinical, histopathological and radiographic findings. The most radiographic changes are increased radiopacity and volume of mandibles and tympanic sounds. Its treatment is symptomatic, having as its main point pain control and nutritional support. The prognosis is heterogeneous. Patients may experience complete remission of the condition in weeks or undergo euthanasia due to ankylosis of the temporomandibular joint.
Martínez Arias L, Panizo García S, Carrillo López N
et al.
Objetivos: Evaluar el papel de la enzima antioxidante catalasa sobre el proceso de calcificación vascular asociada a insuficiencia renal crónica (IRC) y su efecto sobre la masa ósea.
Material y métodos: Se utilizaron ratones C57/BL6J salvajes (WT) y transgénicos (TG), que sobreexpresan la enzima catalasa, a los que se les indujo IRC. Se utilizaron como control ratones WT y TG con intervención simulada. Transcurridas 16 semanas los animales se sacrificaron, obteniendo suero para analizar marcadores bioquímicos, el trozo residual de riñón, la aorta y las tibias. Se utilizó igualmente un modelo in vitro de cultivo primario de células de músculo liso vascular (CMLV) procedentes de aorta de ratón WT y TG sometidas durante 8 días a un medio calcificante con 3 mM de fósforo y 2 mM de calcio.
Resultados: Solo en animales WT con IRC se observó un incremento significativo en la expresión génica de Runx2 y del depósito renal de calcio y un deterioro de la estructura ósea a nivel trabecular. Este efecto no se observó en ratones TG con IRC.
Solo en las CMLV de ratones WT, la adición de medio calcificante produjo un aumento del contenido en calcio, de la expresión proteica de Runx2 y de las especies reactivas de oxígeno mitocondriales con una menor expresión proteica de la enzima catalasa.
Conclusiones: La sobreexpresión de la enzima catalasa redujo el proceso de calcificación tanto in vivo como in vitro, mostrando in vivo que ese descenso se acompañó de una mejora en los parámetros óseos estudiados.
Albin Guillaud, Nelly Darbois, Richard Monvoisin
et al.
<h4>Context</h4>In 2010, the World Health Organization released benchmarks for training in osteopathy in which they considered cranial osteopathy as an important osteopathic skill. However, the evidence supporting the reliability of diagnosis and the efficacy of treatment in this field appears scientifically weak and inconsistent.<h4>Objectives</h4>To identify and critically evaluate the scientific literature dealing with the reliability of diagnosis and the clinical efficacy of techniques and therapeutic strategies used in cranial osteopathy.<h4>Methods</h4>Relevant keywords were used to search the electronic databases MEDLINE, PEDro, OSTMED.DR, Cochrane Library, and in Google Scholar, Journal of American Osteopathy Association and International Journal of Osteopathic Medicine websites. Searches were conducted up to end June 2016 with no date restriction as to when the studies were completed. As a complementary approach we explored the bibliography of included articles and consulted available previous reviews dealing with this topic.<h4>Study selection</h4>Regarding diagnostic processes in cranial osteopathy, we analyzed studies that compared the results obtained by at least two examiners or by the same examiner on at least two occasions. For efficacy studies, only randomized-controlled-trials or crossover-studies were eligible. We excluded articles that were not in English or French, and for which the full-text version was not openly available. We also excluded studies with unsuitable study design, in which there was no clear indication of the use of techniques or therapeutic strategies concerning the cranial field, looked at combined treatments, used a non-human examiner and subjects or used healthy subjects for efficacy studies. There was no restriction regarding the type of disease.<h4>Search results</h4>In our electronic search we found 1280 references concerning reliability of diagnosis studies plus four references via our complementary strategy. Based on the title 18 articles were selected for analysis. Nine were retained after applying our exclusion criteria. Regarding efficacy, we extracted 556 references from the databases plus 14 references through our complementary strategy. Based on the title 46 articles were selected. Thirty two articles were not retained on the grounds of our exclusion criteria.<h4>Data extraction and analysis</h4>Risk of bias in reliability studies was assessed using a modified version of the quality appraisal tool for studies of diagnostic reliability. The methodological quality of the efficacy studies was assessed using the Cochrane risk of bias tool. Two screeners conducted these analyses.<h4>Results</h4>For reliability studies, our analysis leads us to conclude that the diagnostic procedures used in cranial osteopathy are unreliable in many ways. For efficacy studies, the Cochrane risk of bias tool we used shows that 2 studies had a high risk of bias, 9 were rated as having major doubt regarding risk of bias and 3 had a low risk of bias. In the 3 studies with a low risk of bias alternative interpretations of the results, such as a non-specific effect of treatment, were not considered.<h4>Conclusion</h4>Our results demonstrate, consistently with those of previous reviews, that methodologically strong evidence on the reliability of diagnostic procedures and the efficacy of techniques and therapeutic strategies in cranial osteopathy is almost non-existent.
Снижение минеральной плотности костной ткани отмечается при многих хронических заболеваниях, включая инфекционные, и, обычно, является следствием серьезных изменений обменных процессов. Несмотря на значительную распространенность туберкулеза, состояние минеральной плотности костей и риски развития остеопороза у больных с туберкулезом, остается не изученным. Цель. Изучить показатели минеральной плотности костей у больных с легочными формами туберкулеза и выявить факторы риска развития остеопороза. Материал и методы. Показатели минеральной плотности костной ткани исследованы у 40 больных (23 мужского и 17 женского пола) легочными формами туберкулеза. Средний возраст 37,6±14,4 лет. Длительность заболевания с момента установления диагноза составила 173,2±9,6 месяцев. Минеральная плотность костной ткани исследовалась в двух стандартных зонах (поясничный отдел позвоночника, проксимальный отдел бедра) методом двухэнергетической рентгеновской абсорбциометрии на приборе Lunar Prodigy. В качестве контрольной группы использованы референтные данные прибора и результаты исследования минеральной плотности у 75 человек (35 мужчин и 40 женщин) такого же среднего возраста. Результаты. В основной группе у 15 пациентов (7 мужчин и 8 женщин) в анамнезе были указания на перенесенные переломы. У 3 пациентов переломы были только в детстве и юности. У 3 пациентов были указания на повторные переломы. Средние значения минеральной плотности костной ткани в двух стандартных зонах достоверно не отличались от показателей минеральной плотности контрольной группы (p>0,05). У 9 пациентов (7 мужчин и 2 женщин) показатели минеральной плотности позвонков L1-L4 по индексу Z были ниже значения -1,0. Показатели минеральной плотности отрицательно коррелировали с длительностью заболевания и положительно с результатами оценки жизненной емкости легких (p<0,05). Показатели минеральной плотности коррелировали положительно с индексом массы тела (p<0,01). Наиболее низкие показатели минеральной плотности были у пациентов с указанием на большой стаж курения, менопаузу и серьезные сопутствующие заболевания (сахарный диабет 1 го типа, вирусный гепатит С, хронический панкреатит). Выводы. Нам удалось обнаружить прямое негативное влияние продолжительности заболевания легочным туберкулезом на показатели минеральной плотности костной ткани. Также обнаружена положительная связь индекса массы тела, как маркера питательного статуса и жизненной емкости легких с показателями минеральной плотности костей у исследуемых пациентов. Планируется продолжение исследования влияния различных форм туберкулеза и сопутствующих заболеваний на показатели минеральной плотности костей больных различными формами туберкулеза.
Introducción: El tratamiento de la osteoporosis se orienta a prevenir la fractura por fragilidad, siendo la fractura de cadera la que más morbilidad y mortalidad produce. La existencia de una fractura previa es un importante predictor para una nueva fractura.
Objetivo: Pretendemos analizar cómo varía el tratamiento de la osteoporosis antes y después de una fractura de cadera.
Material y métodos: A partir de las 4.126.030 historias clínicas de la Base de Datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP) 2011 de toda España, se obtuvo información de pacientes con una primera fractura de cadera registrada entre 2005-2011, con seguimiento anterior y posterior de al menos un año. Analizamos el tratamiento previo y posterior para la osteoporosis (incluyendo suplementos de calcio y vitamina D).
Resultados: Sufrieron una fractura de cadera 2.763 pacientes mayores de 60 años (media 81 años), de los que el 81,6% eran mujeres. Antes de la fractura, el 26,5% (intervalo de confianza [IC] 95%: 24,8-28,1%) habían recibido algún tratamiento antiosteoporótico, de los que el 12,2%, (IC 95%: 11,0-13,5%) era bisfosfonatos. Tras la fractura lo recibieron un 38,6% (IC 95%: 36,8-40,4%), fueron tratados con bisfosfonato 20,4% (IC 95%: 18,9-22%). Los factores asociados a iniciar un tratamiento tras la fractura fueron ser mujer, más joven y con diagnóstico previo de osteoporosis.
Conclusiones: La mayoría de los pacientes estudiados no estaban recibiendo tratamiento preventivo antes de su fractura de cadera. Tras ella, aumentó modestamente la prescripción. Los fármacos más frecuentemente añadidos fueron calcio, vitamina D y bisfosfonatos.
The meeting of the Russian Council of Experts for improvement the approaches to the treatment of osteoporosis (OP) was held in Moscow on December 4, 2014. Leading Russian and Switzerland specialists in orthopedics, traumatology and rheumatology attended the meeting as well as members of Russian unit of clinical department AOTrauma of the international public (non-government) organization AOFoundation and members of the Russian Osteoporosis Association. The participants of the Russian Council of Experts have discussed the system of care for patients with OP in the Russian Federation. They discussed the need for the development of measures to optimize interdisciplinary interaction between orthopedic surgeons and internal medicine specialists in the treatment of patients with OP to reduce the number of postsurgical complications and prevention of further vertebral and nonvertebral fractures. Experts have noted the need to raise the level of knowledge about OP in orthopedic surgeons, clinical characteristics of fractures in patients with OP and measures to control it; to raise awareness of OP among patients by billboards in clinics and outpatient emergency rooms; to develop and implement into clinical practice of orthopedic surgeons standard of care for elderly patients with fragility fractures; to develop algorithm of secondary fractures prevention through the prescription of pathogenic OP therapy at the level of the trauma unit; to form an interdisciplinary system of the medical care for patient with fragility fractures, as well as contribute to the organization of the service Secondary Fractures Prevention (Fracture Liaison Service) in the Russian health care system.
Background: educational programs may be beneficial in a variety of important factors for the prevention, treatment and management of osteoporosis. Objectives: to evaluate the influence of the three different educational interventions on knowledge, dietary calcium, physical activities and adherence to treatment of osteoporosis. Methods: 117 patients (middle age 63.3 ± 8.1 years old, 95.7% are women) with osteoporosis have been included in this study. All patients were randomized to three groups. The patients of intervention group (n=39) had an osteoporosis school program (4 lessons with using interactive methods in groups of 5-8 patients). The patients of the control group (n=38) received brochures with general information about osteoporosis. The patients of the comparison group(n=40) received lecture (1 x 1.5 h) about osteoporosis. Average changes from baseline in knowledge, dietary calcium, physical activities and time of physical exercises was evaluated in 3, 6 and 12 months. Adherence to treatment was evaluated in 12 months. Results: After educational programs level of knowledge was increased in patients of the intervention group in 3, 6 and 12 months by 23,8%, 22,9%, 21,1%, in the group of brochures - by 0.5%, 1.8%, 4.7%, correspondingly, p<0.01. In the group, who received lecture level of knowledge was increased by 18.0%, 15.8%, 14.6% (р<0.05 when compared with the brochure at visits 3 and 6 months). The using of dietary calcium was increased in 3, 6 and 12 months in the intervention group by 188.5 mg, 211.8 mg and 238.1 mg. In group,whoreceivedbrochuresby 146.8 mg, 106.4 mg, 84.4 mg, in group,whoreceived lecture by 66.0 mg, 80.4 mg and 68.3 mg (p<0.05when compared intervention group with the group,who received lecture at visits 3 months).Physical activity was increased in 3, 6 and 12 months in intervention group by 1.7, 1.9, 0.9 scores and was significantly higher, than in group,whoreceived lecture(0.2, 0.2, 0.1 scores) and in control group,whoreceived brochures(0.1, 0.2, 0 scores). Time of physical exercises was increased by 45.1, 54.2 и 49.9 min in week in the intervention group and was significantly more than in the groups,whoreceived lecture or brochures. Adherence to pathogenetic osteoporosis treatment was higher in the intervention group: 56.4% of intervention group, and 30.0% of the group,whoreceived lecture, and 13.2% of group,whoreceived brochures took pathogenetic medication regularly during the year (p<0.01when compared the intervention group with the control group). Conclusions: educational program with using interactive methods in small groups increases knowledge about of osteoporosis, dietary calcium,physicalactivities and increases adherence to treatment of pathogenetic medication more than brochure and lecture.