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To alleviate bone loss, most current drugs target osteoclasts. Saikosaponin A (Ssa), a triterpene saponin derived from Bupleurum falcatum (also known as Radix bupleuri), has immunoregulatory, neuromodulatory, antiviral, anticancer, anti-convulsant, anti-inflammatory, and anti-proliferative effects. Recently, modulation of bone homeostasis was shown to involve ferroptosis. Herein, we aimed to determine Ssa's inhibitory effects on osteoclastogenesis and differentiation, whether ferroptosis is involved, and the underlying mechanisms. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining, and pit formation assays were conducted to confirm Ssa-mediated inhibition of RANKL-induced osteoclastogenesis in vitro. Ssa could promote osteoclast ferroptosis and increase mitochondrial damage by promoting lipid peroxidation, as measured by iron quantification, FerroOrange staining, Dichloro-dihydro-fluorescein diacetate, MitoSOX, malondialdehyde, glutathione, and boron-dipyrromethene 581/591 C11 assays. Pathway analysis showed that Ssa can promote osteoclasts ferroptosis by inhibiting the Nrf2/SCL7A11/GPX4 axis. Notably, we found that the ferroptosis inhibitor ferrostatin-1 and the Nrf2 activator tert-Butylhydroquinone reversed the inhibitory effects of Ssa on RANKL-induced osteoclastogenesis. In vivo, micro-computed tomography, hematoxylin and eosin staining, TRAP staining, enzyme-linked immunosorbent assays, and immunofluorescence confirmed that in rats with periodontitis induced by lipopolysaccharide, treatment with Ssa reduced alveolar bone resorption dose-dependently. The results suggested Ssa as a promising drug to treat osteolytic diseases.
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RATIONALE AND OBJECTIVES: This study aimed to compare the diagnostic value of dual-energy CT (DECT)-based volumetric material decomposition with that of Hounsfield units (HU)-based values and cortical thickness ratio for predicting the 2-year risk of osteoporosis-associated fractures. METHODS: The L1 vertebrae of 111 patients (55 men, 56 women; median age, 62 years) who underwent DECT between 01/2015 and 12/2018 were retrospectively analyzed. For phantomless bone mineral density (BMD) assessment, a specialized DECT postprocessing software employing material decomposition was utilized. The digital records of all patients were monitored for two years after the DECT scans to track the incidence of osteoporotic fractures. Diagnostic accuracy parameters were calculated for all metrics using receiver-operating characteristic (ROC) and precision-recall (PR) curves. Logistic regression models were used to determine associations of various predictive metrics with the occurrence of osteoporotic fractures. RESULTS: Patients who sustained one or more osteoporosis-associated fractures in a 2-year interval were significantly older (median age 74.5 years [IQR 57-83 years]) compared those without such fractures (median age 50.5 years [IQR 38.5-69.5 years]). According to logistic regression models, DECT-derived BMD was the sole predictive parameter significantly associated with osteoporotic fracture occurrence across all age groups. ROC and PR curve analyses confirmed the highest diagnostic accuracy for DECT-based BMD, with an area under the curve (AUC) of 0.95 [95% CI: 0.89-0.98] for the ROC curve and an AUC of 0.96 [95% CI: 0.85-0.99] for the PR curve. CONCLUSION: The diagnostic performance of DECT-based BMD in predicting the 2-year risk of osteoporotic fractures is greater than that of HU-based metrics and the cortical thickness ratio. DECT-based BMD values are highly valuable in identifying patients at risk for osteoporotic fractures.
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Introduction: Osteoarthritis of the knee (OA knee) is a common geriatric disease that require total knee arthroplasty. Periprosthetic fracture is one of the common complications, which is strongly related to metabolic bone disease. Materials and methods: We conducted a prospective study on 291 outpatients with OA knee between November 2020 and April 2021. Baseline characteristics, dual-energy X-ray absorptiometry and blood test results were analysed using logistic regression analysis and expressed as odds ratio, 95% confidence intervals and P-values. Results: Overall metabolic bone diseases were found in 82.91% of patients. Vitamin D insufficiency (53.38%) was the most prevalent, followed by osteopenia (44.38%), impaired renal function (26.69%), and osteoporosis (17.45%). Risk factors of vitamin D insufficiency are age ≥71 years (OR 0.33, P = 0.003) and bilateral affected side (OR 1.99, P = 0.007). For osteopenia and osteoporosis, risk factors were age, body mass index, affected side, and chronic kidney disease (P < 0.05). Discussion: In the aspect of Vit D insufficiency, age>70 and bilateral OA knee were significantly related in many ways, such as reduction in cutaneous synthesis and daily exposure to sunlight and various diseases, including CKD and GI malabsorption. The risk factors of osteopenia and osteoporosis can be explained throughout several mechanisms. For instance, abnormality in hormone and cytokines metabolism will lead to the increase in adipocyte differentiation and fat accumulation. And that situation may lead to the decrease in osteoblast differentiation and increased osteoclast activity which could lead to negative impact on bone strength. Conclusions: Metabolic bone diseases were common in most patients with OA knee, and the insufficiency in amount of vitamin D(serum 25-hydroxyvitamin D), osteoporosis, and osteopenia conditions were mainly identified. These preventable conditions have risk factors that are mostly correctable These preventable conditions have risk factors that are mostly correctable, for example gain more outdoor activities, consume vitamin D supplement or start osteoporosis treatment program. Further analysis is necessary to establish solid evidence in the comparison of risk factors between the OA and non-OA groups.
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Endomucin (MUC14), encoded by EMCN gene, is an O-glycosylated transmembrane mucin that is mainly found in venous endothelial cells (ECs) and highly expressed in type H vessels of bone tissue. Its main biological functions include promoting endothelial generation and migration through the vascular endothelial growth factor (VEGF) signaling pathway and inhibiting the adhesion of inflammatory cells to ECs. In addition, it induces angiogenesis and promotes bone formation. Due to the excellent functions of Endomucin in the above aspects, it provides a new research target for the treatment of vascular inflammatory-related diseases and bone diseases. Based on the current understanding of its function, the research of Endomucin mainly focuses on the above two diseases. As it is known, the progression of cancer is closely related to angiogenesis. Endomucin recently is found to be differentially expressed in a variety of tumors and correlated with survival rate. The biological role of Endomucin in cancer is opaque. This article introduces the research progress of Endomucin in vascular inflammatory-related diseases and bone diseases, discusses its application value and prospect in the treatment, and collects the latest research situation of Endomucin in tumors, to provide meaningful evidence for expanding the research field of Endomucin.
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OBJECTIVE: Patients with Osteogenesis Imperfecta (OI) have varying degrees of bone fragility and increased fracture rates. There is a paucity of data related to complications to pregnancies in patients with OI and to their offspring. With this study we aim to evaluate the risk of complications to pregnancies, delivery, and offspring in pregnancies where the mother or father have OI. DESIGN: Nationwide, register-based, cohort study. SETTING: Danish health register-based data. POPULATION: All pregnancies registered in the Danish health registers where one parent has OI and a reference population of all other pregnancies in the general population from 1997 to 2018. METHODS: Descriptive epidemiology MAIN OUTCOME MEASURES: Pregnancy and delivery complications (e.g. prevalence of pre-eclampsia, eclampsia and perinatal haemorrhage), and complications in the offspring (e.g. prevalence of low birth weight, low Apgar Score, need of CPAP or NICU, prevalence of congenital malformations (using the EUROCAT classification), incidence of osteogenesis imperfecta, prevalence of birth related fractures and hospital contacts during the first year of life) from pregnancies with parental OI. RESULTS: We identified 433 OI related pregnancies among 134 mothers with OI and 73 fathers with OI. The rates of pregnancy and delivery complications were similar between the OI cohorts and the reference population. More (31 % vs 19 %) children were delivered by caesarean section in the OI cohort than in the reference population. CONCLUSION: Pregnancies, where one parent have OI, result in live births to term with very few complications.
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Osteogênese Imperfeita , Complicações na Gravidez , Resultado da Gravidez , Sistema de Registros , Humanos , Osteogênese Imperfeita/epidemiologia , Osteogênese Imperfeita/complicações , Gravidez , Feminino , Resultado da Gravidez/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Recém-Nascido , Masculino , Dinamarca/epidemiologia , Estudos de Coortes , PrevalênciaRESUMO
Sarcoidosis is a systemic granulomatous disease; however, the incidence of bone sarcoidosis is relatively rare. The short tubular bones of the hands and feet are most frequently affected, while the vertebrae and the pelvic bones are rarely involved. We hereby report a rare case of multiple bone sarcoidosis involving the vertebrae and pelvic bones, evaluated before and after steroid therapy using two different imaging modalities: bone scintigraphy and A 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). FDG-PET/CT is effective for detecting bone lesions; however, whole-body imaging is recommended to detect the short tubular bones of the hands and feet, which are most frequently affected.
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Tumour necrosis factor alpha (TNF-α) is a pleiotropic cytokine synthesised primarily by mononuclear cells; it has a potent pro-inflammatory effect, playing a crucial role in metabolic, immune, and inflammatory diseases. This cytokine has been studied in various biological systems. In bone tissue, TNF-α plays an integral role in skeletal disorders such as osteoporosis, fracture repair and rheumatoid arthritis through its involvement in regulating the balance between osteoblasts and osteoclasts, mediating inflammatory responses, promoting angiogenesis and exacerbating synovial proliferation. The biological effect TNF-α exerts in this context is determined by a combination of the signalling pathway it activates, the type of receptor it binds, and the concentration and duration of exposure. This review summarises the participation and pathophysiological role of TNF-α in osteoporosis, bone damage repair, chronic immunoinflammatory bone disease and spinal cord injury, and discusses its main mechanisms.
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Osteoporose , Fator de Necrose Tumoral alfa , Humanos , Osteoporose/metabolismo , Osteoporose/patologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Inflamação/metabolismo , Inflamação/patologia , Osteoblastos/metabolismo , Doenças Ósseas/metabolismo , Doenças Ósseas/patologia , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Transdução de SinaisRESUMO
BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures. MAIN BODY: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals. CONCLUSION: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.
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BACKGROUND: Most periprosthetic fractures following total hip arthroplasty (THA) are fragility fractures that qualify patients for osteoporosis diagnoses. However, it remains unknown how many patients were diagnosed who had osteoporosis before injury or received the proper evaluation, diagnosis, and treatment after injury. METHODS: We identified 171 Vancouver B2 (109) and B3 (62) periprosthetic femur fractures treated with a modular fluted tapered stem from 2000 to 2018 at 1 institution. The mean patient age was 75 years (range, 35 to 94), 50% were women, and the mean body mass index was 29 (range, 17 to 60). We identified patients who had osteoporosis or osteopenia diagnoses, a fracture risk assessment tool (FRAX), bone mineral density (BMD) testing, an endocrinology consult, and osteoporosis medications. Age-appropriate BMD testing was defined as no later than 1 year after the recommended ages of 65 (women) or 70 years (men). The mean follow-up was 11 years (range, 4 to 21). RESULTS: Falls from standing height caused 94% of fractures and thus, by definition, qualified as osteoporosis-defining events. The prevalence of osteoporosis diagnosis increased from 20% before periprosthetic fracture to 39% after (P < .001). The prevalence of osteopenia diagnosis increased from 13% before the fracture to 24% after (P < .001). The prevalence of either diagnosis increased from 24% before fracture to 44% after (P < .001). No patients had documented FRAX scores before fracture, and only 2% had scores after. The prevalence of BMD testing was 21% before fracture and 22% after (P = .88). By the end of the final follow-up, only 16% had received age-appropriate BMD testing. The proportion of patients who had endocrinology consults increased from 6% before the fracture to 25% after (P < .001). The proportion on bisphosphonate therapy was 19% before fracture and 25% after (P = .08). CONCLUSIONS: Although most periprosthetic fractures following THA are fragility fractures that qualify patients for osteoporosis diagnoses, there remain major gaps in diagnosis, screening, endocrinology follow-up, and treatment. Like nonarthroplasty fragility fractures, a systematic approach is needed after periprosthetic fractures. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
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We present a newborn with transient generalized osteosclerosis and negative genetic workup. The etiology of this condition is unknown. Given overlapping radiologic signs with severe forms of osteopetrosis, familiarity with this condition is crucial for correct diagnosis and management.
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Physiological processes within the human body are regulated in approximately 24-h cycles known as circadian rhythms, serving to adapt to environmental changes. Bone rhythms play pivotal roles in bone development, metabolism, mineralization, and remodeling processes. Bone rhythms exhibit cell specificity, and different cells in bone display various expressions of clock genes. Multiple environmental factors, including light, feeding, exercise, and temperature, affect bone diurnal rhythms through the sympathetic nervous system and various hormones. Disruptions in bone diurnal rhythms contribute to the onset of skeletal disorders such as osteoporosis, osteoarthritis and skeletal hypoplasia. Conversely, these bone diseases can be effectively treated when aimed at the circadian clock in bone cells, including the rhythmic expressions of clock genes and drug targets. In this review, we describe the unique circadian rhythms in physiological activities of various bone cells. Then we summarize the factors synchronizing the diurnal rhythms of bone with the underlying mechanisms. Based on the review, we aim to build an overall understanding of the diurnal rhythms in bone and summarize the new preventive and therapeutic strategies for bone disorders.
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Osso e Ossos , Ritmo Circadiano , Humanos , Ritmo Circadiano/fisiologia , Animais , Osso e Ossos/metabolismo , Osso e Ossos/fisiologia , Doenças Ósseas/fisiopatologia , Doenças Ósseas/metabolismo , Relógios Circadianos/fisiologiaRESUMO
INTRODUCTION: These guidelines aim to provide evidence-based recommendations for the supplementation of Vitamin D in maintaining bone health. An unmet need persists in Latin American regarding the availability of clinical and real-world data for rationalizing the use of vitamin D supplementation. The objective of these guidelines is to establish clear and practical recommendations for healthcare practitioners from Latin American countries to address Vitamin D insufficiency in clinical practice. METHODS: The guidelines were developed according to the GRADE-ADOLOPMENT methodology for the adaptation or adoption of CPGs or evidence-based recommendations. A search for high quality CPGs was complemented through a comprehensive review of recent literature, including randomized controlled trials, observational studies, and systematic reviews evaluating the effects of Vitamin D supplementation on bone health. The evidence to decision framework proposed by the GRADE Working Group was implemented by a panel of experts in endocrinology, bone health, and clinical research. RESULTS: The guidelines recommend Vitamin D supplementation for individuals aged 18 and above, considering various populations, including healthy adults, individuals with osteopenia, osteoporosis patients, and institutionalized older adults. These recommendations offer dosing regimens depending on an individualized treatment plan, and monitoring intervals of serum 25-hydroxyvitamin D levels and adjustments based on individual results. DISCUSSION: The guidelines highlight the role of Vitamin D in bone health and propose a standardized approach for healthcare practitioners to address Vitamin D insufficiency across Latin America. The panel underscored the necessity for generating local data and stressed the importance of considering regional geography, social dynamics, and cultural specificities when implementing these guidelines.
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Suplementos Nutricionais , Osteoporose , Deficiência de Vitamina D , Vitamina D , Humanos , Vitamina D/uso terapêutico , Vitamina D/administração & dosagem , América Latina , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/prevenção & controle , Osteoporose/tratamento farmacológico , Osteoporose/prevenção & controle , Adulto , Idoso , Feminino , MasculinoRESUMO
BACKGROUND: Escala de Calidad de vida Osteoporosis (ECOS-16) was originally developed in Spanish to evaluate the quality of life (QoL) in post-menopausal women (PMW) with osteoporosis or osteopenia based on the osteoporosis-specific QoL instruments. ECOS-16 has been translated into several languages, but the Urdu version is not yet available. OBJECTIVE: To translate the ECOS-16 Questionnaire into Urdu and determine its validity and reliability in PMW with osteopenia. METHODS: This was a linguistic validity and reliability study. ECOS-16 was translated into Urdu using Beaton's guidelines. Content validity was examined using Waltz's four-point ordinal scale. Twenty osteopenia-afflicted PMW aged 48-70 underwent pilot testing for face validity. Discriminant validity was determined by an independent T-test between PMW women with and without osteopenia. Convergent validity was assessed using Spearman's correlation coefficient. Cronbach's alpha and Intraclass correlation coefficient (ICC2,1) assessed internal consistency and test-retest reliability. The factor analysis was used to describe the factors. RESULTS: Each question's content validity ratio (CVR) was 0.83-1.00, while the scale's S-CVR was 0.96. Each question's Likert scale content validity index (CVI) was 0.91-0.93, while the scale's S-CVI was 0.91. Significant discriminant validity was found between groups in weeks I and II (p-value < 0.001). A correlation coefficient of 0.89 and 0.96 (p-value < 0.001) between Urdu ECOS-16 total score and SF-36 and EQ-5D scores suggests convergent validity. One component explained 83.86% of Urdu ECOS-16's variance in factor analysis. Excellent test-retest reliability (ICC2,1 = 0.990, 95% CI, 0.985-0.994, p-value < 0.001). Cronbach's alpha for standardized items was 0.995. CONCLUSION: ECOS-16 translated in Urdu is a valid and reliable questionnaire to assess QoL in PMW with osteopenia. It has a simple and easy language that can be understood easily by the Urdu-speaking population.
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Bone, an actively metabolic organ, undergoes constant remodeling throughout life. Disturbances in the bone microenvironment can be responsible for pathologically bone diseases such as periodontitis, osteoarthritis, rheumatoid arthritis and osteoporosis. Conventional bone tissue biomaterials are not adequately adapted to complex bone microenvironment. Therefore, there is an urgent clinical need to find an effective strategy to improve the status quo. In recent years, nanotechnology has caused a revolution in biomedicine. Cerium(III, IV) oxide, as an important member of metal oxide nanomaterials, has dual redox properties through reversible binding with oxygen atoms, which continuously cycle between Ce(III) and Ce(IV). Due to its special physicochemical properties, cerium(III, IV) oxide has received widespread attention as a versatile nanomaterial, especially in bone diseases. This review describes the characteristics of bone microenvironment. The enzyme-like properties and biosafety of cerium(III, IV) oxide are also emphasized. Meanwhile, we summarizes controllable synthesis of cerium(III, IV) oxide with different nanostructural morphologies. Following resolution of synthetic principles of cerium(III, IV) oxide, a variety of tailored cerium-based biomaterials have been widely developed, including bioactive glasses, scaffolds, nanomembranes, coatings, and nanocomposites. Furthermore, we highlight the latest advances in cerium-based biomaterials for inflammatory and metabolic bone diseases and bone-related tumors. Tailored cerium-based biomaterials have already demonstrated their value in disease prevention, diagnosis (imaging and biosensors) and treatment. Therefore, it is important to assist in bone disease management by clarifying tailored properties of cerium(III, IV) oxide in order to promote the use of cerium-based biomaterials in the future clinical setting. STATEMENT OF SIGNIFICANCE: In this review, we focused on the promising of cerium-based biomaterials for bone diseases. We reviewed the key role of bone microenvironment in bone diseases and the main biological activities of cerium(III, IV) oxide. By setting different synthesis conditions, cerium(III, IV) oxide nanostructures with different morphologies can be controlled. Meanwhile, tailored cerium-based biomaterials can serve as a versatile toolbox (e.g., bioactive glasses, scaffolds, nanofibrous membranes, coatings, and nanocomposites). Then, the latest research advances based on cerium-based biomaterials for the treatment of bone diseases were also highlighted. Most importantly, we analyzed the perspectives and challenges of cerium-based biomaterials. In future perspectives, this insight has given rise to a cascade of cerium-based biomaterial strategies, including disease prevention, diagnosis (imaging and biosensors) and treatment.
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Materiais Biocompatíveis , Doenças Ósseas , Cério , Cério/química , Cério/uso terapêutico , Humanos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Doenças Ósseas/tratamento farmacológico , AnimaisRESUMO
Tooth eruption is an essential process for the development of the oral and maxillofacial system. Several inherited and acquired diseases might affect this tightly regulated process, resulting in premature, delayed, or even failed tooth eruption. The purpose of this article is to review the literature and the clinical parameters of metabolic bone diseases that affect tooth eruption. It examines the physiological aspects of tooth eruption and the pathophysiological changes induced by metabolic bone diseases, including changes in bone metabolism, density, and structure. The search strategy for this review included an electronic search in PubMed, Google Scholar, Medline, Scopus, and the Cochrane Library using the following keywords: "metabolic bone diseases", "tooth eruption", "delayed tooth eruption", and each reported disease in combination with "tooth eruption disorders", covering publications up to March 2024 and limited to English-language sources. Understanding the influence of metabolic bone diseases on tooth eruption is crucial for managing both dental and skeletal manifestations associated with these disorders. This review suggests that a multidisciplinary approach to treatment may significantly improve oral outcomes for patients suffering from such conditions. Clinicians should be aware of the specific dental abnormalities that may arise and consider comprehensive evaluations and individualized treatment plans. These findings underscore the need for further research into targeted therapies that address these abnormalities.
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BACKGROUND: Bone histomorphometry provides comprehensive information on bone metabolism and microstructure. In this retrospective study, we aimed to obtain an overview of the typical indications, referring hospitals, and histomorphometric quantification-based diagnoses of the bone tissue in our histomorphometry laboratory, the only laboratory in Finland carrying out histomorphometric examination of clinical bone biopsies. METHODS: Between January 1, 2005 and December 31, 2020, 553 clinical bone biopsies were sent to our histomorphometry laboratory for histomorphometric examination. The median age of the patients was 55 years (range, 0.2-89.9 years), 51% of them were males, and 18% comprised pediatric patients. We received bone biopsy specimens from 23 hospitals or healthcare units. The majority of the samples we sent by nephrologists. RESULTS: The most common bone biopsy indications were suspicion of renal osteodystrophy (ROD), unknown bone turnover status in osteoporosis, and several or untypical fractures. The most common quantitative bone histomorphometry-based diagnosis was ROD. CONCLUSIONS: This study provides information on the clinical application of bone histomorphometry in Finland. Precise and quantitative ROD evaluation is the most common indication for bone histomorphometry, being crucial in clinical decision-making and targeted treatment of this patient group.
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While understanding the genetic underpinnings of osteogenesis has far-reaching implications for skeletal diseases and evolution, a comprehensive characterization of the osteoblastic regulatory landscape in non-mammalian vertebrates is still lacking. Here, we compared the ATAC-Seq profile of Xenopus tropicalis (Xt) osteoblasts to a variety of non mineralizing control tissues, and identified osteoblast-specific nucleosome free regions (NFRs) at 527 promoters and 6747 distal regions. Sequence analyses, Gene Ontology, RNA-Seq and ChIP-Seq against four key histone marks confirmed that the distal regions correspond to bona fide osteogenic transcriptional enhancers exhibiting a shared regulatory logic with mammals. We report 425 regulatory regions conserved with human and globally associated to skeletogenic genes. Of these, 35 regions have been shown to impact human skeletal phenotypes by GWAS, including one trps1 enhancer and the runx2 promoter, two genes which are respectively involved in trichorhinophalangeal syndrome type I and cleidocranial dysplasia. Intriguingly, 60 osteoblastic NFRs also align to the genome of the elephant shark, a species lacking osteoblasts and bone tissue. To tackle this paradox, we chose to focus on dlx5 because its conserved promoter, known to integrate regulatory inputs during mammalian osteogenesis, harbours an osteoblast-specific NFR in both frog and human. Hence, we show that dlx5 is expressed in Xt and elephant shark odontoblasts, supporting a common cellular and genetic origin of bone and dentine. Taken together, our work (i) unravels the Xt osteogenic regulatory landscape, (ii) illustrates how cross-species comparisons harvest data relevant to human biology and (iii) reveals that a set of genes including bnc2, dlx5, ebf3, mir199a, nfia, runx2 and zfhx4 drove the development of a primitive form of mineralized skeletal tissue deep in the vertebrate lineage.
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Cromatina , Elementos Facilitadores Genéticos , Osteoblastos , Fenótipo , Regiões Promotoras Genéticas , Xenopus , Animais , Humanos , Osteoblastos/metabolismo , Regiões Promotoras Genéticas/genética , Xenopus/genética , Elementos Facilitadores Genéticos/genética , Cromatina/metabolismo , Cromatina/genética , Evolução Biológica , Vertebrados/genética , Osso e Ossos/metabolismo , Osteogênese/genéticaRESUMO
Reduced physical function caused by bone destruction, pain, anemia, infections, and weight loss is common in multiple myeloma (MM). Myeloma bone disease challenges physical exercise. Knowledge on the effects and safety of physical exercise in newly diagnosed patients with MM is limited. In a randomized, controlled trial, we studied the effect of a 10-week individualized physical exercise program on physical function, physical activity, lean body mass (LBM), bone mineral density (BMD), quality of life (QoL), and pain in patients newly diagnosed with MM. Lytic bone disease was assessed, and exercise was adjusted accordingly. Primary outcome: knee extension strength. Secondary outcomes: Six-Minute-Walk-Test, 30-s Sit-to-Stand-Test (SST), grip strength, level of physical activity, LBM, BMD, QoL, and pain. Measurements were conducted pre- and post-intervention, and after 6 and 12 months. We included 100 patients, 86 were evaluable; 44 in the intervention group (IG) and 42 in the control group (CG). No statistically significant differences between groups were observed. Knee extension strength declined in the IG (p = .02). SST, aerobic capacity, and global QoL improved in both groups. Pain decreased consistently in the IG regardless of pain outcome. No significant safety concerns of physical exercise in newly diagnosed patients with MM were observed.
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Densidade Óssea , Exercício Físico , Mieloma Múltiplo , Qualidade de Vida , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Dor/etiologia , Dor/diagnóstico , Resultado do Tratamento , Terapia por Exercício/métodos , Composição Corporal , Índice de Massa CorporalRESUMO
OBJECTIVES: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All healthcare facilities in Taiwan. PARTICIPANTS: A total of 28 772 individuals were enrolled. INTERVENTIONS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted. PRIMARY OUTCOME MEASURE: To identify risk differences in developing osteoporosis among patients with a medical history of NS. RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis. CONCLUSION: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.
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Síndrome Nefrótica , Osteoporose , Humanos , Taiwan/epidemiologia , Osteoporose/epidemiologia , Osteoporose/complicações , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/epidemiologia , Síndrome Nefrótica/complicações , Adulto , Idoso , Fatores de Risco , Comorbidade , Adulto Jovem , Adolescente , Corticosteroides/efeitos adversosRESUMO
The synthesis and absorption of Vitamin D play crucial roles in numerous bodily functions, yet deficiencies persist due to factors like insufficient sunlight exposure and dietary inadequacy. Research underscores the significance of lifestyle elements such as diet, sun exposure, and physical activity in maintaining optimal Vitamin D levels. Strategies aimed at tackling deficiencies emphasize supplementation alongside lifestyle adjustments, especially in regions with abundant sunlight like the Middle East and North Africa (MENA). Despite the abundance of sunshine in the Arab world, there remains a prevalent issue of Vitamin D deficiency. This problem arises from various factors, including cultural practices such as traditional clothing covering most skin areas, which limit sun exposure, and environmental factors like air pollution that reduce UV penetration. Dietary habits and lifestyle choices also contribute to this deficiency. Dealing with the ongoing pandemic requires a focused effort to enhance awareness. While some individuals may recognize common diseases caused by Vitamin D deficiency, such as rickets and osteomalacia, many remain unaware of the broader health risks associated with the condition, including non-skeletal manifestations. Additionally, there is a lack of understanding regarding the numerous hidden benefits of this hormone. Therefore, prioritizing educational initiatives that delve into these aspects is essential to effectively combat the current health crisis. This literature review aims to report both skeletal and extraskeletal consequences of hypovitaminosis and briefly discuss the cause of paradoxical vitamin D deficiency in sunny regions like the MENA. This was done by reviewing pertinent articles published between January 2000 and January 2024, sourced from databases such as PubMed, UpToDate, Scopus, and CINAHL, focusing exclusively on English language literature and using keywords such as "Vitamin D deficiency" and "Extraskeletal manifestations."