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1.
Spine J ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39154948

RESUMO

BACKGROUND CONTEXT: Osteoporotic vertebral compression fractures (OVCFs) are common fragility fractures. Patients who undergo surgical treatment for their initial OVCFs warrant particular attention because there is an elevated risk of subsequent vertebral fractures and other types of fragility fractures. However, the optimal osteoporosis treatment for this specific patient group is less investigated. PURPOSE: This study compares the risk of subsequent osteoporotic fractures and mortality rate for patients who are initiated with denosumab and bisphosphonates and determines the effect of adherence to treatment. STUDY DESIGN: Retrospective nationwide cohort study PATIENT SAMPLE: A total of 2,858 patients who had surgically-managed osteoporotic vertebral compression fractures. OUTCOME MEASURES: The risk of osteoporotic fractures, vertebral fractures, non-vertebral fractures and death. METHODS: This is a retrospective nationwide cohort study that uses the National Health Insurance Research Database. Patients aged ≥50 years who were admitted for surgical interventions for OVCF between 2012 and 2016 and subsequently received denosumab or bisphosphonates for one year were included. Patients were stratified according to their anti-osteoporosis medications and adherence to treatment. A multivariable, time-varying Cox proportional hazards model was used to determine the risk of osteoporotic fractures, vertebral fractures, non-vertebral fractures and death. RESULTS: A total of 2,858 patients were included in this study: 1,123 patients in the denosumab group and 1,735 patients in the bisphosphonates group. Compared to persistent denosumab users, the non-persistent denosumab users, persistent bisphosphonate users and non-persistent bisphosphonate users had a greater risk of osteoporotic fractures, with respective hazard ratios of 1.64 (95% confidence interval [CI], 1.16-2.32), 1.74 (95% CI, 1.25-2.42) and 1.53 (95% CI, 1.14-2.06). If osteoporotic fractures were divided into non-vertebral and vertebral fractures, none of the groups exhibited an increased risk of vertebral fractures compared to persistent denosumab users, with an HR of 1.00 (95% CI: 0.54-1.88) for non-persistent denosumab users, 1.64 (95% CI: 0.96-2.81) for persistent bisphosphonate users and 1.52 (95% CI: 0.95-2.43) for non-persistent bisphosphonate users. However, there was a significantly greater risk of non-vertebral fracture, with respective hazard ratios of 2.04 (95% CI, 1.33-3.11), 1.80 (95% CI, 1.18-2.76) and 1.56 (95% CI, 1.06-2.27) for non-persistent denosumab users, persistent bisphosphonate users and non-persistent users. Noteworthy, non-persistent denosumab users exhibited a significantly greater risk of mortality than persistent denosumab users, with a hazard ratio of 3.12 (95% CI, 2.22-4.38). CONCLUSIONS: In terms of patients with OVCFs who require hospitalization and surgical intervention, those who receive ongoing denosumab treatment exhibit less risk of developing subsequent osteoporotic fractures than those who receive bisphosphonates or non-persistent denosumab treatment. However, discontinuation of denosumab is associated with a significantly increased risk of subsequent fractures and mortality. Therefore, adherence to the treatment is crucial for patients who are initiated with denosumab.

2.
Eur J Med Chem ; 276: 116679, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39018923

RESUMO

The primary focus of bisphosphonate medications is on targeting human farnesyl pyrophosphate synthase (hFPPS), an essential regulator of mammalian isoprenoids. Yet, these drugs encounter limitations due to their restricted "druglike" properties and their effectiveness primarily in treating skeletal disorders. In this study, we synthesized novel non-bisphosphonate compounds, using 4,4'-(ethane-1,2-diylbis(oxy))bis(3-methoxybenzaldehyde) (1) as a starting compound, with the aim of targeting hFPPS through a mixed binding approach. Among the various compounds tested, compounds 4a and 4b exhibited significant inhibition of hFPPS activity, with IC50 values of 1.108 and 1.24 µM, respectively. Docking studies further revealed that both compounds bound within the allylic binding site and near the isopentenyl diphosphate (IPP) site within the hFPPS pocket. Molecular dynamic simulations were performed on the best docking pose of the most potent compound 4a to confirm the formation of a stable complex with hFPPS. In an in vivo study conducted on ovariectomized rats, various biochemical markers including osteocalcin, estradiol, osteoprotegerin, bone mineral content, and density were negatively impacted, while levels of bone specific alkaline phosphatase, receptor activator of nuclear factor kappa-Β ligand, serum/urinary calcium, and phosphate increased. Notably, compound 4a exhibited antiresorptive properties similar to zoledronate, effectively restoring most of the perturbed biochemical estimations. These findings suggest the potential of compound 4a, a non-bisphosphonate compound, as alternative therapeutic agents for combating osteoporosis.


Assuntos
Inibidores Enzimáticos , Geraniltranstransferase , Osteoporose , Ovariectomia , Animais , Ratos , Geraniltranstransferase/antagonistas & inibidores , Geraniltranstransferase/metabolismo , Feminino , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Humanos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Difosfonatos/farmacologia , Difosfonatos/química , Difosfonatos/síntese química , Estrutura Molecular , Ratos Sprague-Dawley , Relação Dose-Resposta a Droga
3.
J Orthop Surg Res ; 19(1): 348, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867268

RESUMO

BACKGROUND: The risk factors for subsequent fractures following an initial hip fracture are not entirely understood. This study examined the clinical characteristics of hip fracture patients to identify potential risk factors associated with a higher risk of experiencing subsequent fractures. METHODS: We conducted a nested case-control study using data from the Chinese PLA General Hospital Hip Fracture Cohort between January 2008 and March 2022. The cases were individuals who experienced subsequent fractures following an initial hip fracture. Each case was matched with up to 2 controls who did not develop subsequent fractures. Important clinical factors were compared across groups, including traditional fracture risk factors and potential risk factors (e.g., comorbidities, falls risk, physical impairment, calcium or vitamin D use, and anti-osteoporosis medications). Conditional logistic regression analyses were used to evaluate the impact of these clinical features as potential risk factors for subsequent fractures. RESULTS: A total of 96 individuals who suffered from subsequent fractures were matched with 176 controls. The median time between the initial hip fracture and the subsequent fracture was 2.1 years. The overall proportion of patients receiving anti-osteoporosis treatment after initial hip fracture was 25.7%. In the multivariable regression analysis, living in a care facility (OR = 3.78, 95%CI: 1.53-9.34), longer hospital stays (OR = 1.05, 95%CI: 1.00-1.11), and falls after discharge (OR = 7.58, 95%CI: 3.37-17.04) were associated with higher odds of subsequent fractures. CONCLUSIONS: This study showed that living in a care facility, longer hospital stays, and falls after discharge may be independent risk factors for repeat fractures following an initial hip fracture. These findings could be used to identify and manage patients at high risk of subsequent fractures.


Assuntos
Fraturas do Quadril , Humanos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Estudos de Casos e Controles , Fatores de Risco , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Acidentes por Quedas/estatística & dados numéricos , Pessoa de Meia-Idade , Tempo de Internação , Osteoporose/complicações , Osteoporose/epidemiologia , Conservadores da Densidade Óssea/uso terapêutico
4.
Osteoporos Sarcopenia ; 10(1): 3-10, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38690538

RESUMO

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition. The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and antiresorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to antiresorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for individuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions: This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

5.
Arch Osteoporos ; 19(1): 36, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740651

RESUMO

This study aimed to estimate societal and healthcare costs incurred before and 1 year after the first fracture liaison services (FLS) visit and to explore differences in fracture type. All costs after 1 year significantly decreased compared to costs preceding the first visit. Fracture type did not significantly affect costs. INTRODUCTION: Limited literature is available on resource utilization and costs of patients visiting fracture liaison services (FLS). This study aimed to estimate the societal and healthcare costs incurred by patients with a recent fracture requiring anti-osteoporosis medication before and 1 year after the first FLS visit and to explore differences according to fracture type. METHODS: Resource utilization was collected through a self-reported questionnaire with a 4-month recall on health resource utilization and productivity losses immediately following the first FLS visit, and 4 and 12 months later. Unit costs derived from the national Dutch guideline for economic evaluations were used to compute societal and healthcare costs. Linear mixed-effect models, adjusted for confounders, were used to analyze societal and healthcare costs over time as well as the effect of fracture type on societal and healthcare costs. RESULTS: A total of 126 patients from two Dutch FLS centers were included, of whom 72 sustained a major fracture (hip, vertebral, humerus, or radius). Societal costs in the 4 months prior to the first visit (€2911) were significantly higher compared to societal costs 4 months (€711, p-value = 0.009) and 12 months later (€581, p-value = 0.001). Fracture type did not have a significant effect on total societal or healthcare costs. All costs 12 months after the initial visit were numerically lower for major fractures compared to others. CONCLUSION: Societal and healthcare costs in the year following the first FLS visit significantly decreased compared to those costs preceding the first visit.


Assuntos
Conservadores da Densidade Óssea , Custos de Cuidados de Saúde , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Masculino , Custos de Cuidados de Saúde/estatística & dados numéricos , Idoso , Fraturas por Osteoporose/economia , Fraturas por Osteoporose/terapia , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/economia , Osteoporose/tratamento farmacológico , Osteoporose/economia , Países Baixos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Efeitos Psicossociais da Doença
6.
Artigo em Inglês | MEDLINE | ID: mdl-38607748

RESUMO

BACKGROUND: The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known. OBJECTIVE: This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF. METHODS: From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (ß-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time. RESULTS: There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, ß-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , ß-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and ß-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05). CONCLUSION: In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.

7.
Eur J Med Chem ; 271: 116414, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38677061

RESUMO

Sclerostin is a secreted glycoprotein that expresses predominantly in osteocytes and inhibits bone formation by antagonizing the Wnt/ß-catenin signaling pathway, and the loop3 region of sclerostin has recently discovered as a novel therapeutic target for bone anabolic treatment without increasing cardiovascular risk. Herein, we used a structural based virtual screening to search for small molecular inhibitors selectively targeting sclerostin loop3. A novel natural product hit ZINC4228235 (THFA) was identified as the sclerostin loop3-selective inhibitor with a Kd value of 42.43 nM against sclerostin loop3. The simplification and derivation of THFA using molecular modeling-guided modification allowed the discovery of an effective and loop3-selective small molecular inhibitor, compound (4-(3-acetamidoprop-1-yn-1-yl)benzoyl)glycine (AACA), with improved binding affinity (Kd = 15.4 nM) compared to the hit THFA. Further in-vitro experiment revealed that compound AACA could attenuate the suppressive effect of transfected sclerostin on Wnt signaling and bone formation. These results make AACA as a potential candidate for development of anti-osteoporosis agents without increasing cardiovascular risk.


Assuntos
Desenho de Fármacos , Osteoporose , Osteoporose/tratamento farmacológico , Humanos , Relação Estrutura-Atividade , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Estrutura Molecular , Animais , Camundongos , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Relação Dose-Resposta a Droga , Modelos Moleculares , Osteogênese/efeitos dos fármacos
8.
Heliyon ; 10(6): e27870, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545153

RESUMO

Eucommia ulmoides (E. ulmoides) is a relict plant belonging to the Eucommiaceae family. Each part of E. ulmoides including the bark, leaf, staminate flower, and seed, contains various active ingredients, that are edible and have medicinal value. This review summarizes the literatures on the functional properties of flavonoids, phenols, terpenoids, and polysaccharides in different parts of E. ulmoides. The prospects for application of the different parts of E. ulmoides as functional foods are also discussed. This review provides a reference for further research and development of the medicinal application of E. ulmoides.

9.
Nat Prod Res ; : 1-6, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38511431

RESUMO

The previously undescribed lactone ring-opening enterolactone and its sulphate were purified along with the lactone counterparts from the urine of dairy sheep fed flaxseed cake. The structures were determined by NMR and MS analyses. The ring-opening and lactone forms underwent mutual transformation with changes in pH and milk could protect the lactone form. Enterolactone exhibited more effective anti-proliferation activity on MDA-MB-231 breast cancer cells than its ring-opening counterpart, while the ring-opening enterolactone demonstrated more effective anti-osteoporosis activity than the lactone form. The results indicated the potential for targeting biological functions through pH and medium manipulation.

10.
Bioorg Chem ; 145: 107253, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38452588

RESUMO

Phytochemical study on Euphorbia milii, a common ornamental plant, resulted in the identification of thirteen new ent-rosane diterpenoids (1-13), three new ent-atisane diterpenoids (14-16), and a known ent-rosane (17). Their structures were delineated using spectroscopic data, quantum chemical calculations, and X-ray diffraction experiments. Euphomilone F (1) represented a rare ent-rosane-type diterpenoid with a 5/7/6 skeleton. Euphoainoid G (8) was a rare rosane diterpenic acid. Compounds 9 and 10 carried infrequent tetrahydrofuran rings, and compounds 11-13 was 18-nor-ent-rosane diterpenoids. All isolates were evaluated for their inhibitory effects on RANKL-induced osteoclasts. Notably, compounds with aromatic ester groups (2-7) showed promising activities (IC50 < 10 µM), underscoring the significance of acylated A-ring moieties in the ent-rosane skeleton for anti-osteoclastogenesis. Thirteen synthetic derivatives were obtained through esterification of 17. Of these, compound 27 exhibited remarkable improvement, with an IC50 of 0.8 µM, more than a 12-fold increase in potency compared to the parent compound 17 (IC50 > 10 µM). This work presents a series of new ent-rosane diterpenoids with potential antiosteoporosis agents.


Assuntos
Diterpenos , Euphorbia , Osteogênese , Euphorbia/química , Extratos Vegetais/química , Osteoclastos , Diterpenos/farmacologia , Diterpenos/química , Estrutura Molecular
11.
Front Pharmacol ; 15: 1338951, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38333006

RESUMO

Osteoporosis (OP) is a bone disease associated with increasing age. Currently, the most common medications used to treat OP are anabolic agents, anti-resorptive agents, and medications with other mechanisms of action. However, many of these medications have unfavorable adverse effects or are not intended for long-term use, potentially exerting a severe negative impact on a patient's life and career and placing a heavy burden on families and society. There is an urgent need to find new drugs that can replace these and have fewer adverse effects. Quercetin (Que) is a common flavonol in nature. Numerous studies have examined the therapeutic applications of Que. However, a comprehensive review of the anti-osteoporotic effects of Que has not yet been conducted. This review aimed to describe the recent studies on the anti-osteoporotic effects of Que, including its biological, pharmacological, pharmacokinetic, and toxicological properties. The outcomes demonstrated that Que could enhance OP by increasing osteoblast differentiation and activity and reducing osteoclast differentiation and activity via the pathways of Wnt/ß-catenin, BMP/SMAD/RUNX2, OPG/RANKL/RANK, ERK/JNK, oxidative stress, apoptosis, and transcription factors. Thus, Que is a promising novel drug for the treatment of OP.

12.
Osteoporos Int ; 35(5): 775-783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38240755

RESUMO

With the analysis of nationwide health claim data, treatment with the composite agent of SERMs and vitamin D reduces the risk of osteoporotic fracture and hip fracture better compared to SERMs treatment in women with osteoporosis aged ≥ 50 years. PURPOSE: This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50 years. METHODS: The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017-2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan-Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups. RESULTS: The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09-0.71; p = 0.009). No difference was observed between the groups regarding mortality. CONCLUSION: The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk.


Assuntos
Fraturas do Quadril , Osteoporose Pós-Menopausa , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Vitamina D/uso terapêutico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/epidemiologia , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Vitaminas
13.
Fitoterapia ; 173: 105836, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286315

RESUMO

Citrisorbicillinol (1), along with six other known compounds (2-7), was isolated from an endphyte Penicillium citrinum ZY-2 of Plantago asiatica L. Citrisorbicillinol (1) was characterized as a skeletally unprecedented hybrid sorbicillinoid, and its unique framework is likely formed by intermolecular [4 + 2] cycloaddition between intermediates derived from citrinin and sorbicillinoid biosynthetic gene clusters. Compounds 1 and 2 demonstrated to promote osteoblastic differentiation in MC3T3-E1 cells, and to be osteogenic in the prednisolone induced osteoporotic zebrafish. Compounds 3-7 exhibited moderate cytotoxicity against four human cancer cell lines.


Assuntos
Citrinina , Penicillium , Animais , Humanos , Estrutura Molecular , Peixe-Zebra
14.
Curr Osteoporos Rep ; 22(1): 1-10, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38093031

RESUMO

PURPOSE OF THE REVIEW: The purpose of the review is to summarise the current scientific evidence on the efficacy of osteoporosis medications in patients with type 2 diabetes. RECENT FINDINGS: Type 2 diabetes (T2D) is a growing global epidemic. The highest prevalence is observed in the elderly, the same population affected by osteoporosis. Despite normal or even increased bone mineral density and low bone turnover, T2D is associated with an increased risk of fractures in most skeletal sites. These findings raised concerns over the efficacy of anti-osteoporosis drugs in this population. There is no randomised controlled trial designed specifically for people with T2D. However, observational studies and post-hoc analyses of randomised controlled trials have provided valuable insights into the effects of various anti-osteoporosis treatments in this population. Overall, most anti-osteoporosis drugs seem to have similar efficacy and safety profiles for people with and without type 2 diabetes. However, continued research and long-term safety data are needed to optimise treatment strategies and improve bone health outcomes in this population. The current evidence suggests that most anti-osteoporosis drugs exhibit comparable efficacy in people with and without T2D.


Assuntos
Conservadores da Densidade Óssea , Diabetes Mellitus Tipo 2 , Fraturas Ósseas , Osteoporose , Idoso , Humanos , Osso e Ossos , Densidade Óssea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Fraturas Ósseas/complicações , Osteoporose/tratamento farmacológico , Osteoporose/complicações , Conservadores da Densidade Óssea/uso terapêutico
15.
Eur J Med Chem ; 265: 116068, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38141284

RESUMO

Thirteen new sirenin derivatives named eupenicisirenins C-O (1-13), along with a biosynthetically related known one (14), were isolated from the mangrove sediment-derived fungus Penicillium sp. SCSIO 41410. The structures, which possessed a rare cyclopropane moiety, were confirmed by extensive analyses of the spectroscopic data, quantum chemical calculations, and X-ray diffraction. Among them, eupenicisirenin C (1) exhibited the strongest NF-κB inhibitory activities, as well as suppressing effects on cGAS-STING pathway. Moreover, 1 showed the significant inhibitory effect on RANKL-induced osteoclast differentiation in bone marrow macrophages cells, and also displayed the therapeutic potential on prednisolone-induced zebrafish osteoporosis. Transcriptome analysis and the following verification tests suggested that its anti-osteoporotic mechanism is related to the extracellular matrix receptor interaction-related pathways. This study provided a promising marine-derived anti-osteoporotic agent for the treatment of skeletal disease.


Assuntos
Osteoporose , Penicillium , Animais , Fungos/metabolismo , Macrófagos , NF-kappa B/metabolismo , Osteoporose/tratamento farmacológico , Penicillium/química , Peixe-Zebra/metabolismo , Compostos Bicíclicos com Pontes/química
16.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1022089

RESUMO

BACKGROUND:Percutaneous vertebroplasty is the most widely used method for the treatment of osteoporotic vertebral compression fractures,and most studies have concluded that percutaneous vertebroplasty increases the probability of adjacent vertebral secondary compression fractures in patients with osteoporotic vertebral compression fractures.However,controversy remains regarding the risk factors associated with adjacent vertebral re-fracture caused after percutaneous vertebroplasty. OBJECTIVE:To summarize the influencing factors of adjacent vertebral compression fractures after percutaneous vertebroplasty in patients with osteoporotic vertebral compression fractures,in order to provide a certain reference for reducing the risk of its occurrence as well as formulating the corresponding treatment plan. METHODS:Using"osteoporosis,fracture,percutaneous vertebroplasty,adjacent vertebral compression fractures,risk factors"as the Chinese search terms,"osteoporosis,osteoporotic vertebral compression fractures,percutaneous vertebroplasty,adjacent vertebral compression fractures,risk factors"as English search terms,computerized searches were conducted on CNKI,Wanfang Medical Network,VIP,PubMed,Springer,ScienceDirect,and Elsevier databases.The search timeframe focuses on January 2018 through September 2023,with the inclusion of a few classic forward literature.The literature was screened by reading the titles and abstracts,and 83 papers were finally included in the review. RESULTS AND CONCLUSION:(1)Osteoporotic vertebral compression fractures are one of the most common complications of osteoporosis,placing elderly patients at a significant risk of disability and death.Percutaneous vertebroplasty is a practical and effective treatment for osteoporotic vertebral compression fractures.(2)With the popularity of percutaneous vertebroplasty,its secondary vertebral compression fractures have gradually increased,with adjacent vertebral compression fractures being the most common.(3)Previous studies have only discussed the effects of factors such as bone mineral density,multiple vertebral fractures,body mass index,age,sex,amount of bone cement,cement leakage,and anti-osteoporosis treatment on secondary compression fractures of adjacent vertebrae after percutaneous vertebroplasty,and summarized the number of vertebral fractures,timing of the operation,surgical approach,cement material,diffuse distribution of bone cement,recovery height of the injured vertebrae,and wearing of a support after surgery,which is not yet comprehensive.The analysis of the specific mechanisms of risk factor-induced adjacent vertebral fractures is relatively rare.(4)The results of the article showed that low bone mineral density,advanced age,perimenopausal women,multiple vertebral fractures,excessive recovery of the height of the injured vertebrae,cement leakage,comorbid underlying diseases,and poor lifestyle habits were the risk factors for secondary adjacent vertebral compression fractures after percutaneous vertebroplasty,and that maintaining a normal body mass index,early surgery,bilateral percutaneous vertebroplasty,use of a new type of cement material,an appropriate volume of bone cement injection and uniform cement dispersion,regular anti-osteoporosis treatment,and postoperative brace wearing are protective factors for secondary adjacent vertebral compression fractures after percutaneous vertebroplasty.

17.
Cureus ; 15(12): e50303, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38089947

RESUMO

Romosozumab is a humanized monoclonal antibody that targets the sclerostin protein, which regulates bone formation and resorption. It is a novel therapy in the treatment of post-menopausal women with osteoporosis. The evidence regarding romosozumab's cardiovascular safety is conflicting. We report the first post-marketing case demonstrating cardiac events (i.e., atrial fibrillation and congestive heart failure) in a female patient with osteoporosis likely triggered by romosozumab. A literature review on romosozumab and cardiovascular disease is discussed extensively. For osteoporotic patients with cardiovascular risk factors (e.g., hypertension, coronary artery disease, and stroke), the benefits of fracture prevention should be weighed against potential cardiovascular risks before prescribing romosozumab. Real-world data on post-marketing surveillance will shed light on the potential safety signals of romosozumab.

18.
Mar Drugs ; 21(11)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37999397

RESUMO

Several sialoglycopeptides were isolated from several fish eggs and exerted anti-osteoporosis effects. However, few papers have explored sialoglycopeptide from tuna eggs (T-ES). Here, a novel T-ES was prepared through extraction with KCl solution and subsequent enzymolysis. Pure T-ES was obtained through DEAE-Sepharose ion exchange chromatography and sephacryl S-300 gel filtration chromatography. The T-ES was composed of 14.07% protein, 73.54% hexose, and 8.28% Neu5Ac, with a molecular weight of 9481 Da. The backbone carbohydrate in the T-ES was →4)-ß-D-GlcN-(1→3)-α-D-GalN-(1→3)-ß-D-Glc-(1→2)-α-D-Gal-(1→2)-α-D-Gal-(1→3)-α-D-Man-(1→, with two branches of ß-D-GlcN-(1→ and α-D-GalN-(1→ linking at o-4 in →2,4)-α-D-Gal-(1→. Neu5Ac in the T-ES was linked to the branch of α-D-GlcN-(1→. A peptide chain, Ala-Asp-Asn-Lys-Ser*-Met-Ile that was connected to the carbohydrate chain through O-glycosylation at the -OH of serine. Furthermore, in vitro data revealed that T-ES could remarkably enhance bone density, bone biomechanical properties, and bone microstructure in SAMP mice. The T-ES elevated serum osteogenesis-related markers and reduced bone resorption-related markers in serum and urine. The present study's results demonstrated that T-ES, a novel sialoglycopeptide, showed significant anti-osteoporosis effects, which will accelerate the utilization of T-ES as an alternative marine drug or functional food for anti-osteoporosis.


Assuntos
Sialoglicoproteínas , Atum , Humanos , Camundongos , Animais , Sequência de Carboidratos , Carboidratos , Hexoses
19.
Arch Osteoporos ; 18(1): 133, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37953310

RESUMO

We retrospectively analyzed 12,999 elderly patients with fragility fracture and found that the detection rate of bone mineral density (BMD) and bone turnover markers (BTMs), the treatment rate of osteoporosis, and the visiting rate to the osteoporosis specialist clinic after discharge are significantly enhanced in fragility fracture patients after receiving health education on osteoporosis-related knowledge during hospitalization. PURPOSE: To observe the effect of health education on the diagnosis and treatment of osteoporosis during hospitalization and the rate of come back to osteoporosis clinic after discharge in elderly patients with fragility fracture. METHODS: A retrospective analysis was performed on 12,999 elderly patients with fragility fracture admitted to Xi'an Honghui Hospital from March 2021 to December 2022. The patients were divided into the health education group and the non-health education group according to whether they received health education on osteoporosis-related knowledge during hospitalization. The diagnosis and treatment of osteoporosis during hospitalization and the outpatient treatment of osteoporosis after discharge were compared between the two groups. RESULTS: Among the 7784 patients in the health education group, 4551 (58.47%) received BMD test, 798 (10.25%) received BTMs test, 3990 (51.26%) received anti-osteoporosis medications (AOMs) treatment, and 1232 (15.83%) came back to the osteoporosis specialist clinic after discharge. Among the 5215 patients in the non-health education group, 681 (13.06%) received BMD test, 6 (0.12%) received BTMs test, 2071 (39.71%) received AOMs treatment, and 440 (8.44%) came back to the osteoporosis specialist clinic within one month after discharge. CONCLUSION: The education of osteoporosis-related knowledge for patients with fragility fracture contribute to enhance the detection rate of BMD and BTMs and the treatment rate of osteoporosis during hospitalization, and increase the rate of coming back to the osteoporosis clinic after discharge.


Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Médicos , Humanos , Idoso , Estudos Retrospectivos , Alta do Paciente , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/terapia , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/terapia , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Hospitalização , Educação em Saúde , Hospitais
20.
BMC Geriatr ; 23(1): 728, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946131

RESUMO

BACKGROUND: There is a gender difference in the acceptance of osteoporosis diagnosis and treatment in patients after fragility fractures, but this difference is rarely assessed during hospitalization, and it is unclear whether these differences are age-dependent. This study aimed to evaluate the differences between male and female fragility fracture patients of different age groups who received the diagnosis and treatment of osteoporosis during hospitalization. METHODS: 31,265 fragility fracture patients aged ≥ 50 years from the Fragility Fracture Management Database in a high-volume orthopedic hospital from December 2019 to February 2023 were included in this study. We compared the differences in the rates of men and women with fragility fracture who received the measurement of bone mineral density (BMD) and bone metabolism biochemical markers (BMBMs) and treatment with anti-osteoporosis medications (AOMs), and follow-up to the internal medicine clinic within 3 months after discharge, across all age groups and across different age stages (50-59, 60-69, 70-79, and ≥ 80 years). RESULTS: The detection rates of female patients receiving BMD and BMBMs during hospitalization were 31.88% and 5.30%, respectively, compared with 22.23% and 2.69% for men. The rate of receiving any AOMs treatment was 44.63% for women and 31.60% for men. The follow-up rate of returning to the internal medicine clinic within 3 months after discharge was 9.79% for women compared to 3.00% for men. There was a significant difference between males compared to females (P < 0.0001). Analysis of patients by different age group revealed that differences in the diagnosis and treatment of osteoporosis were found only in patients under 80 years of age, while gender differences in the return to the internal medicine clinic for follow-up after discharge were present in all age groups. CONCLUSIONS: Gender differences present in osteoporosis management in patients with fragility fracture during hospitalization, especially for patients under 80 years of age. This finding suggests that orthopedic surgeons neglect to manage osteoporosis in male patients with fragility fracture during hospitalization.


Assuntos
Fraturas Ósseas , Osteoporose , Fraturas por Osteoporose , Humanos , Feminino , Masculino , Idoso de 80 Anos ou mais , Fatores Sexuais , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/terapia , Densidade Óssea , Hospitalização , Fraturas por Osteoporose/diagnóstico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/terapia
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