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Frontiers in Physiology 2024O-GlcNAcylation, as a post-translational modification, can modulate cellular activities such as kinase activity, transcription-translation, protein degradation, and... (Review)
Review
O-GlcNAcylation, as a post-translational modification, can modulate cellular activities such as kinase activity, transcription-translation, protein degradation, and insulin signaling by affecting the function of the protein substrate, including cellular localization of proteins, protein stability, and protein/protein interactions. Accumulating evidence suggests that dysregulation of O-GlcNAcylation is associated with disease progression such as cancer, neurodegeneration, and diabetes. Recent studies suggest that O-GlcNAcylation is also involved in the regulation of osteoblast, osteoclast and chondrocyte differentiation, which is closely related to the initiation and development of bone metabolic diseases such as osteoporosis, arthritis and osteosarcoma. However, the potential mechanisms by which O-GlcNAcylation regulates bone metabolism are not fully understood. In this paper, the literature related to the regulation of bone metabolism by O-GlcNAcylation was summarized to provide new potential therapeutic strategies for the treatment of orthopedic diseases such as arthritis and osteoporosis.
PubMed: 38915778
DOI: 10.3389/fphys.2024.1416967 -
Frontiers in Pharmacology 2024Gukang Capsule has been used as a complementary and alternative medicine (CAM) for the treatment of primary osteoporosis (POP) in China. The primary aim of this study...
Gukang Capsule has been used as a complementary and alternative medicine (CAM) for the treatment of primary osteoporosis (POP) in China. The primary aim of this study was to assess the clinical effectiveness and safety of Gukang Capsule in POP patients. A systematic search was conducted across multiple academic databases including PubMed, Web of science, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP Information, and Wanfang database to identify randomized controlled trials investigating the Gukang Capsule in the treatment of POP. The screening process, data extraction, and assessment of methodological quality were conducted independently by two reviewers. Statistical analysis was performed using the Rev Man 5.3 software. Subgroup analysis was carried out through the combination of OPF. Subgroup analysis was performed according to whether OPF were combined. Stata 12.0 was used for sensitivity and bias analysis. Nineteen studies were assessed that included 1804 participants. It was found that compared with the control group, the total effective rate (RR = 1.26, 95% CI, 1.20, 1.33), the Medical Outcomes Study Short-form 36 [RR = 1.26, 95% CI(1.20, 1.33)], the bone mineral density (BMD) of lumbar vertebra (SMD = 0.77, 95% CI, 0.48, 1.07), the BMD of femoral neck [SMD = 0.84, 95% CI(0.53, 1.14)], and the BMD of Ward's triangle (SMD = 0.64, 95% CI, 0.44, 0.85) of the Gukang Capsule experimental group were higher. Compared with the control group, the fracture healing time (SMD = -2.14, 95% CI, -2.45, -1.84), the bone specific alkaline phosphatase (BALP) levels in serum (SMD = -2.00, 95% CI, -2.83, -1.17), the tartrate resistant acid phosphatase 5b (TRACP-5b) levels in serum (SMD = -2.58, 95% CI, -3.87, -1.29) of the Gukang Capsule experimental group were lower. The bone glaprotein (BGP) levels in serum (SMD = -0.22, 95% CI, -1.86, 1.43) and the adverse events (RR = 0.80, 95% CI, 0.40, 1.63) of the experimental group and the control group have no difference. Gukang Capsule, as a CAM for the management of POP, exhibits the potential to enhance BMD and quality of life, expedite the healing time of OPF, diminish levels of BALP and TRACP-5b, and improve the total effective rate without increasing the adverse events. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023477774, PROSPERO CRD42023477774.
PubMed: 38915472
DOI: 10.3389/fphar.2024.1394537 -
Frontiers in Pharmacology 2024To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better...
OBJECTIVE
To comprehensively analyze the ADRs associated with Denosumab (Prolia) in the treatment of osteoporosis using data from the FAERS database, and gain a better understanding of the potential risks and side effects of Denosumab (Prolia) therapy.
METHODS
Data of Denosumab (Prolia) were collected from the FAERS database covering the period from first quarter of 2010 to the third quarter of 2023. Disproportionality analysis was performed by calculating the reporting odds ratios (ROR), proportional reporting ratio (PRR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals.
RESULTS
Totally, 17,985,365 reports were collected from the FAERS database, 1,97,807 reports of Denosumab (Prolia) were identified as the "primary suspected (PS)" ADRs. Denosumab (Prolia) induced ADRs occurred in 27 organ systems. 38 significant disproportionality PTs satisfying with the three algorithms were retained at the same time. Unexpected significant ADRs such as bone density abnormal and immobile also occur. The majority of the ADRs occurred within the first 30 days after Denosumab (Prolia) initiation.
CONCLUSION
Based on the American FAERS database, the high frequency ADRs of Denosumab (Prolia) were hypocalcaemia, bone density abnormal, eczema, rebound effect, spinal deformity, etc. Clinical use of this drug should focus on this part of ADRs. Attention should also be paid to newly discovered ADRs, such as immobile, menopausal symptoms, etc., to avoid more serious consequences. Cohort studies, more detailed and comprehensive case information, and long-term clinical investigations are needed to confirm these results and to further understand the safety profile of Denosumab (Prolia).
PubMed: 38915470
DOI: 10.3389/fphar.2024.1358592 -
Frontiers in Aging Neuroscience 2024Patients with Parkinson's disease (PD) exhibit a heightened risk of falls and related fractures compared to the general population. This study aims to assess the...
BACKGROUND
Patients with Parkinson's disease (PD) exhibit a heightened risk of falls and related fractures compared to the general population. This study aims to assess the clinical characteristics associated with falls in the patient with PD and to gain further insight into these factors through Mendelian randomization analysis.
METHODS
From January 2013 to December 2023, we included 591 patients diagnosed with Parkinson's disease at Shenzhen Baoan People's Hospital. Using univariate and multivariate logistic regression analyses, we identified clinical variables associated with falls. We constructed a nomogram based on these variables and evaluated the predictive efficacy of the model. Additionally, we employed summary statistics from genome-wide association studies to conduct two-sample Mendelian randomization (MR) analyses on key variables influencing falls.
RESULTS
Compared to the control group, we identified osteoporosis, motor dysfunction, higher Hoehn and Yahr scale as significant risk factors for falls in PD patients. Conversely, treatment with levodopa and a higher level of education exhibited a protective effect against the risk of falling. MR analysis further confirmed a causal relationship between osteoporosis, education level and falls in PD patients.
CONCLUSION
Osteoporosis and educational attainment are correlated with falls in Parkinson's disease.
PubMed: 38915347
DOI: 10.3389/fnagi.2024.1420885 -
Chiropractic & Manual Therapies Jun 2024Osteoporosis is significantly associated with fractures and burdens the health of especially older people. Osteoporotic fractures cause pain, disability, and increased... (Review)
Review
BACKGROUND
Osteoporosis is significantly associated with fractures and burdens the health of especially older people. Osteoporotic fractures cause pain, disability, and increased mortality. Early diagnosis of osteoporosis allows earlier initiation of treatment, thereby reducing the risk of osteoporotic fractures. Chiropractors encounter potential osteoporotic patients daily, and perform radiological evaluation of these and other patients, including evaluation of X-rays done for other purposes than osteoporosis. Therefore, chiropractors may identify vertebral fractures, vertebral deformity or osteopenia not otherwise suspected or recorded.
METHODS
This study examines procedures available to the chiropractor to describe conventional X-rays with the focus of osteoporosis related findings. We review the indications for radiological examination in chiropractic practice, and in the realm of osteoporosis we describe radiological methods available for examination of conventional radiographs, and the necessity of inter-disciplinary communication.
RESULTS
National guidelines are available regarding referral for X-rays in chiropractic practice. Standardized protocols ensure image acquisition of the highest quality in the chiropractors' radiological department. Conventional X-ray examination is not indicated on clinical suspicion of osteoporosis alone, as bone mineral density testing is the diagnostic test. Radiological assessment of all available X-rays of patients above the age of 50 years should include evaluation of the bone quality, and hip and vertebral fracture assessment. The Singh index, Genant Semi-Quantitative tool (GSQ), and Algorithm-Based Qualitative method (ABQ) should be used consistently during interpretation. Referral for additional imaging and evaluation should be prompt and systematic when needed.
CONCLUSIONS
This article presents an overview of evidence-based radiological procedures for the purpose of promoting early diagnosis of osteoporosis. We present recommendations to the clinicians where we propose an opportunistic evaluation of X-rays, done for any reason, which include systematic evaluation of bone quality, presence of hip and vertebral fractures, and vertebral deformation of all patients above the age of 50 years. Detailed referral to healthcare professionals for further diagnostic evaluation is performed when needed. Consistent, high-quality radiological procedures in chiropractic practices could feasibly contribute to the timely diagnosis of osteoporosis, ultimately minimizing the impact of osteoporosis-related complications on patients' health.
Topics: Humans; Osteoporosis; Chiropractic; Radiography; Female; Bone Density
PubMed: 38915085
DOI: 10.1186/s12998-024-00545-0 -
BMC Musculoskeletal Disorders Jun 2024Most studies infer increasing incidence of proximal humeral fractures (PHF) from the 1950´s until the 1990´s. Recent time trends are less clear.
BACKGROUND
Most studies infer increasing incidence of proximal humeral fractures (PHF) from the 1950´s until the 1990´s. Recent time trends are less clear.
OBJECTIVES
Our primary objective was to identify time trends in the age- and sex-adjusted adult incidence of PHF in Malmö, Sweden, from year 1944 until 2020. Our secondary objectives were to describe the variation in incidence according to age, the monthly distribution, and to compare data from the two most recent decades with earlier.
STUDY DESIGN AND METHODS
Malmö has one emergency hospital where acute fractures are treated. We identified PHF in adult patients (≥ 18 years) by reviewing relevant radiology examinations during 17 sample years from year 1944 to 2020. We used jointpoint analyses to estimate time trends.
RESULTS
We identified 3 031 PHF during the study period (3 231 161 person years), 73% were sustained by women with mean age of 69 years (mean age in men 59). Joinpoint analyses indicated an increase in the age- and sex-adjusted incidence of PHF from year 1944 (52 per 100 000 person years) until 1977 (120 per 100 000) and thereafter a decrease until 2020 (85 per 100 000). A seasonal variation with more fractures during winter months, was apparent in earlier but not recent decades.
CONCLUSIONS
The age- and sex-adjusted incidence of PHF increased in Malmö, Sweden, from the 1940´s until year 1977 and thereafter decreased until 2020. More fractures were seen during winter months in earlier but not recent decades.
Topics: Humans; Sweden; Female; Male; Aged; Middle Aged; Shoulder Fractures; Incidence; Adult; Aged, 80 and over; Time Factors; Young Adult; Cohort Studies; Seasons; Adolescent
PubMed: 38914972
DOI: 10.1186/s12891-024-07602-y -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2024VD is a crucial vitamin for human health, as it enhances calcium absorption in the intestines and prevent rickets. Calcifediol (25(OH)VD) and calcitriol (1α,25(OH)VD)... (Review)
Review
VD is a crucial vitamin for human health, as it enhances calcium absorption in the intestines and prevent rickets. Calcifediol (25(OH)VD) and calcitriol (1α,25(OH)VD) are two derivatives of vitamin D that play an important role in preventing and treating osteoporosis, as well as regulating human physiological functions. Currently, the production of calcifediol, and calcitriol primarily relies on chemical synthesis, which has disadvantages such as low product yield, numerous by-products, and environmental unfriendliness. Therefore, developing a green, safe, and environmentally friendly biocatalytic synthesis pathway is of utmost importance. This article mainly reviews the biocatalytic synthesis pathways of calcifediol, and calcitriol. The P450 enzymes, including P450 monooxygenases (cytochrome P450 monooxygenases, CYPs) and P450 peroxygenases (unspecific peroxygenases, UPOs), are crucial for the production of calcifediol and calcitriol. The catalytic mechanism of the extensively studied P450 monooxygenases, the selection of suitable redox partners, and the key residues involved in the enzyme's catalytic activity are analyzed. In addition, the review explores HO-driven UPOs, including their catalytic mechanism, strategies for high heterologous expression, and regeneration of HO. UPOs are regarded as highly promising biocatalysts because they can facilitate reactions without the need for expensive cofactors and redox partners. This review offers insights into the engineering of P450 for the efficient production of vitamin D derivatives.
Topics: Calcitriol; Cytochrome P-450 Enzyme System; Calcifediol; Humans; Biocatalysis
PubMed: 38914482
DOI: 10.13345/j.cjb.230664 -
Frontiers in Cellular and Infection... 2024Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral...
INTRODUCTION
Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women.
METHODS
In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis.
RESULTS
The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of was strongly correlated with the gene.
DISCUSSION
Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis.
Topics: Humans; Gastrointestinal Microbiome; Female; Bone Density; Postmenopause; Feces; Middle Aged; RNA, Ribosomal, 16S; Metabolomics; Bacteria; Aged; Metabolome; Biomarkers; Chromatography, Liquid; Mass Spectrometry; Osteoporosis, Postmenopausal; Bone Remodeling
PubMed: 38912210
DOI: 10.3389/fcimb.2024.1367325 -
Iranian Journal of Public Health May 2024We aimed to evaluate the level of knowledge, awareness, and perceptions regarding osteoporosis (OP) and risk factors in China. (Review)
Review
BACKGROUND
We aimed to evaluate the level of knowledge, awareness, and perceptions regarding osteoporosis (OP) and risk factors in China.
METHODS
The databases of PubMed, Medline, Embase, Web of science, VIP, and CNKI were searched for papers published before December 2022 using Chinese and English keywords and their combinations: "knowledge", "osteoporosis", "risk factor", "bone health", "perception", "awareness". The levels of knowledge, awareness, and perception about OP, as well as risk factors, clinical symptoms, and health information sources were narratively synthesized.
RESULTS
Sixteen papers were finally included for analysis. Participants all showed poor levels of knowledge and perception regarding osteoporosis and risk factors. Investigation of clinical symptoms was rarely involved in the included studies due to the asymptomatic features of OP. The findings also suggest a strong association between poor level of knowledge regarding OP and educational attainment, type of participant, and gender. The majority of participants are increasingly turning to the Internet and social media to access information about OP.
CONCLUSION
The findings of this paper provide useful information for intervention providers to prevent and control OP and encourage them to carry out health promotion campaigns to enhance knowledge and awareness of OP.
PubMed: 38912142
DOI: 10.18502/ijph.v53i5.15581 -
International Journal of Chronic... 2024Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) often have other chronic disorders. This study aims to describe the life-course pattern of...
PURPOSE
Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) often have other chronic disorders. This study aims to describe the life-course pattern of morbidity in patients with COPD.
PATIENTS AND METHODS
Among all residents aged 50-90 years in Sweden in 1997, people with a hospital COPD diagnosis were identified using Swedish national registers (1997-2018). Each patient with COPD was matched by sex, birthyear and county of residency with up to five COPD-free controls. Other chronic disease diagnoses were identified during 1987-2018. Conditional logistic regression calculated risk of diseases diagnosed prior to first COPD diagnosis, producing odds ratios (OR) and 95% confidence intervals (95% CI). Cox regression estimated risk of diagnoses after first COPD diagnosis, producing hazard ratios (HR) and 95% CI.
RESULTS
Among 2,706,814 individuals, 225,159 (8.3%) had COPD. The nested case-control sample included 223,945 COPD-cases with 1,062,731 controls. Prior to first COPD diagnosis, future COPD patients had higher risks than controls for most examined conditions. Highest risks were seen for chronic heart failure (OR = 3.25, 3.20-3.30), peripheral arterial disease (OR = 3.12, 3.06-3.18) and lung cancer (OR = 12.73, 12.12-13.37). Following the COPD diagnosis, individuals with COPD had higher risks of most conditions than individuals without COPD. Chronic heart failure (HR = 3.50, 3.46-3.53), osteoporosis (HR = 3.35, 3.30-3.42), depression (HR = 2.58, 2.53-2.64) and lung cancer (HR = 6.04, 5.90-6.18) predominated. The risk of vascular dementia was increased after COPD diagnosis (HR = 1.53, 1.48-1.58) but not Alzheimer's disease.
CONCLUSION
Accumulation of chronic morbidity may precede COPD. Following the diagnosis, an increased burden of cardiovascular disease and cancer is to be expected, but subsequent depression, osteoporosis, and vascular dementia should also be noted. Management strategies for patients with COPD should consider the higher-than-average risk of multimorbidity.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Sweden; Male; Female; Aged; Middle Aged; Registries; Aged, 80 and over; Risk Factors; Time Factors; Risk Assessment; Case-Control Studies; Comorbidity; Cost of Illness; Prognosis
PubMed: 38912053
DOI: 10.2147/COPD.S459784