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Aging Clinical and Experimental Research Jun 2024The Single Point Insulin Sensitivity Estimator (SPISE) index is a surrogate marker for insulin sensitivity. Given the emerging role of bone as an active endocrine organ,...
BACKGROUND
The Single Point Insulin Sensitivity Estimator (SPISE) index is a surrogate marker for insulin sensitivity. Given the emerging role of bone as an active endocrine organ, its associations with non-invasive measures of extra-skeletal functions such as insulin sensitivity warrant investigation.
AIMS
This study aimed to explore the relationship between the SPISE index and Bone Mineral Density (BMD) in an adult population.
METHODS
Data from a total of 1270 Arab adults (84% females, mean age 56.7 ± 8.1 years) from the Osteoporosis Registry Database of the Chair for Biomarkers of Chronic Diseases in King Saud University, Riyadh, Saudi Arabia was used in this study. T-scores and SPISE were calculated. Regression models were used to determine associations between SPISE and bone health indices.
RESULTS
The low BMD group (N = 853; T-score <-1.0) had significantly higher SPISE values than those with normal BMD (N = 417; T-score - 1.0 and above) (4.6 ± 1.3 vs. 4.3 ± 1.2, p < 0.001). Multivariate linear regression, adjusted for covariates, confirmed a significant inverse association between SPISE and BMD for all participants (β=-0.22, p < 0.001), as well as both groups [normal BMD (β = -0.10, p = 0.02) and low BMD groups (β = -0.15, p < 0.001)]. SPISE, family history of T2DM, and history of fractures collectively account for 17% of the variances perceived in T-score for all participants (p < 0.001).
CONCLUSIONS
A significant inverse association between the SPISE index and BMD was observed in adults, suggesting a link between BMD and extra-skeletal health. Underlying mechanisms need to be investigated prospectively using BMD as secondary outcomes in lifestyle modification programs.
Topics: Humans; Female; Male; Middle Aged; Bone Density; Arabs; Insulin Resistance; Saudi Arabia; Osteoporosis; Aged; Adult
PubMed: 38904881
DOI: 10.1007/s40520-024-02789-5 -
Aging Clinical and Experimental Research Jun 2024Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the... (Review)
Review
Radiofrequency Echographic Multi Spectrometry (REMS) is a radiation-free, portable technology, which can be used for the assessment and monitoring of osteoporosis at the lumbar spine and femoral neck and may facilitate wider access to axial BMD measurement compared with standard dual-energy x-ray absorptiometry (DXA).There is a growing literature demonstrating a strong correlation between DXA and REMS measures of BMD and further work supporting 5-year prediction of fracture using the REMS Fragility Score, which provides a measure of bone quality (in addition to the quantitative measure of BMD).The non-ionising radiation emitted by REMS allows it to be used in previously underserved populations including pregnant women and children and may facilitate more frequent measurement of BMD.The portability of the device means that it can be deployed to measure BMD for frail patients at the bedside (avoiding the complications in transfer and positioning which can occur with DXA), in primary care, the emergency department, low-resource settings and even at home.The current evidence base supports the technology as a useful tool in the management of osteoporosis as an alternative to DXA.
Topics: Humans; Osteoporosis; Absorptiometry, Photon; Bone Density; Lumbar Vertebrae; Femur Neck; Female; Ultrasonography
PubMed: 38904870
DOI: 10.1007/s40520-024-02784-w -
Frontiers in Endocrinology 2024Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a... (Review)
Review
Magnesium (Mg), a nutritional element which is essential for bone development and mineralization, has a role in the progression of osteoporosis. Osteoporosis is a multifactorial disease characterized by significant deterioration of bone microstructure and bone loss. Mg deficiency can affect bone structure in an indirect way through the two main regulators of calcium homeostasis (parathyroid hormone and vitamin D). In human osteoblasts (OBs), parathyroid hormone regulates the expression of receptor activator of nuclear factor-κ B ligand (RANKL) and osteoprotegerin (OPG) to affect osteoclast (OC) formation. In addition, Mg may also affect the vitamin D3 -mediated bone remodeling activity. vitamin D3 usually coordinates the activation of the OB and OC. The unbalanced activation OC leads to bone resorption. The RANK/RANKL/OPG axis is considered to be a key factor in the molecular mechanism of osteoporosis. Mg participates in the pathogenesis of osteoporosis by affecting the regulation of parathyroid hormone and vitamin D levels to affect the RANK/RANKL/OPG axis. Different factors affecting the axis and enhancing OC function led to bone loss and bone tissue microstructure damage, which leads to the occurrence of osteoporosis. Clinical research has shown that Mg supplementation can alleviate the symptoms of osteoporosis to some extent.
Topics: Humans; Osteoporosis; Magnesium; Animals; Parathyroid Hormone; RANK Ligand; Osteoblasts; Bone Remodeling; Vitamin D; Magnesium Deficiency; Osteoclasts; Osteoprotegerin
PubMed: 38904051
DOI: 10.3389/fendo.2024.1406248 -
BioRxiv : the Preprint Server For... May 2024B cells are an attractive platform for engineering to produce protein-based biologics absent in genetic disorders, and potentially for the treatment of metabolic...
B cells are an attractive platform for engineering to produce protein-based biologics absent in genetic disorders, and potentially for the treatment of metabolic diseases and cancer. As part of pre-clinical development of B cell medicines, we demonstrate a method to collect, expand, differentiate, radioactively label, and track adoptively transferred non-human primate (NHP) B cells. These cells underwent 10- to 15-fold expansion, initiated IgG class switching, and differentiated into antibody secreting cells. Zirconium-89-oxine labeled cells were infused into autologous donors without any preconditioning and tracked by PET/CT imaging. Within 24 hours of infusion, 20% of the initial dose homed to the bone marrow and spleen and distributed stably and equally between the two. Interestingly, approximately half of the dose homed to the liver. Image analysis of the bone marrow demonstrated inhomogeneous distribution of the cells. The subjects experienced no clinically significant side effects or laboratory abnormalities. A second infusion of B cells into one of the subjects resulted in an almost identical distribution of cells, suggesting a non-limiting engraftment niche and feasibility of repeated infusions. This work supports the NHP as a valuable model to assess the potential of B cell medicines as potential treatment for human diseases.
PubMed: 38903108
DOI: 10.1101/2024.05.24.595782 -
Journal of Otolaryngology - Head & Neck... 2024Minimally invasive cochlear implant surgery by using a microstereotactic frame demands solid connection to the bone. We aimed to determine the stability of commercially...
BACKGROUND
Minimally invasive cochlear implant surgery by using a microstereotactic frame demands solid connection to the bone. We aimed to determine the stability of commercially available orthodontic miniscrews to evaluate their feasibility for frame's fixation. In addition, which substitute material most closely resembles the mechanical properties of the human temporal bone was evaluated.
METHODS
Pull-out tests were carried out with five different types of orthodontic miniscrews in human temporal bone specimens. Furthermore, short fiber filled epoxy (SFFE), solid rigid polyurethane (SRPU50), bovine femur, and porcine iliac bone were evaluated as substitute materials. In total, 57 tests in human specimens and 180 tests in the substitute materials were performed.
RESULTS
In human temporal bone, average pull-out forces ranged from 220 N to 285 N between screws. Joint stiffness in human temporal bone ranged between 14 N/mm and 358 N/mm. Statistically significant differences between the tested screws were measured in terms of stiffness and elastic energy. One screw type failed insertion due to tip breakage. No significant differences occurred between screws in maximum pull-out force. The average pull-out values of SFFE were 14.1 N higher compared to human specimen.
CONCLUSION
Orthodontic miniscrews provided rigid fixation when partially inserted in human temporal bone, as evidenced by pull-out forces and joint stiffness. Average values exceeded requirements despite variations between screws. Differences in stiffness and elastic energy indicate screw-specific interface mechanics. With proper insertion, orthodontic miniscrews appear suitable for microstereotactic frame anchoring during minimally invasive cochlear implant surgery. However, testing under more complex loading is needed to better predict clinical performance. For further pull-out tests, the most suitable substitute material is SFFE.
Topics: Temporal Bone; Humans; Bone Screws; Animals; Swine; Cochlear Implantation; Materials Testing; Cadaver; Cattle; Minimally Invasive Surgical Procedures
PubMed: 38903014
DOI: 10.1177/19160216241248669 -
Military Medical Research Jun 2024Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and... (Review)
Review
Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.
Topics: Humans; Fibroblast Growth Factors; Signal Transduction; Osteoarthritis; Fibroblast Growth Factor-23; Intervertebral Disc Degeneration; Osteoporosis; Sarcopenia; Aging; Animals
PubMed: 38902808
DOI: 10.1186/s40779-024-00544-5 -
BMC Medical Imaging Jun 2024Osteoporosis (OP) is a common chronic metabolic bone disease characterized by decreased bone mineral content and microstructural damage, leading to increased fracture...
BACKGROUND
Osteoporosis (OP) is a common chronic metabolic bone disease characterized by decreased bone mineral content and microstructural damage, leading to increased fracture risk. Traditional methods for measuring bone density have limitations in accurately distinguishing vertebral bodies and are influenced by vertebral degeneration and surrounding tissues. Therefore, novel methods are needed to quantitatively assess changes in bone density and improve the accurate diagnosis of OP.
METHODS
This study aimed to explore the applicative value of the iterative decomposition of water and fat with echo asymmetry and least-squares estimation-iron (IDEAL-IQ) sequence combined with intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the diagnosis of osteoporosis. Data from 135 patients undergoing dual-energy X-ray absorptiometry (DXA), IDEAL-IQ, and IVIM-DWI were prospectively collected and analyzed. Various parameters obtained from IVIM-DWI and IDEAL-IQ sequences were compared, and their diagnostic efficacy was evaluated.
RESULTS
Statistically significant differences were observed among the three groups for FF, R2*, f, D, DDC values, and BMD values. FF and f values exhibited negative correlations with BMD values, with r=-0.313 and - 0.274, respectively, while R2*, D, and DDC values showed positive correlations with BMD values, with r = 0.327, 0.532, and 0.390, respectively. Among these parameters, D demonstrated the highest diagnostic efficacy for osteoporosis (AUC = 0.826), followed by FF (AUC = 0.713). D* exhibited the lowest diagnostic performance for distinguishing the osteoporosis group from the other two groups. Only D showed a significant difference between genders. The AUCs for IDEAL-IQ, IVIM-DWI, and their combination were 0.74, 0.89, and 0.90, respectively.
CONCLUSIONS
IDEAL-IQ combined with IVIM-DWI provides valuable information for the diagnosis of osteoporosis and offers evidence for clinical decisions. The superior diagnostic performance of IVIM-DWI, particularly the D value, suggests its potential as a more sensitive and accurate method for diagnosing osteoporosis compared to IDEAL-IQ. These findings underscore the importance of integrating advanced imaging techniques into clinical practice for improved osteoporosis management and highlight the need for further research to explore the full clinical implications of these imaging modalities.
Topics: Humans; Female; Osteoporosis; Male; Diffusion Magnetic Resonance Imaging; Middle Aged; Aged; Bone Density; Absorptiometry, Photon; Prospective Studies; Least-Squares Analysis; Adult; Aged, 80 and over
PubMed: 38902641
DOI: 10.1186/s12880-024-01326-0 -
Neurobiology of Disease Jun 2024Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to...
Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors in the chronic social defeat stress (CSDS) model of depression. This study investigated whether the spleen contributes to the antidepressant-like effects of arketamine in the CSDS model. We found that splenectomy significantly inhibited arketamine's antidepressant-like effects in CSDS-susceptible mice. RNA-sequencing analysis identified the oxidative phosphorylation (OXPHOS) pathway in the prefrontal cortex (PFC) as a key mediator of splenectomy's impact on arketamine's effects. Furthermore, oligomycin A, an inhibitor of the OXPHOS pathway, reversed the suppressive effects of splenectomy on arketamine's antidepressant-like effects. Specific genes within the OXPHOS pathways, such as COX11, UQCR11 and ATP5e, may contribute to these inhibitory effects. Notably, transforming growth factor (TGF)-β1, along with COX11, appears to modulate the suppressive effects of splenectomy and contribute to arketamine's antidepressant-like effects. Additionally, SRI-01138, an agonist of the TGF-β1 receptor, alleviated the inhibitory effects of splenectomy on arketamine's antidepressant-like effects. Subdiaphragmatic vagotomy also counteracted the inhibitory effects of splenectomy on arketamine's antidepressant-like effects in CSDS-susceptible mice. These findings suggest that the OXPHOS pathway and TGF-β1 in the PFC play significant roles in the antidepressant-like effects of arketamine, mediated through the spleen-brain axis via the vagus nerve.
PubMed: 38901783
DOI: 10.1016/j.nbd.2024.106573 -
BMC Musculoskeletal Disorders Jun 2024The associations between serum uric acid and osteoporosis or osteopenia remain controversial, and few studies have explored whether BMI acts as a mediators in the...
BACKGROUND
The associations between serum uric acid and osteoporosis or osteopenia remain controversial, and few studies have explored whether BMI acts as a mediators in the association between the SUA and OP/ osteopenia.
OBJECTIVE
To explore the relationship between serum uric acid and osteoporosis or osteopenia among US adults.
METHODS
A cross-sectional study was conducted to examine the association between serum uric acid and osteoporosis or osteopenia from four cycles of NHANES. Binary logistic regression models and restricted cubic spline models were used to evaluate the association between serum uric acid and osteoporosis or osteopenia, and interaction analysis was used to test the differences between subgroups. Mediation analysis was utilized to investigate whether BMI acts as a mediator in the association between SUA and OP/ osteopenia.
RESULTS
12581 participants aged ≥ 18 years were included. A U-shape nonlinear relationship between SUA and osteoporosis or osteopenia in all people was found (P < 0.0001, P for nonlinear = 0.0287). There were significant interactions in age subgroups (P for interaction = 0.044), sex subgroups (P for interaction = 0.005), and BMI subgroups (P for interaction = 0.017). We further assessed the subgroups and found the optimal range of serum uric acid levels with a lower risk of osteoporosis or osteopenia was 357-535 µmol/L in males, 327-417 µmol/L in people aged ≥ 50 years, above 309 µmol/L in people aged < 50 years, 344-445 µmol/L in people with BMI ≥ 30, and above 308 µmol/L in people with BMI < 30. BMI fully mediated the association of SUA and OP/osteopenia, with a value of -0.0024(-0.0026--0.0021). These results were robust in sensitivity analyses.
CONCLUSIONS
A complicated relationship between SUA and bone health in different populations was observed. Maintaining SUA within a specific range may be beneficial to bone health. In addition, BMI may play an important role in the association between SUA and bone health, but considering the limitations of this study, further prospective research is required.
Topics: Humans; Cross-Sectional Studies; Male; Uric Acid; Female; Middle Aged; Body Mass Index; Osteoporosis; Adult; Nutrition Surveys; Bone Diseases, Metabolic; Aged; United States; Bone Density; Young Adult; Risk Factors
PubMed: 38898434
DOI: 10.1186/s12891-024-07595-8 -
Archives of Osteoporosis Jun 2024Interviews and focus groups with patients, FLS clinicians, and GPs identified challenges relating to clinical and shared decision-making about bone health and...
UNLABELLED
Interviews and focus groups with patients, FLS clinicians, and GPs identified challenges relating to clinical and shared decision-making about bone health and osteoporosis medicines. Findings will inform the development of the multicomponent iFraP intervention to address identified training needs and barriers to implementation to facilitate SDM about osteoporosis medicines.
PURPOSE
The iFraP (improving uptake of Fracture Prevention treatments) study aimed to develop a multicomponent intervention, including an osteoporosis decision support tool (DST), to support shared decision-making (SDM) about osteoporosis medicines. To inform iFraP intervention development, this qualitative study explored current practice in relation to communication about bone health and osteoporosis medicines, anticipated barriers to, and facilitators of, an osteoporosis DST, and perceived training needs.
METHODS
Patients attending an FLS consultation (n = 8), FLS clinicians (n = 9), and general practitioners (GPs; n = 7) were purposively sampled to participate in a focus group and/or telephone interview. Data were transcribed, inductively coded, and then mapped to the Theoretical Domains Framework (TDF) as a deductive framework to systematically identify possible barriers to, and facilitators of, implementing a DST.
RESULTS
Inductive codes were deductively mapped to 12 TDF domains. FLS clinicians were perceived to have specialist expertise (knowledge). However, clinicians described aspects of clinical decision-making and risk communication as difficult (cognitive skills). Patients reflected on decisional uncertainty about medicines (decision processes). Discussions about current practice and the proposed DST indicated opportunities to facilitate SDM, if identified training needs are met. Potential individual and system-level barriers to implementation were identified, such as differences in FLS configuration and a move to remote consulting (environmental context and resources).
CONCLUSIONS
Understanding of current practice revealed unmet training needs, indicating that using a DST in isolation would be unlikely to produce a sustained shift to SDM. Findings will shape iFraP intervention development to address unmet needs.
Topics: Humans; Qualitative Research; Osteoporosis; Female; Male; Focus Groups; Bone Density Conservation Agents; Decision Making, Shared; Middle Aged; Aged; Osteoporotic Fractures
PubMed: 38898212
DOI: 10.1007/s11657-024-01410-6