[Etiopathogenetic features of bone metabolism in patients with diabetes mellitus and Charcot foot].

Diabetic neuropathy is one of the most common diabetes mellitus complications associated with mediocalcinosis of the lower extremities, a significant decrease in feet bone mineral density, and a high incidence of cardiovascular disease. In most cases, calcium-phosphorus metabolism changes occur in patients with diabetic neuroarthropathy, or Charcot foot, when we can observe feet local osteoporosis, which in 90% of cases associated with a vessel's calcification of the lower extremities in the majority of diabetes population. A large number of studies presented literature have demonstrated that patients with Charcot foot can have accelerated bone metabolism and increased bone resorption. Patients with Charcot foot often have crucial abnormalities in the calcium-phosphorus parameters, bone metabolism, and levels of vitamin D and its metabolites. In addition, the duration of diabetes mellitus, the degree of its compensation widely affects the development of its micro- and macrovascular complications, which could also accelerate the development of mineral and bone disorders in these types of patients. Multifactorial pathogenesis of these disorders complicates the management of patients with a long and complicated course of diabetes mellitus. This review discusses the peculiarities of vitamin D metabolism, the importance of timely diagnosis in phosphorus-calcium disorders, and the specifics of therapy in these patients. Special attention is paid to the timely diagnosis of the Charcot's foots acute stage based on the bone marrow edema by MRI evaluation and the possibility of reducing the immobilization period.

Role of bisphosphonates in osteoporosis caused by adult growth hormone deficiency. / åŒè†¦é ¸ç›åœ¨æˆäººç”Ÿé•¿æ¿€ç´ ç¼ºä¹æ‰€è‡´éª¨è´¨ç–æ¾ç—‡ä¸­çš„ä½œç”¨ï¼ˆè‹±æ–‡ï¼‰.

In recent years, growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling, crucial for maintaining healthy bone mass throughout life. Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling, significantly affecting bone microarchitecture and increasing fracture risk. Although recombinant human growth hormone replacement therapy can mitigate these adverse effects, improving bone density, and reduce fracture risk, its effectiveness in treating osteoporosis, especially in adults with established growth hormone deficiency, seems limited. Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts, and clinical trials have confirmed their efficacy in improving osteoporosis. Therefore, for adult growth hormone deficiency patients with osteoporosis, the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Monitoring of bone matrix acidification by TRAP and ERK biomarkers in the chronic hypercholesterolemia male rats.

Background: Hypercholesterolemia is frequently linked to an elevated risk of cardiovascular diseases, including heart attacks and strokes. Additionally, it could be connected to a higher susceptibility to osteoporosis. Hypercholesterolemia can stimulate the differentiation and activity of osteoclasts, leading to enhanced bone reabsorption and a subsequent net loss of bone tissue. Aim: The purpose of this study was to examine the influence of a high-cholesterol diet on osteoporosis in male rats with differences in biological and oxidative indicators in the hypercholesterolemia diet in male rats. Methods: The samples in this study were twenty male rats, ranging between 1.5 and 2 months, were separated into two groups. In one group, 10 rats were fed a regular diet, while in another group, 10 rats were fed a high-cholesterol diet (2%) over the course of 8 weeks. Samples of blood were obtained at the last stage of the experiment. To calculate physiological and biological markers including extracellular signal-regulated kinase (ERK), tartrate-resistant acid phosphatase (TRAP), hormones, malondialdehyde (MDA), and glutathione (GSH). Results: The results of this study demonstrated a decrease in GSH levels, an increase in ERKs, no significant change in serum TRAP levels, an increase in MDA levels in the blood, and elevated levels of parathyroid hormone, calcitonin, and vitamin D in the cholesterol group. Conclusion: Increased oxidative stress, altered signaling, and disruptions in calcium/bone metabolism associated with cholesterol-related conditions and monitoring biomarker ERK can provide valuable information about disease progression.

Causal link between childhood obesity and adult osteoporosis: An investigation through Mendelian randomization.

The intricate link between childhood obesity and adult osteoporosis has been a subject of numerous clinical inquiries, yet the genetic underpinnings of this association remain enigmatic. Our research aims to unravel the association between adult osteoporosis and childhood obesity using genome-wide association study data for Mendelian randomization (MR) analysis. Utilizing a pool of single-nucleotide polymorphism data associated with childhood obesity obtained from a previous genome-wide association study report involving a study population of 13,848 people in Europe, alongside data of adult osteoporosis sourced from Neale Lab (5266 cases and 331,893 controls). Various methods for MR were used in our research, including weighted mode, simple mode, weighted median, MR-Egger, and the inverse-variance weighted (IVW). We also used Cochran Q test of IVW to assess for heterogeneity, MR-Egger intercept and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis for pleiotropy, and leave-one-out analysis for the result stability. The instrumental variables associated with 11 single-nucleotide polymorphisms were selected. MR analyses unveiled a noteworthy link between genetically forecasted childhood obesity and the onset of adult osteoporosis based on the odds ratio, 95% confidence interval, and P-value from the results of IVW, MR-Egger, weighted median: simple mode, and weighted mode analyses. No significant heterogeneity was found by the assessment using MR-Egger and IVW. Similarly, there was no indication of pleiotropy based on the MR-PRESSO and MR-Egger analyses. Leave-one-out analysis confirmed the stability of the results. Our research suggests that childhood obesity, as predicted by genetic factors, may pose a significant risk for the development of osteoporosis in adulthood.

Persistently Elevated C-Reactive Protein Levels and Low Body Mass Index Are Associated with a Lack of Improvement in Bone Mineral Density in Crohn's Disease.

BACKGROUND: Osteoporosis prevalence is increased in Crohn's disease (CD). Its pathogenesis in these patients is incompletely understood. OBJECTIVES: To identify factors associated with decreased bone mineral density (BMD) status in CD patients on a time-line course. METHODS: A retrospective study was performed that followed CD patients who underwent at least two bone mineral density scans (DEXAs). Follow-up began one year prior to the first DEXA test and lasted at least one year after a second test. Possible correlations between baseline and follow-up variables and changes in BMD status were examined. Change in BMD was defined as a transition from one bone density category to another (normal vs. osteopenia vs. osteoporosis). Binary variables were assessed using the Cochrane-Armitage test. Categorical variables were assessed using the chi-squared test. A multivariate analysis was performed. RESULTS: The study included 141 patients. At baseline, 33 patients (23.4%) had normal BMD, 75 (53.2%) had osteopenia, and 33 (23.4%) had osteoporosis. Patients with low BMD had a lower baseline BMI compared to those with normal BMD (p < 0.0001). After a median follow-up of 48 months (IQR 29-71), BMD status worsened in 19 (13.5%) patients, whereas in 95 (67.3%) and 27 (19.1%) patients, BMD remained unchanged or improved, respectively. On the multivariate analysis, elevated median CRP throughout follow-up (OR = 0.8, 95% CI: 0.68-0.93) and low baseline BMI (OR = 0.9, 95% CI: 0.83-0.98) were associated with a lack of BMD status improvement. CONCLUSIONS: Persistently elevated CRP and low BMI are associated with a lack of improvement in BMD. These findings underscore the importance of effective inflammation control and nutritional support to maintain and improve bone health.

hFcγRIIa: a double-edged sword in osteoclastogenesis and bone balance in transgenic mice.

Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo, highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders.

Mir-381-3p aggravates ovariectomy-induced osteoporosis by inhibiting osteogenic differentiation through targeting KLF5/Wnt/ß-catenin signaling pathway.

BACKGROUND: Increasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis. METHODS: Bilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro. RESULTS: miR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/ß-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/ß-catenin activation induced by miR-381-3p antagomir. CONCLUSION: miR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/ß-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP.

Epimedin A inhibits the PI3K/AKT/NF-κB signalling axis and osteoclast differentiation by negatively regulating TRAF6 expression.

BACKGROUND: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. METHODS: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. RESULTS: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. CONCLUSIONS: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Significant decrease of osteoporosis and osteoporotic fractures in rheumatoid arthritis within a period of 24 years: experiences of a single centre.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk for osteoporosis and osteoporotic fractures. Since the treatment of RA has improved significantly in recent years, we can expect RA-associated osteoporosis to decrease with good disease control. Therefore, we conducted a retrospective study to investigate whether the frequency of osteoporosis and osteoporotic fractures has changed during 24 years in RA. METHODS: We analysed the data of 1.086 RA patients from the time of the first osteological assessment with bone mineral density (BMD) measurement and collection of osteologically important data during the years 1996 and 2019 at our clinic. According to the treatment period, the patients were divided into cohort 1 (investigation between 1996 and 2004; n=539) and cohort 2 (investigation between 2005 and 2019; n=547). The data of the two cohorts were compared, and predictors of BMD were analysed by linear regression analysis. RESULTS: Prevalence of osteoporosis (28.3% vs 48.4%; p<0.001) as well as osteoporotic peripheral fractures (11.5% vs 21%; p<0.001) and vertebral fractures (6.6% vs 10.9%; p=0.011) were significantly lower and treatment with biologicals (19.7% vs 5.0%; p<0.001) significantly more common and glucocorticoid use was significantly less common (p=0.005) in cohort 2. In RA patients with a disease duration of more than 2 years, BMD was significantly higher under treatment with biologicals (p<0.001) despite increased cumulative glucocorticoid dosages (p<0.001). CONCLUSION: Our study showed a significant decline in osteoporosis and osteoporotic fractures in RA for 24 years. This positive effect is associated with the more frequent use of biologicals in the years between 2005 and 2019.

Protocatechualdehyde inhibits iron overload-induced bone loss by inhibiting inflammation and oxidative stress in senile rats.

The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown. Therefore, this study aimed to assess the role of PCA in iron overload-induced bone loss in senile rats. In the aged rat model, we observed that iron overload affects bone metabolism and bone remodeling, manifested by bone loss and decreased bone mineral density. The administration of PCA effectively mitigated the detrimental effects caused by iron overload, and concomitant reduction in MDA serum levels and elevation of SOD were noted. In addition, PCA-treated rats were observed to have significantly increased bone mass and elevated expression of SIRT3，BMP2，SOD2 and reduced expression of TNF-α in bone tissue. We also observed that PCA was able to reduce oxidative stress and inflammation and restore the imbalance in bone metabolism. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclasts differentiation, PCA intervention could significantly recover the restriction of osteogenic differentiation and up-regulation of osteoclast differentiation treated by iron overload. Further, by detecting changes in ROS, SOD, MDA, expression of SIRT3 and mitochondrial membrane potentials, we confirm that the damage caused to cells by iron overload is associated with decreased SIRT3 activity, and that 3-TYP have similar effects on oxidative stress caused by FAC. In conclusion, PCA can resist iron overload-induced bone damage by improving SIRT3 activity, anti-inflammatory and anti-oxidative stress.

The assessment of bone health in children with juvenile idiopathic arthritis; comparison of different imaging-based methods.

BACKGROUND: Osteoporosis is increasingly being recognized in children, mostly secondary to systemic underlying conditions or medication. However, no imaging modality currently provides a full evaluation of bone health in children. We compared DXA, a radiographic bone health index (BHI (BoneXpert) and cone-beam CT for the assessment of low bone mass in children with juvenile idiopathic arthritis (JIA). METHODS: Data used in the present study was drawn from a large multicentre study including 228 children aged 4-16 years, examined between 2015 and 2020. All had a radiograph of the left hand, a DXA scan and a cone-beam CT of the temporomandibular joints within four weeks of each other. For the present study, we included 120 subjects, selected based on DXA BMD and BoneXpert BHI to secure values across the whole range to be tested. RESULTS: One hundred and twenty children (60.0% females) were included, mean age 11.6 years (SD 3.1 years). There was a strong correlation between the absolute values of BHI and BMD for both total body less head (TBLH) (r = 0.75, p < 0.001) and lumbar spine (L1-L4) (r = 0.77, p < 0.001). The correlation between BHI standard deviation score (SDS) and BMD TBLH Z-scores was weak (r = 0.34) but significant (0 = 0.001), varying from weak (r = 0.31) to moderate (r = 0.42) between the three study sites. Categorizing BHI SDS and DXA BMD Z-scores on a 0-5 scale yielded a weak agreement between the two for both TBLH and LS, with w-kappa of 0.2, increasing to 0.3 when using quadratic weights. The agreement was notably higher for one of the three study sites as compared to the two others, particularly for spine assessment, yielding a moderate kappa value of 0.4 - 0.5. For cone-beam CT, based on a 1-3 scale, 59 out of 94 left TMJ's were scored as 1 and 31 as score 2 by the first observer vs. 87 and 7 by the second observer yielding a poor agreement (kappa 0.1). CONCLUSIONS: Categorizing DXA LS and automated radiographic Z-scores on a 0-5 scale gave a weak to moderate agreement between the two methods, indicating that a hand radiograph might provide an adjuvant tool to DXA when assessing bone health children with JIA, given thorough calibration is performed.

The association of weight-adjusted waist index with the risk of osteoporosis in patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: The relationship between obesity and type 2 diabetes with bone health has always been a topic of debate. The weight-adjusted waist index has become a commonly used indicator for assessing central obesity, fat, and muscle mass. However, currently there is no research reporting the association between weight-adjusted waist index and risk of osteoporosis in populations of type 2 diabetes. Therefore, this study aims to provide new information on the association between weight-adjusted waist index and risk of osteoporosis in type 2 diabetes. METHODS: This cross-sectional study involved 963 patients with type 2 diabetes who were admitted to the Department of Endocrinology of Cangzhou Central Hospital. Multivariate logistic regression models were used to assess the association between weight-adjusted waist index and osteoporosis. The potential nonlinear association was evaluated. The effects of interaction between subgroups were assessed using the likelihood ratio test. RESULTS: Weight-adjusted waist index was positively associated with the risk of osteoporosis, regardless of traditional confounding factors. For each 1 unit increased in weight-adjusted waist index, the risk of osteoporosis increased by 67%. Furthermore, there was a nonlinear relationship between weight-adjusted waist index and osteoporosis. The subgroup analysis did not reveal any significant interactions. CONCLUSIONS: Our study indicated a positive association between weight-adjusted waist index and the risk of osteoporosis in adult Chinese type 2 diabetes patients, and this relationship was nonlinear.

Association of HDL and LDL levels with osteoporosis in rheumatoid arthritis: a retrospective cohort study.

OBJECTIVES: A correlation exists between lipids and osteoporosis (OP), as well as between lipids and rheumatoid arthritis (RA). However, lipids, the relationship between RA and OP is still unclear. This study mainly investigates the relationship between lipid levels and OP risk in RA patients. METHODS: Retrospective collection of RA patient data from July 2017 to May 2022, encompassing baseline demographics, treatment regimens, laboratory results, and bone mineral density (BMD) measurements. Analyses, stratified by BMD subgroups, were conducted using propensity score matching (PSM) based on age, sex, and baseline duration, and binary logistic regression to examine the interplay between lipoprotein levels and other risk factors. The relationship between continuous variables and OP risk was assessed using restricted cubic spline (RCS), followed by a reanalysis of the correlation between varying lipoprotein levels and different factors, segmented according to RCS-determined cutoffs. RESULTS: The study included 2673 RA patients. Binary logistic regression revealed significant associations between high-density lipoprotein (HDL), low-density lipoprotein (LDL), and RA-OP (p < 0.01). Specifically, HDL emerged as a protective factor against OP (OR = 0.40, 95% CI 0.250-0.629; p < 0.001), whereas LDL was identified as a risk factor (OR = 1.56, 95% CI 1.290-1.890; p < 0.001). Furthermore, HDL (RCS cutoff point 1.28 mmol/L) showed a negative, linear correlation with RA-related OP, while LDL (RCS cutoff point 2.63 mmol/L) demonstrated a positive, linear correlation. CONCLUSIONS: The levels of HDL and LDL may be indicators of OP occurrence in RA patients.

Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture.

Background: While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear. Objective: Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations. Methods: We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway. Results: Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants. Conclusion: Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.

The causal role of circulating inflammatory markers in osteoporosis: a bidirectional Mendelian randomized study.

Background: Osteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP. Methods: We analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis. Results: Genetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85-0.98, P = 0.008, PFDR = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83-0.94, P = 8.66×10-5, PFDR = 0.008), and LIF (OR = 0.86, 95% CI = 0.76-0.96, P = 0.008, PFDR = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02-1.20, P = 0.012, PFDR = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03-1.30, P = 0.013, PFDR = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants. Conclusion: Despite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP.

Metabolic factors are not the direct mediators of the association between type 2 diabetes and osteoporosis.

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role. Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship. Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio (OR) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship. Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis.

Vitamin D level as a predictor of dysmobility syndrome with type 2 diabetes.

Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups; < 36.2 nmol/L. The vitamin D levels in Group DMS were significantly lower than that in Group Non-DMS (41.74 ± 14.60 vs. 47.19 ± 13.01, P < 0.05). After adjusting confounder factors including sex, age, vitamin D levels, HbA1c, ALB, HDLC, eGFR, diabetes microvascular complications and macrovascular, there was an independent association between risk of DMS and age (OR value = 1.160, 95% CI 1.091-1.234, P = 0.000), HbA1c(OR value = 1.262, 95% CI 1.046-1.532, P = 0.015), and vitamin D deficiency (< 36.2 nmol/L) (OR value = 2.990, 95% CI 1.284-6.964, P = 0.011). Our findings suggest that low levels of vitamin D are a predictor of DMS in middle-aged and elderly patients with poor control of type 2 diabetes.

Sarcopenic obesity and osteoporosis: Research progress and hot spots.

Sarcopenic obesity (SO) and osteoporosis (OP) are associated with aging and obesity. The pathogenesis of SO is complex, including glucolipid and skeletal muscle metabolic disorders caused by inflammation, insulin resistance, and other factors. Growing evidence links muscle damage to bone loss. Muscle-lipid metabolism disorders of SO disrupt the balance between bone formation and bone resorption, increasing the risk of OP. Conversely, bones also play a role in fat and muscle metabolism. In the context of aging and obesity, the comprehensive review focuses on the effects of mechanical stimulation, mesenchymal stem cells (MSCs), chronic inflammation, myokines, and adipokines on musculoskeletal, at the same time, the impact of osteokines on muscle-lipid metabolism were also analyzed. So far, exercise combined with diet therapy is the most effective strategy for increasing musculoskeletal mass. A holistic treatment of musculoskeletal diseases is still in the preliminary exploration stage. Therefore, this article aims to improve the understanding of musculoskeletal -fat interactions in SO and OP, explores targets that can provide holistic treatment for SO combined with OP, and discusses current limitations and challenges. We hope to provide relevant ideas for developing specific therapies and improving disease prognosis in the future.

The great challenge: bone fragility and environment.

Osteoporosis is a worldwide common disease characterised by reduced bone mass and increased risk of fractures.Many genetic variants are associated with the disease, but they account for only a small percentage of variance in individual bone mineral density and fragility fracture risk. Only recently have researchers recognised the role of a broad variety of environmental factors in the pathogenesis of osteoporosis, which has led to a further step: how genetic and environmental factors can interact, which is the next frontier in research on bone fragility.