To explore the associations between hormones, metabolic markers, and low bone mass in perimenopausal and postmenopausal women.

A total of 198 women were enrolled in this study. The correlations between hormones, metabolic markers, and BMD were analyzed. Risk factors for bone loss were identified. Receiver operating characteristic (ROC) curves were used to display the predictive power of these risk factors.

The years since menopause and the levels of glucose (GLU), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were inversely correlated with BMD, while estrogen and testosterone were positively correlated with BMD. Age (odds ratio [OR] 1.232; 95% confidence interval [CI] 1.106-1.372; p < 0.001), GLU (OR 1.848; 95% CI 1.116-3.059; p = 0.017), and FSH (OR 1.089; 95% CI 1.003-1.182; p = 0.042) were identified as risk factors for bone loss. Age (AUC = 0.884, 95% CI 0.833-0.935), FSH (AUC = 0.824, 95% CI 0.760-0.888), and GLU (AUC = 0.683, 95% CI 0.599-0.768) demonstrated significant discrimination capability for bone loss. The combined application of these factors resulted in a better prediction effect (AUC = 0.930, 95% CI 0.893-0.967).

Age, FSH, and GLU were found to be specific risk factors for bone loss. The utilization of these factors offers compelling predictive power for bone loss in perimenopausal and postmenopausal women.

Type 2 diabetic osteoporosis (T2DOP) is a metabolic bone disease characterized by impaired bone structure and decreased bone strength in diabetic patients. Jiangu Decoction (JGD), a traditional Chinese poly-herbal formulation, has shown efficacy in mitigating osteoporosis (OP) and fractures caused by osteoporosis in diabetic patients in clinical trials. In addition, JGD has been proven to promote the proliferation of osteoblasts. However, the specific mechanisms underlying these effects remain unclear.

This study aimed to elucidate the molecular mechanisms underlying the therapeutic effects of JGD in treating T2DOP.

Liquid chromatography-mass spectrometry (LC-MS) was utilized to elucidate the chemical profile of JGD. A T2DOP mouse model (C57BL/6) was established by combining a high-fat diet with streptozotocin (STZ). Micro-computed tomography (micro-CT) imaging, three-point bending tests, and histological staining were utilized to assess alterations in bone mass, bone quality, and bone strength in mice. Mouse Calvaria 3T3-E1 (MC3T3-E1) cells were treated with 33 mmol/L D-glucose (HG), and the protective effect of JGD on the high glucose injury model was observed. Western blotting and qRT-PCR were employed to analyze alterations in biomarkers associated with the Keap1/Nrf2/HO-1 signaling pathway, both in vivo and in vitro.

A total of 909 compounds were identified in JGD using LC-MS. Subsequently, the function of JGD was evaluated both in vitro and in vivo. The findings indicated that JGD promoted bone formation, enhanced bone microstructure, and ameliorated diabetic symptoms in T2DOP mice. Additionally, JGD increased alkaline phosphatase (ALP) activity, facilitated bone mineralization, and upregulated the expression levels of osteogenic marker genes such as runt-related transcription factor 2 (Runx2), osteocalcin (Ocn), and collagen type 1 alpha (Col1a1). Importantly, JGD reduced oxidative stress levels and decreased the accumulation of reactive oxygen species by modulating the Keap1/Nrf2/HO-1 axis both in vivo and in vitro.

Our study suggests that JGD could alleviate T2DOP impairment, closely linked to the Keap1/Nrf2/HO-1 signaling pathway.

Pentosidine (PEN), a surrogate marker of advanced glycation end-product formation, reflects increased non-enzymatic cross-linking in bone collagen, which is thought to be an important determinant of bone fragility in type 2 diabetes mellitus (T2DM). We aimed to investigate serum concentrations of PEN in patients with T2DM and controls without T2DM and to examine its relationship with bone parameters and metabolic state such as glycaemic control, insulin resistance and body weight. In a cross-sectional study-design, data from postmenopausal women and men with T2DM (n = 110) and controls without T2DM (n = 111) were evaluated. Serum PEN was measured using an ELISA-based assay (CSB-E09415h, Cusabio). In addition, biochemical markers of glucose metabolism and bone turnover markers were measured. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry. After adjustment for age, gender and body mass index (BMI), serum PEN was significantly higher in patients with T2DM compared to controls (p = 0.02) and most prominently in women with T2DM (p = 0.09). We found a strong association of serum PEN concentrations with BMI in the entire study population (R = 0.43, p < 0.001) as well as in patients with T2DM (R = 0.28, p < 0.01). While bone turnover markers were significantly decreased, and BMD increased in patients with T2DM, only weak or no associations were observed between these skeletal surrogate markers and serum PEN. We conclude that serum PEN is strongly associated with BMI with highest levels in obese women with T2DM. Adjustment for patient's weight is needed when evaluating serum PEN levels in patients with T2DM.Clinical Trial Information: NCT02551315.

This pivotal study aimed to evaluate circulating levels of bone remodeling markers in children and adolescents at the onset of type 1 diabetes (T1D). Additionally, we assessed their correlation with glucose control, residual β-cell function, and the severity of presentation.

In this single-center cross-sectional study, we recruited children and adolescents newly diagnosed with T1D at our tertiary-care Diabetes Centre. Anamnestic, anthropometric, clinical, and biochemical data at T1D diagnosis were collected. Basal and stimulated C-peptide levels were assessed, along with the following bone remodeling biomarkers: osteocalcin (OC), alkaline phosphatase (ALP), parathormone (PTH), 25-OH Vitamin D (25OH-D), and the C-terminal cross-linked telopeptide of type 1 collagen (CTX).

We enrolled 29 individuals newly diagnosed with T1D, with a slight male prevalence (51.7%). The mean age was 8.4 ± 3.7 years. A positive correlation between OC and stimulated C-peptide (R = 0.538; p = 0.026) and between PTH and serum HCO3- (R = 0.544; p = 0.025) was found. No other correlations between bone remodeling biomarkers and clinical variables were detected.

Our data showed a positive correlation between OC levels and residual β-cell function in children and adolescents at T1D presentation. Further longitudinal studies evaluating OC levels in pediatric subjects with T1D are needed to better understand the complex interaction between bone and glucose metabolisms.

Previous studies have shown a significantly increased prevalence of osteoporosis (OP) in patients with type 2 diabetes mellitus (T2DM), which is closely associated with inflammation and nutrition. This study aimed to investigate the relationship between the advanced lung cancer inflammation index (ALI) and OP in patients with T2DM.

This cross-sectional analysis was conducted based on data from middle-aged and older adults aged 50 years and older with T2DM from the National Health and Nutrition Examination Survey (NHANES).Weighted multivariable logistic regression and linear regression were utilized to investigate the correlation between the ALI and OP with femur bone mineral density (BMD) in individuals with T2DM. Restricted cubic splines (RCS) were employed to assess potential nonlinear relationships, and receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy.

A total of 1596 patients with T2DM were included in this study, among whom 736 had OP. After adjusting for covariates, the multivariable logistic regression model showed that compared to participants in the fourth quartile of log2-transformed ALI, those in the first quartile had an increased prevalence of OP in T2DM (OR = 1.95, 95% CI=1.28-2.96, p < 0.01). The multivariable linear regression model indicated that a low log2-transformed ALI is associated with a low femur BMD.RCS demonstrated a linear dose-response relationship between the ALI index and OP in T2DM (p = 0.686), with the area under the ROC curve being 0.57 (95% CI: 0.54-0.60, p < 0.001), and the optimal cutoff value was 6.04.

Our findings indicate that low levels of ALI are independently associated with an increased prevalence of OP in middle-aged and older adults with T2DM in the United States. ALI may serve as a potential biomarker for assessing the prevalence of OP in middle-aged and older adults with T2DM.

Dairy products, a major source of calcium, demonstrate a number of beneficial effects, not only protecting against the development of osteoporosis (OP) but also suppressing the onset of type-2 diabetes (T2DM) and improving bone mineral density (BMD). Dairy consumption is closely linked to lactose tolerance. One of the genetic factors predisposing individuals to lactose intolerance is rs4988235 polymorphism of the MCM6 gene. The aim of this reported study was to analyse the relationship between the rs4988235 variant of the MCM6 gene and bone mineral density and the risk of type-2 diabetes in women after menopause.

The study was conducted among 607 female patients in the postmenopausal period in whom bone densitometry and vitamin-D3 levels were assayed and genotyping of the rs4988235 polymorphism of MCM6 gene was performed. The obtained results were analysed for the presence of T2DM, obesity surrogates, medical data, and past medical history.

The distribution of genotype frequencies was consistent with the Hardy-Weinberg equilibrium (p > 0.050). Postmenopausal women with the GG homozygote of rs4988235 polymorphism consumed significantly less calcium (dairy), which was probably related to the observed lactose intolerance. The GG homozygote of women with rs4988235 polymorphism was significantly more likely to have T2DM relative to the A allele carriers (p = 0.023). GG homozygotes had significantly lower femoral-vertebral mineral density despite the significantly more frequent supplementation with calcium preparations (p = 0.010), vitamin D (p = 0.01), and anti-osteoporotic drugs (p = 0.040). The obtained results indicate a stronger loss of femoral-neck mineral density with age in the GG homozygotes relative to the A allele carriers (p = 0.038).

In the population of women after menopause, the carriage of the G allele of rs4988235 polymorphism of the MCM6 gene, i.e., among the patients with lactose intolerance, significantly increased the risk of developing T2DM and the loss of BMD.

The objective of this review is to examine the connection between osteoporosis and diabetes, compare the underlying causes of osteoporosis in various forms of diabetes, and suggest optimal methods for diagnosing and assessing fracture risk in diabetic patients. This narrative review discusses the key factors contributing to the heightened risk of fractures in individuals with diabetes, as well as the shared elements impacting the treatment of both diabetes mellitus and osteoporosis. Understanding the close link between diabetes and a heightened risk of fractures is crucial in effectively managing both conditions. There are several review articles of meta-analysis regarding diaporosis. Nevertheless, no review articles showed collected and well-organized medications of antidiabetics and made for inconvenient reading for those who were interested in details of drug mechanisms. In this article, we presented collected and comprehensive charts of every antidiabetic medication which was linked to fracture risk and indicated plausible descriptions according to research articles.

This study was aimed to determine the ideal thresholds for bone mineral densities in our tested Jordanian cohort to initiate bisphosphonate pharmacotherapeutics in order to establish a national protocol for prescribing bisphosphonates that is tailored to the local population, rather than relying on global T and Z scores standards.

This retrospective study analyzed the entire population of adult patients at Prince Rashid bin Al-Hussein Hospital Rehabilitation and Rheumatology Center between August and October 2023 for the purpose of screening, monitoring, diagnosing, and treating osteoporosis. The study included 328 clients suspected to have osteoporosis, selected based on criteria such as primary osteoporosis or potential secondary osteoporosis. The study used two fracture risk assessment tools (FRAX) dichotomized states: <3% (negative state) and ≥3% (positive state), as well as <20% (negative state) and ≥20% (positive state). Binary logistic regression analysis, receiver-operating characteristic, and sensitivity analysis tests were performed sequentially to analyze the performance of prognosticators and sensitivity indices to evaluate their sensitivity, specificity, and accuracy indexes.

The study involved 328 clients at a rehabilitation clinic, with 82.62% (271) females and 17.38% (57) males. The majority were aged between 60 and 69 years, with a slightly higher obesity rate in females. The study found that initiation of bisphosphonates in Jordanian cohorts with optimal bone mineral density thresholds of 0.775 g/cm2 may significantly reduce the risk of hip osteoporosis over 10 years, with sensitivity, specificity, and accuracy indexes of 78.6%, 88.46%, and 50.61%, respectively, with a performance utility of 0.896±0.026 (p-value<0.001), 95% CI (0.846-0.946).

Due to ethnicity differences, exploring regional or national specific bone mineral density thresholds for bisphosphonates initiation may be a better optional choice than adopting global T-score standards.

Icariin (ICA), a natural flavonoid compound monomer, has multiple pharmacological activities. However, its effect on bone defect in the context of type 1 diabetes mellitus (T1DM) has not yet been examined.

To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.

The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining, alizarin red S staining, quantitative real-time polymerase chain reaction, Western blot, and immunofluorescence. Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis. A bone defect model was established in T1DM rats. The model rats were then treated with ICA or placebo and micron-scale computed tomography, histomorphometry, histology, and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.

ICA promoted bone marrow mesenchymal stem cell (BMSC) proliferation and osteogenic differentiation. The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers (alkaline phosphatase and osteocalcin) and angiogenesis-related markers (vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1) compared to the untreated group. ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs. In the bone defect model T1DM rats, ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation. Lastly, ICA effectively accelerated the rate of bone formation in the defect area.

ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Obesity and diabetes mellitus are prevalent metabolic disorders that have a detrimental impact on overall health. In this regard, there is now a clear link between these metabolic disorders and compromised bone health. Interestingly, both obesity and diabetes lead to elevated risk of bone fracture which is independent of effects on bone mineral density (BMD). In this regard, gastrointestinal (GIT)-derived peptide hormones and their related long-acting analogues, some of which are already clinically approved for diabetes and/or obesity, also seem to possess positive effects on bone remodelling and microarchitecture to reduce bone fracture risk. Specifically, the incretin peptides, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as well as glucagon-like peptide-2 (GLP-2), exert key direct and/or indirect benefits on bone metabolism. This review aims to provide an initial appraisal of the relationship between obesity, diabetes and bone, with a focus on the positive impact of these GIT-derived peptide hormones for bone health in obesity/diabetes. Brief discussion of related peptides such as parathyroid hormone, leptin, calcitonin and growth hormone is also included. Taken together, drugs engineered to promote GIP, GLP-1 and GLP-2 receptor signalling may have potential to offer therapeutic promise for improving bone health in obesity and diabetes.

Osteoporotic fractures impose a substantial burden on patients with diabetes due to their unique characteristics in bone metabolism, limiting the efficacy of conventional fracture prediction tools. Artificial intelligence (AI) algorithms have shown great promise in predicting osteoporotic fractures. This review aims to evaluate the application of traditional fracture prediction tools (FRAX, QFracture, and Garvan FRC) in patients with diabetes and osteoporosis, review AI-based fracture prediction achievements, and assess the potential efficiency of AI algorithms in this population. This comprehensive literature search was conducted in Pubmed and Web of Science. We found that conventional prediction tools exhibit limited accuracy in predicting fractures in patients with diabetes and osteoporosis due to their distinct bone metabolism characteristics. Conversely, AI algorithms show remarkable potential in enhancing predictive precision and improving patient outcomes. However, the utilization of AI algorithms for predicting osteoporotic fractures in diabetic patients is still in its nascent phase, further research is required to validate their efficacy and assess the potential advantages of their application in clinical practice.

Summarize the recent literature that investigates how advanced medical imaging has contributed to our understanding of skeletal phenotypes and fracture risk across the lifespan.

Characterization of bone phenotypes on the macro-scale using advanced imaging has shown that while wide bones are generally stronger than narrow bones, they may be more susceptible to age-related declines in bone strength. On the micro-scale, HR-pQCT has been used to identify bone microarchitecture phenotypes that improve stratification of fracture risk based on phenotype-specific risk factors. Adolescence is a key phase for bone development, with distinct sex-specific growth patterns and significant within-sex bone property variability. However, longitudinal studies are needed to evaluate how early skeletal growth impacts adult bone phenotypes and fracture risk. Metabolic and rare bone diseases amplify fracture risk, but the interplay between bone phenotypes and disease remains unclear. Although bone phenotyping is a promising approach to improve fracture risk assessment, the clinical availability of advanced imaging is still limited. Consequently, alternative strategies for assessing and managing fracture risk include vertebral fracture assessment from clinically available medical imaging modalities/techniques or from fracture risk assessment tools based on clinical risk factors. Bone fragility is not solely determined by its density but by a combination of bone geometry, distribution of bone mass, microarchitecture, and the intrinsic material properties of bone tissue. As such, different individuals can exhibit distinct bone phenotypes, which may predispose them to be more vulnerable or resilient to certain perturbations that influence bone strength.

Continuous microwave-assisted flow synthesis has been used as a simple, more efficient, and low-cost route to fabricate a range of nanosized (<100 nm) strontium-substituted calcium phosphates. In this study, fine nanopowder was synthesized via a continuous flow synthesis with microwave assistance from the solutions of calcium nitrate tetrahydrate (with strontium nitrate as Sr2+ ion source) and diammonium hydrogen phosphate at pH 10 with a time duration of 5 min. The morphological characterization of the obtained powder has been carried out by employing techniques such as transmission electron microscopy, X-ray diffraction, and Brunauer-Emmett-Teller surface area analysis. The chemical structural analysis to evaluate the surface properties was made by using X-ray photoelectron spectroscopy. Zeta potential analysis was performed to evaluate the colloidal stability of the particles. Antimicrobial studies were performed for all the compositions using four bacterial strains and an opportunistic human fungal pathogen Macrophomina phaseolina. It was found that the nanoproduct with high strontium content (15 wt% of strontium) showed pronounced antibacterial potential against M. luteus while it completely arrested the fungal growth after 48 h by all of its concentrations. Thus the synthesis strategy described herein facilitated the rapid production of nanosized Sr-substituted CaPs with excellent biological performance suitable for a bone replacement application.

Diabetes confers an increased risk of fracture. However, whether prediabetes is also a risk factor of osteoporotic fracture has not been comprehensively examined. We performed a meta-analysis to evaluate the relationship between prediabetes and osteoporotic fracture risk.

This meta-analysis included relevant prospective cohort studies from Medline, Embase, and Web of Science databases. A random-effect model after incorporation of the intra-study heterogeneity was selected to pool the results. Subgroup analyses were applied to evaluate the influences of study characteristics on relationship between prediabetes and osteoporotic fracture risk.

Eight studies including 33,136 community dwelling adult patients were included, and 7429 (22.4%) patients were prediabetic. Prediabetes was not independently associated with a higher risk of osteoporotic fracture compared with normoglycemia (adjusted risk ratio: 1.03, 95% confidence interval: 0.88-1.21, P = 0.69, I²  = 42%). Sensitivity limited to the elderly population showed consistent results (RR: 1.10, 95% CI: 0.91-1.24, P = 0.15, I²  = 0%). Subgroup analysis suggested that prediabetes defined by HbA1c (approximately 5.7%-6.4%) was associated with a higher risk of osteoporotic fracture (RR: 1.24, 95% CI: 1.01-1.53, P = 0.04), but not that defined by impaired fasting glucose or impaired glucose tolerance (P = 0.60). Sex, follow-up duration, and adjustment of bone mineral density did not significantly affect the outcome.

Current evidence does not support that prediabetes is independently associated with osteoporotic fracture risk. Different definitions of prediabetes may affect the association between prediabetes and osteoporotic fracture risk.

The widely recommended fracture prediction tool FRAX was developed based on and for the general population. Although several adjusted FRAX methods were suggested for type 2 diabetes (T2DM), they still need to be evaluated in T2DM cohort.

This study was undertaken to develop a prediction model for Chinese diabetes fracture risk (CDFR) and compare its performance with those of FRAX.

In this retrospective cohort study, 1730 patients with T2DM were enrolled from 2009.08 to 2013.07. Major osteoporotic fractures (MOFs) during follow-up were collected from Electronic Health Records (EHRs) and telephone interviews. Multivariate Cox regression with backward stepwise selection was used to fit the model. The performances of the CDFR model, FRAX, and adjusted FRAX were compared in the aspects of discrimination and calibration.

6.3% of participants experienced MOF during a median follow-up of 10 years. The final model (CDFR) included 8 predictors: age, gender, previous fracture, insulin use, diabetic peripheral neuropathy (DPN), total cholesterol, triglycerides, and apolipoprotein A. This model had a C statistic of 0.803 (95%CI 0.761-0.844) and calibration χ² of 4.63 (p = 0.86). The unadjusted FRAX underestimated the MOF risk (calibration χ² 134.5, p < 0.001; observed/predicted ratio 2.62, 95%CI 2.17-3.08), and there was still significant underestimation after diabetes adjustments. Comparing FRAX, the CDFR had a higher AUC, lower calibration χ², and better reclassification of MOF.

The CDFR model has good performance in 10-year MOF risk prediction in T2DM, especially in patients with insulin use or DPN. Future work is needed to validate our model in external cohort(s).

Osteoporosis and type 2 diabetes (T2D) have been recognized as a widespread comorbidity leading to excess mortality and an enormous healthcare burden. In T2D, bone mineral density (BMD) may underestimate the risk of low-energy fractures as bone quality is reduced. It was hypothesized that a decrease in the trabecular bone score (TBS), a parameter assessing bone microarchitecture, may be an early marker of impaired bone health in women with T2D.

To identify clinical and body composition parameters that affect TBS in postmenopausal women with T2D and normal BMD.

A non-interventional cross-sectional comparative study was conducted. Potentially eligible subjects were screened at tertiary referral center. Postmenopausal women with T2D, aged 50-75 years, with no established risk factors for secondary osteoporosis, were included. BMD, TBS and body composition parameters were assessed by dual-energy X-ray absorptiometry. In women with normal BMD, a wide range of anthropometric, general and diabetes-related clinical and laboratory parameters were evaluated as risk factors for TBS decrease using univariate and multivariate regression analysis and analysis of receiver operating characteristic (ROC) curves.

Three hundred twelve women were initially screened, 176 of them met the inclusion criteria and underwent dual X-ray absorptiometry. Those with reduced BMD were subsequently excluded; 96 women with normal BMD were included in final analysis. Among them, 43 women (44.8%) showed decreased TBS values (≤ 1.31). Women with TBS ≤ 1.31 were taller and had a lower body mass index (BMI) when compared to those with normal TBS (Р = 0.008 and P = 0.007 respectively). No significant differences in HbA1c, renal function, calcium, phosphorus, alkaline phosphatase, PTH and 25(ОН)D levels were found. In a model of multivariate linear regression analysis, TBS was positively associated with gynoid fat mass, whereas the height and androgen fat mass were associated negatively (all P < 0.001). In a multiple logistic regression, TBS ≤ 1.31 was associated with lower gynoid fat mass (adjusted odd ratio [OR], 0.9, 95% confidence interval [CI], 0.85-0.94, P < 0.001), higher android fat mass (adjusted OR, 1.13, 95%CI, 1.03-1.24, P = 0.008) and height (adjusted OR, 1.13, 95%CI, 1.05-1.20, P < 0.001). In ROC-curve analysis, height ≥ 162.5 cm (P = 0.04), body mass index ≤ 33.85 kg/m2 (P = 0.002), gynoid fat mass ≤ 5.41 kg (P = 0.03) and android/gynoid fat mass ratio ≥ 1.145 (P < 0.001) were identified as the risk factors for TBS reduction.

In postmenopausal women with T2D and normal BMD, greater height and central adiposity are associated with impaired bone microarchitecture.

Type 1 diabetes (T1D)-induced osteoporosis is characterized by decreased bone mineral density, bone quality, rate of bone healing, bone formation, and increased bone resorption. Patients with T1D have a 2-7-fold higher risk of osteoporotic fracture. The mechanisms leading to increased risk of osteoporotic fracture in T1D include insulin deficiency, hyperglycemia, insulin resistance, lower insulin-like growth factor-1, hyperglycemia-induced oxidative stress, and inflammation. In addition, a higher probability of falling, kidney dysfunction, weakened vision, and neuropathy indirectly increase the risk of osteoporotic fracture in T1D patients. Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of T1D-induced osteoporotic fracture. This review discusses the role of NO in osteoblast-mediated bone formation and osteoclast-mediated bone resorption in T1D. In addition, the mechanisms involved in reduced NO bioavailability and activity in type 1 diabetic bones as well as NO-based therapy for T1D-induced osteoporosis are summarized. Available data indicates that lower NO bioavailability in diabetic bones is due to disruption of phosphatidylinositol 3‑kinase/protein kinase B/endothelial NO synthases and NO/cyclic guanosine monophosphate/protein kinase G signaling pathways. Thus, NO bioavailability may be boosted directly or indirectly by NO donors. As NO donors with NO-like effects in the bone, inorganic nitrate and nitrite can potentially be used as novel therapeutic agents for T1D-induced osteoporosis. Inorganic nitrites and nitrates can decrease the risk for osteoporotic fracture probably directly by decreasing osteoclast activity, decreasing fat accumulation in the marrow cavity, increasing osteoblast activity, and increasing bone perfusion or indirectly, by improving hyperglycemia, insulin resistance, and reducing body weight.

Diabetic osteoporosis (DOP) belongs to secondary osteoporosis caused by diabetes; it has the characteristics of high morbidity and high disability. In the present study, we constructed a type 1 diabetic rat model and administered chondroitin sulfate (200 mg/kg) for 10 weeks to observe the preventive effect of chondroitin sulfate on the bone loss of diabetic rats. The results showed that chondroitin sulfate can reduce blood glucose and relieve symptoms of diabetic rats; in addition, it can significantly increase the bone mineral density, improve bone microstructure, and reduce bone marrow adipocyte number in diabetic rats; after 10 weeks of chondroitin sulfate administration, the SOD activity level was upregulated, as well as CAT levels, indicating that chondroitin sulfate can alleviate oxidative stress in diabetic rats. Chondroitin sulfate was also found to reduce the level of serum inflammatory cytokines (TNF-α, IL-1, IL-6, and MCP-1) and alleviate the inflammation in diabetic rats; bone metabolism marker detection results showed that chondroitin sulfate can reduce bone turnover in diabetic rats (decreased RANKL, CTX-1, ALP, and TRACP 5b levels were observed after 10 weeks of chondroitin sulfate administration). At the same time, the bone OPG and RUNX 2 expression levels were higher after chondroitin sulfate treatment, the bone RANKL expression was lowered, and the OPG/RANKL ratio was upregulated. All of the above indicated that chondroitin sulfate could prevent STZ-induced DOP and repair bone microstructure; the main mechanism was through anti-oxidation, anti-inflammatory, and regulating bone metabolism. Chondroitin sulfate could be used to develop anti-DOP functional foods and diet interventions for diabetes.