Diabetic osteoporosis (DOP) can cause abnormal brain neural activity, but its mechanism is still unclear. This study aims to further explore the abnormal functional connectivity between different brain regions based on the team's previous research.

Resting-state functional magnetic resonance imaging (rs-fMRI) data were obtained from 14 participants diagnosed with type 2 diabetes mellitus (T2DM) and osteoporosis. For comparison, data from 13 T2DM patients without osteoporosis were analyzed. The seed regions for functional connectivity (FC) analysis were chosen according to brain areas previously reported to exhibit abnormal regional homogeneity (ReHo).

DOP patients exhibited significantly decreased BMD, T-scores, MoCA scores, and osteocalcin (OC) levels compared to controls (p<0.05). FC analysis revealed: 1) Reduced connectivity between the left middle temporal gyrus (increased ReHo) and middle occipital gyrus; 2) Enhanced connectivity between the right angular gyrus (increased ReHo) and left Rolandic operculum; 3) Weakened the left precuneus (increased ReHo) and right superior/left middle frontal gyri. These alterations correlated with deficits in visual processing, working memory, and executive function.

Distinct FC reorganization in DOP patients reflects synergistic effects of metabolic and skeletal pathologies on neural networks, potentially mediating cognitive decline through visual pathway disruption and prefrontal-default mode network decoupling. The findings highlight neuroimaging biomarkers for metabolic bone disease-related cognitive disorders.

Embryonic muscle activity is involved in various aspects of bone morphogenesis and growth. Normal mechanical stimuli of muscle contraction are important in most cases, and when the muscles are immobilized, the developing bones are abnormally shaped. In chick embryos, a characteristic curved deformity is reproducibly induced in the developing tibiotarsus using the bone-weakening agent, beta-aminopropionitrile (bAPN). In this study, we applied decamethonium bromide (DMB), a well-established neuromuscular blocking agent, to embryos treated with bAPN, to test the hypothesis that the deformity is triggered and formed depending on the balance between the decrease in stiffness of the bAPN-affected tibiotarsus and the normal physiological increase in embryonic skeletal muscle activity. The occurrence of curved morphology induced by bAPN administered at 4 or 8 days of incubation (embryonic day [ED]) was temporally consistent with the posterior displacement of the leg muscles, which occurred just before ED8. The displaced muscles were assumed to exert a contraction force comparable to that of untreated normal muscles. When treated with DMB at ED8, the muscles atrophied and exhibited degenerative changes, and the degree of curved morphology was alleviated and reduced to 50% or more in the morphometric evaluation at ED10. These findings indicated that the coordinated development of skeletal element stiffness and muscle activity must be temporally regulated, particularly during the early stages of skeletogenesis.

Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. However, its ability to predict fractures is still uncertain. This study aimed to determine the association between BMSi and 10 year fracture probability, as calculated by the FRAX algorithm.

BMSi was measured using the OsteoProbe in 388 men (ages 40-90 yr) from the Geelong Osteoporosis Study. The probabilities for a major osteoporotic fracture (MOF) and hip fracture (HF) were calculated using the Australian FRAX tool. Hip (HF) and major osteoporotic (MOF) fracture probabilities were computed with and without the inclusion of femoral neck bone mineral density (BMD). For each participant, four 10 year probability scores were therefore generated: (i) HF-FRAXnoBMD; (ii) HF-FRAXBMD; (iii) MOF-FRAXnoBMD; (iv) MOF-FRAXBMD.

BMSi was negatively correlated with age (r = - 0.114, p = 0.025), no associations were detected between BMSi and femoral neck BMD (r = + 0.035, p = 0.507). BMSi was negatively correlated with HF-FRAXnoBMD (r = - 0.135, p = 0.008) and MOF-FRAXnoBMD (r = - 0.153, p = 0.003). These trends held true for HF-FRAXBMD (r = - 0.087, p = 0.094) and MOF-FRAXBMD (r = - 0.111, p = 0.034), but only the latter reached significance.

BMSi captures the cumulative effect of clinical risk factors in the FRAX algorithm, suggesting that it could provide additional information that may be useful in predicting risk of fractures. Further studies are warranted to establish its efficacy in predicting fracture risk.

The prevalence of osteoporosis (OP) on a global scale is significantly elevated that causes life threatening issues. The potential of groundbreaking biomolecular therapeutics in the field of OP is highly encouraging. The administration of biomolecular agents has the potential to mitigate the process of bone demineralization while concurrently augmenting the regenerative capacity of bone tissue, thereby facilitating a personalized therapeutic approach. Biomolecules-based therapies showed promising results in term of bone mass protection and restoration in OP.

We summarized the recent biomolecular therapies with notable progress in clinical, demonstrating the potential to transform illness management. These treatments frequently utilize different biomolecule based strategies. Biomolecular therapeutics has a targeted character, which results in heightened specificity and less off-target effects, ultimately leading to increased patient outcomes. These aspects have the capacity to greatly enhance the management of OP, thus resulting in a major enhancement in the quality of life encountered by individuals affected by this condition.

Inflammatory bowel diseases (IBD), including ulcerative colitis, are characterized by chronic inflammation and oxidative stress, necessitating novel therapeutic approaches. This study explores the therapeutic potential of snail mucus derived from snails fed different concentrations of carob (SSCS) and compares its efficacy to aqueous carob extracts (AECS). Both SSCS and AECS are rich in bioactive compounds with potential anti-inflammatory, antioxidant and tissue-regenerative effects.

Snail mucus was found to be rich in collagen and allantoin, which are crucial for tissue repair and cell regeneration, whereas carob extracts contained high levels of phenolics, tannins and flavonoids, contributing to their antioxidant properties. In a rat model of acetic acid-induced ulcerative colitis, pretreatment with SSCS, AECS or sulfasalazine significantly alleviated colonic damage. The SSCS30% group exhibited the strongest protective effects, comparable to sulfasalazine, in reducing mucosal injury, inflammation and immune activation. Biochemical analyses demonstrated that SSCS30% effectively decreased systemic inflammation markers (CRP), pancreatic stress indicators (amylase) and liver enzyme levels (AST, ALT, ALP), while enhancing antioxidant defenses and preserving colonic sulfhydryl content.

These findings underscore the therapeutic potential of snail mucus, particularly from snails fed a 30% carob-enriched diet, as a promising natural therapy for IBD. Its potent anti-inflammatory, antioxidant and tissue-regenerative properties suggest that the use of SSCS30% could serve as an innovative approach for managing ulcerative colitis and other inflammatory disorders. These findings suggest that carob-enriched snail mucus could serve as a complementary therapy for ulcerative colitis patients, though clinical validation remains necessary. While these preclinical results are promising, further clinical studies are needed to validate the therapeutic potential of this natural combination in human ulcerative colitis. © 2025 Society of Chemical Industry.

To evaluate bone marrow fat concentration changes after sleeve gastrectomy in metabolic syndrome patients with and without diabetes.

A total of 58 metabolic syndrome patients (29 metabolic syndrome patients with diabetes (35.10 years ± 6.62) and 29 metabolic syndrome patients without diabetes (35.07 years ± 6.47)) who underwent sleeve gastrectomy received prospective follow-up for 2 years. Echo asymmetry, least square estimation-MRI, and laboratory tests were performed on all patients before and 2 years after surgery. The differences between baseline and end-of-study parameters were analyzed with the paired Student's t test. In addition, the associations of vertebral bone marrow fat concentration (denoted by proton density fat fraction, PDFF) with other variables were determined using multiple linear regression analysis.

Bone proton density fat fraction decreased significantly among patients with diabetes (from 38.62 ± 8.01 to 34.54 ± 7.54, P = 0.003) and without diabetes (from 36.82 ± 8.80 to 35.09 ± 8.33, P = 0.011) after sleeve gastrectomy. Among patients with diabetes, multivariable predictors of changes in proton density fat fraction by descending order of standardized coefficient were changes in HbA1c (2.690, P < 0.001), baseline HbA1c (2.354, P < 0.001), changes in insulin (0.627, P < 0.001), changes in low-density lipoprotein cholesterol (0.597, P = 0.013), and changes in C-peptide (-0.664, P = 0.001). Among patients without diabetes, multivariable predictors of changes in proton density fat fraction were changes in low-density lipoprotein cholesterol (1.486, P < 0.001), changes in high-density lipoprotein cholesterol (0.460, P = 0.003), baseline low-density lipoprotein cholesterol (0.438, P = 0.014), changes in triglyceride (0.383, P = 0.007), and changes in total cholesterol (-1.614, P < 0.001).

Sleeve gastrectomy may decrease bone marrow fat concentration of MetS patients regardless of diabetes status. Changes in bone marrow fat concentration may be influenced by different factors based on diabetes status.

Osteoporosis (OP) is characterized by degraded bone microstructure, loss of bone mass and increased risk of fragility fractures. Currently, T-score determined by dual-energy X-ray absorptiometry (DEXA) measurements has been regarded as the gold standard for the diagnosis of osteoporosis. However, multiple factors have indicated that the T-score is insufficient to identify individuals with osteoporosis at a potentially high risk of fracture, or accurately detect those who require treatment, or continuously monitor the risk of re-fracture and clinical outcomes after treatment. This review covers publications in a range of ten years and comprehensively summarizes the studies in laboratory-based biomarkers for osteoporotic fractures (OF), aiming to provide physicians and surgeons with an update of clinical research in identification, verification and application of these tools, and to provide useful information for the design of future clinical studies.

It was found that bone formation markers (such as PINP, BGP, ECM1 and SOST), bone resorption markers (such as β-CTX, TRAcP5b, osteocalcin, RANKL, RANKL/OPG ratio, and t-PINP/β-CTX), hormonal biomarkers (such as IGF- 1, PTH, leptin, adiponectin and AMH), indicators of inflammation and oxidative stress (SII, IL- 6, LTL, FlOP_360, FlOP_400, and GGT), microRNAs (such as miR- 21, miR- 320a- 3p, miR- 491 - 5p, miR- 485 - 3p, miR- 19b- 1- 5p, miR- 203a, miR- 31 - 5p, miR- 502 - 3p, miR- 4739, miR- 497, miR- 19b, and miR- 107), other biomarkers (SAF-AGEs and glycine), adipocytokines (irisin and Omentin- 1), senescence biomarkers (RDW), and lncRNAs (MIAT) may be useful biomarkers for clinical practice. Further validation of these biomarkers and a better understanding of the underlying molecular mechanisms may help in the development and application of these biomarkers for risk prediction of OF, differential diagnosis among OP, OF and healthy individuals, as well as post-operative monitoring of re-fracture risk and treatment outcomes.

The degradation of extracellular matrix proteins such as collagen and elastin with aging leads to skin sagging. Polycaprolactone (PCL) microspheres are used as facial fillers because of their ability to provide volume, biodegradability, and collagen-stimulating properties. The direct biological effects of PCL microspheres on fibroblasts, particularly in stimulating sustained collagen production, require further investigation. We detected the safety and effect of PCL microspheres on human fibroblasts and investigated new collagen synthesis and the thickness of C57BL/6 mouse skin. Through an RNA-seq analysis of differentially expressed genes, we identified a key regulator of collagen production in PCL-stimulated fibroblasts. Our research revealed that PCL microspheres are safe for human fibroblasts, promoting their proliferation and increasing new collagen synthesis and skin thickness. We identified sterile alpha motif domain containing 11 (SAMD11) as a key regulator of collagen production in PCLstimulated fibroblasts through an RNA-seq analysis. By increasing SAMD11 expression, PCL microspheres increase collagen synthesis and rejuvenate skin through the upregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1). This study elucidates the mechanism by which SAMD11 regulates the effects of PCL microspheres as collagen stimulants for skin rejuvenation, providing a foundation for the future development and refinement of similar materials.

Diabetes and osteoporosis are frequent long-term conditions. There is little information on the relationship between diabetes and the risk of refracture in people who have osteoporotic fractures (OPFs), even though both conditions have been individually associated with increased fracture risk.

We conducted a retrospective cohort study using the Osteoporotic Fracture Registry System of the Affiliated Kunshan Hospital of Jiangsu University. The study included 2,255 patients aged 50 years or older who were admitted with OPFs, comprising 107 with diabetes and 2,148 without. The risk of refracture within 1, 3, and 5 years was evaluated using Cox proportional hazard regression models based on whether or not a diabetes diagnosis was made during the admission assessment. Furthermore, the rates of refracture between individuals with and without diabetes were compared using Kaplan-Meier curves.

In patients with OPFs, diabetes was significantly positively correlated with refracture risk. For the follow-up periods of 1, 3, and 5 years, the hazard ratios (HRs) in the fully adjusted model were 2.83 (95% confidence interval [CI]: 1.09 to 7.39, P-value = 0.033), 2.65 (95% CI: 1.27 to 5.52, P-value = 0.009), and 2.72 (95% CI: 1.39 to 5.32, P-value = 0.004), respectively.

The findings highlight the importance of monitoring bone health and implementing preventative interventions in individuals with diabetes, since they reveal that diabetic patients face a risk of refracture that is more than twice as high as that of non-diabetic individuals.

Hip fractures pose a significant health challenge, particularly in aging populations, leading to substantial morbidity and economic burden. Most hip fractures result from a combination of osteoporosis and falls. Accurate assessment of hip fracture risk is essential for identifying high-risk individuals and implementing effective preventive strategies. Current clinical tools, such as the Fracture Risk Assessment Tool (FRAX), primarily rely on statistical models of clinical risk factors derived from large population studies. However, these tools often lack specificity in capturing the individual biomechanical factors that directly influence fracture susceptibility. Consequently, image-based biomechanical approaches, primarily leveraging dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT), have garnered attention for their potential to provide a more precise evaluation of bone strength and the impact forces involved in falls, thereby enhancing risk prediction accuracy. Biomechanical approaches rely on two fundamental components: assessing bone strength and predicting fall-induced impact forces. While significant advancements have been made in image-based finite element (FE) modeling for bone strength analysis and dynamic simulations of fall-induced impact forces, substantial challenges remain. In this review, we examine recent progress in these areas and highlight the key challenges that must be addressed to advance the field and improve fracture risk prediction.

Both trabecular and cortical bone undergo changes at multiple scales. We previously demonstrated the multi-scale changes in trabecular bone quality that contribute to bone fragility in type 2 diabetes (T2D). The link between increased fragility in T2D and multi-scale changes in cortical bone and their interaction with glycation remains unclear. This study presents, first-ever, multi-scale cortical bone quality parameters in T2D patients after their first hip fracture. The study objective was to determine the association between cortical porosity (Ct.Po.), mechanical, material, and bone compositional properties in T2D. Inferomedial femoral neck (FN) bone tissue specimens were collected from patients (n = 10 with T2D, n = 25 age- and sex-matched non-diabetes controls) who underwent hip replacement surgery following the first hip fragility fracture. Bone mineral density at FN was found to be similar between groups. In T2D, Ct.Po was higher (p = 0.038), while ultimate stress (p = 0.021), ultimate strain (p = 0.040), post-yield strain (p = 0.011), toughness (p = 0.005), yield energy (p = 0.003), and post-yield energy (p = 0.004) were notably lower. Tissue compositional differences included lower gravimetric mineral/matrix (p = 0.017), higher non-enzymatic collagen cross-link ratio (NE-xLR) (p = 0.049) and higher sugar/matrix ratio (p = 0.042) in T2D. Fluorescent advanced glycation end-products (fAGEs) content was higher in T2D bone (p = 0.043). At the mesoscale, the fAGEs in the bone matrix are inversely related to the yield- and ultimate strain of T2D bone, and NE-xLR is negatively correlated with yield- and ultimate- stress in the T2D group. In conclusion, study findings demonstrate that elevated glycation weakens the mechanical integrity of cortical bone by reducing its ability to absorb energy and resist deformation, thereby contributing to bone fragility in T2D. The strong association of fAGEs with lower yield strain, along with the association of NE-xLR with lower yield- and ultimate stress, establishes a causal link between AGEs and the deterioration of cortical bone mechanical properties. These findings underscore the need for strategies targeting glycation and collagen quality to mitigate fracture risk in T2D patients.

Joint injury is a risk factor for post-traumatic osteoarthritis. However, metabolic and microarchitectural changes within the joint post-injury in both sexes remain unexplored. This study identified tissue-specific and spatially-dependent metabolic signatures in male and female mice using matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) and LC-MS metabolomics. Male and female C57Bl/6J mice were subjected to non-invasive joint injury. Eight days post-injury, serum, synovial fluid, and whole joints were collected for metabolomics. Analyses compared between injured, contralateral, and naïve mice, revealing local and systemic responses. Data indicate sex influences metabolic profiles across all tissues, particularly amino acid, purine, and pyrimidine metabolism. MALDI-MSI generated 2D ion images of bone, the joint interface, and bone marrow, highlighting increased lipid species in injured limbs, suggesting physiological changes across injured joints at metabolic and spatial levels. Together, these findings reveal significant metabolic changes after injury, with notable sex differences.

This study explored the association between serum Hcy level and the all-cause mortality among osteoarthritis (OA) patients. This cohort study included patients diagnosed as OA from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Abbott Homocysteine assay, a fully automated fluorescence polarization immunoassay (FPIA) method, was used to measure the level of serum Hcy. Covariates included sociodemographic information, lifestyles, history of diseases and medications were extracted from the database. The weighted univariate, multivariate Cox proportional hazard models and restricted cubic splines (RCS) were utilized to explore the association between Hcy level and all-cause mortality in OA patients, with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender, duration of OA, complications and C-reactive protein (CRP) were further assessed by this association. Totally 1384 OA patients were included in this study, of which 817 (59.03%) died by 31 December 2019. After adjusting all covariates, high Hcy level was associated with the high all-cause mortality among OA patients (HR=1.31, 95%CI: 1.02-1.67), especially in females (HR=1.43, 95%CI: 1.07-1.91), aged >60 years (HR=1.49, 95%CI: 1.14-1.94), duration of OA >10 years (HR=1.40, 95%CI: 1.01-1.95), with the history of hypertension (HR=1.37, 95%CI: 1.03-1.80), without the history of diabetes (HR=1.36, 95%CI: 1.01-1.82) or CRP >0.29 mg/l (HR=1.51, 95%CI: 1.04-2.19). High serum Hcy level was associated with high risk of all-cause mortality in OA patients. Our results suggest that serum Hcy is a promising biomarker for the prognosis of OA patients.

Background: This study aimed at investigating the prolonged effects of glucocorticoids and bisphosphonates on bone. Methods: Six-to-eight-month-old skeletally mature male Sprague Dawley rats were randomized to receive a cancer therapy combination of zoledronic acid (ZA = 0.13 mg/kg) and dexamethasone (DX = 3.8 mg/kg) (treatment group, n = 10) or sterile phosphate buffer saline solution (control group, n = 10). The rats received weekly intraperitoneal injections for 8 weeks, which were stopped 6 weeks before euthanasia. Mineralized bone samples were characterized by three-point bending tests, micro-CT imaging, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Bone collagen was assessed using tensile tests on the demineralized bones and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy on mineralized and demineralized bones. Results: The samples in the treatment group showed increased tibial cortical thickness, mineral crystal size, and toughness. Analyses of demineralized tibiae revealed decreased collagen tensile strength in the experimental group. The spectroscopic and TGA/DSC analyses showed that the ZA + DX treatment increased the collagen amide I 1660/1690 cm-1 area ratio and collagen denaturalization temperature, indicating a higher level of collagen cross-linking. Conclusions: Bisphosphonates and glucocorticoids led to prolonged changes in the mechanical properties of bone as a result of increased cortical thickness, increased crystal size, and the deterioration of collagen quality.

The purpose of this review is to investigate the impacts of blood glucose fluctuations on diabetic osteoporosis, a complication of Type 2 diabetes mellitus (T2DM) that remains poorly understood. We reviewed the current evidence of the relationship between blood glucose fluctuations and diabetic osteoporosis in patients with T2DM. The findings indicate that blood glucose fluctuations may contribute to inhibiting the processes of bone formation and resorption, promoting diabetic osteoporosis and fractures in T2DM. Mechanistic studies, both in vitro and in vivo, reveal that these effects are largely mediated by oxidative stress, advanced glycation end products, inflammatory mediators, and multiple pathways inducing cell apoptosis or autophagy. Thus, maintaining the long-term stability of blood glucose levels emerges as a target to be pursued in clinical practice in order to safely reduce mean blood glucose and for its direct effects on osteoporosis and fractures in T2DM.

Osteocalcin has attracted attention for its potential role in diabetes management. However, there has been no bibliometric assessment of scientific progress in this field.

We analysed 1680 articles retrieved from the Web of Science Core Collection (WoSCC) between 1 January 1986 and 10 May 2024 using various online tools.

These papers accumulated 42,714 citations,with an average of 25.43 citations per paper. Publication output increased sharply from 1991 onwards. The United States and China are at the forefront of this research area.

The keywords were grouped into four clusters: 'Differential and functional osteocalcin genes', 'Differential expression of osteocalcin genes in relation to diabetes mellitus', 'Role of osteocalcin in the assessment of osteoporosis and diabetes mellitus', and 'Indirect involvement of osteocalcin in metabolic processes'. Analysis using the VoS viewer suggests a shift in research focus towards the correlation between osteocalcin levels and diabetic complications, the clinical efficacy of therapeutic agents or vitamins in the treatment of osteoporosis in diabetic patients, and the mechanisms by which osteocalcin modulates insulin action. The proposed focus areas are "osteocalcin genes", "insulin regulation and osteoporosis ", "different populations", "diabetes-related complications" and "type 2 diabetes mellitus","effect of osteocalcin expression on insulin sensitivity as well as secretion","osteocalcin expression in different populations of diabetic patients and treatment-related studies".

This study aimed to assess the effects of a single-dose radiation therapy (15 Gy) on grafted and non-grafted defects, bone microarchitecture, and collagen maturity.

Bone defects were surgically created in rat femurs. The right femur defect was filled with blood clot (group "Clot") and the left femur defect by deproteinized bovine bone mineral graft (group "Xenograft"). The animals were divided into two groups: without radiation therapy (nRTX) and with radiation therapy (RTX). Microtomographic (bone volume fraction, BV/TV; trabecular thickness, Tb.Th; trabecular number, Tb.N; trabecular separation, Tb.Sp), histological, and histomorphometric analyses were performed 14 days after the surgery. Two-way ANOVA with Tukey post hoc test was used to compare the groups (α=5%).

Microtomographic analysis revealed that radiation therapy led to smaller BV/TV and Tb.N in both Clot and Xenograft groups. Regardless of radiation therapy, defects filled with xenografts showed a larger Tb.N. In contrast, the Clot group demonstrated increased BV/TV and Tb.Th. The histomorphometric results were consistent with those obtained by microtomography. Intermediately and densely packed collagen were predominant among the groups. Histological analysis revealed disorganized bone formation bridging the cortical borders of the lesions in the RTX group. The involvement of primary bone with graft particles was commonly observed in all xenograft groups, and radiation therapy did not affect the percentage of bone-graft contact.

Single-dose radiation therapy affected bone repair, resulting in a smaller amount of newly formed bone in both grafted and non-grafted defects.

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.

Osteoporosis is a chronic condition characterized by reduced bone strength and an elevated risk of fractures. The influence of diet and glucose metabolism on bone health and the development of osteoporosis has been an area of interest. This study aimed to investigate the potential association between dietary glycemic index (DGI), dietary glycemic load (DGL), dietary insulin index (DII), dietary insulin load (DIL), and the odds of osteoporosis among Iranian adults.

Data from 12,696 Iranian teachers (35-50 years) in a cross-sectional study on diet, nutrition, physical activity, and diseases were analyzed. The participants had no history of diabetes, cardiovascular diseases, stroke, thrombosis, or cancer and consumed between 800 and 4,200 kcal/day. We estimated DGI, DGL, DII, and DIL from a validated semi-quantitative food-frequency questionnaire (FFQ). We also diagnosed osteoporosis using dual-energy X-ray absorptiometry.

In the fully adjusted model, higher DGI and DGL were significantly associated with increased odds of osteoporosis (OR = 1.78 and 1.46 for the highest vs. the lowest tertile; P trend < 0.05). Nonetheless, no significant association was found between DII or DIL and osteoporosis prevalence. Moreover, higher DIL and DGL were associated with a higher intake of calorie-dense/nutrient-poor foods and a lower intake of antioxidant-rich foods.

Although our study showed that high DGI/DGL increased osteoporosis risk in Iranian teachers, no association was found between DII/DIL and osteoporosis prevalence. More research is needed to confirm these results and understand the mechanisms involved.

Frailty and fractures are closely associated with adverse clinical outcomes. This retrospective study investigated the prognostic impact of frailty, prevalent fractures, and the coexistence of both in patients with cirrhosis. Frailty was defined according to the Fried frailty phenotype criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Prevalent fractures were assessed using questionnaires and lateral thoracolumbar spine radiographs. Cumulative survival rates were compared between the frailty and non-frailty groups, fracture and non-fracture groups, and all four groups stratified by the presence or absence of frailty and/or prevalent fractures. Among 189 patients with cirrhosis, 70 (37.0%) and 74 (39.2%) had frailty and prevalent fractures, respectively. The median observation period was 64.4 (38.6-71.7) months, during which 50 (26.5%) liver disease-related deaths occurred. Multivariate analysis identified frailty and prevalent fractures as significant independent prognostic factors in the overall cohort (p < 0.001 and p = 0.003, respectively). The cumulative survival rates were lower in the frailty or fracture groups than in the non-frailty or non-fracture groups, respectively, in the overall cohort and in patients with compensated and decompensated cirrhosis. Patients with both frailty and prevalent fractures showed the lowest cumulative survival rates, whereas those without these comorbidities showed the highest cumulative survival rates among the four stratified groups. Frailty and prevalent fractures were independently associated with mortality in patients with cirrhosis. Additionally, the coexistence of both comorbidities worsened the prognosis.

To investigate the effects of surgical menopause on bone mineral density and bone quality because bilateral salpingo-oophorectomy for the treatment of gynecological malignancies is common even in premenopausal patients. This study is prospective one of bone mineral density and quality measurements after surgery for perimenopausal gynecologic malignancies.

In 50 women who underwent surgical menopause for a diagnosis of gynecological malignancies, bone mineral density (BMD), blood levels of tartrate-resistant acid phosphatase 5b (TRACP-5b) and bone-specific alkaline phosphatase (BAP) as bone metabolism markers, and urinary pentosidine level as bone quality marker were measured before surgery and at multiple points up to 24 months after surgery.

In a group of 22 patients who did not undergo hormone replacement therapy (HRT) (HRT- group), BMD of the lumbar spine and total hip continued to decrease significantly from 6 months postoperatively. Percentages of changes in BMD progressively increased over time after surgery. TRACP-5b and urinary pentosidine levels significantly increased 6 months postoperatively compared with preoperative levels. Comparisons between 10 patients who underwent HRT (HRT+ group) and the HRT- group revealed significant reductions in the percentage of change in lumbar spine BMD only and TRACP-5b and urinary pentosidine levels 12 months postoperatively in the former group.

In this pilot study, we showed that BMD and bone-related markers are altered in patients with surgical menopause. It also suggested that HRT may reduce these influences on bone metabolism.

This study aimed to identify whether the ratio of the vertebral Hounsfield unit to serum pentosidine (H/P ratio), which reflects bone density and quality, can predict screw loosening after spinal fusion surgery.

A retrospective case-control study was conducted in 35 patients (mean age 71 ± 10.4 years, 18 men) who underwent spinal interbody fusion for lumbar spine disease between June 2020 and February 2022. Screw loosening was evaluated by computed tomography at 12 months postoperatively. Information was collected on patient background characteristics, including age, sex, body mass index, diagnosis, dialysis status, smoking history, diabetes, steroid use, and osteoporosis. Imaging parameters, the surgical method used, number of fixed intervertebral segments, intervertebral level (including L5/S1 or not), and the H/P ratio were also investigated. Risk factors associated with screw loosening and pseudarthrosis were examined in univariable and multivariable logistic regression analyses. A P-value of < 0.05 was considered statistically significant.

Screw loosening occurred in 14 of 35 patients (40%). Multivariate analysis revealed that the H/P ratio (odds ratio 0.09, confidence interval 0.02-0.53, P = 0.007) was a significant risk factor for screw loosening at 12 months postoperatively.

This study demonstrates that the H/P ratio, which reflects both bone density and deterioration of bone quality in the vertebral body, may serve as a predictor of screw loosening at 12 months after lumbar spinal surgery.

Glycan-protein interactions play a crucial role in biology, providing additional functions capable of inducing biochemical and cellular responses. In the extracellular matrix of bone, this type of interactions is ubiquitous. During the synthesis of the collagen molecule, glycans are post-translationally added to specific lysine residues through an enzymatically catalysed hydroxylation and subsequent glycosylation. During and after fibril assembly, proteoglycans are essential for maintaining tissue structure, porosity, and integrity. Glycosaminoglycans (GAGs), the carbohydrate chains attached to interstitial proteoglycans, are known to be involved in mineralization. They can attract and retain water, which is critical for the mechanical properties of bone. In addition, like other long-lived proteins, collagen is susceptible to glycation. Prolonged exposure of the amine group to glucose eventually leads to the formation of advanced glycation end-products (AGEs). Changes in the degree of glycosylation and glycation have been identified in bone pathologies such as osteogenesis imperfecta and diabetes and appear to be associated with a reduction in bone quality. However, how these changes affect mineralization is not well understood. Based on the literature review, we hypothesize that the covalently attached carbohydrates may have a water-attracting function similar to that of GAGs, but at different lengths and timescales in the bone formation process. Glycosylation potentially increases the hydration around the collagen triple helix, leading to increased mineralization (hypermineralization) after water has been replaced by mineral. Meanwhile, glycation leads to the formation of crosslinking AGEs, which are associated with a decrease in hydration levels, reducing the mechanical properties of bone.

Polarization-resolved second harmonic generation (pSHG) is a label-free method that has been used in a range of tissue types to describe collagen orientation. In this work, we develop pSHG analysis techniques for investigating cranial bone collagen assembly defects occurring in a mouse model of hypophosphatasia (HPP), a metabolic bone disease characterized by a lack of bone mineralization. After observing differences in bone collagen lamellar sheet structures using scanning electron microscopy, we found similar alterations with pSHG between the healthy and HPP mouse collagen lamellar sheet organization. We then developed a spatial polarimetric gray-level co-occurrence matrix (spGLCM) method to explore polarization-mediated textural differences in the bone collagen mesh. We used our spGLCM method to describe the collagen organizational differences between HPP and healthy bone along the polarimetric axis that may be caused by poorly aligned collagen molecules and a reduction in collagen density. Finally, we applied machine learning classifiers to predict bone disease state using pSHG imaging and spGLCM methods. Comparing random forest (RF) and XGBoost technique on spGLCM, we were able to accurately separate unknown images from the two groups with an averaged F1 score of 92.30%±3.11% by using RF. Our strategy could potentially allow for monitoring of therapeutic efficacy and disease progression in HPP, or even be extended to other collagen-related ailments or tissues.

Calcification of tissues involves the formation and deposition of calcium-containing crystals in the extracellular matrix (ECM). While this process is normal in bones, it becomes pathological when it occurs in cardiovascular and musculoskeletal soft tissues. Pathological calcification (PC) triggers detrimental pathways such as inflammation and oxidative stress, contributing to tissue damage and dysregulated tissue biomechanics, ultimately leading to severe complications and even death. The underlying mechanisms of PC remain elusive. Emerging evidence suggests a significant role of lysyl oxidases (LOX(L)) in PC. LOX(L) are a group of five enzymes involved in collagen cross-linking and ECM maturation. Beyond their classical role in bone mineralization, recent investigations propose new non-classical roles for LOX(L) that could be relevant in PC. In this review, we analyzed and summarized the functions of LOX(L) in cardiovascular and musculoskeletal PC, highlighting their deleterious roles in most studies. To date, specific inhibitors targeting LOX(L) isoforms are under development. New therapeutic tools targeting LOX(L) are warranted in PC and must avoid adverse effects on physiological bone mineralization.

To assess and improve the reliability of the ultrashort echo time quantitative magnetization transfer (UTE-qMT) modeling of the cortical bone.

Simulation-based digital phantoms were created that mimic the UTE-qMT properties of cortical bones. A wide range of SNR from 25 to 200 was simulated by adding different levels of noise to the synthesized MT-weighted images to assess the effect of SNR on UTE-qMT fitting results. Tensor-based denoising algorithm was applied to improve the fitting results. These results from digital phantom studies were validated via ex vivo rat leg bone scans.

The selection of initial points for nonlinear fitting and the number of data points tested for qMT analysis have minimal effect on the fitting result. Magnetization exchange rate measurements are highly dependent on the SNR of raw images, which can be substantially improved with an appropriate denoising algorithm that gives similar fitting results from the raw images with an 8-fold higher SNR.

The digital phantom approach enables the assessment of the reliability of bone UTE-qMT fitting by providing the known ground truth. These findings can be utilized for optimizing the data acquisition and analysis pipeline for UTE-qMT imaging of cortical bones.

Pentosidine is representative of the cross-linked structure of advanced glycation end products (AGEs) and has been suggested as a biomarker to assess bone and muscle quality. As studies on pentosidine in young adult men remain limited, we aimed to clarify the associations of urinary pentosidine with musculoskeletal status and physical performance in young men. Participants in this study comprised 32 men (age range: 19-39 years). Anthropometric measurements (body composition by InBody 430; stiffness index by ultrasound), muscle performance (grip strength by dynamometer, thigh muscle thickness by ultrasound), physical performance (functional reach test, 30-s chair stand test, and timed up and go test), and urinary biomarkers (pentosidine, N-telopeptide of type I collagen, and creatinine) were measured. In partial correlation analysis adjusted for age and height, higher urinary pentosidine levels were significantly associated with lower fat-free mass index (rho = - 0.368, p = 0.046), grip strength (rho = - 0.433, p = 0.017), rectus femoris thickness (rho = - 0.393, p = 0.032), and anterior thigh thickness (rho = - 0.416, p = 0.022), and a marginally inverse correlation was noted between urinary pentosidine levels and functional reach test (rho = - 0.327, p = 0.078). Our findings suggest that pentosidine correlates inversely with a few muscle and physical performance indicators. Pending future validations, urinary pentosidine may be a biomarker of AGEs in young men.

Quasi-brittle fracture mechanics is used to evaluate fracture of human cortical bone in aging. The approach is demonstrated using cortical bone bars extracted from one 92-year-old human male cadaver. In-situ fracture mechanics experiments in a 3D X-ray microscope are conducted. The evolution of the fracture process zone is documented. Fully developed fracture process zone lengths at peak load are found to span about three osteon diameters. Crack deflection and arrest at cement lines is a key process to build extrinsic toughness. Strength and toughness are found as size-dependent, not only for laboratory-scale experimental specimens but also for the whole femur. A scaling law for the length fracture process zone is used. Then, size-independent, tissue fracture properties are calculated. Linear elastic fracture mechanics applied to laboratory beam specimens underestimates the tissue toughness by 60%. Tissue fracture properties are used to predict the load capacity of the femur in bending within the range of documented data. The quasi-brittle fracture mechanics approach allows for the assessment of the combined effect of bone quantity and bone quality on fracture risk. However, further work is needed considering a larger range of subjects and in the model validation at the organ length scale.

THCA (Thyroid carcinoma) is the most common endocrine malignancy in the world. The PLOD1 is highly expressed in THCA, but the mechanism is still unclear. It is found that the cell proliferation and migration were inhibited in si-PLOD1 group, and promoted with PLOD1 overexpression. MAZ is the transcription factor of PLOD1. The cell activities induced MAZ were reversed by si-PLOD1. The Glucose uptake, lactate production and ATP/ADP ratio were decreased with si-PLOD1. The glycolysis related proteins GLUT1, HK2, PFKP, PKM2, LDHA and Wnt/β-catenin pathway proteins WNT5A, cyclin D1, β-catenin were inhibited, GSK-3β is increased in si-PLOD1 group. BML-284 could reversed the si-PLOD1 effects on cell activities and Wnt/β-catenin pathway. The tumor xenografts were inhibited in si-PLOD1 group. As a potential therapeutic target, PLOD1 is regulated by MAZ in THCA. PLOD1 depletion could inhibit THCA cell proliferation and metastasis by glycolysis, which is inhibited by Wnt/β-catenin pathway in THCA.

Metabolic syndromes (eg, obesity, type 2 diabetes (T2D), atherosclerosis, and neurodegenerative diseases) and aging, they all have a strong component of carbonyl and reductive-oxidative (redox) stress. Reactive carbonyl (RCS) and oxidant (ROS) stress species are commonly generated as products or byproducts of cellular metabolism or are derived from the environment. RCS and ROS can play a dual role in living organisms. Some RCS and ROS function as signaling molecules, which control cellular defenses against biological and environmental assaults. However, due to their high reactivity, RCS and ROS inadvertently interact with different cellular and extracellular components, which can lead to the formation of undesired posttranslational modifications of bone matrix proteins. These are advanced glycation (AGEs) and glycoxidation (AGOEs) end products generated in vivo by non-enzymatic amino-carbonyl reactions. In this review, metabolic processes involved in generation of AGEs and AGOEs within and on protein surfaces including extracellular bone matrix are discussed from the perspective of cellular metabolism and biochemistry of certain metabolic syndromes. The impact of AGEs and AGOEs on some characteristics of mineral is also discussed. Different therapeutic approaches with the potential to prevent the formation of RCS, ROS, and the resulting formation of AGEs and AGOEs driven by these chemicals are also briefly reviewed. These are antioxidants, scavenging agents of reactive species, and newly emerging technologies for the development of synthetic detoxifying systems. Further research in the area of in vivo glycation and glycoxidation should lead to the development of diverse new strategies for halting the progression of metabolic complications before irreversible damage to body tissues materializes.

Currently, principles of tissue engineering and implantology are uniformly applied to all bone sites, disregarding inherent differences in collagen, mineral composition, and healing rates between craniofacial and long bones. These differences could potentially influence bone quality during the healing process. Evaluating bone quality during healing is crucial for understanding local mechanical properties in regeneration and implant osseointegration. However, site-specific changes in bone quality during healing remain poorly understood. In this study, we assessed newly formed bone quality in sub-critical defects in the maxilla and femur, while impairing collagen cross-linking using β-aminopropionitrile (BAPN). Our findings revealed that femoral healing bone exhibited a 73 % increase in bone volume but showed significantly greater viscoelastic and collagen changes compared to surrounding bone, leading to increased deformation during long-term loading and poorer bone quality in early healing. In contrast, the healing maxilla maintained equivalent hardness and viscoelastic constants compared to surrounding bone, with minimal new bone formation and consistent bone quality. However, BAPN-impaired collagen cross-linking induced viscoelastic changes in the healing maxilla, with no further changes observed in the femur. These results challenge the conventional belief that increased bone volume correlates with enhanced tissue-level bone quality, providing crucial insights for tissue engineering and site-specific implant strategies. The observed differences in bone quality between sites underscore the need for a nuanced approach in assessing the success of regeneration and implant designs and emphasize the importance of exploring site-specific tissue engineering interventions. STATEMENT OF SIGNIFICANCE: Accurate measurement of bone quality is crucial for tissue engineering and implant therapies. Bone quality varies between craniofacial and long bones, yet it's often overlooked in the healing process. Our study is the first to comprehensively analyze bone quality during healing in both the maxilla and femur. Surprisingly, despite significant volume increase, femur healing bone had poorer quality compared to the surrounding bone. Conversely, maxilla healing bone maintained consistent quality despite minimal bone formation. Impaired collagen diminished maxillary healing bone quality, but had no further effect on femur bone quality. These findings challenge the notion that more bone volume equals better quality, offering insights for improving tissue engineering and implant strategies for different bone sites.

This study evaluated the mechanical properties of demineralized dentin matrix submitted to different bleaching treatments, as well as the changes in mass and collagen biodegradation brought about by endogenous protease. Dentin collagen matrices were prepared to receive the following treatments (n=12): no bleaching treatment (C-control), 10% carbamide peroxide (CP-Opalescence PF, Ultradent, South Jordan, UT, USA) 10%/8 hours/ day/14 days, and 40% hydrogen peroxide (HP-Opalescence Boost, Ultradent), 40 minutes per session/3 sessions. The dentin matrices were evaluated for elastic modulus and mass before and after treatments and ultimate tensile strength after treatments. The solution collected during storage was evaluated for hydroxyproline release. There was no statistically significant difference between CP and C in terms of the elastic modulus (p=0.3697) or mass variation (p=0.1333). Dentin beams treated with HP and C presented significant mass loss after the first session (p=0.0003). HP treatment led to complete degradation of collagen matrices after the second bleaching session. After the second session, CP showed higher hydroxyproline concentration than C (p<0.0001). Ultimate tensile strength was lower for CP than C (p=0.0097). CP did not affect the elastic modulus or the dentin collagen matrix mass but did promote hydroxyproline release by endogenous protease and reduce the ultimate tensile strength. HP significantly affected the mechanical properties of dentin and promoted complete degradation of the demineralized dentin collagen matrix.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions.

The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs).

A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses.

Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias.

Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs.

PROSPERO registration number: CRD42023427508.

Diabetes mellitus is associated with inadequate bone health and quality and heightened susceptibility to fractures, even in patients with normal or elevated bone mineral density. Elevated advanced glycation end-products (AGEs) and a suppressed incretin pathway are among the mechanisms through which diabetes affects the bone. Accordingly, the present review aimed to investigate the effects of antidiabetic medications on bone quality, primarily through AGEs and the incretin pathway. Google Scholar, Cochrane Library, and PubMed were used to examine related studies until February 2024. Antidiabetic medications influence AGEs and the incretin pathway directly or indirectly. Certain antidiabetic drugs including metformin, glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl-peptidase-4 (DDP-4) inhibitors, α-glucosidase inhibitors (AGIs), sodium-glucose co-transporter-2 inhibitors, and thiazolidinediones (TZDs), directly affect AGEs through multiple mechanisms. These mechanisms include decreasing the formation of AGEs and the expression of AGEs receptor (RAGE) in tissue and increasing serum soluble RAGE levels, resulting in the reduced action of AGEs. Similarly, metformin, GLP-1RA, DDP-4 inhibitors, AGIs, and TZDs may enhance incretin hormones directly by increasing their production or suppressing their metabolism. Additionally, these medications could influence AGEs and the incretin pathway indirectly by enhancing glycemic control. In contrast, sulfonylureas have not demonstrated any obvious effects on AGEs or the incretin pathway. Considering their favorable effects on AGEs and the incretin pathway, a suitable selection of antidiabetic drugs may facilitate more protective effects on the bone in diabetic patients.

Bone health is a critical aspect of overall well-being, and disorders such as osteoporosis pose significant challenges worldwide. East Asian Herbal Medicine (EAHM), with its rich history and holistic approach, offers promising avenues for enhancing bone regeneration. In this critical review article, we analyze the intricate mechanisms through which EAHM compounds modulate bone health. We explore the interplay between osteogenesis and osteoclastogenesis, dissect signaling pathways crucial for bone remodeling and highlight EAHM anti-inflammatory effects within the bone microenvironment. Additionally, we emphasize the promotion of osteoblast viability and regulation of bone turnover markers by EAHM compounds. Epigenetic modifications emerge as a fascinating frontier where EAHM influences DNA methylation and histone modifications to orchestrate bone regeneration. Furthermore, we highlight EAHM effects on osteocytes, mesenchymal stem cells and immune cells, unraveling the holistic impact in bone tissue. Finally, we discuss future directions, including personalized medicine, combinatorial approaches with modern therapies and the integration of EAHM into evidence-based practice.

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [-0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: -0.23, 95% CI [-0.39, -0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies' number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

Osteoporosis is a common diabetic consequence that negatively affects patients' health and quality of life. Nevertheless, there is mutual interference between clinical drugs intended to regulate blood glucose and bone metabolism. Therefore, it is crucial to look for new treatment targets that effectively control blood glucose and safely protect the bone health of patients with diabetes. In this study, mice given a high-fat diet were shown to be resistant to osteoporosis and diabetes when protein phosphatase 5 (PP5) knockout (KO) mice were used. Serum markers of bone remodeling show that PP5 KO mice are resistant to decreased bone formation and increased bone resorption brought on by diabetes. The absence of PP5 resists the reduction of osteoblast differentiation and the enhancement of osteoclast differentiation in diabetic mice, according to the in vitro osteoblast differentiation of bone mesenchymal stem cells and osteoclast differentiation of bone marrow-derived macrophages. Subsequent investigation revealed that PP5 deficiency increases the expression of the key regulator of osteoblast differentiation, runt-related transcription factor 2, and decreases the activity of the receptor activator of the nuclear factor-κB ligand/osteoprotegerin pathway, a crucial regulatory signaling pathway for osteoclast differentiation. In conclusion, we discovered that PP5 deficiency protects diabetic mice against osteoporosis for the first time.

This study aimed to investigate the effect of collagen cross-link deficiency on collagen fiber formation around an implant and its effect on the osseointegration process.

Wistar rats were fed 0.1% beta-aminopropionitrile (BAPN) dissolved in water to induce collagen cross-link deficiency. Custom-made mini-implants with machined surfaces were placed proximal to the tibia. At 1, 2, and 4 weeks postoperatively, the bone area around the implant, bone-implant contact ratio, osteoclast/osteocyte activity, and osseointegration strength were evaluated using histological and immunohistochemical analyses and biomechanical tests.

Long-term disturbance of collagen cross-link formation in the BAPN group resulted in faster collagen fiber maturation than that in controls, with a defective collagen structure, low bone formation quantity, and low bone-implant contact values. Deficiency of collagen cross-links resulted in increased bone resorption and decreased osteocyte activity.

Collagen cross-linking is important for the formation of the collagen matrix, and their deficiency may impair bone activity around implants, affecting the osseointegration process.

Copper is an essential trace element for the human body. Abnormalities in copper metabolism can lead to bone defects, mainly by directly affecting the viability of osteoblasts and osteoclasts and their bone remodeling function, or indirectly regulating bone metabolism by influencing enzyme activities as cofactors. Copper ions released from biological materials can affect osteoblasts and osteoclasts, either directly or indirectly by modulating the inflammatory response, oxidative stress, and rapamycin signaling. This review presents an overview of recent progress in the impact of copper on bone metabolism. Translational potential of this article: The impact of copper on bone metabolism can provide insights into clinical application of copper-containing supplements and biomaterials.

The liver is a vital organ involved in nutrient metabolism, hormone regulation, immunity, cytokine production, and gut homeostasis. Impairment in liver function can result in malnutrition, chronic inflammation, decreased anabolic hormone levels, and dysbiosis. These conditions eventually cause an imbalance in osteoblast and osteoclast activities, resulting in bone loss. Osteoporosis is a frequent complication of chronic liver disease (CLD) that adversely affects quality of life and increases early mortality. Sarcopenia is another common complication of CLD characterized by progressive loss of skeletal muscle mass and function. Assessment criteria for sarcopenia specific to liver disease have been established, and sarcopenia has been reported to be associated with an increase in the risk of liver disease-related events and mortality in patients with CLD. Owing to their similar risk factors and underlying pathophysiological mechanisms, osteoporosis and sarcopenia often coexist (termed osteosarcopenia), progress in parallel, and further exacerbate the conditions mentioned above. Therefore, comprehensive management of these musculoskeletal disorders is imperative. This review summarizes the clinical implications and characteristics of osteoporosis, extending to sarcopenia and osteosarcopenia, in patients with CLD caused by different etiologies.

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.