BACKGROUND: Both bone fragility and poor cognitive functions are known to contribute to fracture occurrence, but it remains unclear whether their contribution is independent of each other and which cognitive dysfunctions are most involved. This study aimed to clarify the involvement of various cognitive abilities in fall-related fractures among community-dwelling fallers aged 55 and over, and to determine whether poor cognitive abilities is a risk factor independent of bone fragility.
METHODS: In a cross-sectional study, we collected sociodemographic and medical data, including bone mineral density (BMD), and performed cognitive and mobility assessments in 189 individuals with a history of fall in the previous year.
RESULTS: Fallers with a fracture had poorer cognitive and mobility performance than non-injured fallers. Multivariate regressions revealed that cognition, BMD and other risk factors were independently associated with fracture among all participants (OR = 1.04, 95% CI = 1.01-1.08, p = 0.034 for completion time on part A of the Trail Making Test [TMT-A], and OR = 0.53, 95% CI = 0.33-0.84, p < 0.001 for BMD), particularly in women (OR = 0.77, 95% CI = 0.60-0.98, p = 0.039 for backward digit span score, and OR = 0.43, 95% CI = 0.25-0.75, p = 0.001 for BMD).
CONCLUSIONS: Thus, poor cognition, especially poor processing speed and working memory, is associated with an increased risk of fracture in fallers, particularly in women, regardless of BMD or other fracture risk factors. Hence, an in-depth cognitive evaluation should enhance the detection of fallers at risk of fracture, particularly in the absence of signs of osteoporosis, and thus ensure the best possible prevention.

BACKGROUND: Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility.
METHODS: A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA.
RESULTS: Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic β cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur.
CONCLUSIONS: LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic β-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture.
CONCLUSIONS: In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.

Bone marrow stromal cells (BMSCs) play a significant role in bone metabolism as they can differentiate into osteoblasts, bone marrow adipocytes (BMAds), and chondrocytes. BMSCs chronically exposed to nutrient overload undergo adipogenic programming, resulting in bone marrow adipose tissue (BMAT) formation. BMAT is a fat depot transcriptionally, metabolically, and morphologically distinct from peripheral adipose depots. Reactive oxygen species (ROS) are elevated in obesity and serve as important signals directing BMSC fate. ROS produced by the NADPH oxidase (NOX) family of enzymes, such as NOX4, may be responsible for driving BMSC adipogenesis at the expense of osteogenic differentiation. The dual nature of ROS as both cellular signaling mediators and contributors to oxidative stress complicates their effects on bone metabolism. This review discusses the complex interplay between ROS and BMSC differentiation in the context of metabolic bone diseases.Special attention is paid to the role of NOX4-ROS in regulating cellular processes within the bone marrow microenvironment and potential target in metabolic bone diseases.

UNASSIGNED: Improved bone health during adolescence can have lifelong implications, reducing the risk of bone fragility.
UNASSIGNED: This study aims to evaluate the effectiveness of an e-book in increasing knowledge about and promoting healthy practices related to bone health among Malay adolescents in Kuala Lumpur, Malaysia.
UNASSIGNED: A total of 72 adolescents (female: n=51, 71%; age: mean 15, SD 0.74 y) were recruited from selected secondary schools. The participants answered a pretest web-based questionnaire on sociodemographic data, knowledge about osteoporosis, and physical activity. A video call was conducted to assess dietary calcium intake. Participants were provided with a link to an e-book on bone health and instructed to read it within 2 weeks. Postintervention assessments included those for knowledge, physical activity, dietary calcium intake, and acceptance of the e-book.
UNASSIGNED: There was a significant increase in the median knowledge score, which was 40.6% (IQR 31.3%-46.9%) during the pretest and 71.9% (IQR 53.9%-81.3%) during the posttest (P<.001). However, no changes were observed in dietary calcium intake or physical activity levels. Most participants did not meet the recommended calcium requirements (61/62, 98%) and exhibited sedentary behavior (pretest: 51/62, 82%; posttest: 48/62, 77%). The e-book, however, was well accepted, with the majority reporting that they understood the contents (70/72, 97%), liked the graphics (71/72, 99%), and approved of the layout (60/72, 83%) and font size (66/72, 92%) used.
UNASSIGNED: The developed e-book effectively increases knowledge levels related to bone health and is well accepted among participants. However, this educational material did not improve bone health practices. Additional strategies are necessary to bridge the gap between knowledge and behavior change.

OBJECTIVE: Increasing ratio of bone fragility, and susceptibility to fractures constitutes a major health problem worldwide. Therefore, we aimed to identify new compounds with a potential to increase proliferation and differentiation of osteoblasts.
METHODS: Cellular and molecular assays, such as ALP activity, alizarin staining, and flow cytometry were employed to check the effect of TMF on osteogenesis. Moreover, gene expression analysis of certain important genes and transcriptional factors was also performed.
RESULTS: Our findings report for the first time that 7,3\',4\'-trimethoxyflavone is capable of enhancing proliferation, and differentiation in osteoblast cells. Results from flow cytometry analysis also indicated that TMF increases the number of cells in S-phase. Furthermore, treatment with TMF altered the expression of osteogenic genes, OCN and Axin-2 indicating possible activation of Wnt signaling pathway.
CONCLUSIONS: Taken together, this study identified that 7,3\',4\'-trimethoxyflavone has the potential to enhance osteoblast proliferation and differentiation, possibly due to the activation of Wnt/β-catenin pathway. Thus, demonstrating TMF as naturally occurring agent to promote osteogenesis and prevention of bone fragility, and related disorders.

This study investigates the biomechanics of type 2 diabetic bone fragility through a multiscale experimental strategy that considers structural, mechanical, and compositional components of ex vivo human trabecular and cortical bone. Human tissue samples were obtained from the femoral heads of patients undergoing total hip replacement. Mechanical testing was carried out on isolated trabecular cores using monotonic and cyclic compression loading and nanoindentation experiments, with bone microdamage analysed using micro-computed tomography (CT) imaging. Bone composition was evaluated using Raman spectroscopy, high-performance liquid chromatography, and fluorometric spectroscopy. It was found that human type 2 diabetic bone had altered mechanical, compositional, and morphological properties compared to non-type 2 diabetic bone. High-resolution micro-CT imaging showed that cores taken from the central trabecular region of the femoral head had higher bone mineral density (BMD), bone volume, trabecular thickness, and reduced trabecular separation. Type 2 diabetic bone also had enhanced macro-mechanical compressive properties under mechanical loading compared to non-diabetic controls, with significantly higher apparent modulus, yield stress, and pre-yield toughness evident, even when properties were normalised against the bone volume. Using nanoindentation, there were no significant differences in the tissue-level mechanical properties of cortical or trabecular bone in type 2 diabetic samples compared to controls. Through compositional analysis, higher levels of furosine were found in type 2 diabetic trabecular bone, and an increase in both furosine and carboxymethyl-lysine (an advanced glycation end-product) was found in cortical bone. Raman spectroscopy showed that type 2 diabetic bone had a higher mineral-to-matrix ratio, carbonate substitution, and reduced crystallinity compared to the controls. Together, this study shows that type 2 diabetes leads to distinct changes in both organic and mineral phases of the bone tissue matrix, but these changes did not coincide with any reduction in the micro- or macro-mechanical properties of the tissue under monotonic or cyclic loading.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic diseases in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search for differences in clinical characteristics. Methods: This is a single-center retrospective, case-controlled study. A total of 589 patients attending CTO Bone Unit between 2 January 2010 and 31 May 2023, due to osteoporosis and fragility fractures, were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 12.7%. Compared to patients without DM, the median age at the time of first fracture was similar: 72 years ± 13.5 interquartile range (IQR) vs. 71 years ± 12 IQR; prevalence of combination of vertebral and hip fractures was higher (p = 0.008), as well as prevalence of males (p = 0.016). Bone mineral density (BMD) at all sites was higher in DM group; trabecular bone score (TBS), instead, was significantly lower (p < 0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and, therefore, might be used as a diagnostic tool in clinical practice.

Musculoskeletal alterations in hepatocellular carcinoma (HCC) are less common than liver-related complications. However, they can significantly impact the quality of life and overall prognosis of patients with HCC. The main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asymptomatic and unapparent during routine clinical evaluations. This narrative literature review aimed to provide a comprehensive overview of the contemporary literature related to the changes in the musculoskeletal system in patients with HCC, focusing on its clinical implications and underlying etiopathogenetic mechanisms. Osteolytic bone metastases are the most common skeletal alterations associated with HCC, which could be associated with an increased risk of low-trauma bone fracture. Moreover, previous studies reported that osteopenia, sarcopenia, and myosteatosis are associated with poor clinical outcomes in patients with HCC. Even though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients, these complications are frequently overlooked in the clinical management of patients with HCC. Taken together, contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient prognosis. Further research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

Osteoid osteoma (OO) is a common, benign bone tumor. However, there are no case reports of OO associated with osteogenesis imperfecta (OI), or pathological fractures in OO. A 3-year-old girl with OI sustained a complete right tibial diaphyseal fracture. Bony fusion was completed after 4 months of conservative therapy; nevertheless, 18 months later spontaneous pain appeared at the fracture site, without any cause. Plain radiographs showed a newly apparent, rounded area of translucency 1 cm in diameter, just overlapping the previous fracture. Images obtained using three-dimensional time-resolved contrast-enhanced magnetic resonance angiography showed strong central enhancement in the early phase, with an apparent nidus, suggesting the diagnosis of OO. Nineteen months after the first fracture, while skipping, the patient refractured her tibial diaphysis at the site of the previous fracture. This is a very rare case of OO, apparently co-existing with OI and leading to a bony fracture. In our case, the combination of bone fragility in OI and a recent fracture at the site of the OO may have caused the re-fracture.

BACKGROUND: Osteoporosis in males is largely under-diagnosed and under-treated, with most of the diagnosis confirmed only after an osteoporotic fracture. Therefore, there is an urgent need for highly accurate and precise technologies capable of identifying osteoporosis earlier, thereby avoiding complications from fragility fractures.
OBJECTIVE: This study aimed to evaluate the diagnostic accuracy and precision of the non-ionizing technology Radiofrequency Echographic Multi Spectrometry (REMS) for the diagnosis of osteoporosis in a male population in comparison with conventional Dual-energy X-ray Absorptiometry (DXA).
METHODS: A cohort of 603 Caucasian males aged between 30 and 90 years were involved in the study. All the enrolled patients underwent lumbar and femoral scans with both DXA and REMS. The diagnostic agreement between REMS and DXA-measured BMD was expressed by Pearson correlation coefficient and Bland-Altman method. The accuracy of the diagnostic classification was evaluated by the assessment of sensitivity and specificity considering DXA as reference.
RESULTS: A significant correlation between REMS- and DXA-measured T-score values (r = 0.91, p < 0.0001) for lumbar spine and for femoral neck (r = 0.90, p < 0.0001) documented the substantial equivalence of the two measurement techniques. Bland-Altman outcomes showed that the average difference in T-score measurement is very close to zero (-0.06 ± 0.60 g/cm2 for lumbar spine and - 0.07 ± 0.44 g/cm2 for femoral neck) confirming the agreement between the two techniques. Furthermore, REMS resulted an effective technique to discriminate osteoporotic patients from the non-osteoporotic ones on both lumbar spine (sensitivity = 90.1%, specificity = 93.6%) and femoral neck (sensitivity = 90.9%, specificity = 94.6%). Precision yielded RMS-CV = 0.40% for spine and RMS-CV = 0.34% for femur.
CONCLUSIONS: REMS, is a reliable technology for the diagnosis of osteoporosis also in men. This evidence corroborates its high diagnostic performance already observed in previous studies involving female populations.