The influence of osteoporosis on mechanical complications in lumbar fusion surgery: a systematic review.

Background: Adults undergoing spine surgery often have underlying osteoporosis, which may be a risk factor for postoperative complications. Although these associations have been described, osteoporosis remains profoundly underdiagnosed and undertreated in the spine surgery population. A thorough, comprehensive systematic review summarizing the relationships between bone mineral density (BMD) and specific complications of lumbar fusion surgery could be a valuable resource for raising awareness and supporting clinical practice changes. Methods: PubMed, Embase, and Web of Science databases were searched for original clinical research articles reporting on BMD, or surrogate measure, as a predictor of complications in adults undergoing elective lumbar fusion for degenerative disease or deformity. Endpoints included cage subsidence, screw loosening, pseudarthrosis, vertebral fracture, junctional complications, and reoperation. Results: A total of 71 studies comprising 12,278 patients were included. Overall, considerable heterogeneity in study populations, methods of bone health assessment, and definition and evaluation of clinical endpoints precluded meta-analysis. Nevertheless, low BMD was associated with higher rates of implant failures like cage subsidence and screw loosening, which were often diagnosed with concomitant pseudarthrosis. Osteoporosis was also a significant risk factor for proximal junctional kyphosis, particularly due to fracture. Many studies found surgical site-specific BMD to best predict focal complications. Functional outcomes were inconsistently addressed. Conclusions: Our findings suggest osteoporosis is a significant risk factor for mechanical complications of lumbar fusion. These results emphasize the importance of preoperative osteoporosis screening, which allows for medical and surgical optimization of high-risk patients. This review also highlights current practical challenges facing bone health evaluation in patients undergoing elective surgery. Future prospective studies using standardized methods are necessary to strengthen existing evidence, identify optimal predictive thresholds, and establish specialty-specific practice guidelines. In the meantime, an awareness of the surgical implications of osteoporosis and utility of preoperative screening can provide for more informed, effective patient care.

Biportal endoscopic paraspinal decompression for epidural cement leakage removal: A technical note.

OBJECTIVE: We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy (UBE) for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression. METHODS: A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage. A transforaminal biportal endoscopic surgery was performed to remove the leaked cement, and the left L1 and bilateral L2 nerves were decompressed. RESULTS: The patient's postoperative clinical course was uneventful. CONCLUSIONS: A paraspinal approach that avoids a posterior approach reduces the need to remove stabilizing facet bone, is truly minimally invasive and does not involve an instrumented fusion, maybe a helpful addition in the minimally invasive spine surgeon's armamentarium.

Acod1-mediated inhibition of aerobic glycolysis suppresses osteoclast differentiation and attenuates bone erosion in arthritis.

OBJECTIVES: Metabolic changes are crucially involved in osteoclast development and may contribute to bone degradation in rheumatoid arthritis (RA). The enzyme aconitate decarboxylase 1 (Acod1) is known to link the cellular function of monocyte-derived macrophages to their metabolic status. As osteoclasts derive from the monocyte lineage, we hypothesised a role for Acod1 and its metabolite itaconate in osteoclast differentiation and arthritis-associated bone loss. METHODS: Itaconate levels were measured in human peripheral blood mononuclear cells (PBMCs) of patients with RA and healthy controls by mass spectrometry. Human and murine osteoclasts were treated with the itaconate derivative 4-octyl-itaconate (4-OI) in vitro. We examined the impact of Acod1-deficiency and 4-OI treatment on bone erosion in mice using K/BxN serum-induced arthritis and human TNF transgenic (hTNFtg) mice. SCENITH and extracellular flux analyses were used to evaluate the metabolic activity of osteoclasts and osteoclast progenitors. Acod1-dependent and itaconate-dependent changes in the osteoclast transcriptome were identified by RNA sequencing. CRISPR/Cas9 gene editing was used to investigate the role of hypoxia-inducible factor (Hif)-1α in Acod1-mediated regulation of osteoclast development. RESULTS: Itaconate levels in PBMCs from patients with RA were inversely correlated with disease activity. Acod1-deficient mice exhibited increased osteoclast numbers and bone erosion in experimental arthritis while 4-OI treatment alleviated inflammatory bone loss in vivo and inhibited human and murine osteoclast differentiation in vitro. Mechanistically, Acod1 suppressed osteoclast differentiation by inhibiting succinate dehydrogenase-dependent production of reactive oxygen species and Hif1α-mediated induction of aerobic glycolysis. CONCLUSION: Acod1 and itaconate are crucial regulators of osteoclast differentiation and bone loss in inflammatory arthritis.

Associations between new obesity indices and abnormal bone density in type 2 diabetes mellitus patients.

The clinical data analysis found that, compared with the traditional obesity index, the waist-weight ratio (WWR) has more advantages in predicting abnormal bone mineral density in subjects with type 2 diabetes. WWR may serve as a new predictive indicator for osteoporosis in T2DM patients. PURPOSE: This study was designed to explore the correlation between obesity-related indices and bone mineral density (BMD) and its influencing factors in type 2 diabetes mellitus (T2DM) patients. METHODS: A total of 528 patients with type 2 diabetes were recruited. Glucose tolerance, insulin stimulation, and blood biochemical tests were conducted on all participants. All subjects underwent dual-energy X-ray bone density testing and were grouped based on the bone density results. RESULTS: Compared with those in the normal BMD group, the waist-to-body weight ratio (WWR) and weight-adjusted-waist index (WWI) in the osteopenia and osteoporosis groups were significantly greater, while body mass index (BMI) was significantly lower (P < 0.05). The logistic regression results showed that the WWR, WWI, and BMI were independently correlated with abnormal BMD in T2DM patients (P < 0.05). WWR and the WWI were negatively correlated with the T-value of bone density in various parts of the body, while BMI was positively correlated with the T-value of bone density (P < 0.05). The area under the working characteristic curve (AUC) for T2DM patients with abnormal bone mass predicted by the WWR [0.806, 95% CI = (0.770-0.843), P < 0.001] was greater than that for patients with other obesity indicators, such as the WWI and BMI. CONCLUSION: We found a positive correlation between the WWR and bone density in T2DM patients. Compared with other obesity indicators, such as BMI and WWI, the WWR has a stronger discriminative ability for T2DM patients with abnormal bone density. Therefore, more attention should be given to the WWR in T2DM patients.

Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

Birth weight and birth length affect future fracture risk differently in men and women.

We wanted to determine if there are any associations between birth factors and adult fracture risk. For women only, shorter birth length was associated with lower relative fracture risk. For women and men, individuals who were long at birth as well as tall in adulthood had a substantially higher relative fracture risk. PURPOSE: We aimed to examine associations between birth anthropometry and adult fracture risk and to investigate if developmental mismatch is associated with fracture risk. METHODS: We included 4635 participants (476 women and 4159 men; born 1921-1950) with hospital and national registry-based data on birth anthropometry and adult fractures (≥ 50 years). We tested associations by Cox proportional hazards regressions and present hazard ratios (HR) with 95% confidence intervals. RESULTS: In total, 1215 (26%) suffered ≥ 1 fracture during a mean observation period of 26 years. In women, unadjusted analyses indicated that both higher birth weight (HR 1.42 per kg (1.10-1.84)) and birth length (1.10 per cm (1.05-1.17)) were associated to higher adult fracture risk. After adjustment (year of birth and gestational age), statistical significance remained only for birth length, HR 1.10 per cm (1.04-1.17). For men, no associations were apparent. We found no associations between developmental mismatch (lower birth weight followed by higher adult weight) and adult fracture risk. However, for both sexes, being born tall and staying tall into adulthood was associated with a markedly higher (55-105%) relative fracture risk (HR women 2.09 (1.18-3.68), men 1.55 (1.19-2.03)) compared to being born short and remaining short in adulthood. CONCLUSION: In this study, being born shorter and lighter was associated with a lower risk for fractures ≥ 50 years in women. However, analyses indicated that tall adults who were also long at birth may be at markedly higher risk of fractures; this warrants further examinations.

Assessing causality between obstructive sleep apnea with the dyslipidemia and osteoporosis: a Mendelian randomization study.

Purpose: This study aims to assess the causal relationship between Obstructive Sleep Apnea (OSA), dyslipidemia, and osteoporosis using Mendelian Randomization (MR) techniques. Methods: Utilizing a two-sample MR approach, the study examines the causal relationship between dyslipidemia and osteoporosis. Multivariable MR analyses were used to test the independence of the causal association of dyslipidemia with OSA. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on genome-wide significance, independence, and linkage disequilibrium criteria. The data were sourced from publicly available Genome-Wide Association Studies (GWAS) of OSA (n = 375,657) from the FinnGen Consortium, the Global Lipids Genetics Consortium of dyslipidemia (n = 188,577) and the UK Biobank for osteoporosis (n = 456,348). Results: The MR analysis identified a significant positive association between genetically predicted OSA and triglyceride levels (OR: 1.15, 95% CI: 1.04-1.26, p = 0.006) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (OR: 0.84, 95% CI: 0.77-0.93, p = 0.0003). Conversely, no causal relationship was found between dyslipidemia (total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol) and OSA or the relationship between OSA and osteoporosis. Conclusion: The study provides evidence of a causal relationship between OSA and dyslipidemia, highlighting the need for targeted prevention and management strategies for OSA to address lipid abnormalities. The absence of a causal link with osteoporosis and in the reverse direction emphasizes the need for further research in this area.

RNA-binding proteins in bone pathophysiology.

Bone remodelling is a highly regulated process that maintains mineral homeostasis and preserves bone integrity. During this process, intricate communication among all bone cells is required. Indeed, adapt to changing functional situations in the bone, the resorption activity of osteoclasts is tightly balanced with the bone formation activity of osteoblasts. Recent studies have reported that RNA Binding Proteins (RBPs) are involved in bone cell activity regulation. RBPs are critical effectors of gene expression and essential regulators of cell fate decision, due to their ability to bind and regulate the activity of cellular RNAs. Thus, a better understanding of these regulation mechanisms at molecular and cellular levels could generate new knowledge on the pathophysiologic conditions of bone. In this Review, we provide an overview of the basic properties and functions of selected RBPs, focusing on their physiological and pathological roles in the bone.

Integrated analysis of genes shared between type 2 diabetes mellitus and osteoporosis.

Background: The relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OP) has been widely recognized in recent years, but the mechanism of interaction remains unknown. The aim of this study was to investigate the genetic features and signaling pathways that are shared between T2DM and OP. Methods: We analyzed the GSE76894 and GSE76895 datasets for T2DM and GSE56815 and GSE7429 for OP from the Gene Expression Omnibus (GEO) database to identify shared genes in T2DM and OP, and we constructed coexpression networks based on weighted gene coexpression network analysis (WGCNA). Shared genes were then further analyzed for functional pathway enrichment. We selected the best common biomarkers using the least absolute shrinkage and selection operator (LASSO) algorithm and validated the common biomarkers, followed by RT-PCR, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA) to validate the expression of these hub genes in T2DM and OP mouse models and patients. Results: We found 8,506 and 2,030 DEGs in T2DM and OP, respectively. Four modules were identified as significant for T2DM and OP using WGCNA. A total of 19 genes overlapped with the strongest positive and negative modules of T2DM and OP. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed these genes may be involved in pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin system signaling pathway. The LASSO algorithm calculates the six optimal common biomarkers. RT-PCR results show that LTB, TPBG, and VNN1 were upregulated in T2DM and OP. Immunofluorescence and Western blot show that VNN1 is upregulated in the pancreas and bones of T2DM model mice and osteoporosis model mice. Similarly, the level of VNN1 in the sera of patients with T2DM, OP, and T2DM and OP was higher than that in the healthy group. Conclusion: Based on the WGCNA and LASSO algorithms, we identified genes and pathways that were shared between T2DM and OP. Both pantothenate and CoA biosynthesis and the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate and renin-angiotensin systems may be associated with the pathogenesis of T2DM and OP. Moreover, VNN1 may be a potential diagnostic marker for patients with T2DM complicated by OP. This study provides a new perspective for the systematic study of possible mechanisms of combined OP and T2DM.

Osteoporosis and Alzheimer´s disease (or Alzheimer´s disease and Osteoporosis).

Alzheimer's disease (AD) and osteoporosis are two diseases that mainly affect elderly people, with increases in the occurrence of cases due to a longer life expectancy. Several epidemiological studies have shown a reciprocal association between both diseases, finding an increase in incidence of osteoporosis in patients with AD, and a higher burden of AD in osteoporotic patients. This epidemiological relationship has motivated the search for molecules, genes, signaling pathways and mechanisms that are related to both pathologies. The mechanisms found in these studies can serve to improve treatments and establish better patient care protocols.

Assessment of the Admission and Follow-up Characteristics of Children Diagnosed with Secondary Osteoporosis.

Objective: Secondary osteoporosis is a condition when the underlying disease or its treatment causes the bone mass to decrease and the bone structure to deteriorate, increasing the risk of fracture. The importance of diagnosis and treatment during childhood and adolescence is due to its long-term negative effects. In this study, our objectives were to determine the diagnostic findings, treatment efficacy, and follow-up characteristics of childhood with secondary osteoporosis. Methods: 61 patients diagnosed with secondary osteoporosis between January 2000 and January 2021 were included in the study. The research is a cross-sectional and descriptive study. Study participants had to be under 18 years of age when the primary underlying disease was diagnosed and received treatment for secondary osteoporosis. Patient data were collected from patient files. Patient data were obtained from patient files in hospitals and were interpreted through the IBM SPSS Statistics for Windows version 20.0 (IBM Corp, Armonk, NY, USA). Results: 61 patients (28 women/33 men) were evaluated. The most common underlying primary diseases in patients with secondary osteoporosis were inflammatory diseases (57.7%), neuromuscular diseases (26.2%), immunodeficiency (13.1%), acute lymphoblastic leukemia (8.2%), metabolic diseases (8.2%), and solid organ transplantation. (8.2%), bone marrow transplantation (6.6%) and epilepsy (6.6%). The average chronological age when secondary osteoporosis was diagnosed was 11.89±4.88 years. They were evaluated for osteoporosis 6.39±5.13 years after the onset of the underlying primary chronic diseases. 78.7% of the patients had one or more chronic drug use. Systemic steroid use was 59%, chemotherapeutics 23%, immunomodulatory drugs 19.7%, antiepileptic drugs 8.2%, inhaled steroids 4.9%, IVIG 1.6%, and antituberculosis drugs 1.6%. Additionally, 1.6% of the patients were using testosterone as replacement, 3.3% L-Thyroxine, 1.6% estrogen, and 1.6% growth hormone. Bone pain was detected in 49.2% of the patients. All patients had vertebral fractures before treatment. Bisphosphonate treatment was given to 45 patients with secondary osteoporosis. There was a statistically significant increase in mean bone mineral density (BMD) and bone mineral content values six months after treatment, (p<0.001). There was a significant increase in BMD Z-score values for chronological and height age (p<0.001). The patients' BMD values increased on average by 31.15% with treatment. Following bisphosphonate treatment, there was a significant reduction in both fracture number and bone pain in patients (p<0.01). When patients who received and did not receive steroid treatment were compared, both groups received similar benefits from bisphosphonate treatment. Conclusion: Secondary osteoporosis is a condition that is influenced by many factors, such as the primary disease causing osteoporosis, chronic medication use, especially steroids. If left untreated, osteoporosis leads to important diseases such as bone pain, bone fractures, immobilization, and reduced linear growth of bone. When used to treat childhood secondary osteoporosis, Bisphosphonates significantly improve BMD and reduce fracture risk.

Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures. PURPOSE: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. METHODS: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. RESULTS: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). CONCLUSION: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

Prevalence and associated factors of low bone mineral density in people living with HIV: a cross-sectional study.

This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE: HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS: We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS: A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION: The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.

Does total hip arthroplasty in elderly patients with femoral neck fractures reduce complications?: A Japanese DPC study.

BACKGROUND: The global increase in femoral neck fractures due to aging and osteoporosis is a major clinical challenge. The debate on the optimal surgical intervention for femoral neck fractures remains unresolved. This large-scale study explores femoral neck fractures among the elderly, focusing on the comparative outcomes of Total Hip Arthroplasty (THA) versus Bipolar Hemiarthroplasty (BHA) in Japanese patients. METHODS: Using the Japanese National Administrative Diagnosis Procedure Combination (DPC) database, we studied cases of femoral neck fracture from April 2016 to March 2023, and after propensity score matching by age, sex, and comorbidities, we examined the association between THA, complications, and clinical outcomes, and the usefulness of THA for elderly patients with femoral neck fracture. RESULTS: One-to-one propensity score matching identified 7741 pairs of THA and BHA cases. There was no difference in length of stay between the THA and BHA groups. Significantly more blood transfusions were required in the THA group. There was no significant difference in mortality between the THA and BHA groups, but there was a reduced risk of pneumonia in the THA group, with a ratio of 0.547 (95% CI: 0.418-0.715). On the other hand, the THA group had a higher risk of pulmonary embolism, with a ratio of 1.607 (95% CI: 1.379-1.874). The THA group shows improved discharge rates directly home from the facility where the operation was performed, with a ratio of 1.798 (95% CI: 1.675-1.929). CONCLUSION: The findings of this research indicate that THA is more effective than BHA in enabling elderly Japanese patients with femoral neck fractures to be discharged directly home and in preventing pneumonia, despite concerns about pulmonary embolism. These findings suggest that THA may improve functional prognosis in elderly patients with femoral neck fractures, although there is a trade-off with an increased risk of pulmonary embolism.

Role of oxidative stress in the concurrent development of osteoporosis and tendinopathy: Emerging challenges and prospects for treatment modalities.

Both osteoporosis and tendinopathy are widely prevalent disorders, encountered in diverse medical contexts. Whilst each condition has distinct pathophysiological characteristics, they share several risk factors and underlying causes. Notably, oxidative stress emerges as a crucial intersecting factor, playing a pivotal role in the onset and progression of both diseases. This imbalance arises from a dysregulation in generating and neutralising reactive oxygen species (ROS), leading to an abnormal oxidative environment. Elevated levels of ROS can induce multiple cellular disruptions, such as cytotoxicity, apoptosis activation and reduced cell function, contributing to tissue deterioration and weakening the structural integrity of bones and tendons. Antioxidants are substances that can prevent or slow down the oxidation process, including Vitamin C, melatonin, resveratrol, anthocyanins and so on, demonstrating potential in treating these overlapping disorders. This comprehensive review aims to elucidate the complex role of oxidative stress within the interlinked pathways of these comorbid conditions. By integrating contemporary research and empirical findings, our objective is to outline new conceptual models and innovative treatment strategies for effectively managing these prevalent diseases. This review underscores the importance of further in-depth research to validate the efficacy of antioxidants and traditional Chinese medicine in treatment plans, as well as to explore targeted interventions focused on oxidative stress as promising areas for future medical advancements.

XAF1 promotes osteoclast apoptosis by antagonizing the XIAP-caspase axis.

Background: Over-activated osteoclast (OC) is a major cause of diseases related to bone loss and bone metabolism. Both bone resorption inhibition and apoptosis induction of osteoclast are crucial in treating these diseases. X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) is an important interferon-stimulated and apoptotic gene. However, how XAF1 regulates bone formation and remodeling is unknown. Methods: We generate global and chimeric Xaf1 knockout mouse models and utilize these models to explore the function and mechanism of XAF1 in regulating bone formation and remodeling in vivo and in vitro. Results: We show that XAF1 depletion enhances osteoclast generation in vitro. XAF1 knockout increases osteoclast number and bone resorption, thereby exacerbating bone loss in both OVX and osteolysis models. Activation of XAF1 with BV6 (a potent XIAP inhibitor) suppresses osteoclast formation. Mechanistically, XAF1 deletion decreases osteoclast apoptosis by facilitating the interaction between XIAP and caspase-3/7. Conclusions: Our data illustrates an essential role of XAF1 in controlling osteoclastogenesis in both osteoporosis and osteolysis mouse models and highlights its underlying mechanism, indicating a potential role in clinical treatment.The translational potential of this article: The translation potential of this article is that we first indicated that osteoclast apoptosis induced by XAF1 contribute to the progression of osteoporosis and osteolysis, which provides a novel strategy in the prevention of osteoporosis and osteolysis.

Prevalence and risk factors for atypical femoral fracture among Lebanese patients with hip and shaft fractures.

This retrospective study investigates the prevalence of atypical femoral fractures (AFFs) among patients admitted with hip and shaft fractures at a tertiary referral center in Beirut, Lebanon. We analyzed electronic medical records and radiology studies of patients aged above 40 admitted with hip and shaft fractures between January 2006 and December 2019. Fractures were confirmed by ICD9 or ICD10 codes. All cases were reviewed by radiologists, and AFFs were identified according to the 2013 revised ASBMR criteria. We identified 1366 hip and shaft fracture patients, of which 14 female patients had 19 AFFs. This represents a prevalence of 1.0% among all hip and shaft fractures patients and 1.7% among all female hip and shaft fracture patients. Bilateral AFFs were found in 5 of the 14 patients. Patients with AFF tended to be younger, with a mean age of 74.3 (±8.6) yr compared to 78.0 (±10.6) for patients with non-AFF fractures. A total of 36% of AFF patients had a prior history of non-traumatic fracture at first admission. A high percentage of patients with AFFs reported intake of proton pump inhibitors (42.9%) and glucocorticoids (21.4%). Bisphosphonate exposure was noted in 64.3% of AFF patients. None of the AFF patients were active smokers or consumed alcohol regularly. BMD assessments were available for 7 AFF patients, indicating osteoporosis in 4 and osteopenia in 3 cases. Hip axis length measurements showed no significant difference between AFF patients (N = 7) and sex and age-matched controls (N = 21). The study underlines the prevalence and characteristics of AFFs in Lebanon, which is consistent with the numbers reported in the literature (0.32%-5%). A larger prospective study that includes hospitals across the nation is needed to gain a more comprehensive view of the prevalence of AFFs in the Lebanese population.

Correlation between bone mineral density and type 2 diabetes mellitus in elderly men and postmenopausal women.

The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1-4 (L1-L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P < 0.05), and the probability of major osteoporotic fracture in the next 10 years (PMOF) was significantly higher than that in T2DM group (P < 0.001). However, with the prolongation of the course of T2DM, the BMD significantly decreased, while fracture risk and the prevalence of osteoporosis significantly increased (P < 0.05). We also found that the BMD of L1-4, LFN and LHJ were negatively correlated with homeostatic model assessment-insulin resistance (HOMA-IR) (P = 0.028, P = 0.01 and P = 0.047, respectively). The results also showed that the BMD of LHJ was positively correlated with indirect bilirubin (IBIL) (P = 0.018). Although the BMD was lower in the non-T2DM group than in the T2DM group, the prolongation of the course of T2DM associated with the lower BMD. And the higher prevalence of osteoporosis and fracture risk significantly associated with the prolongation of the course of T2DM. In addition, BMD was significantly associated with insulin resistance (IR) and bilirubin levels in T2DM patients.Registration number: China Clinical Trials Registry: MR-51-23-051741; https://www.medicalresearch.org.cn/search/research/researchView?id=c0e5f868-eca9-4c68-af58-d73460c34028 .

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway.

BACKGROUND: Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. METHODS: We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. RESULTS: Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. CONCLUSIONS: Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.