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Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach.

Osteoporosis is characterized by reduced bone mass due to imbalanced bone metabolism. Exosomes derived from bone mesenchymal stem cells (BMSCs) have been shown to play roles in various diseases. This study aimed to clarify the regulatory function and molecular mechanism of BMSCs-derived exosomes in osteogenic differentiation and their potential therapeutic effects on osteoporosis. Exosomes were extracted from BMSCs. Bone marrow-derived macrophages (BMDMs) were cultured and internalized with BMSCs-derived exosomes. Real-time quantitative PCR was used to detect the expression of macrophage surface markers and tripartite motif (TRIM) family genes. BMDMs were co-cultured with human osteoblasts to assess osteogenic differentiation. Western blot was performed to analyze the ubiquitination of triggering receptor expressed on myeloid cell 1 (TREM1) mediated by TRIM25. An ovariectomized mice model was established to evaluate the role of TRIM25 and exosomes in osteoporosis. Exosomes were successfully isolated from BMSCs. BMSCs-derived exosomes upregulated TRIM25 expression, promoting M2 macrophage polarization and osteogenic differentiation. TRIM25 facilitated the ubiquitination and degradation of TREM1. Overexpression of TREM1 reversed the enhanced M2 macrophage polarization and osteogenic differentiation caused by TRIM25 overexpression. TRIM25 enhanced the protective effect of BMSCs-derived exosomes against bone loss in mice. These findings suggested that BMSCs-derived exosomes promoted osteogenic differentiation by regulating M2 macrophage polarization through TRIM25-mediated ubiquitination and degradation of TREM1. This mechanism might provide a novel approach for treating osteoporosis., Competing Interests: Declarations Ethics approval and consent to participate The study was approved by the Ethics Committee of Capital Medical University Affiliated Beijing Jishuitan Hospital. All experiments were performed in accordance with the ARRIVE guidelines. Consent for publication Not applicable. Competing interests The authors confirm that no competing interests exist in this work., (© 2024. The Author(s).)

Employing a two-sample Mendelian randomization (MR) analysis, we aimed to investigate the potential causal effect of Parkinson disease (PD) on osteoporosis. We conducted an in-depth MR analysis by leveraging extensive genome-wide association study datasets from the International Parkinson Disease Genomics Consortium and the Genetic Factors for Osteoporosis Consortium. We meticulously selected instrumental variables based on strict criteria, including significance thresholds, linkage disequilibrium, and the exclusion of confounding single-nucleotide polymorphisms. Our investigation utilized diverse MR methods, including inverse variance weighted, MR Egger regression, weighted median, and MR-PRESSO, to robustly evaluate the causal relationship. Our comprehensive analysis revealed noteworthy associations between PD and distinct measures of bone mineral density (BMD) (forearm BMD, femoral neck BMD, lumbar spine BMD). Specifically, the inverse variance weighted method underscored potential significant relationships between PD and forearm BMD (P = .037; odds ratio [OR], 1.04; 95% confidence interval [CI], 1.00-1.09), femoral neck BMD (P = .034; OR, 1.02; 95% CI, 1.00-1.05), and lumbar spine BMD (P = .043; OR, 1.03; 95% CI, 1.00-1.06). The consistency of results across various methods and sensitivity analyses indicated both robustness and minimal pleiotropy concerns. Through a two-sample MR approach, this study establishes a plausible causal relationship between PD and decreased BMD. The outcomes underscore the urgency of targeted interventions to mitigate bone loss and manage osteoporosis in individuals with PD., Competing Interests: The authors have no conflicts of interests to disclose, (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by the synovitis and bone erosion. The combination therapy of glucocorticoids (GCs) and methotrexate (MTX) is recommended in early RA management, although the precise underlying mechanism of action remains unclear. This study is aimed to clarify the mechanism of MTX in combined with GC in treating RA., Methods: GC-induced osteoporosis (GIOP) mouse model was used to investigate the bone-protective role of MTX. Lipopolysaccharide-induced arthritis mouse model was used to evaluate the anti-inflammatory effects of GCs and MTX. Functional role of MTX on osteoclastogenesis was assessed by trap staining and micro-computer tomography. Western blot, RT-qPCR and coimmunoprecipitation were used to explore the underlying mechanisms., Results: We demonstrate that GCs, but not MTX, rapidly inhibited synovitis in arthritis model. MTX treatment was observed to inhibit osteoclastogenesis induced by GC in vitro and mitigate bone loss attributed by GIOP. GCs were found to augment the interaction between the membrane GC receptor (mGR) and signal transducer and activator of transcription 1 (STAT1), leading to the suppression of IFN-γR/STAT1 signalling pathways. Interestingly, MTX was found to inhibit osteoclastogenesis induced by GCs through the enhancement of the A2AR and IFN-γR interaction, thereby activating the IFN-γR/STAT1 signalling cascade. Consequently, this process results in a reduction in the mGR and STAT1 interaction., Conclusions: Our study provides compelling evidence that MTX can make GCs effectively to suppress synovitis and reduce bone loss induced by GCs. This sheds light on the potential mechanistic insights underlying the efficacy of GCs in conjunction with MTX for treating RA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Pulsatilla koreana Nakai ( P. koreana ) is a perennial herb traditionally used to treat malaria and fever. Although the pharmacological properties of P. koreana have been explored in various contexts, its effects on bone diseases, such as osteoporosis, remain poorly studied. In this study, we investigated the effects of water extracts of P. koreana (WEPK) on osteoclasts, which play a crucial role in bone remodeling, and an ovariectomized (OVX) mouse model, which mimics osteoporosis. Phytochemical profiling of WEPK revealed several compounds that regulate bone or fat metabolism. WEPK suppressed osteoclast differentiation by downregulating the expression of receptor activator of nuclear factor-κB ligand (RANKL), a cytokine that induces osteoclastogenesis. Additionally, WEPK directly inhibited RANKL-induced differentiation of osteoclast precursors by downregulating nuclear factor of activated T cells 1 (NFATc1), the master transcription factor for osteoclastogenesis, by modulating its upstream regulators. In vivo, oral administration of WEPK suppressed bone loss, reduced weight gain, and mitigated fat accumulation in the liver and gonadal tissues of OVX mice. Given its positive impact on bone and fat accumulation under estrogen deficiency, WEPK may serve as a promising alternative therapy for postmenopausal osteoporosis, especially when accompanied by other metabolic disorders, such as obesity and fatty liver.

Background: Anorexia Nervosa is a highly lethal illness that is also associated with many medical complications. Food restriction and weight loss define this illness. Most of its physical complications are reversible with weight restoration, with the notable exception of the loss of bone density, which is commonly present in anorexia nervosa., Methods: A comprehensive scientific literature review was performed in order to explore bone disease in anorexia nervosa., Results: The pathophysiology of the loss of bone mineral density in anorexia nervosa was elucidated, along with the diagnosis and treatment of osteoporosis in patients with anorexia nervosa, including the nutritional approach to weight restoration., Conclusions: Loss of bone mineral density in anorexia nervosa is very aggressive. Nutritional rehabilitation is a cornerstone to treating this, along with medicinal considerations.

Chronic kidney disease (CKD) is a significant global health issue and often involves CKD-mineral and bone disorder (MBD) and sarcopenia. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. PAI-1 has been implicated in the pathogenesis of osteoporosis and muscle wasting induced by inflammatory conditions. However, the roles of PAI-1 in CKD-MBD and sarcopenia remain unknown. Therefore, the present study investigated the roles of PAI-1 in bone loss and muscle wasting induced by adenine in PAI-1-deficient mice. CKD was induced in PAI-1+/+ and PAI-1-/- mice by administration of adenine for ten weeks. Muscle wasting was assessed by grip strength test, quantitative computed tomography (CT) analysis and muscle weight measurement. Osteoporosis was assessed by micro-CT analysis of femoral microstructural parameters. PAI-1 deficiency did not affect adenine-induced decreases in body weight and food intake or renal dysfunction in male or female mice. PAI-1 deficiency also did not affect adenine-induced decreases in grip strength, muscle mass in the lower limbs, or the tissue weights of the gastrocnemius, soleus, and tibialis anterior muscles in male or female mice. PAI-1 deficiency aggravated trabecular bone loss in CKD-induced male mice, but significantly increased trabecular bone in CKD-induced female mice. On the other hand, PAI-1 deficiency did not affect cortical bone loss in CKD-induced mice. In conclusion, PAI-1 is not critical for the pathophysiology of CKD-MBD or CKD-induced sarcopenia in mice. However, PAI-1 may be partly related to bone metabolism in trabecular bone in the CKD state with sex differences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mizukami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Extensive observational data suggest a link between celiac disease (CeD) and osteoporosis, but the causality and mediating mechanism remain undetermined. Herein, we performed a Mendelian randomization (MR) study to address these concerns., Methods: We obtained the summary-level statistics for CeD from a large genome-wide association study (GWAS) comprising 4,533 cases and 10,750 controls of European ancestry. The GWAS data for osteoporosis-related traits and inflammatory cytokines were derived from the UK Biobank, FinnGen, IEU OpenGWAS database, or GWAS catalog. Two-sample MR with the inverse variance-weighted methods were employed to evaluate the genetic association between CeD and osteoporosis-related traits. The potential inflammatory mediators from CeD to osteoporosis were explored using two-step mediation analyses., Results: The primary MR analyses demonstrated causal associations between genetically predicted CeD and osteoporosis (odds ratio [OR]: 1.110, 95% confidence interval [CI]: 1.043-1.182, p =0.001), total body bone mineral density (β: -0.025, p =0.039), and osteoporotic fracture (OR: 1.124, 95% CI: 1.009-1.253, p =0.034). Extensive sensitivity analyses consolidated these findings. Among the candidate inflammatory cytokines, only interleukin-18 was observed to mediate the effects of CeD on osteoporosis, with an indirect OR of 1.020 (95% CI: 1.000-1.040, p =0.048) and a mediation proportion of 18.9%. The mediation effects of interleukin-18 could be validated in other datasets (OR: 1.015, 95% CI: 1.001-1.029, p =0.041). Bayesian colocalization analysis supported the role of interleukin-18 in osteoporosis., Conclusion: The present MR study reveals that CeD is associated with an increased risk of developing osteoporosis, which may be partly mediated by upregulation of interleukin-18., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xiang, Zheng, Luo and Yang.)

Angiogenesis-osteogenesis coupling is critical for proper functioning and maintaining the health of bones. Any disruption in this coupling, associated with aging and disease, might lead to loss of bone mass. Osteoporosis (OP) is a debilitating bone metabolic disorder that affects the microarchitecture of bones, gradually leading to fracture. Computational analysis revealed that normal angiogenesis is disrupted during the progression of OP, especially postmenopausal osteoporosis (PMOP). The genes associated with OP and PMOP were retrieved from the DisGeNET database. Hub gene analysis and molecular pathway enrichment were performed via the Cytoscape plugins STRING, MCODE, CytoHubba, ClueGO and the web-based tool Enrichr. Twenty-eight (28) hub genes were identified, eight of which were transcription factors (HIF1A, JUN, TP53, ESR1, MYC, PPARG, RUNX2 and SOX9). Analysis of SNPs associated with hub genes via the gnomAD, I-Mutant2.0, MUpro, ConSurf and COACH servers revealed the substitution F201L in IL6 as the most deleterious. The IL6 protein was modeled in the SWISS-MODEL server and the substitution was analyzed via the YASARA FoldX plugin. A positive ΔΔG (1.936) of the F201L mutant indicates that the mutated structure is less stable than the wild-type structure is. Thirteen hub genes, including IL6 and the enriched molecular pathways were found to be profoundly involved in angiogenesis/endothelial function and immune signaling. Mechanical loading of bones through weight-bearing exercises can activate osteoblasts via mechanotransduction leading to increased bone formation. The present study suggests proper mechanical loading of bone as a preventive strategy for PMOP, by which angiogenesis and the immune status of the bone can be maintained. This in silico analysis could be used to understand the molecular etiology of OP and to develop novel therapeutic approaches., (© 2024. The Author(s).)

Objective: To investigate the prevalence of low bone mineral density (BMD) along with its possible risk factors in male Han Chinese patients with alcohol dependence (AD)., Methods: This retrospective, cross-sectional study included male patients with AD, classified into normal and low BMD groups according to bone densitometry T scores. Demographic and alcohol-related data, and routine laboratory parameters were compared between the two groups. Binary logistic regression analysis was employed to evaluate risk factors associated with low BMD, and correlations between the T-score and demographic, alcohol-related, and routine laboratory data were evaluated., Results: Among a total of 107 patients with AD included in the study, the prevalence of low BMD was 70.09% (75/107). Patients with low BMD were older, consumed more alcohol daily, and had higher lactate dehydrogenase (LDH) and lower Ca 2+ levels than patients with normal BMD. Regression analysis revealed that increased daily alcohol intake, low serum Ca 2+ levels, high serum LDH levels, and comorbid hypertension was related to low BMD in patients with AD. Further correlation analysis revealed a positive association between T-score and serum Ca 2+ levels., Conclusion: Increased daily alcohol intake, low serum Ca 2+ levels, high serum LDH levels, and comorbid hypertension may be risk factors for low BMD., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Background: The aim of this systematic review and meta-analysis was to analyze the factors associated of osteoporosis in patients with rheumatoid arthritis (RA) in China., Methods: PubMed, Embase, Web of Science, Cochrane Library, CINAHL, and four Chinese electronic databases were searched for observational studies without language restrictions that reported the factors associated of osteoporosis from inception to February 2023. A modified Newcastle-Ottawa Scale evaluated the risk of bias. Statistical heterogeneity among the included studies was analyzed using Cochran Q and I2 tests. Begg and Egger tests were used to assess the publication bias., Results: A total of 15 studies were finally included. The meta-analysis showed that 10 factors were grouped into three themes with statistical significance: (1) demographics theme: age ≥50 (odds ratio [OR] = 1.161; 95% CI, 1.111-1.231; p < 0.001), low body mass index (BMI) (OR = 1.248; 95% CI, 1.192-1.312; p < 0.001), female (OR = 5.174; 95% CI, 3.058-7.290; p < 0.001), and menopause (OR = 4.917; 95% CI, 1.558-15.523; I2 = 0.0%; p = 0.007); (2) RA-related factor theme: disease duration (OR = 1.083; 95% CI, 1.038-1.127; p < 0.001), and glucocorticoids (OR = 2.740; 95% CI, 2.000-3.750; p < 0.001); (3) relevant physiological indicators or scores theme: low 25(OH)D 3 (OR = 1.009; 95% CI, 1.003-1.016; p < 0.001), erythrocyte sedimentation rate (ESR) (OR = 1.489; 95% CI, 1.041-2.130; p = 0.029), high Disease Activity Score in 28 joints (DAS28) score (OR = 2.5991; 95% CI, 1.094-6.138; p < 0.001); and β-isomerized C-terminal telopeptide (β-CTx) (OR = 1.009; 95% CI, 1.003-1.016; p = 0.005)., Conclusion: Osteoporosis in patients with RA is associated with various factors. Therefore, patients with RA should be monitored in a timely manner and targeted interventions should be taken. In addition, further longitudinal studies are needed to confirm the direct link between multiple factors and osteoporosis., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: Periprosthetic bone loss is a well-known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA., Methods: A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta-analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over., Results: Twenty-nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75)., Conclusion: Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

Sarcopenic obesity (SO) and osteoporosis (OP) are associated with aging and obesity. The pathogenesis of SO is complex, including glucolipid and skeletal muscle metabolic disorders caused by inflammation, insulin resistance, and other factors. Growing evidence links muscle damage to bone loss. Muscle-lipid metabolism disorders of SO disrupt the balance between bone formation and bone resorption, increasing the risk of OP. Conversely, bones also play a role in fat and muscle metabolism. In the context of aging and obesity, the comprehensive review focuses on the effects of mechanical stimulation, mesenchymal stem cells (MSCs), chronic inflammation, myokines, and adipokines on musculoskeletal, at the same time, the impact of osteokines on muscle-lipid metabolism were also analyzed. So far, exercise combined with diet therapy is the most effective strategy for increasing musculoskeletal mass. A holistic treatment of musculoskeletal diseases is still in the preliminary exploration stage. Therefore, this article aims to improve the understanding of musculoskeletal -fat interactions in SO and OP, explores targets that can provide holistic treatment for SO combined with OP, and discusses current limitations and challenges. We hope to provide relevant ideas for developing specific therapies and improving disease prognosis in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Individuals with spinal cord injury (SCI) experience a notable decrease in bone mass below the level of injury. While studies have primarily focused on the acute phase with a small cohort, this study aimed to provide comprehensive insights into bone loss patterns over time. A total of 427 individuals with SCI who underwent dual-energy X-ray absorptiometry (DXA) testing at the Korea National Rehabilitation Center (2010-2021) were included and analyzed by categorizing the DXA results into 1-year intervals based on postinjury duration. Demographic characteristics (age, sex, body mass index, and alcohol/smoking history) and SCI-related factors (etiology, severity, extent of injury, motor score, and Korean Spinal Cord Independence Measure 3rd edition) were collected and analyzed. Linear mixed models and Bonferroni post hoc tests were performed to assess temporal changes in bone mass and linear regression analysis to assess the associations between possible risk factors and bone loss. DXA results revealed that substantial annual bone loss occurred in the total hip site up to 3 years postinjury and in the femoral neck site up to 2 years postinjury. Old age, women, and low body mass index were significant risk factors for bone loss in the SCI population. Additionally, during the chronic phase, lower Korean Spinal Cord Independence Measure 3rd edition scores were associated with low bone mass. Significant annual bone loss in the hip region persists for up to 3 years postinjury in individuals with SCI. While prioritizing the risk factors for osteoporosis commonly used in the general population, applying the SCIM score in the chronic phase may provide additional information on bone loss risk., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Osteoporosis (OP) is characterized by decreased bone mineral density (BMD) and increased fracture risk, poses a significant global health burden. Recent research has shed light on the bidirectional relationship between gut microbiota (GM) and bone health, presenting a novel avenue for understanding OP pathogenesis and developing targeted therapeutic interventions. This review provides a comprehensive overview of the GM-bone axis, exploring the impact of GM on OP development and management. We elucidate established risk factors and pathogenesis of OP, delve into the diversity and functional changes of GM in OP. Furthermore, we examine experimental evidence and clinical observations linking alterations in GM composition or function with variations in BMD and fracture risk. Mechanistic insights into microbial mediators of bone health, such as microbial metabolites and products, are discussed. Therapeutic implications, including GM-targeted interventions and dietary strategies, are also explored. Finally, we identify future research directions and challenges in translating these findings into clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hao, Yan, Huang and Li.)

Introduction and Objective: The medical records were examined of 222 patients of the Osteoporosis Treatment Clinic at the Central Clinical Hospital of the Medical University of Łódź, Poland. The influence was analyzed of 27 clinical risk factors on the occurrence of low-energetic fractures in this population. The aim of the research was to find possible dependencies between different risk factors, and the actual fractures that were recorded in the database., Material and Methods: For each risk factor and for each category (e.g., patients with diabetes and patients without diabetes), the percentage was computed of patients who had incidents osteoporotic fractures, and the percentage of those without fractures. Student's t-test and Pearson's chi-squared test were used to find statistically significant risk factors., Results: Statistically significant risk factors were found: age, chronic kidney disease, T-scores of the femoral neck and T-score of the lumbar spine, serum phosphate levels, FRAX-BMD, FRAX-BMI, and the type of diet., Conclusions: Some observations concerning the influence of individual risk factors on the occurrence of fractures are consistent with those presented in the literature. However, it was also noticed that the patients with hyperthyroidism, rheumatic diseases, diabetes, cancer or gastrointestinal diseases, had a smaller percentage of fractures than the patients who did not have these diseases. This may be explained by the small number of those having these diseases, or by the fact that they had already received appropriate treatment.

A cross-sectional study was performed in healthy adults (mean age 28 y, 67% women) whose habitual diet was an omnivore, lacto-ovo vegetarian, or vegan diet. The total sample ( n = 297) was divided into two groups according to the parathormone (PTH) cut-off value of 65 pg/mL of either normal-PTH ( n = 228) or high-PTH ( n = 69). Vitamin D status (25-hydroxycholecalciferol, 25-OHD), PTH, and bone formation (bone alkaline phosphatase, BAP) and bone resorption (N-telopeptides of type I collagen, NTx) markers were determined. Hematocrit, erythrocytes, hemoglobin, platelets, serum iron, serum transferrin, transferrin saturation, and serum ferritin were also measured. In the total sample, 25-OHD and PTH were negatively correlated, and all subjects with high PTH presented vitamin D insufficiency (25-OHD < 75 nmol/L). High bone remodeling was observed in the high-PTH group, with significantly higher NTx and marginally higher BAP compared to the normal-PTH group. Hematocrit and ferritin were significantly lower in the high-PTH compared to the normal-PTH group. However, serum iron was higher in the high-PTH group, which was only observed for the lacto-ovo vegetarian and vegan subjects. It is concluded that both low vitamin D and low iron status are associated with elevated PTH and bone resorption, more in vegetarians than omnivores, which is in line with the hypothesis that chronic iron deficiency in adulthood mainly predisposes to osteoporosis in postmenopausal women and the elderly.

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

The intricate link between childhood obesity and adult osteoporosis has been a subject of numerous clinical inquiries, yet the genetic underpinnings of this association remain enigmatic. Our research aims to unravel the association between adult osteoporosis and childhood obesity using genome-wide association study data for Mendelian randomization (MR) analysis. Utilizing a pool of single-nucleotide polymorphism data associated with childhood obesity obtained from a previous genome-wide association study report involving a study population of 13,848 people in Europe, alongside data of adult osteoporosis sourced from Neale Lab (5266 cases and 331,893 controls). Various methods for MR were used in our research, including weighted mode, simple mode, weighted median, MR-Egger, and the inverse-variance weighted (IVW). We also used Cochran Q test of IVW to assess for heterogeneity, MR-Egger intercept and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis for pleiotropy, and leave-one-out analysis for the result stability. The instrumental variables associated with 11 single-nucleotide polymorphisms were selected. MR analyses unveiled a noteworthy link between genetically forecasted childhood obesity and the onset of adult osteoporosis based on the odds ratio, 95% confidence interval, and P-value from the results of IVW, MR-Egger, weighted median: simple mode, and weighted mode analyses. No significant heterogeneity was found by the assessment using MR-Egger and IVW. Similarly, there was no indication of pleiotropy based on the MR-PRESSO and MR-Egger analyses. Leave-one-out analysis confirmed the stability of the results. Our research suggests that childhood obesity, as predicted by genetic factors, may pose a significant risk for the development of osteoporosis in adulthood., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Alveolar bone loss in elderly populations is highly prevalent and increases the risk of tooth loss, gum disease susceptibility, and facial deformity. Unfortunately, there are very limited treatment options available. Here, we developed a bone-targeted gene therapy that reverses alveolar bone loss in patients with osteoporosis by targeting the adaptor protein Schnurri-3 (SHN3). SHN3 is a promising therapeutic target for alveolar bone regeneration, because SHN3 expression is elevated in the mandible tissues of humans and mice with osteoporosis while deletion of SHN3 in mice greatly increases alveolar bone and tooth dentin mass. We used a bone-targeted recombinant adeno-associated virus (rAAV) carrying an artificial microRNA (miRNA) that silences SHN3 expression to restore alveolar bone loss in mouse models of both postmenopausal and senile osteoporosis by enhancing WNT signaling and osteoblast function. In addition, rAAV-mediated silencing of SHN3 enhanced bone formation and collagen production of human skeletal organoids in xenograft mice. Finally, rAAV expression in the mandible was tightly controlled via liver- and heart-specific miRNA-mediated repression or via a vibration-inducible mechanism. Collectively, our results demonstrate that AAV-based bone anabolic gene therapy is a promising strategy to treat alveolar bone loss in osteoporosis., Competing Interests: Declaration of interests G.G. and J.H.S. have submitted a patent application concerning the methodology described in this study. G.G. and J.H.S. are scientific co-founders of AAVAA Therapeutics and hold equity in this company. G.G. is also a scientific co-founder of Voyager Therapeutics, Adrenas Therapeutics, and Aspa Therapeutics, and holds equity in these companies. G.G. is an inventor on patents with potential royalties licensed to Voyager Therapeutics, Adrenas Therapeutics, Aspa Therapeutics, and other biopharmaceutical companies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied., Objective: To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis., Methods: Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models., Results: In this cohort, 53.4% ( n  = 174) were male, 46.6% ( n  = 152) were female, and 21.8% ( n  = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% ( n  = 48) were female and 32.4% ( n  = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage., Conclusion: Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.

Background: Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health., Methods: We studied the database of the National Health and Nutrition Examination Survey, 2005-2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8-1.0, 1.0-1.2, and >1.2 g/kg/day)., Results: Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores ( p  < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8-1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062-1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057-1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015-1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051-1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098-1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8-1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group., Conclusions: In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied by local and systemic bone loss. FcγRs, especially FcγRIIa (hFcγRIIa), have been implicated in the pathogenesis of RA. However, the contribution of hFcγRIIa to bone loss has not been fully elucidated. In the present study, we demonstrated the double-edged sword role of hFcγRIIa on osteoclast differentiation through investigations involving hFcγRIIa-transgenic (hFcγRIIa-Tg) mice. Our findings reveal that hFcγRIIa-Tg mice, previously shown to exhibit heightened susceptibility to collagen-induced arthritis (CIA), displayed increased osteoporosis during CIA or at advanced ages (40 weeks), accompanied by heightened in vivo osteoclast differentiation. Notably, bone marrow cells from hFcγRIIa-Tg mice exhibited enhanced efficiency in differentiating into osteoclasts and bone resorption in vitro compared to wild-type mice when stimulated with receptor activators of NF-κB ligand (RANKL). Additionally, hFcγRIIa-Tg mice exhibited augmented sensitivity to RANKL-induced bone loss in vivo , highlighting the osteoclast-promoting role of hFcγRIIa. Mechanistically, bone marrow cells from hFcγRIIa-Tg mice displayed heightened Syk self-activation, leading to mTOR-pS6 pathway activation, thereby promoting RANKL-driven osteoclast differentiation. Intriguingly, while hFcγRIIa crosslinking hindered RANKL-induced osteoclast differentiation, it activated the kinase cAbl, subsequently triggering STAT5 activation and inhibiting the expression of osteoclast-associated genes. This study provides novel insights into hFcγRIIa-mediated osteoclast biology, suggesting promising therapeutic targets for managing bone remodeling disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Miao, Wang, Pan, Gong, Gao and Gong.)

Objectives: A correlation exists between lipids and osteoporosis (OP), as well as between lipids and rheumatoid arthritis (RA). However, lipids, the relationship between RA and OP is still unclear. This study mainly investigates the relationship between lipid levels and OP risk in RA patients., Methods: Retrospective collection of RA patient data from July 2017 to May 2022, encompassing baseline demographics, treatment regimens, laboratory results, and bone mineral density (BMD) measurements. Analyses, stratified by BMD subgroups, were conducted using propensity score matching (PSM) based on age, sex, and baseline duration, and binary logistic regression to examine the interplay between lipoprotein levels and other risk factors. The relationship between continuous variables and OP risk was assessed using restricted cubic spline (RCS), followed by a reanalysis of the correlation between varying lipoprotein levels and different factors, segmented according to RCS-determined cutoffs., Results: The study included 2673 RA patients. Binary logistic regression revealed significant associations between high-density lipoprotein (HDL), low-density lipoprotein (LDL), and RA-OP (p < 0.01). Specifically, HDL emerged as a protective factor against OP (OR = 0.40, 95% CI 0.250-0.629; p < 0.001), whereas LDL was identified as a risk factor (OR = 1.56, 95% CI 1.290-1.890; p < 0.001). Furthermore, HDL (RCS cutoff point 1.28 mmol/L) showed a negative, linear correlation with RA-related OP, while LDL (RCS cutoff point 2.63 mmol/L) demonstrated a positive, linear correlation., Conclusions: The levels of HDL and LDL may be indicators of OP occurrence in RA patients., (© 2024. The Author(s).)

Background: The relationship between obesity and type 2 diabetes with bone health has always been a topic of debate. The weight-adjusted waist index has become a commonly used indicator for assessing central obesity, fat, and muscle mass. However, currently there is no research reporting the association between weight-adjusted waist index and risk of osteoporosis in populations of type 2 diabetes. Therefore, this study aims to provide new information on the association between weight-adjusted waist index and risk of osteoporosis in type 2 diabetes., Methods: This cross-sectional study involved 963 patients with type 2 diabetes who were admitted to the Department of Endocrinology of Cangzhou Central Hospital. Multivariate logistic regression models were used to assess the association between weight-adjusted waist index and osteoporosis. The potential nonlinear association was evaluated. The effects of interaction between subgroups were assessed using the likelihood ratio test., Results: Weight-adjusted waist index was positively associated with the risk of osteoporosis, regardless of traditional confounding factors. For each 1 unit increased in weight-adjusted waist index, the risk of osteoporosis increased by 67%. Furthermore, there was a nonlinear relationship between weight-adjusted waist index and osteoporosis. The subgroup analysis did not reveal any significant interactions., Conclusions: Our study indicated a positive association between weight-adjusted waist index and the risk of osteoporosis in adult Chinese type 2 diabetes patients, and this relationship was nonlinear., (© 2024. The Author(s).)

Background: Osteoporosis is increasingly being recognized in children, mostly secondary to systemic underlying conditions or medication. However, no imaging modality currently provides a full evaluation of bone health in children. We compared DXA, a radiographic bone health index (BHI (BoneXpert) and cone-beam CT for the assessment of low bone mass in children with juvenile idiopathic arthritis (JIA)., Methods: Data used in the present study was drawn from a large multicentre study including 228 children aged 4-16 years, examined between 2015 and 2020. All had a radiograph of the left hand, a DXA scan and a cone-beam CT of the temporomandibular joints within four weeks of each other. For the present study, we included 120 subjects, selected based on DXA BMD and BoneXpert BHI to secure values across the whole range to be tested., Results: One hundred and twenty children (60.0% females) were included, mean age 11.6 years (SD 3.1 years). There was a strong correlation between the absolute values of BHI and BMD for both total body less head (TBLH) (r = 0.75, p < 0.001) and lumbar spine (L1-L4) (r = 0.77, p < 0.001). The correlation between BHI standard deviation score (SDS) and BMD TBLH Z-scores was weak (r = 0.34) but significant (0 = 0.001), varying from weak (r = 0.31) to moderate (r = 0.42) between the three study sites. Categorizing BHI SDS and DXA BMD Z-scores on a 0-5 scale yielded a weak agreement between the two for both TBLH and LS, with w-kappa of 0.2, increasing to 0.3 when using quadratic weights. The agreement was notably higher for one of the three study sites as compared to the two others, particularly for spine assessment, yielding a moderate kappa value of 0.4 - 0.5. For cone-beam CT, based on a 1-3 scale, 59 out of 94 left TMJ's were scored as 1 and 31 as score 2 by the first observer vs. 87 and 7 by the second observer yielding a poor agreement (kappa 0.1)., Conclusions: Categorizing DXA LS and automated radiographic Z-scores on a 0-5 scale gave a weak to moderate agreement between the two methods, indicating that a hand radiograph might provide an adjuvant tool to DXA when assessing bone health children with JIA, given thorough calibration is performed., (© 2024. The Author(s).)

Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups; < 36.2 nmol/L. The vitamin D levels in Group DMS were significantly lower than that in Group Non-DMS (41.74 ± 14.60 vs. 47.19 ± 13.01, P < 0.05). After adjusting confounder factors including sex, age, vitamin D levels, HbA1c, ALB, HDLC, eGFR, diabetes microvascular complications and macrovascular, there was an independent association between risk of DMS and age (OR value = 1.160, 95% CI 1.091-1.234, P = 0.000), HbA1c(OR value = 1.262, 95% CI 1.046-1.532, P = 0.015), and vitamin D deficiency (< 36.2 nmol/L) (OR value = 2.990, 95% CI 1.284-6.964, P = 0.011). Our findings suggest that low levels of vitamin D are a predictor of DMS in middle-aged and elderly patients with poor control of type 2 diabetes., (© 2024. The Author(s).)

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

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Objectives: Rheumatoid arthritis (RA) is associated with an increased risk for osteoporosis and osteoporotic fractures. Since the treatment of RA has improved significantly in recent years, we can expect RA-associated osteoporosis to decrease with good disease control. Therefore, we conducted a retrospective study to investigate whether the frequency of osteoporosis and osteoporotic fractures has changed during 24 years in RA., Methods: We analysed the data of 1.086 RA patients from the time of the first osteological assessment with bone mineral density (BMD) measurement and collection of osteologically important data during the years 1996 and 2019 at our clinic. According to the treatment period, the patients were divided into cohort 1 (investigation between 1996 and 2004; n=539) and cohort 2 (investigation between 2005 and 2019; n=547). The data of the two cohorts were compared, and predictors of BMD were analysed by linear regression analysis., Results: Prevalence of osteoporosis (28.3% vs 48.4%; p<0.001) as well as osteoporotic peripheral fractures (11.5% vs 21%; p<0.001) and vertebral fractures (6.6% vs 10.9%; p=0.011) were significantly lower and treatment with biologicals (19.7% vs 5.0%; p<0.001) significantly more common and glucocorticoid use was significantly less common (p=0.005) in cohort 2. In RA patients with a disease duration of more than 2 years, BMD was significantly higher under treatment with biologicals (p<0.001) despite increased cumulative glucocorticoid dosages (p<0.001)., Conclusion: Our study showed a significant decline in osteoporosis and osteoporotic fractures in RA for 24 years. This positive effect is associated with the more frequent use of biologicals in the years between 2005 and 2019., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Increasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis., Methods: Bilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro., Results: miR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/β-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/β-catenin activation induced by miR-381-3p antagomir., Conclusion: miR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP., (© 2024. The Author(s).)

Background: Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways., Methods: Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively., Results: After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed., Conclusions: The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis., (© 2024. The Author(s).)

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

Backgruound: Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer., Methods: We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured., Results: Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025)., Conclusion: Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.

Bone homeostasis is maintained by an intricate balance between osteoclasts and osteoblasts, which becomes disturbed in osteoporosis. Metallothioneins (MTs) are major contributors in cellular zinc regulation. However, the role of MTs in bone cell regulation has remained unexplored. Single-cell RNA sequencing analysis discovered that, unlike the expression of other MT members, the expression of MT3 was unique to osteoclasts among various macrophage populations and was highly upregulated during osteoclast differentiation. This unique MT3 upregulation was validated experimentally and supported by ATAC sequencing data analyses. Downregulation of MT3 by gene knockdown or knockout resulted in excessive osteoclastogenesis and exacerbated bone loss in ovariectomy-induced osteoporosis. Transcriptome sequencing of MT3 knockdown osteoclasts and gene set enrichment analysis indicated that the oxidative stress and redox pathways were enriched, which was verified by MT3-dependent regulation of reactive oxygen species (ROS). In addition, MT3 deficiency increased the transcriptional activity of SP1 in a manner dependent on intracellular zinc levels. This MT3-zinc-SP1 axis was crucial for the control of osteoclasts, as zinc chelation and SP1 knockdown abrogated the promotion of SP1 activity and osteoclastogenesis by MT3 deletion. Moreover, SP1 bound to the NFATc1 promoter, and overexpression of an inactive SP1 mutant negated the effects of MT3 deletion on NFATc1 and osteoclastogenesis. In conclusion, MT3 plays a pivotal role in controlling osteoclastogenesis and bone metabolism via dual axes involving ROS and SP1. The present study demonstrated that MT3 elevation is a potential therapeutic strategy for osteolytic bone disorders, and it established for the first time that MT3 is a crucial bone mass regulator., (© 2024. The Author(s).)

Background: While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear., Objective: Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations., Methods: We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway., Results: Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants., Conclusion: Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kang, Wu, Li, Zhao, Wang and Yu.)

Objective: The causal relationship between type 2 diabetes mellitus (T2DM) and osteoporosis (OS) remains unclear. This study aims to investigate the causal relationship and explore the potential metabolic mechanism and its mediating role., Methods: We conducted a comprehensive study, gathering data on 490,089 T2DM patients from the genome-wide association study (GWAS) database and selecting OS data from FinnGen and MRC-IEU sources, including 212,778 and 463,010 patients, respectively, for causal analysis. Simultaneously, we explored the potential roles of three obesity traits and 30 metabolic and inflammation-related mediating variables in the causal relationship., Results: There is a strong causal relationship between T2DM and OS. The data from our two different database sources appeared in the same direction, but after correcting for body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR), the direction became the same. T2DM may increase the risk of OS [odds ratio ( OR ) > 1.5, p < 0.001]. Steiger's test results show that there is no reverse causality. No risk factors related to glycolipid metabolism, amino acid metabolism, and inflammation were found to mediate the causal relationship., Conclusion: This study's findings indicate a robust causal relationship between T2DM and OS, influenced by relevant factors such as BMI. Our results shed light on the pathogenesis of OS and underscore the importance for clinicians to treat metabolic disorders to prevent osteoporosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Wang, Liu, Liu and Zhu.)

Background: Artesunate (ART) has the potential to modulate the nuclear factor kappa B (NF-κB) and Notch1/Hes1 signaling pathways, which play crucial roles in the pathogenesis of osteoporosis. This study aims to explore whether ART participates in the progression of osteoporosis by regulating these signaling pathways., Methods: In the in vitro experiments, we treated bone marrow mesenchymal stem cells (BMSCs) with different concentrations of ART (0, 3, 6, 12 µM) and evaluated osteogenic differentiation using alkaline phosphatase staining (ALP) and alizarin red S staining (ARS) staining. The expression levels of osteocalcin (OCN), RUNT-related transcription factor 2 (RUNX2), osteoprotegerin (OPG), and receptor activator of the nuclear factor kappa ligand (RANKL) were detected by real-time quantitative PCR (RT-qPCR). The effects of ART on NF-κB p65 and Notch1 protein expression were analyzed by Western blot (WB) and immunofluorescence (IF). In the in vivo experiments, a postmenopausal osteoporosis rat model was established via ovariectomy. Bone tissue pathological injury was evaluated using hematoxylin eosin (HE) staining. Serum ALP levels were measured using a kit, bone density was determined by dual-energy X-ray absorptiometry, and serum levels of bone gla protein (BGP), OPG, RANKL, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). Additionally, the expression of NF-κB p65 and Notch1 in tissues was assessed by immunohistochemistry., Results: In vitro experiments revealed that compared to the control group, ART dose-dependently promoted BMSCs proliferation and enhanced their osteogenic differentiation capability. The expression of OCN, RUNX2, and OPG significantly increased in the ART-treated group, while RANKL expression decreased significantly ( p < 0.05). ART significantly inhibited the expression of NF-κB p65 and Notch1/Hes1 signaling pathway proteins ( p < 0.05). Compared to ART treatment alone, combined treatment with ART and phorbol myristate acetate (PMA) or valproic acid (VPA) resulted in increased expression of NF-κB p65 and Notch1 proteins and decreased osteogenic differentiation capability ( p < 0.05). In vivo experiments showed that in rats treated with ART, bone damage was significantly reduced, bone density and mineral content were restored considerably, and the expression of inflammatory factors (TNF-α, IL-6, IL-1β) decreased significantly ( p < 0.05). Additionally, ART treatment significantly reduced the expression of NF-κB p65 and Notch1 proteins, increased OPG expression, and decreased BGP and RANKL levels ( p < 0.05)., Conclusion: In summary, ART facilitates the osteogenic differentiation of BMSCs by inhibiting the NF-κB and Notch1/Hes1 signaling pathways, thereby exerting significant protective effects against osteoporosis., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: Previous studies have shown that the inflammatory potential of the diet is associated with a variety of chronic noncommunicable diseases characterized by a chronic low-grade inflammatory response. However, the relationships between dietary inflammatory potential and organismal inflammatory status and osteoporosis have been less studied. This study aimed to investigate the relationships among inflammatory diet, inflammatory state and osteoporosis in the Xinjiang multiethnic population., Methods: The participants consisted of 4452 adults aged 35 to 74 years from Xinjiang, China. The dietary inflammatory index (DII) was calculated using dietary data collected with a semiquantitative food frequency questionnaire, and information about osteoporosis was derived from quantitative ultrasound measurements. The relationships of the DII score and inflammatory factors with the risk of osteoporosis were analysed using multivariate logistic regression, and the nonlinear associations between DII and osteoporosis were further analysed using restricted cubic splines., Results: The results showed that proinflammatory diets were associated with a greater risk of osteoporosis (T3 vs. T1: OR = 1.87; 95% CI = 1.44, 2.45) and that there was no nonlinear relationship between the DII and the risk of osteoporosis. Increased concentrations of the inflammatory factors IL-6, IL-10, IL-12p70, IL-17, and IL-23 were associated with a greater risk of osteoporosis., Conclusions: The risk of osteoporosis can be reduced by increasing the consumption of an appropriate anti-inflammatory diet., (© 2024. The Author(s).)

Background: Osteoporosis (OP) associated with aging exerts substantial clinical and fiscal strains on societal structures. An increasing number of research studies have suggested a bidirectional relationship between circulating inflammatory markers (CIMs) and OP. However, observational studies are susceptible to perturbations in confounding variables. In contrast, Mendelian randomization (MR) offers a robust methodological framework to circumvent such confounders, facilitating a more accurate assessment of causality. Our study aimed to evaluate the causal relationships between CIMs and OP, identifying new approaches and strategies for the prevention, diagnosis and treatment of OP., Methods: We analyzed publicly available GWAS summary statistics to investigate the causal relationships between CIMs and OP. Causal estimates were calculated via a systematic analytical framework, including bidirectional MR analysis and Bayesian colocalization analysis., Results: Genetically determined levels of CXCL11 (OR = 0.91, 95% CI = 0.85-0.98, P = 0.008, P FDR = 0.119), IL-18 (OR = 0.88, 95% CI = 0.83-0.94, P = 8.66×10-5, P FDR = 0.008), and LIF (OR = 0.86, 95% CI = 0.76-0.96, P = 0.008, P FDR = 0.119) were linked to a reduced risk of OP. Conversely, higher levels of ARTN (OR = 1.11, 95% CI = 1.02-1.20, P = 0.012, P FDR = 0.119) and IFNG (OR = 1.16, 95% CI = 1.03-1.30, P = 0.013, P FDR = 0.119) were associated with an increased risk of OP. Bayesian colocalization analysis revealed no evidence of shared causal variants., Conclusion: Despite finding no overall association between CIMs and OP, five CIMs demonstrated a potentially significant association with OP. These findings could pave the way for future mechanistic studies aimed at discovering new treatments for this disease. Additionally, we are the first to suggest a unidirectional causal relationship between ARTN and OP. This novel insight introduces new avenues for research into diagnostic and therapeutic strategies for OP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dong, Wu, Zhang, Luo and Wu.)

Background: Osteoporosis is a considerable public health challenge in Moyu County, Xinjiang. Here, we evaluated the influencing factors of osteoporosis in this region., Methods: We recruited 7,761 participants and randomized them into normal and osteoporotic populations based on T-score. The effects of general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet on osteoporosis were analyzed. Furthermore, a structural equation model was constructed to uncover the direct and indirect influencing factors of osteoporosis., Results: Among the participants, 1,803 (23.23%) had normal bone mass while 1,496 (19.28%) had osteoporosis. The univariate analysis showed significant differences in the general conditions, body composition, calcium sources and exercise, respiratory exposure, and daily diet. Stratification based on age (45 years) and body mass index (BMI) (18.5 kg/m 2 ) showed variations in the body composition between the two groups; however, the visceral fat differed significantly. Logistic regression analysis affirmed the association of visceral fat index as it was included in all equations, except for age and female menopause. The structural equation exhibited that the general conditions, body composition, and, calcium sources, and exercise were direct factors of osteoporosis, while respiratory exposure and daily diet were indirect factors. The standardized path coefficient was highest in general conditions, followed by body composition, and lastly, calcium sources and exercise., Conclusion: Obesity, besides age and female menopause, is also an influencing factor of osteoporosis. The visceral fat index plays a vital role in osteoporosis. Our findings may provide experimental evidence for early prevention and treatment of osteoporosis., (© 2024. The Author(s).)

Low bone mineral density (BMD) is common in adults with coeliac disease (CD), even in individuals adhering to a gluten-free diet (GFD). Women are more likely to have low BMD and have an increased risk of osteoporosis, so women with pre-existing low BMD related to CD are at an even higher risk. BMD assessed by dual X-ray absorptiometry (DXA) and bone quality assessed through quantitative ultrasound (QUS) were investigated in 31 premenopausal women with CD consuming a GFD, and 39 matched healthy controls from the Lower North Island, New Zealand. In addition, bone metabolism and nutrient status were assessed, and four-day diet diaries were used to estimate nutrient intake. No statistically significant differences were found in BMD assessed by DXA between the two groups at the hip, lumbar spine or forearm. However, the parameters measured by the QUS were significantly lower in CD participants. Dietary data indicated significantly lower intakes of energy, dietary fibre, magnesium and phosphorus in women with CD, likely as a result of a reduced intake of wholegrain foods, and suggested that both groups had inadequate intake of calcium. No significant differences were demonstrated in biochemical parameters. BMD and bone biomarkers indicated no differences between coeliac and healthy women in New Zealand. However, these findings suggest that QUS may be more sensitive for the coeliac population, due to the disease's affect on the trabecular bone, and warrant further research.

Background: To aim of this study is to assess the mechanism through which Desertliving Cistanche modulates the PI3K/AKT signaling pathway in the treatment of hyperlipidemic osteoporosis in ovariectomized rats., Methods: We randomly assigned specific-pathogen-free (SPF) rats into five groups (n = 10 per group). The normal control group received a standard diet, while the model group, atorvastatin group, diethylstilbestrol group, and treatment group were fed a high-fat diet. Four weeks later, bilateral ovariectomies were conducted, followed by drug interventions. After six weeks of treatment, relevant indicators were compared and analyzed., Results: Compared to the normal control group, rats in the model group exhibited blurred trabecular morphology, disorganized osteocytes, significantly elevated levels of bone-specific alkaline phosphatase (BALP), bone Gla-protein (BGP), total cholesterol (TC), tumor necrosis factor-α (TNF-α), and receptor activator of NF-κB ligand (RANKL). Also, the model group revealed significantly reduced levels of ultimate load, fracture load, estradiol (E2), bone mineral density (BMD), osteoprotegerin (OPG), and phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in femoral tissue. The atorvastatin group presented with higher TC and TNF-α levels compared to the normal control group. Conversely, the treatment group demonstrated enhanced trabecular morphology, denser structure, smaller bone marrow cavities, and reduced BALP, BGP, TC, TNF-α, and RANKL levels. Furthermore, the treatment group exhibited higher levels of E2, BMD, OPG, and PI3K and Akt in bone tissue compared to the model group. The treatment group also had lower TC and TNF-α levels than the atorvastatin group. Biomechanical analysis indicated that after administration of Desertliving Cistanche, the treatment group had reduced body mass, increased ultimate and fracture load of the femur, denser bone structure, smaller bone marrow cavities, and altered periosteal arrangement compared to the model group., Conclusion: Our study revealed that Desertliving Cistanche demonstrated significant efficacy in preventing and treating postmenopausal hyperlipidemic osteoporosis in rats., (© 2024. The Author(s).)

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

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 ., (© 2024. The Author(s).)

Hyperlipidemia-induced osteoporosis is marked by increased bone marrow adiposity, and treatment with statins for hyperlipidemia often leads to new-onset osteoporosis. Endosome-associated trafficking regulator 1 (ENTR1) has been found to interact with different proteins in pathophysiology, but its exact role in adipogenesis is not yet understood. This research aimed to explore the role of ENTR1 in adipogenesis and to discover a new small molecule that targets ENTR1 for evaluating its effectiveness in treating hyperlipidemia-induced osteoporosis. We found that ENTR1 expression increased during the adipogenesis of bone marrow mesenchymal cells (BMSCs). ENTR1 gain- and loss-of-function assays significantly enhanced lipid droplets formation. Mechanistically, ENTR1 binds peroxisome proliferator-activated receptor γ (PPARγ) and enhances its expression, thereby elevating adipogenic markers including C/EBPα and LDLR. Therapeutically, AN698/40746067 attenuated adipogenesis by targeting ENTR1 to suppress PPARγ. In vivo, AN698/40746067 reduced bone marrow adiposity and bone loss, as well as prevented lipogenesis-related obesity, inflammation, steatohepatitis, and abnormal serum lipid levels during hyperlipidemia. Together, these findings suggest that ENTR1 facilitates adipogenesis by PPARγ involved in BMSCs' differentiation, and targeted inhibition of ENTR1 by AN698/40746067 may offer a promising therapy for addressing lipogenesis-related challenges and alleviating osteoporosis following hyperlipidemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Sclerostin, a peptide secreted primarily by osteocytes, suppresses osteoblast maturation, thus reducing bone formation. Here, we evaluated the relationship between sclerostin levels and osteoporosis in kidney transplant recipients., Materials and Methods: This cross-sectional study included 78 kidney transplantrecipients > 18 years old and at least 6 months posttransplant. In our center, unrelated living-donor kidney transplants are not performed. Patients with parathyroid adenoma or parathyroidectomy history were excluded. Lumbar and femoral neck bone mineral densities andT and Z scores were obtained by dual-energy X-ray absorptiometry; results were used to divide patients into osteoporotic and nonosteoporotic groups. Serum sclerostin was measured by enzyme-linked immunosorbent assay., Results: Of total patients, 43% had osteoporosis, mean age was 40.8 years, and 70% were male. Groups had similar ages, male-female distribution, time posttransplant, cumulative corticosteroid dose, estimated glomerular filtration rates, and 25-hydroxyvitamin D2 levels (P > .05). The osteoporotic group had lower sclerostin (405.9 ± 234.9 vs 521.7 ± 233.5 ng/dL; P = .035) and higherintact parathyroid hormone levels (110.9 ± 68.0 vs 84.8 ± 41.4 pg/mL; P = .04) than the nonosteoporotic group. Sclerostin levels were not correlated with cumulative corticosteroid dose, intact parathyroid hormone, bone mineral density, and T scores at any site but were weakly negatively correlated with age (P = .04, r = -0.25). In multiple regression analyses, only intact parathyroid hormone had negative effects on lumbar bone mineral density (P = .02) andT scores (P = .036). Serum sclerostin levels, age, and cumulative corticosteroid dose did not affect lumbar or hip bone mineral density and T scores (P > .05)., Conclusions: Sclerostin levels were low in our osteoporotic patients;therefore, sclerostin may not be a contributing factor to osteoporosis development. Because sclerostin is an osteocyte-derived peptide, its serum levels only reflect total osteocyte number and bone mass.

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

Introduction: Introduction: the prevalence of osteoporosis among candidates for lung transplantation is high and its pathophysiology is multifactorial. Objectives: to evaluate differences in bone mineral density, risk of fractures and bone remodeling markers in patients with terminal lung disease, at the time they are evaluated for lung transplantation, comparing two types of pathologies. Material and methods: fifty-nine subjects, proposed to receive a lung transplant due to advanced lung disease, were included in this study. They were divided into two groups according to their respiratory pathology: chronic obstructive pulmonary disease (COPD) and diffuse interstitial pulmonary disease (ILD). Demographic data were collected and bone densitometry, blood analysis with markers of bone remodeling, spirometry, six-minute walk test (6MWT), echocardiography and cardiac catheterization were performed Results: no differences were found between the groups, regarding their age, sex, BMI or exposure to tobacco. A higher prevalence of osteoporosis and a higher FRAX were observed in the group with COPD. Regarding bone remodeling markers, higher parathyroid hormone (PTH) and higher osteocalcin were found in the COPD group. Vitamin D was lower in COPD patients. Conclusions: two out of three of the patients evaluated for lung transplantation had osteopenia or osteoporosis. The prevalence of osteoporosis and FRAX is higher in COPD patients. Vitamin D supplementation should be considered in certain patients. Differences in bone remodeling markers may be useful for suspected osteoporosis and therapeutic management.

Background: A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients., Method: This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model., Results: Prevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (β=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (β=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (β=-0.48, 95% CI -0.91 to -0.04, p=0.031)., Conclusion: This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ananvutisombat, Tantiworawit, Punnachet, Hantrakun, Piriyakhuntorn, Rattanathammethee, Hantrakool, Chai-Adisaksopha, Rattarittamrong, Norasetthada, Fanhchaksai and Charoenkwan.)