Journal of Bone and Mineral Metabolism最新文献

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

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

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

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

Purpose: Several osteoanabolic agents have been developed to build new bone more efficiently than anti-resorptive drugs. Among them, romosozumab, an anti-sclerostin antibody, is a potent pharmacological tool to prevent fractures in osteoporosis patients. The efficacy of romosozumab in preventing osteoporotic fractures is robust. However, there remains a concern about increased cardiovascular (CV) adverse events related to romosozumab. Available data have been reviewed to address this concern.

Methods: Published articles on romosozumab of which pivotal randomized controlled trials (RCTs), meta-analyses of RCTs, pharmacovigilance investigations, and retrospective observational clinical studies using real-world data were collected through PubMed and other available tools.

Results: Meta-analyses of RCTs of romosozumab compared to placebo and other anti-osteoporosis drugs have left room for controversy in the CV safety of romosozumab. Investigations of the real-world data also provide no conclusive evidence in this issue.

Conclusion: We need more robust evidence to establish an appropriate and reasonable guide to prescribe romosozumab in our clinical practice.

Introduction: To investigate the relationship between serum high-density lipoprotein (HDL) cholesterol and bone mineral density (BMD) in vitamin D-deficient population.

Materials and methods: This study was a cross-sectional study. From January to December 2020, 2583 middle-aged and older adult aged 40 and above were randomly selected in the Health Management Center of the Affiliated Hospital of Guizhou Medical University for health examination and questionnaire survey. The correlation was determined by Pearson correlation method, and the independent correlation was analyzed by multiple linear regression. The receiver Operating characteristic (ROC) curve estimates HDL-C cutoff levels for predicting osteoporosis risk.

Results: The prevalence of osteoporosis in the study population was 11.4%, the overall prevalence of 25 (OH) D deficiency was 78.2%. There was no correlation between HDL-C and BMD of lumbar spine, femoral neck and total hip in normal vitamin D group (P > 0.05). HDL-C in the deficient group was negatively correlated with BMD of lumbar spine and femoral neck (P < 0.05), but not with BMD of total hip. Serum HDL-C concentration increased with the progression of osteoporosis. When serum 25 (OH) D level was lower than normal level, HDL-C ≥ 1.215 mmol/L was an independent predictor of osteoporosis (sensitivity = 75%, specificity = 53%, Area = 0.625).

Conclusions: HDL-C was inversely associated with BMD in the lumbar spine and femoral neck in people aged 40 years and older with vitamin D deficiency. When serum HDL-C concentration ≥ 1.215 mmol/L, it can better predict the occurrence of osteoporosis.

Introduction: Despite many studies on the prevalence of vertebral fractures (VFs), the VF prevalence at death in the Japanese population remains unclear.

Materials and methods: We evaluated the VF prevalence at death in a Japanese cohort using autopsy imaging computed tomography (AiCT). We enrolled 365 cadavers (188 men, 177 women, mean age of 84.6 years) donated for anatomical dissection at Shimane University School of Medicine. The VFs were diagnosed using the semiquantitative technique of Genant from the first cervical vertebra to the fifth lumbar vertebra.

Results: The overall VF prevalence was 69.6% (58.5%/81.4% in men/women), of which 46.0% (29.8%/63.3% in men/women) had thoracic VFs, and 58.1% (50.5%/66.1% in men/women) had lumbar VFs. The most frequent fracture site was lumbar spine 1 (L1) with 31.5% (22.9%/40.7% in men/women), followed by thoracic spine 12 (T12) with 31.0% (20.7%/41.8% in men/women). In terms of severity, 3.8% (4.8%/2.8% in men/women), 23.8% (27.1%/20.3% in men/women), and 41.9% (26.6%/58.2% in men/women) were Grades 1, 2, and 3. The VFs from T3 to L5 and of Grade 3 severity were significantly higher in women. VF and Grade 3 fractures were associated with a history of surgical intervention for femoral neck fractures. VFs were not associated with the following underlying causes of death: cancer, heart disease, senile death, cerebrovascular disease, pneumonia, and aspiration pneumonia.

Conclusion: The VF prevalence at death, assessed by AiCT in cadavers donated for anatomical dissection, was higher in both men and women compared with previous studies conducted on individuals aged ≥ 80 years in Japan.

Introduction: Numerous observational studies have identified a link between osteoporosis and stroke. However, the causal genetic relationship between these conditions remains unclear. This study employs a two-sample bidirectional Mendelian randomization (MR) approach to ascertain the causal relationship between osteoporosis and stroke.

Materials and methods: We conducted a two-sample Mendelian randomization (MR) study to investigate the potential causal relationship between osteoporosis and stroke, including its subtypes. Genetic data for osteoporosis and stroke, along with their subtypes, were sourced from published genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNPs) demonstrating genome-wide significance (p < 5 × 10^ - 8) and independence (r^2 < 0.001) were selected for further analysis, provided they had an F-statistic ≥ 10. The inverse-variance weighted (IVW) method was employed to evaluate causality, with results reported as odds ratios (ORs). Heterogeneity was assessed using Cochran's Q test, while pleiotropy was tested using the MR-Egger intercept test. A leave-one-out sensitivity analysis was performed to ensure the robustness of the results.

Results: Employing the IVW method, MR Egger method, and median-weighted method, we found no significant bidirectional causal relationship between osteoporosis and stroke or its subtypes, irrespective of the inclusion of potential pleiotropic SNPs. Sensitivity analyses affirmed the reliability and stability of these findings.

Conclusion: Our study findings indicate that there is no direct causal relationship between osteoporosis and stroke or its subtypes in either direction. Based on our results, although no direct link was found, secondary effects do exist.

Introduction: Osteoarthritis (OA) is a chronic degenerative joint disorder characterized by an imbalance in chondrocyte metabolism. Ferroptosis has been implicated in the pathogenesis of OA. The role of Sirt1, a deacetylase, in mediating deacetylation during ferroptosis in OA chondrocytes remains underexplored. This study aimed to elucidate the mechanisms by which Sirt1 influences chondrocyte ferroptosis in the development of OA.

Materials and methods: In vitro and in vivo models of OA were established using IL-1β-induced mouse chondrocytes and a destabilization of the medial meniscus (DMM) mouse model, respectively. Ferroptosis was evaluated through measurements of cell viability, lactate dehydrogenase (LDH) release, intracellular levels of Fe2+, glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (ROS), propidium iodide staining, and Western blot analysis. The underlying mechanisms were further investigated using quantitative real-time polymerase chain reaction, Western blotting, immunoprecipitation (IP), co-immunoprecipitation (Co-IP), and glutathione-S-transferase pulldown assays. In vivo validation was performed via Safranin O staining.

Results: IL-1β induced ferroptosis and increased histone acetylation, effects that were partially reversed by Sirt1 overexpression. Mechanistically, Sirt1 overexpression upregulated ferritin light polypeptide (Ftl) expression by deacetylating Ftl at the K181 residue. Ftl knockdown inhibited the ferroptosis-enhancing effect of Sirt1 overexpression in chondrocytes. In vivo studies showed that Sirt1 overexpression mitigated the progression of OA and reduced ferroptosis in the DMM-induced OA mouse model.

Conclusion: Our findings confirm that Sirt1 overexpression promotes Ftl expression through deacetylation at the K181 site, thereby suppressing chondrocyte ferroptosis and attenuating the progression of OA. These results suggest a potential therapeutic target for OA treatment.

Introduction: Proximal femoral fractures are critically associated with increased risk of mortality and secondary fractures. Identifying prognosis predictors related to sagittal imbalance that are known to have negative impact on fracture risk and mortality is crucial. This study aimed to explore the relationship between various sagittal imbalance parameters and the prognosis of proximal femoral fractures to identify the most important prognostic indicators.

Materials and methods: This multi-center prospective cohort study included patients with proximal femoral fractures treated surgically from April 2020 to March 2021. Spinal standing radiographs were obtained to measure various sagittal spine parameters. Postoperative follow-ups were conducted at 6, 12, 18, 24, and 36 months to assess mortality and secondary fracture rates and examine the predictors and their effects.

Results: Among the 137 patients who underwent spinal standing radiographs, 22 died and 23 developed secondary fractures. Multivariate analyses identified the number of previous vertebral fractures and thoracolumbar kyphosis (TLK) as significant risk factors for mortality and secondary fractures. Survival analysis revealed that patients with TLK < 20° had significantly higher survival rates than those with TLK ≥ 20° (P = 0.002 and P < 0.001 for mortality and secondary fractures, respectively). In addition, serum albumin was associated with mortality, and the intake of sleeping pills and antidepressants was associated with secondary fractures.

Conclusion: TLK after surgery and the number of previous vertebral fractures affected both mortality and secondary fractures. When each risk factor, such as low serum albumin levels, intake of sleeping pills and antidepressants, was also considered, it was found that comprehensive postoperative care is essential.

Objectives: As many patients with osteoporosis remain undiagnosed, we aimed to develop a simple method to efficiently screen for osteoporosis using a combination of anteroposterior hip X-ray assessment and the Osteoporosis Self-Assessment Tool for Asians (OSTA), which is calculated as (body weight - age) × 0.2.

Methods: One hundred Japanese women (age: 73 ± 11 years, body weight: 54.4 ± 11.1 kg) who underwent hip surgery, anteroposterior hip X-ray, and DXA were included. Based on the DXA results of the total proximal femur, 35 cases were diagnosed with osteoporosis. Fifteen orthopaedic surgeons visually inspected the hip X-ray images and scored the suspicion of osteoporosis on a scale of 1-4 (1: very unlikely, 4: very suspicious), which is referred to as "pred-score." In addition, OSTA was calculated as a continuous variable (OSTA score). Osteoporosis was screened using the pred-score and OSTA score, and both scores were analyzed using the receiver operating characteristic curves.

Results: The area under the curves (AUCs) of the pred-score and OSTA score were 0.626-0.875 and 0.817 across surgeons, respectively. When both scores were used, the AUC for screening osteoporosis ranged from 0.821 to 0.915 across surgeons. Significant improvement from AUCs calculated with the pred-score or OSTA score was found in 11 surgeons (73.3%).

Conclusion: The combination of X-ray assessment and OSTA can be used to screen for osteoporosis and has the potential to be used as a new simple screening tool in daily clinical practice.