Journal of Bone and Mineral Metabolism最新文献

Introduction: Osteoporosis (OP) is a chronic bone metabolic disease, which causes a great social and economic burden. The gut microbiota (GM) has become a recent topic of interest in the role of many disease states. Changes in the GM are correlated with the maintenance of bone mass and bone quality. However, research results in this field remain highly controversial. We performed a mate-analysis to explore and compare the alterations of GM in OP patients.

Materials and methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we comprehensively searched the databases of PubMed, Web of Science, Embase, Cochrane Library, CNKI, VIP, CBM, and Wanfang. In addition, we applied the Stata 17.0 software for data analysis. Bias controls were evaluated with the Newcastle-Ottawa scale (NOS), funnel plot analysis, and Egger's and Begg's tests.

Results: This research ultimately considered 16 studies, which included the fecal GM data of 2340 people (664 with OP and 1676 healthy controls). The pooled estimate showed an increase of borderline significance on ACE index in patients with OP compared with control participants (SMD = 1.05; 95% CI 0.00-2.10; P = 0.05). There were no significant differences in Chao1, Shannon and Simpson indices. At the phylum level, no significant differences were observed between the OP patients and HCs in the overall analysis. At the genus level, the relative abundance of Blautia presented a decrease of borderline significance between OP and the control group (SMD = - 0.32, 95% CI - 0.65 to - 0.00, P = 0.05).

Conclusion: This systematic review and meta-analysis suggests that patients with OP may exhibit dysbiosis in their gut microbiota, characterized by a reduction in certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacterial populations.

Introduction: Bone homeostasis depends on the regulation of β-catenin in osteoblasts. Glucocorticoids (GCs) are known to diminish β-catenin activity via Wnt pathway signaling, leading to osteoporosis. Conversely, activating β-catenin in osteoblasts through mitogen-activated protein kinase kinase kinase 2 (Mekk2) offers an innovative approach to combat GC-induced osteoporosis (GIOP). Fufang Zhenshu Tiaozhi (FTZ) capsules have shown effectiveness in treating GIOP, but the mechanisms behind this are still unclear.

Materials and methods: In this study, Mekk2 knockout mice (Mekk2^-/-) was generated by CRISPR/Cas9. These mice were then subjected to Alcian Blue-Alizarin Red staining and immunofluorescence to assess their bone and cartilage development. To establish models of GIOP, both Mekk2^-/- and wild-type (WT) mice were treated with dexamethasone (DXMS) and subsequently given FTZ capsules. We analyzed the resulting phenotypic changes in these mice using Micro-CT scans and histomorphological studies. Primary osteoblasts, isolated from both Mekk2^-/- and WT mice, underwent qRT-PCR to measure key osteogenesis markers, including Runx2, Sp7, Bgalp, Col1a1 and Alp. Cells were then exposed to treatments with either FTZ or Wnt3a and the phosphorylation levels of β-catenin and Mekk2, along with the protein expression of Runx2, were evaluated using Western blotting and immunoprecipitation. Additionally, C3H10T1/2 cells transfected with TOPflash-luciferase and Renilla luciferase reporters were treated with FTZ and Wnt3a to measure β-catenin activity.

Results: In our study, administering FTZ in vivo effectively prevented bone loss typically induced by GCs. However, it's important to note that this protective effect was substantially reduced in mice lacking Mekk2. Additionally, FTZ showed a significant ability to enhance osteogenic differentiation in primary osteoblasts, doing so by altering the expression of Mekk2. Intriguingly, the impact of FTZ on Mekk2 appears to function through a pathway separate from the traditional Wnt signaling route. Furthermore, our findings indicate that FTZ also promotes the deubiquitination of β-catenin, contributing further to its positive effects on bone health.

Conclusions: This study suggests that FTZ plays a significant role in protecting bone mass in cases of GIOP. The mechanism through which FTZ confers this benefit involves the activation of Mekk2/β-catenin signaling pathways, which represents a promising alternative strategy to counteract the deleterious effects of GIOP by augmenting osteoblastogenesis.

Introduction: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis.

Materials and methods: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated.

Results: Six trials (7990 patients; follow-up period, 6-12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months.

Conclusion: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

Introduction: This study aimed to compare treatment satisfaction with two dosing regimens (two teriparatide [TPTD] self-injection systems) in osteoporosis patients at high risk of fracture.

Materials and methods: In this open-label crossover randomized trial comparing self-injected once-daily (1/D)-TPTD with self-injected twice-weekly (2/W)-TPTD, three satisfaction variables were evaluated by questionnaire for 2 years. The primary endpoint was overall satisfaction and secondary endpoints were satisfaction with treatment effectiveness and with utility of the self-injection device. Changes in quality of life (QOL) assessed by EuroQol-5 Dimension, pain assessed by visual analogue scale (VAS), and anthropometric parameters were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs).

Results: The 1/D-TPTD and 2/W-TPTD groups consisted of 180 (75.9 ± 7.3 years) and 179 (age: 75.5 ± 6.9 years) patients, respectively. After 26 weeks of treatment, no significant between-group difference in the persistence rate (79.4% vs 72.6% in the 1/D-TPTD and 2/W-TPTD groups, respectively), distributions of overall satisfaction scores, and satisfaction with treatment (p > 0.05) were observed. However, several items of satisfaction with the utility of the injection device were significantly higher in the 2/W-TPTD group (p < 0.05). Statistical improvements from baseline values were observed in QOL and pain VAS in both groups (p < 0.05). No serious AEs were reported.

Conclusion: The between-group similarity of overall treatment satisfaction and effectiveness scores and between-group difference in satisfaction with the utility of the self-injection device was useful information for real-world treatment of osteoporosis. Both medication regimens were well tolerated.

Introduction: The efficacy of early surgery in preventing complications among Japanese elderly patients with hip fractures requires further investigation. This study aims to use a comprehensive Japanese hip fracture case database to determine whether surgery within the day of admission and the following day reduces the incidence of complications and mortality during hospitalization in elderly hip fracture patients.

Materials and methods: We retrospectively analyzed the Japanese National Administrative DPC (Diagnosis Procedure Combination) database from April 2016 to March 2022. Approximately 1100 DPC-affiliated hospitals consistently provided medical records with consent for research. The study investigated the association between postoperative pneumonia, deep vein thrombosis, pulmonary embolism, and mortality during hospitalization after propensity score matching, focusing on surgeries conducted on the day of admission and the following day.

Results: After one-to-one propensity score matching for age, gender, and comorbidity, we identified 146,441 pairs of patients who underwent surgery either within the day of admission and the following day or after the third day of admission. Surgery on the third day or later was independently associated with increased risks of pneumonia, deep vein thrombosis, pulmonary embolism, and mortality during hospitalization with risk ratios of 1.367 (95% CI 1.307-1.426), 1.328 (95% CI 1.169-1.508), 1.338 (95% CI 1.289-1.388), and 1.167 (95% CI 1.103-1.234), respectively.

Conclusion: A comprehensive study of elderly Japanese patients with hip fractures in the DPC database showed that surgery on admission and the following day is crucial for preventing complications like pneumonia, deep vein thrombosis, pulmonary embolism, and mortality during hospitalization.

Introduction: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification.

Materials and methods: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis.

Results: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament.

Conclusions: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Lntroduction: Postmenopausal osteoporosis (PMOP) can cause postmenopausal women to experience pain and interference. Identifying and exploring potential early diagnostic biomarkers of PMOP is of substantial clinical value and social significance. This study aimed to screen for potential novel diagnostic biomarkers of PMOP through a multiomics approach, providing new directions and ideas for the early prevention and treatment of this disease.

Materials and methods: Fifteen postmenopausal women with osteoporosis and 12 without were recruited. Clinical information was collected, and various clinical biochemical parameters were tested. Plasma and fecal samples were collected and analyzed using Olink proteomics and gut microbial metabolomics.

Results: The functions of the differentially abundant metabolites were mainly related to autophagy and arginine and proline metabolism and were involved in immunoinflammatory metabolic processes. Olink showed significant differences in the expression of seven inflammation-related proteins between the two groups.

Conclusion: We demonstrated that metabolic differences between PMOP patients and healthy controls were associated with inflammatory responses and found seven proteins with significant differences. Among these proteins, CDCP1, IL10, and IL-1alpha combined with clinical indicators had high discriminant efficiency in identifying PMOP. This is also the first study to demonstrate noteworthy changes in CDCP1 levels in patients with PMOP.

Introduction: This study aimed to use the Mendelian randomization study method to verify the causal relationship between grip strength and bone mineral density (BMD) in different ages and different parts of the body.

Materials and methods: The analysis was based on pooled data from genome-wide association studies (GWAS). Hand grip strength (right) was used as the exposure variable and total body bone mineral density (BMD) of different age groups was used as the outcome variable. Single-nucleotide polymorphisms highly correlated with exposure variables were used as instrumental variables. The inverse variance weighted (IVW) method was used as the primary analysis method, and the Mendelian randomization Egger (MR-Egger) regression and weighted median methods were used as supplementary evidence for the IVW results. Horizontal pleiotropy and heterogeneity tests were conducted to ensure the stability of the results.

Results: Analyzing the GWAS data on osteoporosis as the outcome variable, the IVW analysis showed that osteoporosis risk was associated with decreased grip strength in the 45-60 age group and the risk of declining lumbar spine BMD was associated with decreased grip strength. However, there was no significant correlation between the risk of osteoporosis in other age groups and changes in grip strength.

Conclusion: A causal relationship exists between decreased grip strength and osteoporosis risk in people aged 45-60 years. The risk of BMD declining in the lumbar spine was associated with reduced grip strength.