1.Treatment and repair of musculoskeletal degenerative diseases and injuries from the perspective of muscle-bone crosstalk mechanism
Xingyu ZHANG ; Dou WU ; Enzhe ZHAO ; Xubin SONG ; Xiaolun ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(24):5179-5186
BACKGROUND:Degenerative diseases caused by bone and muscle degeneration are major reasons for the decline in physical function and mobility,increased fragility fractures,and high mortality rates in the elderly,significantly affecting their health and quality of life.OBJECTIVE:To review the research progress in the mechanisms of muscle-bone interaction and the etiology,prevention,and treatment of related diseases.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature published from 2014 to 2024.The search terms were"muscle-bone crosstalk,musculoskeletal system,inter-tissue communication,myokines,osteokines,osteosarcopenia,sarcopenia,osteoporosis,bone regeneration,fibro-adipogenic progenitors"in Chinese and English.By reading the articles,we eliminated irrelevant,outdated,and poorly focused literature,and finally 94 articles were included for review.RESULTS AND CONCLUSION:Mechanical interaction,secretion factor interaction,and stem cell interaction between muscle and bone are crucial for the metabolism and regeneration regulation of the musculoskeletal system.Systemic interventions targeting biochemical signals of muscle factors(such as myostatin and irisin)and bone factors(such as nuclear factor-κB receptor-activating factor ligand and sclerostin)can improve the quality and function of skeletal muscle and bone,and have positive effects on fracture healing.In recent years,it has been found that related stem cells in the musculoskeletal system can interact,with the activation of muscle progenitor cells(such as fibro-adipogenic progenitors)having a significant impact on bone growth,repair,and regeneration.Research on the mechanisms of muscle-bone interaction can provide insights into the etiology,prevention,and treatment of related diseases.However,there are currently no effective clinical treatments for muscle-bone comorbidities,with most research still at the cellular and animal experiment stage.Therefore,extensive research is needed in the future to gradually move from experiments to clinical applications,developing more targeted therapies and drugs to better serve clinical needs.
2.Research on the causal association of gut microbiota with senile osteoporosis
Xinghua JI ; Yifan KANG ; Enzhe ZHAO ; Xiaoqiong LI ; Zejun XING
Chinese Journal of Geriatrics 2025;44(11):1522-1528
Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.
3.Finite element analysis of a new femoral neck spiral blade system to treat femoral intertrochanteric fractures
Xubin SONG ; Dou WU ; Enzhe ZHAO ; Xingyu ZHANG ; Xiaolun ZHANG ; Chuheng WANG
Chinese Journal of Tissue Engineering Research 2025;29(33):7041-7047
BACKGROUND:At present,there is a main kind of operation,which is represented by the proximal femoral nail antirotation,to treat femoral intertrochanteric fractures,but some sequelae still occur such as internal fixation loosening,failure,and nail withdrawal.We designed a new femoral neck spiral blade system to solve this problem,so we analyze the mechanical structure by the finite element method that can be regard as the theoretical basis for the system.OBJECTIVE:To compare the mechanical properties of the new femoral neck spiral blade system and the proximal femoral nail antirotation in the treatment of femoral intertrochanteric fracture by the finite element method.METHODS:Based on the finite element model of the femur,the A1.2 and A2.2 femoral intertrochanteric fracture models were established according to the AO fracture classification principle of 2018 edition.The models were fixed with the proximal femoral nail antirotation and the new internal fixation system,applying an axial load of 700,1 400,and 2 100 N above the femoral head.The mechanical characteristics of the two internal fixation methods were respectively compared and analyzed by observing the maximum equivalent stress and the maximum deformation of each group.RESULTS AND CONCLUSION:(1)The maximum equivalent stress of the new internal fixation group under different compressive loads was smaller than that of the proximal femoral nail antirotation group.(2)In the A1.2 fracture model,under different compression loads,the deformation of the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.113 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 2.017 mm between the two.(3)In the A1.2 fracture model,under different compressive loads,the maximum deformation of the spiral blade fixed by the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.062 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 1.891 mm between the two.(4)The results indicate that the new femoral neck spiral blade system has a lower internal fixation stress value compared to the proximal femoral nail antirotation,and a smaller displacement value of the femur after fixation and internal fixation.It can more effectively fix fractures and prevent the spiral blade from retracting or cutting out in the femoral neck.
4.Treatment and repair of musculoskeletal degenerative diseases and injuries from the perspective of muscle-bone crosstalk mechanism
Xingyu ZHANG ; Dou WU ; Enzhe ZHAO ; Xubin SONG ; Xiaolun ZHANG
Chinese Journal of Tissue Engineering Research 2025;29(24):5179-5186
BACKGROUND:Degenerative diseases caused by bone and muscle degeneration are major reasons for the decline in physical function and mobility,increased fragility fractures,and high mortality rates in the elderly,significantly affecting their health and quality of life.OBJECTIVE:To review the research progress in the mechanisms of muscle-bone interaction and the etiology,prevention,and treatment of related diseases.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature published from 2014 to 2024.The search terms were"muscle-bone crosstalk,musculoskeletal system,inter-tissue communication,myokines,osteokines,osteosarcopenia,sarcopenia,osteoporosis,bone regeneration,fibro-adipogenic progenitors"in Chinese and English.By reading the articles,we eliminated irrelevant,outdated,and poorly focused literature,and finally 94 articles were included for review.RESULTS AND CONCLUSION:Mechanical interaction,secretion factor interaction,and stem cell interaction between muscle and bone are crucial for the metabolism and regeneration regulation of the musculoskeletal system.Systemic interventions targeting biochemical signals of muscle factors(such as myostatin and irisin)and bone factors(such as nuclear factor-κB receptor-activating factor ligand and sclerostin)can improve the quality and function of skeletal muscle and bone,and have positive effects on fracture healing.In recent years,it has been found that related stem cells in the musculoskeletal system can interact,with the activation of muscle progenitor cells(such as fibro-adipogenic progenitors)having a significant impact on bone growth,repair,and regeneration.Research on the mechanisms of muscle-bone interaction can provide insights into the etiology,prevention,and treatment of related diseases.However,there are currently no effective clinical treatments for muscle-bone comorbidities,with most research still at the cellular and animal experiment stage.Therefore,extensive research is needed in the future to gradually move from experiments to clinical applications,developing more targeted therapies and drugs to better serve clinical needs.
5.Finite element analysis of a new femoral neck spiral blade system to treat femoral intertrochanteric fractures
Xubin SONG ; Dou WU ; Enzhe ZHAO ; Xingyu ZHANG ; Xiaolun ZHANG ; Chuheng WANG
Chinese Journal of Tissue Engineering Research 2025;29(33):7041-7047
BACKGROUND:At present,there is a main kind of operation,which is represented by the proximal femoral nail antirotation,to treat femoral intertrochanteric fractures,but some sequelae still occur such as internal fixation loosening,failure,and nail withdrawal.We designed a new femoral neck spiral blade system to solve this problem,so we analyze the mechanical structure by the finite element method that can be regard as the theoretical basis for the system.OBJECTIVE:To compare the mechanical properties of the new femoral neck spiral blade system and the proximal femoral nail antirotation in the treatment of femoral intertrochanteric fracture by the finite element method.METHODS:Based on the finite element model of the femur,the A1.2 and A2.2 femoral intertrochanteric fracture models were established according to the AO fracture classification principle of 2018 edition.The models were fixed with the proximal femoral nail antirotation and the new internal fixation system,applying an axial load of 700,1 400,and 2 100 N above the femoral head.The mechanical characteristics of the two internal fixation methods were respectively compared and analyzed by observing the maximum equivalent stress and the maximum deformation of each group.RESULTS AND CONCLUSION:(1)The maximum equivalent stress of the new internal fixation group under different compressive loads was smaller than that of the proximal femoral nail antirotation group.(2)In the A1.2 fracture model,under different compression loads,the deformation of the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.113 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 2.017 mm between the two.(3)In the A1.2 fracture model,under different compressive loads,the maximum deformation of the spiral blade fixed by the new internal fixation system was smaller than that of the proximal femoral nail antirotation group,and the average value of difference between the two was 1.062 mm;the result of the A2.2 type fracture model was the same as that in the A1.1 with an average value of difference of 1.891 mm between the two.(4)The results indicate that the new femoral neck spiral blade system has a lower internal fixation stress value compared to the proximal femoral nail antirotation,and a smaller displacement value of the femur after fixation and internal fixation.It can more effectively fix fractures and prevent the spiral blade from retracting or cutting out in the femoral neck.
6.Research on the causal association of gut microbiota with senile osteoporosis
Xinghua JI ; Yifan KANG ; Enzhe ZHAO ; Xiaoqiong LI ; Zejun XING
Chinese Journal of Geriatrics 2025;44(11):1522-1528
Objective:To elucidate the causal association between gut microbiota and osteoporosis, we conducted a two-sample Mendelian randomization(MR)analysis to evaluate the causality between gut microbiota and osteoporosis.Methods:We assessed genome-wide association study (GWAS)summary statistics for gut microbiota and osteoporosis in older patients to perform the MR analysis.Independent single nucleotide polymorphisms closely associated with 211 gut bacterial taxa were identified as instrumental variables.The summary statistic data for osteoporosis were obtained from the latest release from the FinnGen consortium as the outcome of interest.Two-sample MR was performed to evaluate the causal effect of gut microbiota on osteoporosis, including the inverse-variance-weighted(IVW)method, weighted median method, MR-Egger, mode-based estimation, and MR-PRESSO.A series of sensitivity analyses were conducted to validate the robustness of the results.The robustness of the estimation was assessed through a series of sensitivity analyses, including Cochran's Q test, MR-Egger intercept analysis, leave-one-out analysis, and funnel plot to evaluate the causal association. Results:The population primarily consisted of individuals from Europe, with a total sample size of 7 300, including 1 762 males and 5 538 females, and average ages of 65.6 years for males and 67.8 years for females, respectively.The mean ages of the 5 538 patients were 65.6 years for males and 67.8 years for females, respectively.Through MR analysis in this study, 10 intestinal flora(comprising 1 class, 7 genera, and 2 orders)were identified as being associated with senile osteoporosis.Notably, the phylum Firmicutes( OR=1.324, P=0.019), Clostridium difficile( OR=1.274, P=0.038), fecal coliforms( OR=1.565, P=0.009), Verrucomicrobium( OR=1.231, P=0.033), and Selenomonas( OR=1.324, P=0.019)may serve as risk factors for senile osteoporosis.Conversely, Coprococcus( OR=0.620, P=0.024), Haemophilus( OR=0.815, P=0.016), Prevotella( OR=0.813, P=0.027), Sellimonas( OR=0.858, P=0.034), and RF9( OR=0.821, P=0.021)may function as protective factors against senile osteoporosis. Conclusions:This study suggests a causal relationship between the Firmicutes phylum and its nine subgroups and senile osteoporosis, thereby providing new insights into the mechanisms by which gut microbiota mediate senile osteoporosis and confirming the significant role of gut microbiota in this condition.
7.Efficacy of proximal femoral nail antirotation fixation combined with zoledronic acid in treatment of osteoporotic intertrochanteric fracture
Shangtuan ZHENG ; Dou WU ; Enzhe ZHAO ; Liang TIAN ; Genqiang ZHENG ; Zhenwu GAO ; Qiang LIU
Chinese Journal of Trauma 2016;32(4):320-324
Objective To compare the clinical outcomes between proximal femoral nail antirotation (PFNA) combined with zoledronic acid and PFNA only in the treatment of osteoporotic intertrochanteric fracture in the elderly patients.Methods A retrospective analysis was made on 72 patients that completed the follow-up after PFNA for osteoporotic intertrochanteric fracture from November 2011 to May 2014.According to the application of zoledronic acid (5 mg,once a year) after PFNA,the patients were divided into study group (n =30) and control group (n =42).Bone healing and subsequent refracture were assessed with X-ray postoperatively.Harris hip score was recorded.Bone mineral density before operation and one year after operation were compared between the two groups.Adverse effect of zoledronic acid was recorded during hospitalization.Results Mean period of follow-up was 15 months (range,12-26 months).One year after operation,Harris score,new fracture incidence,mean fracture union time were (82.65 ± 6.24) points,3% (1/30) and (14.26-± 2.24) weeks in study group,while (81.85 ± 5.38) points,14% (6/42) and (15.26 ± 3.05) weeks in control group.There were no statistical differences between the two groups (P > 0.05),but the subsequent fracture was higher in control group.One year after operation,lumbar and contralateral non-injury hip bone marrow density were (0.78 ± 0.16)g/cm2 and (0.71 ± 0.14)g/cm2 in study group,higher than (0.75 ± 0.13)g/cm2 and (0.69 ±0.13)g/cm2 in control group (P <0.05).But there were no significant differences between the two groups before operation.All fractures were healed at postoperative 1 year.No intolerable adverse events occurred in study group.Conclusions PFNA is effective in the treatment of osteoporotic intertrochanteric fracture.In the meantime,the combination with zoledronic acid has no influence on bone healing while increasing bone mineral density,and may decrease the occurrence of subsequent fragile fractures.

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