Association Of Serum Bone Turnover Markers And Femoral Neck Biochemical Markers With Bone Strength

Objective:To observe the change of serum bone turnover markers（BTMs）and femoral neck biochemical markers during the progress of osteoporosis（OP）,investigate the relationship of these markers,femoral neck bone mineral density（BMD）and bone strength.Preliminarily selected the indicator which can reflect the early change of femoral neck bone loss and bone strength.Methods:A total of 108 patients who underwent total hip replacement in our hospital were recruited from January 2017 to December 2019.F emoral neck BMD was measured by Dual-energy X-ray absorptiometry.Based on the world health organization diagnostic criteria and the Guidelines for the diagnosis and management of primary osteoporosis（2017）,patients were divided into normal group（n=27）,osteopenia group（n=27）,OP group（n=27）and severe OP group（n=27）.The levels of serum osteocalcin（OC）,type I procollagen N-terminal propeptide（PINP）,and cross-linked C-telopeptide of collagen（CTX）were measured by enzyme-linked immunosorbent assay.Protein expression of femoral neck OC,alkaline phosphatase（ALP）,osteopontin（OPN）,and type I collagen（COL-I）were all determined by western blot.Axial compression test was used to measure the femoral neck maximum load(L_max).The correlation among femoral neck BMD,femoral neck L_max,serum BTMs and femoral neck biochemical markers were analyzed by Pearson correlation coefficient analysis and multiple linear regression analysis.Receiver operating characteristic（ROC）curves were used to evaluate the diagnostic value of each marker in femoral neck osteopenia and OP.Results:1.Comparison of serum BTMs among different groups:（1）The levels of serum OC in the severe OP group and the OP group were significantly higher than those in the normal group and the osteopenia group（P<0.05）,the differences of the other groups were not statistically significant（P>0.05）.（2）The levels of serum PINP in the severe OP group and the OP group were significantly increased compared to the normal group（P<0.05）,no significant difference was observed among groups（P>0.05）.（3）The levels of serum CTX in the severe OP group were significantly higher than those in the normal group and the osteopenia group（P<0.05）.Serum CTX levels in the OP group and the osteopenia group were significantly higher than that in the normal group（P<0.05）.The remaining comparisons were not found to be statistically different（P>0.05）.（4）CTX in the osteopenia group was evaluated 79.31%compared to the normal group.2.Comparison of femoral neck biochemical markers protein expression among different groups:（1）Femoral neck COL-I protein expression in the severe OP group and the OP group were significantly decreased compared to the normal group and the osteopenia group（P<0.05）.The remaining comparisons were not found to be statistically different（P>0.05）.（2）Femoral neck OPN protein expression in the severe OP group and the OP group were significantly increased compared to the normal group and the osteopenia group.OPN in the osteopenia group was significantly higher than that in the normal group（P<0.05）,the differences of the other groups were not statistically significant（P>0.05）.（3）OPN in the osteopenia group was evaluated 233.33%compared to the normal group.3.Comparison of femoral neck L_maxamong different groups:Femoral neck L_maxin the severe OP group was significantly decreased compared to the normal group,osteopenia group,and OP group（P<0.05）.Femoral neck L_maxin the OP group and the osteopenia group were significantly decreased compared to the normal group（P<0.05）.The remaining comparisons were not found to be statistically different（P>0.05）.4.Correlation of the femoral neck BMD,femoral neck L_max,and other markers:After adjusting age,gender and body mass index（BMI）,we found that CTX and OPN were negatively correlated with femoral neck BMD and femoral neck L_max（P<0.05）.CTX and OPN were both independent influencing factors for the femoral neck BMD and femoral neck L_max（P<0.05）.COL-I was positively correlated with femoral neck L_max（P<0.05）,and it was the independent influencing factors for the femoral neck L_max（P<0.05）.Among them,CTX had the strongest correlation with femoral neck BMD.5.Correlation of femoral neck biochemical markers and serum BTMs:After adjusting age,gender and BMI,we found that CTX was negatively correlated with OPN,and positively correlated with COL-I（P<0.05）.CTX was the independent influencing factor for COL-I and OPN.6.ROC curve analysis:（1）The area under curve（AUC）of CTX and OPN were significantly greater than that of PINP and OC for the diagnosis of femoral neck osteopenia（P<0.01）.The differences between other groups were not statistically significant（P>0.05）.（2）The AUC of COL-I and OPN were significantly greater than that of PINP and OC for the diagnosis of femoral neck OP（P<0.05）.The differences between other groups were not statistically significant（P>0.05）.Conclusions:1.During the progression of OP,protein expression of OPN in the femoral neck and the level of serum OC,PINP,and CTX gradually increase,while protein expression of femoral neck COL-I gradually decreases.Among these markers,CTX and OPN show obvious changes during early stage of femoral neck osteopenia.2.OPN and CTX were both independent influencing factors for femoral neck BMD and femoral neck L_maxadjusted for age,gender,and BMI.Meanwhile,COL-I was the independent influencing factor for femoral neck L_max.3.CTX was the independent influencing factors for OPN and COL-I adjusted for age,gender and BMI.CTX can be used as a prognostic indicator for OPN and COL-I.4.CTX can better reflect femoral neck bone loss and the change of femoral neck bone strength,early measurement of it can not only contribute to notice femoral neck osteopenia patients in time,but also provide a theoretical basis for delaying the occurrence of femoral neck OP and femoral neck osteoporotic fractures.