Low T3 Syndrome is Associated with Imbalance of Bone Turnover Biomarker in Patients with Type 2 Diabetes.

Objectives: To investigate the variation in bone turnover biomarkers among patients with type 2 diabetes (T2D) and low triiodothyronine levels (Low T3 syndrome). Materials and Methods: This retrospective analytic study included 418 inpatient records from Shanghai Pudong Hospital covering the years 2021 to 2023. Laboratory data related to metabolic and bone turnover biomarkers in patients were analyzed with T2D and the low T3 syndrome. Results: The results indicated that patients with reduced serum T3 levels exhibited statistically significant variations in thyroid function, age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), and the proportion of medication history associated with diabetes in comparison to euthyroid patients. In addition to parathyroid hormones, bone turnover biomarkers including N-terminal middle molecular fragment of osteocalcin (NMID), plasma calcium (Ca2+), ß C-terminal cross-linking telopeptide of type 1 collagen (ß-CTX), and 25-hydroxyvitamin D3 (25 OH VitD3) exhibited significant changes in patients with decreased T3 levels. Evident irregularities were observed in patients with a decreased T3 level, including elevated serum creatinine (SCr), decreased concentrations of albumin and total protein, and a decreased estimated glomerular filtration rate (eGFR), as assessed through hepatic and renal testing, respectively. Significant associations between bone turnover biomarkers and the subsequent variables (gender, adiposity, hepatic, renal, and thyroid function) were revealed through the correlational analysis. Further investigation utilized multivariate linear regression to determine that, in addition to thyroid function, several other factors such as age, gender, bodyweight, pancreatic, hepatic, and renal function, affected the variability in bone turnover biomarkers among patients demonstrating a low serum T3 level. Conclusions: This comparative study demonstrated that despite age, gender, bodyweight, hepatic, renal function, thyroid hormone and pancreatic function were significant factors associated with bone metabolism in patients with T2D and Low T3 syndrome, which may increase the risk of osteoporosis.

The association between the triglyceride-glucose index and bone turnover markers in osteoporotic fractures patients aged 50 and above who are hospitalized for surgical intervention: a retrospective cross-sectional study.

Objective: To evaluate the correlation between the triglyceride-glucose (TyG) index and bone turnover markers (BTMs) in osteoporotic fractures (OPFs) patients hospitalized for surgical intervention. Methods: A retrospective cross-sectional study was conducted on 3558 OPFs patients hospitalized for surgical intervention between January 2017 and July 2022. The study obtained baseline values for various biomarkers and covariates, including fasting blood glucose, ß-C-terminal telopeptide of type I collagen (ß-CTX), procollagen type 1 N-terminal propeptide (P1NP), triglycerides, age, sex, body mass index, smoking, drinking, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, uric acid, the score of American society of anesthesiologists, homocysteine, parathyroid hormone, apolipoprotein B, apolipoprotein A, magnesium, phosphorus and calcium. Multiple linear regression, curve fitting, threshold effects, and subgroup analyses were also applied. Results: After adjusting for covariates in the regression analysis, the results revealed a negative correlation between ß-CTX and P1NP levels and the baseline TyG index. Specifically, a one-unit increase in the TyG index was associated with a reduction in ß-CTX levels of -0.06 (95% CI: -0.10, -0.01; P-value = 0.012) and a reduction in P1NP levels of -4.70 (95% CI: -9.30, -0.09; P-value = 0.046). Additionally, the inflection points for the nonlinear correlation between the TyG index and ß-CTX and P1NP were found to be K = 6.31 and K = 6.63, respectively. Conclusion: The study demonstrated a negative, non-linear relationship among the TyG index, ß-CTX and P1NP in OPFs patients hospitalized for surgical intervention. These findings suggest that elevated TyG index levels may adversely affect bone turnover, potentially contributing to the progression of OP.

Divergent associations of inflammatory markers with bone turnover markers in elderly patients with osteoporotic fractures.

The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient's complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (ß = -1.1788, 95% CI: -1.7230 to -0.6345, P-value < 0.0001) and ß-C-terminal telopeptide of type I collagen (ß-CTX) (ß = -0.0104, 95% CI: -0.0145 to -0.0062, P-value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (ß = -17.4523, 95% CI: -27.7335 to -7.1710, P-value = 0.0009) and ß-CTX (ß = -0.1327, 95% CI: -0.2211 to -0.0443, P-value = 0.0034). However, PLR indicated a positive correlation with P1NP (ß = 0.0326, 95% CI: 0.0007 to 0.0645, P-value = 0.0458) and ß-CTX (ß = 0.0003, 95% CI: 0.0001 to 0.0006, P-value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, ß-CTX. In addition, the stratified analysis validated the result's stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with ß-CTX, whereas PLR demonstrates a positive correlation with ß-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism.

The correlation between serum bone metabolism indexes and bone disease and survival in newly diagnosed multiple myeloma patients.

Objective Myeloma-related bone disease (MBD) is one of the most common complications of multiple myeloma (MM). This study aims to investigate the correlation between serum bone metabolism indexes (BMIs), the clinical characteristics and prognosis of newly diagnosed MM (NDMM) patients. METHODS: The serum BMIs of 148 patients with NDMM in a single hematological disease treatment center from April 2014 to December 2019 were analyzed retrospectively, including type I collagen amino terminal elongation peptide (PINP), ß-C-terminal telopeptide of type I collagen (ß-CTX) and N-terminal osteocalcin (N-MID). Other clinical indexes were simultaneously collected and the degree of bone damage in patients was evaluated. We explored the effect of serum BMIs on the prognosis and identified independent prognostic factors. Another 77 NDMM patients from April 2018 to February 2021 served as the validation cohort. RESULTS: The area under the curve (AUC) predicted by ß-C-terminal telopeptide of type I collagen (ß-CTX), type I collagen amino terminal elongation peptide (PINP), and N-terminal osteocalcin (N-MID) for overall survival (OS) were 0.708, 0.613, and 0.538, respectively. Patients with high serum levels had shorter OS (p < .001, p = .004, p = .027, respectively). Cox multivariate analysis indicated that serum ß- CTX、lactic dehydrogenase、hemoglobin and the degree of bone injury were independent prognostic factors. A COX regression model was established with a C-index of 0.782 and validated with a C-index of 0.711. CONCLUSION: The serum BMIs are correlated with the patients' OS, and ß- CTX can be an independent prognostic factor.

Establishment of Reference Intervals for Bone Turnover Biomarkers in Healthy Populations in Northern China.

Aim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations. Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations. Results: We found that gender were associated with 25(OH)D, OC, ß-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P<0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in ß- CTX levels between seasons. Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.

Early diagnostic value of ECT whole-body bone imaging combined with PINP and ß-CTX for bone metastasis of lung cancer.

OBJECTIVE: This research was aimed at investigating the early diagnostic value of emission computed tomograph (ECT) whole-body bone imaging combined with PINP and ß-CTX for bone metastasis of lung cancer. METHODS: Case data of 86 lung cancer patients were categorized into lung cancer with bone metastasis (LCWBM, 46 cases) and lung cancer without bone metastasis (LCWOBM, 40 cases) groups according to the presence or absence of bone metastasis. Patients' general information were collected. ECT whole-body bone imaging was used to detect bone metastases and the grading of the extent of disease (EOD) in both groups, and electrochemiluminescence was utilized to detect the serum levels of PINP and ß-CTX. Spearman correlation analysis was employed to evaluate the correlation between EOD grading and PINP and ß-CTX levels. Logistic univariate and multivariate regression was implemented to analyze the risk factors of bone metastasis of lung cancer. Receiver operating characteristic (ROC) curve was applied to analyze the diagnostic efficacy of the single test of ECT whole-body bone imaging, PINP, or ß-CTX and the combination of the three tests. RESULTS: The differences in pathological type, clinical stage and EOD grading, the number of positive ECT cases, and the expression levels of PINP and ß-CTX between the LCWBM and LCWOBM groups were statistically significant. In LCWBM patients with different EOD grading, the trends of the expression of PINP and ß-CTX were grade 3 > grade 2 > grade 1 and grade 0. Further correlation analyses revealed that EOD grading showed a significant positive correlation with the PINP and ß-CTX expression levels. Univariate logistic regression analysis demonstrated that adenocarcinoma, TNM stage IV, ECT positivity, and high expression of PINP and ß-CTX were associated with bone metastasis of lung cancer, and multivariate logistic regression analysis indicated that ECT positivity, high expression of PINP and ß-CTX were independent risk factors for bone metastasis of lung cancer. The area under the curve (AUC) of ECT, PINP, and ß-CTX alone for the diagnosis of bone metastasis of lung cancer were 0.872, 0.888, and 0.874, respectively, and the AUC for the combined diagnosis of the three was 0.963, which was greater than that of any one of the individual indices, with a sensitivity of 86.96% and a specificity of 97.50% at a Youden index of 0.845. CONCLUSION: ECT whole-body bone imaging combined with PINP and ß-CTX has high diagnostic value for bone metastasis of lung cancer.

Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy and their association with age and estimated glomerular filtration rate (eGFR). This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over 1 year. Patients' clinical data were collected. The levels of BTMs and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decreased levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.

Reference intervals for plasma ß-CTX and P1NP in children: A systematic review and pooled estimates.

OBJECTIVE: Reference intervals for plasma P1NP and ß-CTX in children and adolescents from several studies have recently been published. The aim of this study was to combine the available data into a set of reference intervals for use in clinical laboratories. DESIGN AND METHODS: A systematic literature search for primary studies reporting reference intervals for plasma P1NP and ß-CTX in infants, children and adolescents using the Roche methods was carried out. Reference limits were extracted. For each year of age, mean upper and lower reference limits were calculated, weighted by the number of subjects in each study, and were plotted against age. Proposed reference limits were developed from the weighted mean data with age partitions determined pragmatically. RESULTS: Reference limits for clinical use for females to 25 years and males to 18 years, based on the weighted mean reference data, are presented. Ten studies contributed to the pooled analysis. The proposed reference limits are identical for males and females <9 years age, prior to the pubertal growth spurt. For ß-CTX, the weighted mean reference limits showed relatively constant values during the pre-pubertal years but a marked increase during puberty before a rapid decline towards adult values. Those for P1NP showed high values declining rapidly in the first 2 years of life, followed by a modest increase during early puberty. Limited published information for late adolescent and young adult subjects was noted. CONCLUSIONS: The proposed reference intervals may be useful for clinical laboratories reporting these bone turnover markers measured by the Roche assays.

Vitamin D deficiency linked to abnormal bone and lipid metabolism predicts high-risk multiple myeloma with poorer prognosis.

Purpose: Vitamin D deficiency is frequent in patients with multiple myeloma (MM), however, its prognostic relevance in MM was rather inconclusive. We first investigated the association of vitamin D deficiency with abnormal bone and lipid metabolism in newly diagnosed multiple myeloma (NDMM), and next assessed the impact of serum ratio of vitamin D to carboxy-terminal telopeptide of type I collagen (ß-CTX) on progression-free survival (PFS) and overall free survival (OS) in patients with NDMM. Methods: The data of 431 consecutive patients with NDMM at Beijing Jishuitan Hospital from September 2013 to December 2022 were collected and retrospectively reviewed through our electronic medical record system. The measurement of 25-hydroxyvitamin D in the blood is an indicator of an individual's overall vitamin D status. Results: The serum levels of vitamin D were negatively correlated with ß-CTX in NDMM patients. Of note, positive correlation between vitamin D and cholesterol levels in the serum was found in this study. The cohort (n = 431) was divided into two groups based on the serum ratio of vitamin D to ß-CTX. Compared to the group with a higher vitamin D to ß-CTX ratio, the group with a lower vitamin D to ß-CTX ratio (n = 257, 60%) exhibited hypocholesterolemia, inferior PFS and OS, along with increased cases of ISS stage-III and R-ISS stage-III, a higher number of plasma cells in the bone marrow, and elevated serum calcium levels. Consistent with this, multivariate analysis confirmed that the vitamin D to ß-CTX ratio was an independent unfavorable indicator for survival in NDMM patients. Conclusion: Our data demonstrated the ratio of vitamin D to ß-CTX in the serum is a unique biomarker for NDMM patients to identify the high-risk cases with poor prognosis, which is superior to vitamin D itself for predicting PFS and OS in NDMM. Also, it is worth mentioning that our data on the connection between vitamin D deficiency and hypocholesterolemia might help clarify novel mechanistic aspects of myeloma development.

Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide ß glypeptide: A cross-sectional study in elder Chinese population.

Type I collagen carboxyl-terminal peptide ß (ß-CTX) increases in osteoporosis. The study aimed to explore the relationship between serum ß-CTX and the risk of osteoporosis as well as sarcopenia in Chinese elderly inpatients. Around 228 patients whose age >65 years were recruited in this cross-sectional study. Dual-energy X-ray scanning was used to access skeletal muscle and bone mass. Serum concentration of ß-CTX as well as the prevalence of osteoporosis were significantly higher in low skeletal muscle index (SMI) group than that in the normal SMI group (P < 0.05). Serum ß-CTX levels negatively correlated with SMI and bone mass (P < 0.05). Total muscle mass, appendicular skeletal muscle mass, SMI, total bone mass, and bone mass at various sites including the limbs, spine, and pelvis decreased significantly, and the prevalence of low SMI increased with the increase of the quartiles of ß-CTX. Higher serum ß-CTX had an increased risk of low SMI and osteoporosis (P < 0.05). Summarily, with increasing serum ß-CTX levels, both muscle and bone mass decreased in Chinese elderly inpatients. Serum ß-CTX was positively associated with the risk of not only osteoporosis but also skeletal muscle loss.

Risk of primary osteoporosis score (RPOPs): an algorithm model for primary osteoporosis risk assessment in grass-roots hospital.

BACKGROUND: This study aimed to develop and validate a lasso regression algorithm model which was established by correlation factors of bone mineral density (BMD) and could be accurately predicted a high-risk population of primary osteoporosis (POP). It provides a rapid, economical and acceptable early screening method for osteoporosis in grass-roots hospitals. METHODS: We collected 120 subjects from primary osteoporosis screening population in Zhejiang Quhua Hospital between May 2021 and November 2021 who were divided into three groups (normal, osteopenia and osteoporosis) according to the BMD T-score. The levels of three micro-RNAs in the plasma of these people were detected and assessed by qRT-PCR. At the same time, the levels of ß-CTX and t-P1NP in serum of the three groups were determined. Based on the cluster random sampling method, 84 subjects (84/120, 70%) were selected as the training set and the rest were the test set. Lasso regression was used to screen characteristic variables and establish an algorithm model to evaluate the population at high risk of POP which was evaluated and tested in an independent test cohort. The feature variable screening process was used 10-fold cross validation to find the optimal lambda. RESULTS: The osteoporosis risk score was established in the training set: Risk of primary osteoporosis score (RPOPs) = -0.1497785 + 2.52Age - 0.19miR21 + 0.35miR182 + 0.17ß-CTx. The sensitivity, precision and accuracy of RPOPs in an independent test cohort were 79.17%, 82.61% and 75%, respectively. The AUC in the test set was 0.80. Some risk factors have a significant impact on the abnormal bone mass of the subjects. These risk factors were female (p = 0.00013), older than 55 (p < 2.2e-16) and BMI < 24 (p = 0.0091) who should pay more attention to their bone health. CONCLUSION: In this study, we successfully constructed and validated an early screening model of osteoporosis that is able to recognize people at high risk for developing osteoporosis and remind them to take preventive measures. But it is necessary to conduct further external and prospective validation research in large sample size for RPOPs prediction models.

Positive association of glucagon with bone turnover markers in type 2 diabetes: A cross-sectional study.

AIMS: The osteo-metabolic changes in type 2 diabetes (T2D) patients are intricate and have not been fully revealed. It is not clear whether glucagon is entirely harmful in the pathogenesis of diabetes or a possible endocrine counter-regulation mechanism to reverse some abnormal bone metabolism. This study aimed to investigate the association between glucagon and bone turnover markers (BTMs) in T2D patients. METHODS: A total of 3984 T2D participants were involved in a cross-sectional study in Shanghai, China. Serum glucagon was measured to elucidate its associations with intact N-terminal propeptide of type I collagen (P1NP), osteocalcin (OC), and ß-C-terminal telopeptide (ß-CTX). Glucagon was detected with a radioimmunoassay. Propeptide of type I collagen, OC, and ß-CTX were detected using chemiluminescence. The diagnosis of T2D was based on American Diabetes Association criteria. RESULTS: The concentration of glucagon was positively correlated with two BTMs [OC-ß: 0.034, 95% CI: 0.004, 0.051, p = 0.024; CTX-ß: 0.035, 95% CI: 0.004, 0.062, p = 0.024]. The result of P1NP was [P1NP-regression coefficient (ß): 0.027, 95% CI: -0.003, 0.049, p = 0.083]. In the glucagon tertiles, P for trend of the BTMs is [P1NP: 0.031; OC: 0.038; CTX: 0.020], respectively. CONCLUSIONS: Glucagon had a positive effect on bone metabolism. The concentrations of the three BTMs increased as glucagon concentrations rose. This implied that glucagon might speed up skeletal remodelling, accelerate osteogenesis, and promote the formation of mature bone tissue. At the same time, the osteoclastic process was also accelerated, providing raw materials for osteogenesis to preserve the dynamic balance. In view of the successful use of single-molecule as well as dual/triple agonists, it would be feasible to develop a preparation that would reduce osteoporosis in diabetic patients.

Efficacy of Yigu® versus Aclasta® in Chinese postmenopausal women with osteoporosis: a multicenter prospective study.

Zoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population. INTRODUCTION: Yigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL. METHODS: This was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups. RESULTS: A total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: - 0.71 to 1.00, equivalence margin: - 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and ß-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (ß-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups. CONCLUSION: Intravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

Novel serological biomarker models composed of bone turnover markers, vitamin D, and estradiol and their auxiliary diagnostic value in girls with idiopathic central precocious puberty.

OBJECTIVE: To establish serological biomarker models composed of bone turnover markers (BTMs), vitamin D (Vit D), and estradiol (E2) and to explore their auxiliary diagnostic value in girls with idiopathic central precocious puberty (ICPP). METHODS: Ninety-three girls with ICPP and 93 healthy girls were included in the ICPP group and the control group, respectively. The serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin (N-MID), ß-C-terminal telopeptide of type 1 collagen (ß-CTX), Vit D, E2, and other biochemical parameters were detected in all participants. Serological biomarker models for assistance with ICPP diagnosis were established by logistic regression analyses. RESULTS: Serum P1NP, ß-CTX, Vit D, and E2 levels differed significantly between the two groups (p < 0.05). Three models were established. Model 1 consisted of P1NP and ß-CTX, and had an area under curve (AUC) of 0.764, sensitivity of 74.19%, and specificity of 72.04%. Model 2 consisted of P1NP, ß-CTX, and Vit D, and had an AUC of 0.840, sensitivity of 83.87%, and specificity of 72.04%. Model 3 consisted of P1NP, ß-CTX, Vit D, and E2, and had an AUC of 0.917, sensitivity of 82.80%, and specificity of 86.02%. CONCLUSIONS: Serum P1NP, ß-CTX, Vit D, and E2 levels may be effective indicators for auxiliary diagnosis of ICPP. Serological biomarker models composed of P1NP, ß-CTX, Vit D, and E2 (models 1, 2, and 3) may have auxiliary diagnostic value for ICPP.

Modern markers for evaluating bone disease in multiple myeloma (Review).

Multiple myeloma (MM) is a bone marrow neoplasia with increasing incidence compared to previous years. Although new therapeutic molecules have been introduced, it remains an incurable disease with severe repercussions to patients. For many patients, bone disease represents a severe problem often causing pain, pathological bone fractures, and spinal cord compression, which affects the quality of life. This article analyzes the main markers of bone destruction in MM as well as risk factors for severe bone damage. Bone complications have a negative impact on the quality of life of patients with MM, along with other associated complications (renal failure, hypogammaglobulinemia, osteolytic bone disease, hypercalcemia, anemia). The markers of bone destruction described in this article include: interleukin (IL)-6, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX, CTX), human bone sialoprotein (BSP) and dickkopf-1 secreted glycoprotein (DKK1). The future practical applicability of this literature review would be the large-scale determination of markers of bone destruction that correlate with the negative evolution to complications of bone disease or the implications that these markers have in regards to treatment.

Association of Insulin Resistance and ß-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients.

Background: The interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, ß-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism. Methods: A total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.chictr.org.cn, ChiCTR1800017573) in Shanghai, China. Homeostasis model assessment of insulin resistance (HOMA-IR) and ß-cell dysfunction (HOMA-%ß) were applied to elucidate the nexus between ß-C-terminal telopeptide (ß-CTX), intact N-terminal propeptide of type I collagen (P1NP) and osteocalcin (OC). ß-CTX, OC and P1NP were detected by chemiluminescence. Results: HOMA-IR was negatively associated with ß-CTX, P1NP and OC (regression coefficient (ß) -0.044 (-0.053, -0.035), Q4vsQ1; ß -7.340 (-9.130, -5.550), Q4vsQ1 and ß -2.885 (-3.357, -2.412), Q4vsQ1, respectively, all P for trend <0.001). HOMA-%ß was positively associated with ß-CTX, P1NP and OC (ß 0.022 (0.014, 0.031), Q4vsQ1; ß 6.951 (5.300, 8.602), Q4vsQ1 and ß 1.361 (0.921, 1.800), Q4vsQ1, respectively, all P for trend <0.001). Conclusions: Our results support that lower bone turnover biomarker (ß-CTX, P1NP and OC) levels were associated with a combination of higher prevalence of insulin resistance and worse ß-cell function among dysglycemia patients. It is feasible to detect bone turnover in diabetes or hyperglycemia patients to predict the risk of osteoporosis and fracture, relieve patients' pain and reduce the expenses of long-term cure.

A Multicenter Study to Evaluate Harmonization of Assays for C-Terminal Telopeptides of Type I Collagen (ß-CTX): A Report from the IFCC-IOF Committee for Bone Metabolism (C-BM).

BACKGROUND: Biochemical bone turnover markers are useful tools to assess bone remodeling. C-terminal telopeptide of type I collagen (ß-CTX) has been recommended as a reference marker for bone resorption in research studies. METHODS: We describe the results of a multicenter study for routine clinical laboratory assays for ß-CTX in serum and plasma. Four centers (Athens GR, Copenhagen DK, Liege BE and Sheffield UK) collected serum and plasma (EDTA) samples from 796 patients presenting to osteoporosis clinics. Specimens were analyzed in duplicate with each of the available routine clinical laboratory methods according to the manufacturers' instructions. Passing-Bablok regressions, Bland-Altman plots, V-shape evaluation method, and Concordance correlation coefficient for ß-CTX values between serum and plasma specimens and between methods were used to determine the agreement between results. A generalized linear model was employed to identify possible variables that affected the relationship between the methods. Two pools of serum were finally prepared and sent to the four centers to be measured in 5-plicates on 5 consecutive days with the different methods. RESULTS: We identified significant variations between methods and between centers although comparison results were generally more consistent in plasma compared to serum. We developed univariate linear regression equations to predict Roche Elecsys®, IDS-iSYS, or IDS ELISA ß-CTX results from any other assay and a multivariable model including the site of analysis, the age, and weight of the patient. The coefficients of determination (R2) increased from approximately 0.80 in the univariate model to approximately 0.90 in the multivariable one, with the site of analysis being the major contributing factor. Results observed on the pools also suggest that long-term storage could explain the difference observed with the different methods on serum. CONCLUSION: Our results show large within- and between-assay variation for ß-CTX measurement, particularly in serum. Stability of the analyte could be one of the explanations. More studies should be undertaken to overcome this problem. Until harmonization is achieved, we recommend measuring ß-CTX by the same assay on EDTA plasma, especially for research purposes in large pharmacological trials where samples can be stored for long periods before they are assayed.

The changes in bone turnover markers of female systemic lupus erythematousus patients without glucocorticoid.

OBJECTIVES: SLE is a chronic autoimmune disease, which can affect the level of bone metabolism and increase the risk of osteoporosis and fracture. The purpose of this research is to study the effect of SLE on bone turnover markers without the influence of glucocorticoids. METHODS: A total of 865 female subjects were recruited from Zhejiang Provincial People's Hospital and the First Hospital of Jiaxing, including 391 SLE patients without the influence of glucocorticoids and 474 non-SLE people. We detected Bone turnover markers including amino-terminal propeptide of type 1 procollagen (P1NP), C-terminal turnover of ß - I collagen (ß-CTX), N-terminal midfragment of osteocalcin (NMID) and 25(OH)D, and analyzed the difference in Bone turnover markers between the SLE group and the control group, as well as the influence of age and season on bone metabolism in female SLE patients. RESULTS: In the SLE group, the average age was 43.93±13.95 years old. In the control group, the average age was 44.84±11.42 years old. There was no difference between the two groups (t = 1.03, P = 0.30). P1NP, NMID and 25(OH)D in the SLE group were significantly lower than those in the control group (Z = 8.44, p < 0.001; Z = 14.41, p < 0.001; Z = 2.19, p = 0.029), and ß-CTX in the SLE group was significantly higher than that in the control group (Z = 2.61, p = 0.009). In addition, the levers of ß-CTX, NMID, P1NP and 25(OH)D in older SLE female patients were statistically significantly higher than those in younger (ρ = 0.104, p = 0.041; ρ = 0.223, p < 0.001; ρ = 0.105, p = 0.038; ρ = 0.289, p < 0.001). Moreover, ß-CTX reached a high value in summer and PINP reached a low value in winter. CONCLUSION: The bone formation markers of female SLE patients without glucocorticoid were lower than those of normal people and the bone resorption marker was higher than that of normal people. The 25 (OH) D of female SLE patients without glucocorticoid was lower than that of normal people. The risk of osteoporosis and fracture may be higher in elderly women with SLE. The bone resorption level of female SLE patients is high in summer and the bone formation level is low in winter.

Association of environmental cadmium exposure and bone remodeling in women over 50 years of age.

Chronic cadmium (Cd) toxicity is a significant health concern, and the mechanism of long-term low-dose Cd exposure on bone has not been fully elucidated yet. This study aimed to assess the association between long-term environmental Cd exposure and bone remodeling in women who aged over 50. A total of 278 non-smoking subjects from Cd-polluted group (n = 191) and non-Cd polluted group (n = 87) were investigated. Bone mineral density (BMD), the levels of three bone turnover markers (BTMs), including total procollagen type 1 amino-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (ß-CTX), bone-specific alkaline phosphatase (BALP), together with serum soluble receptor activator of nuclear factor-κB ligand (sRANKL) and osteoprotegerin (OPG) were determined. Early markers of renal dysfunction were measured as well. Urinary Cd concentrations ranged from 0.41 to 87.31 µg/g creatinine, with a median of 4.91 µg/g creatinine. Age, BMD, T-score, and prevalence of osteoporosis showed no statistical differences among the quartiles of urinary Cd concentrations, while serum levels of P1NP, ß-CTX, and OPG were higher in the upper quartiles. Multivariate linear regression models indicated significantly positive associations of urinary Cd concentration with serum levels of P1NP, ß-CTX, BALP, sRANKL, and OPG. A ridge regression analysis with T-score and the three BTMs, sRANKL, and OPG, adjusted for age and body mass index (BMI), indicated that except for age and Cd exposure, ß-CTX was a predictor of T-score. These findings demonstrated that Cd may directly accelerate bone remodeling. Serum ß-CTX might be an appropriate biochemical marker for evaluating and monitoring Cd-related bone loss. Capsule: Cadmium (Cd) may directly accelerate bone remodeling and serum ß-CTX is a valuable biochemical marker for evaluating Cd-related bone loss.

Analytical considerations and plans to standardize or harmonize assays for the reference bone turnover markers PINP and ß-CTX in blood.

Procollagen type I N-propeptide (PINP) and the C-terminal telopeptide of type I collagen (ß-CTX) in blood have been designated as reference bone turnover markers in osteoporosis by the International Osteoporosis Foundation (IOF) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). The IFCC Committee on Bone Metabolism (C-BM) has examined current commercial assays and performed a multicentre study to examine the agreement between assays for PINP and ß-CTX in serum and plasma. The results of these studies will inform our work towards the harmonization of PINP assays and the standardization of ß-CTX assays in blood, with the development of common calibrators and reference measurement procedures in collaboration with the reagent manufacturing industry. Successful achievement of these goals will help develop universally acceptable practice guidelines for the management of osteoporosis with the inclusion of common reference intervals and treatment targets for PINP and ß-CTX.