Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

BACKGROUND: Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. MATERIALS AND METHODS: A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. RESULTS: Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. CONCLUSIONS: We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Effectiveness of anthocyanin-rich foods on bone remodeling biomarkers of middle-aged and older adults at risk of osteoporosis: a systematic review, meta-analysis, and meta-regression.

CONTEXT: Current osteoporosis pharmacological treatment has undesirable side effects. There is increasing focus on naturally derived food substances that contain phytonutrients with antioxidant effects in promoting health and regulating immune response. OBJECTIVE: This review aims to systematically evaluate the effectiveness of anthocyanin-rich foods on bone remodeling biomarkers in middle-aged and older adults (≥40 y old) at risk of osteoporosis. DATA SOURCES: Randomized controlled trials were searched on 8 bibliographic databases of PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Food Science and Technology Abstracts, Cochrane Library, and ProQuest. DATA EXTRACTION AND ANALYSIS: Thirteen studies were included in the meta-analysis. Receptor activator of nuclear factor kappa-B ligand (RANKL) is exhibited from osteoblastic cells that gathered osteoclasts to bone sites for bone resorption, accelerating bone loss. Anthocyanin-rich food consumption showed statistically nonsignificant effects, with no substantial heterogeneity on bone remodeling biomarkers. However, there was a significant increase in lumbar spine L1-L4 bone mineral density. Mild-to-small effects were seen to largely favor the consumption of anthocyanin-rich foods. Berries (d = -0.44) have a larger effect size of RANKL than plums (d = 0.18), with statistically significant subgroup differences. Random-effects meta-regression found body mass index, total attrition rate, total energy, and dietary carbohydrate and fat intake were significant covariates for the effect size of RANKL. All outcomes had low certainty of evidence. CONCLUSION: Anthocyanin-rich foods may improve bone health in middle-aged and older adults at risk of osteoporosis. This review contributes to the growing interest in nutrient-rich foods as a low-cost and modifiable alternative to promote human health and reduce disease burden. Future high-quality studies with larger sample sizes and longer treatment durations are required to fully understand the effect of anthocyanin-rich foods on bone health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022367136.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Application of bone alkaline phosphatase and 25-oxhydryl-vitamin D in diagnosis and prediction of osteoporotic vertebral compression fractures.

BACKGROUND: Osteoporosis is a bone metabolic disease that usually causes fracture. The improvement of the clinical diagnostic efficiency of osteoporosis is of great significance for the prevention of fracture. The predictive and diagnostic values of bone alkaline phosphatase (B-ALP) and 25-oxhydryl-vitamin D (25-OH-VD) for osteoporotic vertebral compression fractures (OVCFs) were evaluated. METHODS: 110 OVCFs patients undergoing percutaneous vertebroplasty were included as subjects and their spinal computed tomography (CT) images were collected. After that, deep convolutional neural network model was employed for intelligent fracture recognition. Next, the patients were randomly enrolled into Ctrl group (65 cases receiving postoperative routine treatment) and VD2 group (65 cases injected with vitamin D2 into muscle after the surgery). In addition, 100 healthy people who participated in physical examination were included in Normal group. The differences in Oswestry dysfunction indexes (ODI), imaging parameters, B-ALP and 25-OH-VD expressions, and quality of life (QOL) scores of patients among the three groups were compared. The values of B-ALP and 25-OH-VD in predicting and diagnosing OVCFs and their correlation with bone density were analyzed. RESULTS: It was demonstrated that computer intelligent medical image technique was more efficient in fracture CT recognition than artificial recognition. In contrast to those among patients in Normal group, B-ALP rose while 25-OH-VD declined among patients in Ctrl and VD2 groups (P < 0.05). Versus those among patients in Ctrl group, ODI, Cobb angle, and B-ALP reduced, while bone density, the height ratio of the injured vertebrae, 25-OH-VD, and QOL score increased among patients in VD2 group after the treatment (P < 0.05). The critical values, accuracy, and areas under the curve (AUC) of the diagnosis of OVCFs by B-ALP and 25-OH-VD amounted to 87.8 µg/L versus 30.3 nmol/L, 86.7% versus 83.3%, and 0.86 versus 0.82, respectively. B-ALP was apparently negatively correlated with bone density (r = - 0.602, P < 0.05), while 25-OH-VD was remarkably positively correlated with bone density (r = 0.576, P < 0.05). CONCLUSION: To sum up, deep learning-based computer CT image intelligent detection technique could improve the diagnostic efficacy of fracture. B-ALP rose while 25-OH-VD declined among patients with OVCFs and OVCFs could be predicted and diagnosed based on B-ALP and 25-OH-VD. Postoperative intramuscular injection of VD2 could effectively improve the therapeutic effect on patients with OVCFs and QOL.

Peptide modified geniposidic acid targets bone and effectively promotes osteogenesis.

Background: Geniposidic acid (GPA), one of the active components of Eucommia ulmoides, promote bone formation and treat osteoporosis by activating farnesoid X receptor (FXR). However, GPA has low oral availability and lack of bone targeting in the treatment of bone related diseases. With the development of modern technology, small molecules, amino acids, or aptamers are used for biological modification of drugs and target cells in bone tissue, which has become the trend of bone targeted research. Methods: In this study, SDSSD (an osteoblast-targeting peptide) were modified in GPA using Fmoc solid-phase synthesis technique to form a new SDSSD-GPA conjugate (SGPA). The bone targeting of SGPA was evaluated using in vivo imaging and cell co-culture. In vitro, the effect of SGPA on cytotoxicity, osteoblastic activity, and mineralization ability were studied in mouse primary osteoblasts (OBs). In vivo, the therapeutic effect of SGPA on osteoporosis using an ovariectomized (OVX) mouse model. The bone mass, histomorphometry, serum biochemical parameters, and the molecular mechanism were evaluated. Results: SGPA was enriched in OBs and tends to accumulate in bone tissue. In vitro, SGPA significantly enhanced the osteogenic activity and mineralization of OBs compared with GPA. In vivo, SGPA enhanced serum BALP and P1NP levels, increased the trabecular bone mass of the mice, and SGPA administration have a higher bone mineralization deposition rate than the GPA-treated mice. Moreover, SGPA significantly activated FXR and Runt-related transcription factor 2 (RUNX2). Conclusions: Collectively, SGPA is enriched into OBs, and promotes bone formation by activating FXR-RUNX2 signalling, effectively treating osteoporosis at relatively low doses. The translational potential of this article: This study demonstrates a more efficient and safe application of GPA in treating osteoporosis, provide a new concept for the bone targeted application of natural compounds.

Coordination-induced self-assembly based carbon dot dendrimers as efficient signal labels for electrochemiluminescent immunosensor construction.

In this work, an "on-off" electrochemiluminescent immunosensor for bone alkaline phosphatase (BALP) detection was constructed based on the carbon dot dendrimers (CD DRs) as signal labels and Pt nanoparticles functionalized Ni-phenolic coordination spheres (Pt@Ni-PCS) as quenching labels. The prepared CD DRs with low cytotoxicity were synthesized via coordination-induced self-assembly of carboxyl groups-rich N-doped carbon dots and zirconium oxygen clusters, of which the ECL efficiency was 2-fold enhancement than that of discrete N-doped carbon dots. Benefiting from the efficient quenching effect of Pt@Ni-PCS toward Zr-CD DRs/triethylamine-based ECL system, the prepared immunoassay for BALP detection exhibited a broad linear range with 1 pg/mL to 50 ng/mL and a low limit of detection of 24.9 fg/mL. Importantly, this highlights coordination-induced self-assembly as a tool for carbon dots enrichment to construct efficient ECL nanocomposites, which conceptualizes a pathway to expand the application of carbon dots in clinical ECL analysis technology.

Bone Turnover Markers: Basic Biology to Clinical Applications.

Bone turnover markers (BTMs) are used widely, in both research and clinical practice. In the last 20 years, much experience has been gained in measurement and interpretation of these markers, which include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide); and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). BTMs are usually measured by enzyme-linked immunosorbent assay or automated immunoassay. Sources contributing to BTM variability include uncontrollable factors (eg, age, gender, ethnicity) and controllable factors, particularly relating to collection conditions (eg, fasting/feeding state, and timing relative to circadian rhythms, menstrual cycling, and exercise). Pregnancy, season, drugs, and recent fracture(s) can also affect BTMs. BTMs correlate with other methods of assessing bone turnover, such as bone biopsies and radiotracer kinetics, and can usefully contribute to diagnosis and management of several diseases such as osteoporosis, osteomalacia, Paget's disease, fibrous dysplasia, hypophosphatasia, primary hyperparathyroidism, and chronic kidney disease-mineral bone disorder.

Alkaline Phosphatases: Biochemistry, Functions, and Measurement.

Alkaline phosphatases (ALPs) are a group of isoenzymes, situated on the external layer of the cell membrane; they catalyze the hydrolysis of organic phosphate esters present in the extracellular space. Zinc and magnesium are significant co-factors for the biological activity of these enzymes. Although ALPs are available in various body tissues and have distinct physiochemical properties, they are true isoenzymes since they catalyze a similar reaction. In the liver, ALP is cytosolic and present in the canalicular membrane of the hepatocytes. ALPs are available in placenta, ileal mucosa, kidney, bone, and liver. However, most of the ALPs in serum (over 80%) are delivered from liver and bone and in more modest quantities from the intestines. Despite the fact that alkaline phosphatases are found in numerous tissues all through the body, their exact physiological function remains largely unknown.

Romosozumab improves low bone mineral density in a postmenopausal woman undergoing chronic hemodialysis and treated with a calcium-sensing receptor agonist.

Preventing osteoporotic fractures is an issue requiring urgent attention to reduce mortality. However, unlike chronic kidney disease-mineral and bone disorder (CKD-MBD), osteoporosis is inadequately addressed in patients undergoing chronic dialysis. In fact, little is known about the proper use of anti-osteoporotic drugs for patients with CKD-MBD. A recent study showed that romosozumab, an anti-osteoporotic drug, increased bone mineral density in osteoporotic patients on hemodialysis without clinically significant adverse events. However, the efficacy and safety of coadministering romosozumab with a calcium-sensing receptor (CaSR) agonist, a pivotal drug used in the management of CKD-MBD, remain unclear. Here, we report the case of a postmenopausal woman undergoing chronic hemodialysis and treated with add-on romosozumab for osteoporosis to CaSR agonist for secondary hyperparathyroidism. After 1 year of treatment, her bone mineral density increased; however, hypocalcemia occurred during the treatment. These results suggest that the concomitant use of romosozumab with CaSR agonist may be a possible treatment option for severe osteoporosis in postmenopausal women receiving chronic hemodialysis with a high fracture risk, but serum calcium levels should be monitored closely and those at risk of ectopic calcification might not be ideal candidates for such treatment.

[Effect of Bone Marrow Mesenchymal Stem Cells on Mechanical Dynamics and BALP/CTX-1 Expression in Rats with Osteoporotic Vertebral Fracture].

Objective: To analyze the effects of bone marrow mesenchyml stem cells (BMSCs) on bone alkaline phosphatase (BALP)/C-terminal telopeptide of type-Ⅰ collagen (CTX-1) expression and mechanical dynamics in rats with osteoporotic (OP) vertebral fracture. Methods: A total of 60 female Sprague-Dawley rats were evenly divided into three groups, a control group that received sham operation (sham group), a group consisting of rats with OP vertebral fracture (OP group), and the last group consisting of OP vertebral fracture rats given BMSCs treatment (BMSCs group). Comparison of the three groups of animals was made in terms of bone dynamic change, bone quantitative broadband ultrasound attenuation (BUA) measurement, and bone mineral density (BMD). HE staining was done to examine the bone histological morphological parameters of the vertebral body. Serum CTX-1 and BALP levels were determined by ELISA. Results: Mechanical comparison showed that there were significant differences in mechanical changes of L 5 vertebra body and right femur among the three experimental groups ( P<0.05). The elastic modulus and maximum load of the OP group significantly decreased compared with those of the sham group ( P<0.05). After the intervention, the maximum load and elastic modulus of the BMSCs group were significantly higher than those of the OP group ( P<0.05). Compared with the sham group, BUA and BMD values in the OP group were significantly downregulated ( P<0.05). After intervention, BUA and BMD of the BMSCs group were significantly higher than those of the OP group and were comparable to those of the sham group ( P<0.05). Compared with the sham group, the number of trabeculae in the OP group was significantly fewer, and the distribution of trabeculae was disorderly and lacked regularity. Compared with the OP group, there were more trabeculae in the BMSCs group, and their distribution was more regular. Compared with sham group, bone histological morphological parameters of the vertebral body of rats in the OP group were significantly changed--mean trabecular plate thickness (MTPT) and trabecular bone volume (TBV) parameters were significantly decreased, while mineral apposition rate (MAR) and trabecula bone surface (TRS) parameters were significantly upregulated (all P<0.05). After the experimental intervention, bone histological morphological parameters of the vertebral body in the BMSCs group showed significant improvement compared with those of the OP group ( P<0.05). Compared with the sham group, serum BALP content in the OP group was greatly decreased, while the CTX-1 level was upregulated ( P<0.05). After the intervention, the BMSCs group had higher serum BALP content than that of the OP group and substantially lower CTX-1 content than that of the OP group ( P<0.05). Conclusion: BMSCs can improve the mechanical changes in rats with OP vertebral fracture, and can increase the maximum load and elastic modulus of bone tissue. In addition, BMSCs can upregulate the expression of BALP in serum and downregulate the expression of CTX-1, thus helping rats with OP vertebral fracture heal early.

Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease.

Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and kidney tissues. Beyond the well-known effects on bone mineralization, the bone ALP (BALP) isoforms (B/I, B1, B1x, and B2) are also involved in the pathogenesis of ectopic calcification. This narrative review summarizes the recent clinical investigations and mechanisms that link ALP and BALP to inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality. The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed. Recent advances in different pharmacological strategies are highlighted, with the potential to modulate the expression of ALP directly and indirectly in CKD-mineral and bone disorder (CKD-MBD), e.g., epigenetic modulation, phosphate binders, calcimimetics, vitamin D, and other anti-fracture treatments. We conclude that the significant evidence for ALP as a pathogenic factor and risk marker in CKD-MBD supports the inclusion of concrete treatment targets for ALP in clinical guidelines. While a target value below 120 U/L is associated with improved survival, further experimental and clinical research should explore interventional strategies with optimal risk-benefit profiles. The future holds great promise for novel drug therapies modulating ALP.

Cancellous bone-like tissue replacement from calcinosis in patients with systemic sclerosis with multiple external root resorption.

Calcinosis is frequently observed in patients with systemic sclerosis (SSc). The fundamental treatment of calcinosis has not yet been established. During follow-up, calcinosis in the subcutaneous surface is often spontaneously extracted or remains confined by fibrous tissues. We previously identified a new symptom in SSc patients, multiple external root resorption (MERR), and these patients had calcifications in the nasal spine. Here, we report for the first time that calcinosis at the nasal spine in patients with MERR can be replaced by cancellous bone-like tissue. Patients 1 and 2 were a 62-year-old Japanese female and a 45-year-old Japanese female (respectively) with MERR who had been previously treated for SSc (Patient 1: limited type, positive for anti-centromere antibody; Patient 2: diffuse type, positive for anti-Scl70 and anti-SS-A antibodies). Patient 3 was a 57-year-old female with MERR who had been previously treated for SSc (diffuse type, positive anti-Scl-70 antibody) and underwent denosumab injection for osteoporosis. Cone-beam computed tomography (CBCT) and CT images in the calcifications at the nasal spine in Patient 1 and 2 were replaced with cancellous bone-like tissue, but not in Patient 3. Serum laboratory examination was performed to assess the systemic bone disease. All three patients had normal clinical data within the references, apart from slightly higher 1,25-dihydroxyvitamin D levels in Patient 1. SSc patients with calcinosis in the maxillofacial area need to be examined carefully for bone replacement using CBCT or CT.

Parathormone, bone alkaline phosphatase and 25-hydroxyvitamin D status in a large cohort of 1200 children and teenagers.

Objectives: 25-Hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone alkaline phosphatase (BALP) are biomarkers of calcium/phosphate metabolism and bone turnover. Although vitamin D deficiency is a well-known cause of secondary hyperparathyroidism, few studies have considered vitamin D status when establishing reference ranges. In this study, we report PTH levels according to the vitamin D status and BALP levels in a large cohort of 1200 children. Additionally, we provide PTH pediatric reference values according to 25(OH)D status as well as BALP pediatric reference ranges.Methods: Serum samples from 1200 children (equally distributed from 5 months to 20 years old) who underwent blood sampling for allergy exploration were used to quantify 25(OH)D, PTH and BALP.Results: The percentage of vitamin D deficient children (<20 ng/ml) progressively increased during childhood starting from 7% in the 0 to 2 year-old subgroup to a mean of at least 50% among teenagers. PTH levels inversely mirrored 25(OH)D concentrations for all age and gender subgroups, and 25(OH)D deficient subgroups presented higher PTH levels than their non-deficient counterparts. In the non-deficient 25(OH)D population, PTH levels were the highest at 11 years old for girls and 14 years old for boys. BALP results were slightly increased during childhood and showed a constant decrease during teenage years starting from 12 years old for girls and 14 years old for boys.Conclusion: Our results highlight the inverse relationship between PTH and 25(OH)D in children and the need for a well characterized 25(OH)D population to establish pediatric reference ranges for PTH.

Dysregulated expression of miR-92a-3p in senile osteoporosis and its diagnostic value in hip fragility fractures / 中华内分泌外科杂志

Objective:To investigate the expression of miR-92a-3p in senile osteoporosis (OP) and its diagnostic value in hip fragility fractures.Methods:With the help of the National Center for Biotechnology Information (NCBI) website, the data sets related to OP and miRNA were retrieved and analyzed and screened to obtain the target miRNA. Serum samples were collectedfrom 53 OP patients and 24 healthy people, and the OP patients were divided into hip fragility fracture group (OP_F; n=30) and no hip fragility fracture group (OP_WF; n=23). The subjects' bone mineral density and serum bone metabolism markers were measured: calcium, phosphorus, parathyroid hormone, 25-hydroxyvitamin D, bone alkaline phosphatase, serum C-terminal peptide. The expression levels of target miRNAs in serum samples were detected by qRT-PCR. Chi-square test, t test, Spearman rank correlation and receiver operating characteristic curve (ROC curve) were used to analyze the potential relationship between the expression level of miR-92a-3p and the clinical characteristics of patients.Results:According to the analysis of NCBI website, the expression of miR-92a-3p in OP patients was higher ( t=3.41, P=0.007) than that in healthy people, and the expression level of miR-1304-5p was lower ( t=5.13, P<0.001). qRT-PCR experiments confirmed the above results, and further found that the expression of miR-92a-3p in the OP_F group was significantly higher than that in the OP_WF group (t=3.01, P=0.004), but there was no significant difference in miR-1304-5p between the two groups (t=0.71, P=0.480). Compared with the healthy control group, the BMI ( t=2.71, P=0.008), bone mineral density score ( t=29.02, P<0.001), calcium ( t=61.20, P<0.001), phosphorus ( t=2.54, P=0.013), 25-hydroxyvitamin D (t=3.01, P=0.004) ,bone alkaline phosphatase ( t=12.56, P<0.001), and serum C-terminal peptide ( t=7.52, P<0.001) levels were statistically different between the OP patient group and the healthy control group. Compared with the OP_WF group, the bone mineral density score ( t=2.08, P=0.042), calcium ( t=15.75, P<0.001), bone alkaline phosphatase ( t=2.02, P=0.049) and serum C-terminal peptide ( t=3.39, P=0.001) levels were statistically different between the OP_F group and the OP_WF group. Bone mineral density score and bone alkaline phosphatase concentration were related to the expression of miR-92a-3p and were negatively and positively correlated ( r=0.416, P=0.022), respectively ( r=-0.403, P=0.027). The area under the ROC curve was 0.723, and the level of miR-92a-3p had potential significance in the diagnosis of hip fragility fractures ( P=0.006) . Conclusion:miR-92a-3p is highly expressed in OP and has biological significance for the diagnosis of hip fragility fractures.

The Novel Bone Alkaline Phosphatase Isoform B1x Is Associated with Improved 5-Year Survival in Chronic Kidney Disease.

Circulating alkaline phosphatase (ALP) is an independent cardiovascular risk marker. Serum bone ALP (BALP) isoforms indicate bone turnover and comprise approximately 50% of total circulating ALP. In chronic kidney disease (CKD), mortality is highest in patients with increased ALP and BALP and low bone turnover. However, not all low bone turnover states are associated with increased mortality. Chronic inflammation and oxidative stress, features of protein energy wasting syndrome, induce cardiovascular BALP activity and fibro-calcification, while bone turnover is suppressed. Circulating BALP isoform B1x is associated with low ALP and low bone turnover and has been exclusively detected in CKD. We investigated the association of serum B1x with survival, abdominal aortic calcification (AAC) score, and aortic pulse wave velocity (PWV) in CKD. Serum ALP, BALP isoforms, parathyroid hormone (PTH), PWV, and AAC were measured repeatedly over 2 years in 68 prevalent dialysis patients. Mortality was assessed after 5 years. B1x was detected in 53 patients. A competing risk analysis revealed an association of B1x with improved 5-year survival; whereas, baseline PWV, but not AAC score, predicted mortality. However, PWV improved in 26 patients (53%), and B1x was associated with variation of PWV over time (p = 0.03). Patients with B1x had lower PTH and total ALP, suggesting an association with lower bone turnover. In conclusion, B1x is associated with time-varying PWV, lower circulating ALP, and improved survival in CKD, and thus may be an indicator of a reduced cardiovascular risk profile among patients with low bone turnover.

Effect of sequential eradication therapy on serum osteoprotegerin levels in patients with Helicobacter pylori infection and co-existing inflammatory bowel disease.

OBJECTIVE: To investigate the effect of sequential Helicobacter pylori eradication therapy on serum osteoprotegerin levels in patients with H. pylori infection and co-existing inflammatory bowel disease (IBD). METHODS: Three groups of patients were involved in this observational cross-sectional study: IBD (n = 83), H. pylori infection (HP, n = 68), and H. pylori infection with co-existing IBD (HP + IBD, n = 52). These groups were compared with a normal control group (NC, n = 50). Serum osteoprotegerin, serum bone alkaline phosphatase (BALP), and fecal calprotectin (FC) levels were measured. RESULTS: Serum osteoprotegerin levels were significantly correlated with the simple endoscopic score for Crohn's disease and Mayo score for ulcerative colitis. The receiver operating characteristic analysis of osteoprotegerin revealed high values for the area under the curve, sensitivity, and specificity. Discriminant analysis illustrated that osteoprotegerin levels significantly differentiated patients with IBD from healthy controls. Osteoprotegerin and FC levels distinguished the IBD and HP + IBD groups from the NC and HP groups. CONCLUSIONS: Sequential eradication therapy did not affect serum osteoprotegerin levels in patients with H. pylori infection and co-existing IBD. Serum osteoprotegerin elevation might be a marker for IBD development in patients with past or current H. pylori infection.

Insulin-like growth factor-1 positively associated with bone formation markers and creatine kinase in adults with general physical activity.

BACKGROUND: The Insulin-like growth factor-1 (IGF-1) is primarily synthesized by hepatocytes in a growth hormone (GH)-dependent manner, it is also produced by bone and muscle. The effects of exercise on the associations between IGF-1 levels and bone turnover markers (BTM) were found in the previous studies. However, the associations between the levels of IGF-1 and BTM, liver function tests, and skeletal muscle markers in adults with general physical activity were not clear. METHODS: Ninety-four participants were recruited from healthy survey. Blood samples were collected to analyze the levels of IGF-1, total protein (TP), albumin (Alb), total bilirubin (T-Bil), direct bilirubin (D-Bil), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), lactate dehydrogenase (LDH), creatine kinase (CK), creatinine (CRTN), and glucose. Urine samples were collected to analyze the CRTN and deoxypyridinoline (Dpd) levels. RESULTS: The positively significant associations were found between the IGF-1 levels and the levels of ALP, BALP, and CK, respectively. No significant associations were found between the IGF-1 levels and the levels of TP, Alb, A/G, T-Bil, D-Bil, AST, ALT, LDH, glucose, urinary CRTN, urinary Dpd, and Dpd/CRTN ratios, respectively. CONCLUSION: The serum IGF-1 levels associated with the levels of skeletal muscle and bone formation markers (BFM), not the bone resorption markers under general physical activity in the healthy adults. The physician needs to consider the effects of bone formation and skeletal muscle markers on the IGF-1 levels in the management of IGF-1-related disorders.

Long-Term Efficacy of Intensive Zoledronate Therapy and Predictors of Retreatment in Paget's Disease of Bone.

Despite the current debate on the best therapeutic approach, i.e. symptomatic vs intensive strategy, one zoledronate (Zol) infusion is effective in most patients with Paget's disease of bone (PDB), whereas few need retreatment, whose predictors are not well established. We aimed to evaluate long-term efficacy of intensive Zol therapy and predictors of retreatment in PDB. Pagetic complications, clinical and biochemical response to Zol together with frequency of retreatment were retrospectively assessed in forty-seven PDB patients (age, mean ± SD: 72.5 ± 8.9 years, M/F: 24/23; symptomatic/asymptomatic: 16/31). Statistical analysis for retreatment prediction were based on Mann-Whitney U test, Pearson's Χ2 and ROC curve analysis. During seven-year follow-up, all patients achieved pain relief and only one underwent arthroplasty. Bone alkaline phosphatase (BAP) detected three non-responder (6%) and six relapsing (13%) patients needing retreatment. Retreated patients had less old age (66.1 ± 11.2 vs 74.0 ± 7.7 years), higher frequency of polyostotic disease (78% vs 40%) and higher baseline (96.5 ± 24.8 vs 44.9 ± 27.7 mcg/l) and post-Zol nadir BAP levels (24.7 ± 24.1 vs 8.1 ± 4.1 mcg/l) than patients treated once (p < 0.05 for all comparisons). In multivariate analysis both serum baseline and post-Zol nadir BAP significantly predicted retreatment (OR 1.09, 95%CI 1.01-1.17 and 1.29, 1.03-1.62, respectively), with ROC curve analysis showing the greatest accuracies for threshold values of 75.6 and 9.9 mcg/l (sensitivity 88 and 90%, specificity 94 and 86%, AUC 0.92 and 0.93, respectively). Our data in mostly asymptomatic, metabolically active PDB patients treated with intensive Zol therapy show a negligible incidence of pagetic complications and long-term optimal disease control, with BAP being the best predictor of retreatment.

New bone-like tissue formation in calcific tendinopathy: A case report.

Currently, the pathogenesis of nontraumatic heterotopic ossification (HO), e.g., bone-like tissue in calcific tendinopathy remains unclear. Here, we report a 75-year-old, right-handed Japanese woman who had been on hemodialysis for 3 years and was admitted to our hospital to evaluate pain and swelling of the right forearm. She worked as a cook, and her main job over the 3 most recent years had been the frequent and continuous shredding of cabbage. A radiograph showed the highly radiopaque material on the dorsal aspect of the right wrist and in the right shoulder. The biopsy of this radiopaque material revealed HO with marrow, as well as calcified material. Histomorphometric analysis of the HO identified a severe type of osteitis fibrosa with a fibrous tissue volume to total volume of 19.8% (>0.5% required for diagnosis) and an osteoid volume to bone volume of 20.0% (>15% required for diagnosis). We found more woven bone-like tissue than lamellar bone-like tissue. However, the intact parathyroid hormone level was 3-times the normal upper limit with 203 pg/mL, but histomorphometric analysis of the right iliac crest revealed normal bone structure. These findings indicate that the frequent and continuous shredding action with the right hand contributed to the nontraumatic HO localized on the dorsal aspect of the right wrist.