Levels Of Bone Metabolic Markers Research Articles

A Risk Assessment Tool for Identifying Osteoporosis in Older Women with Type 2 Diabetes Mellitus.

To develop a simple and clinically useful assessment tool for osteoporosis in older women with type 2 diabetes mellitus (T2DM). A total of 601 women over 60 years of age with T2DM were enrolled in this study. The levels of serum sex hormones and bone metabolism markers were compared between the osteoporosis and non-osteoporosis groups. The least absolute shrinkage and selection operator regularization (LASSO) model was applied to generate a risk assessment tool. The risk score formula was evaluated using receiver operating characteristic analysis and the relationship between the risk score and the bone mineral density (BMD) and T-value were investigated. Serum sex hormone-binding globulin (SHBG), cross-linked C-telopeptide of type 1 collagen (CTX), and osteocalcin (OC) were significantly higher in the osteoporosis group. After adjustment for age and body mass index (BMI), SHBG was found to be correlated with the T-value or BMD. Then, a risk score was specifically generated with age, BMI, SHBG, and CTX using the LASSO model. The risk score was significantly negatively correlated with the T-value and BMD of the lumbar spine, femoral neck, and total hip (all P<0.05). A risk score using age, BMI, SHBG, and CTX performs well for identifying osteoporosis in older women with T2DM.

Tibial plateau inclination is associated with bone marrow lesions in early knee osteoarthritis

Purpose: While varus inclination of proximal tibia and bone marrow lesion (BML) are important factor for understanding knee osteoarthritis (OA) etiology, the relationship between these wo factors remain unclear. This study aimed to investigate the effect of proximal tibial inclination and serum bone metabolic markers on bone marrow lesion (BML) in the Japanese general population with early knee osteoarthritis (EKOA). Methods: A total of 441 female volunteers who participated in the Iwaki Health Promotion Project in 2017 were enrolled. Participants without radiographic abnormalities were divided into normal and EKOA groups according to Luyten’s classification criteria for EKOA (Figure 1). In this study, proximal tibial inclination was assessed with reference to growth plate (GP). The GP-tibial plateau (TP) angle was defined as the angle between the GP and TP lines (a), whereas the GP-medial tibial plateau (MTP) angle was defined as the angle between the GP and MTP lines (b) The medial proximal tibial angle (MPTA), GP-TP angle, and GP-MTP angle were measured on standing anteroposterior radiographs of the knees. BML severity on T2-weighted fat-suppressed magnetic resonance imaging (MRI) was scored using the Whole-Organ MRI Score method. Serum levels of N-telopeptide of type I collagen (NTx), tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, pentosidine, and homocysteine were assessed. Serum concentrations of bone metabolic markers and radiographic measurements were compared using the Wilcoxon rank sum test. To investigate the relationship among BML, proximal tibial inclination, and serum bone metabolic markers, multiple linear regression analyses were conducted with the total BML score as the dependent variable and with age, body mass index, MPTA, GP-MTP angle, GP-TP angle, and serum bone metabolic markers as independent variables in patients with and without EKOA. To estimate the predictive cut-off level of proximal tibial inclination for detecting BML, receiver operating characteristic (ROC) analysis was performed for the EKOA group. Finally, in order to evaluate the cut-off values, the participants were divided into three groups according to the cut-off values estimated from the ROC analysis—the neutral group, tibia vara (extra-articular deformity) group, and genu varum (intra-articular deformity) group. Serum bone metabolic marker levels were compared among these three groups using one-way analysis of variance and Tukey’s test. Of these 309 participants, 48 participants (16%) had EKOA. With reference to the GP line, the GP-TP angle was inclined at 3.6±1.1° and the GP-MTP angle was 9.9±2.6°.Tabled 1Clinical characteristics of the participantsGP not observedGP observedp valueTotalNon-OAEKOASample number13130926148nsAge (years)52.7±14.154.5±9.554.4±9.755.0±8.8nsHeight (cm)156.1±6.0157.4±6.0157.5±6.0156.8±6.1nsBMI (kg/m2)22.4±3.622.0±3.121.9±3.122.3±3.2nsMPTA (°)86.6±1.286.1±5.986.4±1.586.6±1.4nsGP-TP (°)3.6±1.13.6±1.23.6±0.9nsGP-MTP (°)9.9±2.69.9±2.69.8±2.6nsNTx (nM)15.0±5.114.9±3.815.0±3.814.5±3.7nsTRACP-5b (mU/dL)415±190422.4±185431±14393.5±27nsBAP (μg/L)13.8±5.013.0±8.913.1±4.99.8±4.3nsPINP (μg/L)51.0±19.647.4±18.447.8±1.545.9±2.6nsPentosidine (pmol/mL)27.4±9.630.5±24.329.3±16.837.1±47.2nsHomocysteine (nmol/mL)9.0±3.18.5±2.78.5±0.28.3±0.4ns Open table in a new tab Serum bone metabolic marker levels did not significantly differ between the non-OA and EKOA groups. The MPTA was negatively correlated with the GP-TP and GP-MTP angles (r=−0.253, p<0.001 and r=−0.369, p<0.001, respectively). The BML was detected in 64 participants (31%) out of 205 participants who were performed MRI (). The MPTA was smaller in participants with EKOA who had BML than in those who did not (p=0.020), and the GP-MTP angle was larger in participants with BML than in those without BML (p=0.018).Tabled 1Radiographic measurements between participants with and without BMLNon-OAp valueEKOAp valueBML (-)BML (+)BML (-)BML (+)MPTA86.4±1.486.3±1.8ns86.8±1.386.0±1.20.020GP-TP3.5±1.33.5±1.1ns3.5±1.03.9±0.7nsGP-MTP10.0±2.59.9±2.9ns9.4±2.711.1±2.00.018 Open table in a new tab Linear regression analysis revealed that age was positively associated with BML severity in overall participants. In the non-OA group, serum TRACP-5b level was positively associated with BML (β=0.236, p=0.047). Proximal tibial inclination (MPTA and GP-MTP angle) was associated with BML only in the EKOA group (β=−0.281, p=0.011 and β=0.262, p=0.046, respectively).Tabled 1Relationship among bone marrow lesion, tibial inclination, and serum bone metabolic markersParameterNon-OApEKOApββAge0.1340.0090.503<0.0001BMI−0.014ns−0.072nsMPTA−0.056ns−0.2890.011GP-MTP−0.053ns0.2620.046GP-TP0.082ns0.137nsTotal PINP0.052ns0.060nsTRACP-5b0.2360.0470.076nsBAP−0.004ns−0.039nsNTx−0.032ns−0.074nsPentosidine0.024ns−0.136nsHomocysteine−0.011ns−0.136ns Open table in a new tab The ROC analysis indicated that the cutoff values for detecting BML were 86.7° for the MPTA (AUC: 0.703, p=0.030) and 9.7° for the GP-MTP angle (AUC: 0.706, p=0.028). Based on these cutoff values, tibial bone morphology was divided into the following three groups: neutral (MPTA ≥86.7°). (a), tibia vara (extra-articular deformity: MPTA <86.7° and GP-MTP angle <9.7°) (b), and genu varum (intra-articular deformity: MPTA <86.7° and GP-MTP angle ≥9.7°) groups (c). In the neutral group, 55 (46%) participants out of 120 participants had GP-MTP angle ≥9.7°. The serum NTx level was significantly lower in the genu varum group than in the tibia vara group (p=0.023). The serum TRACP-5b level was significantly lower in the genu varum group than in the neutral group (p=0.012).Tabled 1Serum bone metabolic marker levels among proximal tibial inclination typesNeutral (MPTA ≥86.7°)Inclined (MPTA <86.7°)p valueTibia vara (MTP-GP <9.7°)Genu varum (MTP-GP ≥9.7°)Sample number12075114MPTA87.6±0.785.5±0.985.1±1.2<0.001GP-MTP9.1±2.47.7±1.512.2±1.7<0.001NTx14.9±3.515.9±7.913.8±3.90.023BAP13.1±0.412.5±0.511.7±0.4nsTRACP-5b421±193409±202351±1680.012PINP46.8±18.249.4±27.245.1±19.7nsPentosidine32.6±2.230.5±28.228.2±2.2nsHomocysteine8.4±2.58.6±3.08.3±2.5ns Open table in a new tab Conclusions: The GP was a reasonable reference for assessing TP inclination. The presence of BML was associated with greater TP inclination and higher bone formation activity, even in participants without radiographic abnormalities. Residual medial tibial inclination may potentially result in knee pain and symptoms in EKOA.

A Cross-sectional Study of Osteoporosis and Cardiovascular Calcification in Patients with Chronic Kidney Disease at Different CKD Stages

To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and β-crosslaps (β-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. Compared with control group, levels of serum P, iPTH, BALP, PINP and β-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and β-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and β-CTX ( P<0.05). The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.

The Level of Bone Metabolism Indexes in Patients with Chronic Obstructive Pulmonary Disease and Its Clinical Significance

To determine the level of bone metabolism indexes in patients with chronic obstructive pulmonary disease and its clinical significance. A total of 164 patients with chronic obstructive pulmonary disease admitted to the outpatient and inpatient departments of our hospital from April 2019 to April 2020 were selected as the study objects. Patients were divided into acute exacerbation group (n=78) and remission group (n=52) according to relevant criteria in chronic obstructive pulmonary disease. There was no significant difference in gender, age, body mass index and other general data among the three groups (p>0.05), showing comparability. The bone mineral density of femoral neck, lumbar spine and Ward’s triangle in the three groups had statistical significance (p<0.05). The bone metabolism indexes of beta-isomerized C-terminal telopeptides, procollagen type I N propeptide and osteocalcin in the acute exacerbation group were significantly higher than those in the remission group, the levels of 25-hydroxyvitamin D3 in the acute exacerbation group were lower than those in the remission group and the differences had statistical significance (p<0.05). Pearson correlation analysis showed that bone mineral density of chronic obstructive pulmonary disease patients was negatively correlated with beta-isomerized C-terminal telopeptides, procollagen type I N propeptide, osteocalcin and positively correlated with 25-hydroxyvitamin D3 (p<0.05). According to Pearson correlation analysis, there was a positive correlation between bone mineral density and 25-hydroxyvitamin D3 in patients with chronic obstructive pulmonary disease (p<0.05), which was consistent. In conclusion, chronic obstructive pulmonary disease secondary osteoporosis is a high conversion type and bone mineral density and bone metabolism marker levels can effectively predict chronic obstructive pulmonary disease secondary osteoporosis.

Beneficial effects of switching to denosumab from bisphosphonates or selective estrogen receptor modulators in postmenopausal women with type2 diabetes and osteopenia/osteoporosis.

Aims/IntroductionPatients with type 2 diabetes mellitus have a higher bone fracture risk than patients without diabetes. Although denosumab (Dmab) is a potent bone resorption inhibitor, its efficacy in patients with type 2 diabetes mellitus has not been elucidated. In this study, we investigated the effects of switching to Dmab from bisphosphonates (BP) or a selective estrogen receptor modulator (SERM) in postmenopausal type 2 diabetes mellitus patients.Materials and MethodsThis was a three medical institutions, prospective, observational study for postmenopausal patients with type 2 diabetes mellitus whose T‐score of femoral neck or lumbar spine bone mineral density was under −1.0 standard deviation, even after >6 months of BP or SERM administration. After obtaining consent, participants were treated for osteopenia/osteoporosis by either continuing BP (BP‐BP group)/SERM (SERM‐SERM group), or by switching to Dmab (BP‐Dmab or SERM‐Dmab groups). Changes in bone mineral density and bone metabolism marker levels were evaluated after 6 months.ResultsA total of 48 patients were included in this study, and each group comprised 12 patients. No significant difference existed in baseline characteristics among the groups. The average age and glycated hemoglobin were 71 ± 8 years and 7.2 ± 0.9%, respectively. In the SERM‐Dmab group, lumbar spine bone mineral density was significantly increased by 5.0% compared with the SERM‐SERM group (P < 0.04). Serum bone‐specific alkaline phosphatase and tartrate‐resistant acid phosphatase 5b were significantly decreased in the BP‐Dmab and SERM‐Dmab groups compared with the BP‐BP and SERM‐SERM groups, respectively.ConclusionsSwitching to Dmab from BP or SERM is beneficial to prevent osteoporosis progression in postmenopausal patients with type 2 diabetes mellitus patients.

Comparison of Vitamin D Levels, Bone Metabolic Marker Levels, and Bone Mineral Density among Patients with Thyroid Disease: A Cross-Sectional Study.

Thyroid hormones have a catabolic effect on bone homeostasis. Hence, this study aimed to evaluate serum vitamin D, calcium, and phosphate and bone marker levels and bone mineral density (BMD) among patients with different thyroid diseases. This cross-sectional study included patients with underlying thyroid diseases (n = 64, hyperthyroid; n = 53 euthyroid; n = 18, hypothyroid) and healthy controls (n = 64). BMD was assessed using z-score and left hip and lumbar bone density (g/cm2). The results showed that the mean serum vitamin D Levels of all groups was low (<50 nmol/L). Thyroid patients had higher serum vitamin D levels than healthy controls. All groups had normal serum calcium and phosphate levels. The carboxy terminal collagen crosslink and procollagen type I N-terminal propeptide levels were high in hyperthyroid patients and low in hypothyroid patients. The z-score for hip and spine did not significantly differ between thyroid patients and control groups. The hip bone density was remarkably low in the hyperthyroid group. In conclusion, this study showed no correlation between serum 25(OH)D levels and thyroid diseases. The bone markers showed a difference between thyroid groups with no significant difference in BMD.

The relationship between urinary kidney injury molecule-1 and blood bone metabolism markers in patients with chronic kidney disease .

The aim of this study was to evaluate the changes of urinary kidney injury molecule-1(uKIM-1) in chronic kidney disease (CKD) at different stages, and to determine the relationships between uKIM-1 and circulating bone metabolism markers. This cross-sectional study included CKD patients (n = 121) and controls (n = 65). CKD stages were assigned to each individual according to their estimated glomerular filtration rate (eGFR), which was calculated with the modification of diet in renal disease (MDRD) equation. We evaluated the relationships of bone metabolism markers (including calcium, phosphorus, intact parathyroid hormone (iPTH), 25 hydroxy vitamin D (25(OH)D), alkaline phosphatase (ALP), fibroblast growth factor 23 (FGF23), and α-Klotho), uKIM-1, and eGFR. We also compared the levels of bone metabolism markers and uKIM-1 at different CKD stages. The uKIM-1 level was standardized with urine creatinine (uCr). Compared with healthy controls, CKD patients had higher levels of uKIM-1/uCr, serum creatinine, urea, phosphorus, iPTH, and plasma FGF23, whereas they had lower levels of serum calcium, α-Klotho, and plasma 25(OH)D. In CKD patients, eGFR was positively correlated with levels of serum calcium, α-Klotho, and plasma 25(OH)D, whereas it was negatively correlated with serum phosphorus, iPTH, plasma FGF23, and uKIM-1/uCr. Serum calcium and α-Klotho were significantly decreased in patients with stage 5 CKD compared to those with stage 1 CKD. Serum phosphorus, iPTH, and plasma FGF23 were significantly elevated in patients with stage 4 CKD when compared to those with stage 1 CKD. UKIM-1/uCr was significantly elevated in patients with stage 5 CKD when compared to those with stage 1 CKD. In CKD patients, uKIM-1/uCr levels were positively correlated with levels of serum phosphorus and plasma FGF23, whereas they were negatively correlated with serum calcium and plasma 25(OH)D. UKIM-1/uCr levels are increased with the deterioration of CKD stage and are correlated with the development of CKD-mineral and bone disorder (CKD-MBD).

Bone remodeling features in elderly and senile patients with the proximal femur fractures after hip replacement

The aim of this study is to identify the dependence of the result of surgical treatment of patients of elderly and senile age with fractures of the proximal femur on the characteristics of the response cytokine-mediated regulatory response to trauma and surgery. Materials and methods: In 74 patients after hip arthroplasty, serum levels of bone metabolism markers were determined using enzyme-linked immunosorbent assay. Patients were divided into 2 groups depending on the results of treatment. Results: It was found that compared with group 2 (treatment outcome is worse) in group 1 (treatment outcome is better) there was a greater number of correlations. In group 1, correlations were found between OPG and RANKL (r = 0.88; p = 0.000), OPG and OPG/RANKL (r = 0.44; p = 0.006), TGF-β1 and OPG/RANKL (r = 0.66; p = 0.000) , IL-6 and OPG (r = 0.67; p = 0.000), IL-6 and RANKL (r = 0.53; p = 0.001), IL-6 and OPG/RANKL (r = 0.39; p = 0.016). In group 2, only between OPG and OPG/RANKL (r = 0.72; p = 0.000), RANKL and OPG/RANKL (r = -0.53; p = 0.0007). In patients of group 2, there was a decrease in the level of OPG relative to the control and a less significant increase in TGF-β1 and IL-6 relative to group 1. Conclusion: The prognosis of the results of treatment of patients with proximal femur fractures is largely determined by the nature of the adaptive response to injury and theimplant, the synchronism of the mechanism of stress remodeling of the bone. A less favorable prognosis after arthroplasty is associated with exacerbation of the initial metabolic disorders in the bone tissue due to severe cytokine-mediated dysfunction of the regulatory pathways.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Effects of zoledronic acid on bone mineral density around prostheses and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis.

To investigate the effect of zoledronic acid on periprosthetic bone mineral density (BMD) and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis. From November 2015 to April 2016, 40 female patients who met the inclusion criteria were randomized into two groups: a control group (calcium + calcitriol) and a zoledronic acid group (calcium + calcitriol + zoledronic acid). At 1week and 3, 6, and 12months after operation, BMD was obtained through dual-energy X-ray absorptiometry (DEXA). At pre-operation and at 3, 6, and 12months after the operation, levels of bone metabolism markers were obtained by serum examination. Loss of BMD was significantly more pronounced in the control group than in the ZOL group in zones 1, 4, 6, and 7 at 6months and in zones 1, 2, 4, 6, and 7 at 12months after the operation. The levels of bone-resorption marker (β-CTX) were significantly lower in the ZOL group than in the control group at 3, 6, and 12months after operation. The levels of bone-formation marker (TP1NP) performed statistically differences only at 12months after the operation in these two groups. Receiving an intravenous infusion of 5mg zoledronic acid after THA can effectively reduce periprosthetic BMD loss and improve bone remodeling in females with postmenopausal osteoporosis. Zoledronic acid significantly inhibited bone mass loss in zones 1, 2, 4, 6, and 7 after THA and inhibited bone-resorption marker (β-CTX) to improve bone remodeling. Zoledronic acid treatment is potentially important for patients with osteoporosis after THA.

Bufalin suppresses the migration and invasion of prostate cancer cells through HOTAIR, the sponge of miR-520b.

Bufalin, the major active component of the traditional Chinese medicine ChanSu obtained from the skin and parotid venom glands of toads, has long been known as an anticancer agent. Recent studies show that microRNAs (miRs) are involved in the anticancer activities of bufalin, while long non-coding RNAs (lncRNAs) are known to interact with miRNAs to regulate various biological functions. In this paper, we investigated the possible network related to the antimetastatic effect of bufalin in prostate cancer (PCa) cells. We demonstrated that bufalin (0.05-10 µM) dose-dependently suppressed the proliferation of prostate cancer DU145 and PC3 cells with IC50 values of 0.89 and 1.28 µM, respectively. Furthermore, bufalin treatment significantly suppressed the cell migration and invasion. To explore the role of lncRNAs in the antimetastatic activity of bufalin, we used an lncRNA microarray and found that HOX transcript antisense RNA (HOTAIR) was the most markedly downregulated lncRNA in bufalin-treated PCa cells. Overexpression of HOTAIR counteracted the suppressing effects of bufalin on DU145 and PC3 cells. We then predicted and verified that HOTAIR upregulated FGFR1 expression by sponging miR-520b in PCa cells. In 40 patients with PCa bone metastasis, we used in situ hybridization or immunohistochemical assay to assess the HOTAIR and FGFR1 expression, which revealed that both HOTAIR and FGFR1 expression were significantly higher in bone metastasis tissues than in the primary PCa tissues. In addition, the level of serum HOTAIR was positively associated with the levels of serum bone metabolic markers (CTx, OST, B-ALP and PINP) and may serve as a reasonable biomarker for PCa bone metastasis. Taken together, this is the first study revealing that HOTAIR promotes PCa bone metastasis, and bufalin may be a promising candidate for the treatment of this disease.

Daily oligofructose-enriched inulin intake impacts bone turnover markers but not the cytokine profile in pediatric patients with celiac disease on a gluten-free diet: Results of a randomised, placebo-controlled pilot study.

Bone metabolism disturbances are commonly observed in patients with newly diagnosed celiac disease (CD). The only available treatment for CD-the intake of a gluten-free diet (GFD)-has been found to be insufficient in effectively improving bone health in some patients. Therefore, there is an urgent need to modify the GFD so as to allow for the provision of all the necessary nutrients and improved absorption. Prebiotics intake reportedly improves the absorption of bone-related vitamin D and calcium as well as bone metabolism. The effect of prebiotic intake on bone health in CD patients has not been studied yet. This study aimed to evaluate the effect of oligofructose-enriched inulin intake on bone metabolism and immune response in children with CD on a GFD. A total of 34 children with CD were randomised into two groups receiving 10 g of oligofructose-enriched inulin (Synergy 1) or a placebo (maltodextrin) for three months, together with a strict GFD. The children's bone metabolism marker levels and cytokine profiles were analysed before and after the intervention. After supplementation, the concentration of osteocalcin increased significantly in children receiving Synergy 1, while the concentration of bone alkaline phosphatase increased in both groups, independent of supplementation. After the intervention, the level of pyridinoline increased significantly in the placebo group, resulting in a concentration that was two times higher than that in the Synergy 1 group, in which it remained stable. Moreover, the plasma concentrations of N-terminal telopeptides of type I collagen decreased in both the groups, whereas the tartrate-resistant acid phosphatase 5b level increased particularly in the Synergy 1 group. The intervention did not lead to immunological response changes. The proposed supplementation beneficially altered bone metabolism, through increased bone formation rates and decreased bone resorption process rates. Supplementation of GFD with prebiotic oligofructose-enriched inulin may be a promising auxiliary therapy for bone metabolism improvements in children with CD.

Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients.

Chronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status. We compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor-α; and C-reactive protein (CRP). We also evaluated biomarkers among subsets of patients, examining factors including time since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus, vitamin supplementation, and pancreatic enzyme replacement. After correcting for multiple comparisons, CP patients had significantly lower levels than controls of the following: vitamin A (40.9 vs 45.4 μg/dL) and vitamin E (α-tocopherol [8.7 vs 10.3 mg/L] and γ-tocopherol [1.8 vs 2.2 mg/L]), as well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both patients and controls who took vitamin supplements had higher serum levels of vitamins than those not taking supplements. Compared with controls, in controlled analyses, CP patients had significantly lower levels of vitamins A, D, and E (both α-tocopherol and γ-tocopherol). CP patients also had significantly lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and higher CRP. CP patients demonstrated lower levels of selected nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement therapy improved nutrition biomarkers in CP patients.

Safety data from a phase II randomized trial of radium-223 dichloride (Ra-223) plus enzalutamide (Enza) vs. Enza alone in men with metastatic castration refractory prostate cancer (mCRPC).

5057Background: Ra-233, a bone targeting alpha radiopharmaceutical, and Enza, are approved for mCRPC. Per SWOG0421, the subset of men with mCRPC with the highest bone metabolism marker levels had i...

The Assessment of Bone Regulatory Pathways, Bone Turnover, and Bone Mineral Density in Vegetarian and Omnivorous Children.

Vegetarian diets contain many beneficial properties as well as carry a risk of inadequate intakes of several nutrients important to bone health. The aim of the study was to evaluate serum levels of bone metabolism markers and to analyze the relationships between biochemical bone markers and anthropometric parameters in children on vegetarian and omnivorous diets. The study included 70 prepubertal children on a lacto-ovo-vegetarian diet and 60 omnivorous children. Body composition, bone mineral content (BMC), and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. Biochemical markers—bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), nuclear factor κB ligand (RANKL), sclerostin, and Dickkopf-related protein 1 (Dkk-1)—were measured using immunoenzymatic assays. In vegetarians, we observed a significantly higher level of BALP (p = 0.002) and CTX-I (p = 0.027), and slightly lower spine BMC (p = 0.067) and BMD (p = 0.060) than in omnivores. Concentrations of OPG, RANKL, sclerostin, and Dkk-1 were comparable in both groups of children. We found that CTX-I was positively correlated with BMC, total BMD, and lumbar spine BMD in vegetarians, but not in omnivores. A well-planned vegetarian diet with proper dairy and egg intake does not lead to significantly lower bone mass; however, children following a lacto-ovo-vegetarian diet had a higher rate of bone turnover and subtle changes in bone regulatory markers. CTX-I might be an important marker for the protection of vegetarians from bone abnormalities.

Analysis of effect of 1α-hydroxyvitamin D3 on benign paroxysmal positional vertigo and risk factors.

The purpose of this study was to investigate the curative effect of 1α-hydroxyvitamin D3 on the benign paroxysmal positional vertigo (BPPV). Fifty BPPV patients diagnosed in the ENT Department of Anzhen Hospital from October 2015 to December 2016 were randomly selected as the treatment group, and treated with 0.25 µg 1α-hydroxyvitamin D3 once per day, in addition to the routine diagnosis and treatment. Moreover, 50 BPPV patients in the same period were selected as the control group, and received the routine diagnosis and treatment. The detection results of bone mineral density (BMD) t-value, vitamin D3 and bone metabolic markers before and after treatment were compared, and statistical analysis was performed on the results. There were no differences in the general data between treatment group and control group. There were no statistically significant differences in the BMD and age distribution of males and females between treatment group and control group (P>0.05). The BMD of male BPPV patients in each age group in the treatment group was significantly increased after treatment, and the difference was statistically significant (P<0.05). Although the BMD of male BPPV patients in each age group in control group was somewhat increased after treatment, the difference was not statistically significant (P>0.05). The BMD of female BPPV patients in each age group in treatment group was increased after treatment, and the difference was statistically significant (P<0.05). Similarly, although the BMD of female BPPV patients in each age group in control group was somewhat increased after treatment, the difference was not statistically significant (P>0.05). The average BMD of female BPPV patients in each age group was significantly lower than that of male patients, and the difference was statistically significant (P<0.05) (Table II). The BMD t-value of patients in treatment group showed a decreasing trend with the increase of age (Fig. 1). The levels of 25-hydroxyvitamin D3 and bone metabolic markers in treatment group were significantly improved compared with those before treatment (P<0.05). Multivariate Logistic regression analysis was performed to identify whether the treatment of BPPV was effective or not as a dependent variable, and six items, including the sex (female), hypertension, diabetes mellitus, age (>50 years), 25-hydroxyvitamin D3 and osteopenia/osteoporosis, as the independent variables, and the results suggested that the level of 25-hydroxyvitamin D3 and osteopenia/osteoporosis are the clinical features of whether the BPPV treatment is effective (P<0.05). The results showed that the treatment of BPPV with 1α-hydroxyvitamin D3 can effectively improve the symptoms of patients, and the level of vitamin D3 and the occurrence of osteopenia/osteoporosis are the clinical indexes of whether the BPPV treatment is effective.

A Prospective Cohort Study Showing No Association Between Serum Sclerostin Level and Mortality in Maintenance Hemodialysis Patients

Background/Aims: Potential relationships between serum sclerostin levels and the levels of bone metabolic markers in maintenance hemodialysis (MHD) patients have yet to be evaluated. This study sought to determine whether serum sclerostin levels are associated with mortality in MHD patients. Methods: We measured serum sclerostin levels in a Japanese MHD cohort, classified the patients into tertiles according to these levels, and followed their course for a 42-month period. Results: The cohort consisted of 389 MHD patients and there were 75 deaths. Kaplan-Meier analyses showed that the tertile of serum sclerostin was not associated with mortality risk. Cox analyses showed that there were no significant associations between serum sclerostin level and mortality. Conclusion: Serum sclerostin level was not an independent predictor of mortality in MHD patients after adjustment for several confounders. However, whether clinical interventions to modulate serum sclerostin levels in MHD patients would improve their survival remains to be determined.

Effect of dosing frequency of teriparatide (PTH 1-34) on bone formation in rats: comparison of bone metabolism marker levels

Teriparatide, a drug used in the treatment of osteoporosis, was administered to rats subcutaneously for the duration of 3 months, at a frequency of either once weekly or once daily to demonstrate the varying levels of anabolic action the drug can have on bone depending on the dosing frequency. The levels of biomarkers in the blood were compared and found to vary in osteocalcin (OC), a biomarker of bone formation, and cross-linked N-telopeptide of type 1 collagen (NTx), a biomarker of bone resorption, according to the dosing frequency. In the once-weekly regimen, teriparatide did not affect NTx levels at any of the doses studied, while OC levels increased with dose, peaking at 72 hr, then returning to normal before the next injection (after 1 week). Bone mineral density (BMD) levels increased moderately with no difference between doses. This was thought to result from the steady state achieved following increases in bone formation and bone absorption. In the once-daily dosing regimen, meanwhile, NTx levels increased with dose, and OC levels were markedly higher when compared to those with the once-weekly dosing. BMD levels were higher than those with the once-weekly dosing, but with no difference between doses. This was considered a result of unlimited, excessive increases in bone formation due to daily administration of the drug. These results suggest that teriparatide promotes normal bone metabolism ("stationary mini-modeling") when administered once weekly, and has an anabolic action with high metabolic turnover ("high-turnover remodeling") when administered once daily.

Coenzyme Q10 promotes osteoblast proliferation and differentiation and protects against ovariectomy-induced osteoporosis.

Coenzyme Q10 (CoQ10) is a fat‑soluble vitamin‑like substance used for the treatment of a variety of disorders, including osteoporosis. The exact mechanism underlying CoQ10‑mediated protection against osteoporosis remains to be elucidated. The present study aimed to evaluate the effect of CoQ10 on osteoblastic cell proliferation and differentiation, and therapeutic effects on a rat model of osteoporosis. Following treatment with different concentrations of CoQ10, cell proliferation and differentiation of rat bone marrow stromal cells (BMSCs), and expression of osteoblastogenic markers, were measured. Rats with osteoporosis subjected to ovariectomy (OVX) were treated with different concentrations of CoQ10. Serum levels of estrogen and bone metabolism markers were measured. Micro computed tomography scans were used to analyze morphological changes in bones. In addition, mRNA and protein levels of phosphatidylinositol 3,4,5‑trisphosphate 3‑phosphatase and dual‑specificity protein phosphatase PTEN (PTEN)/phosphatidylinositol 4,5‑bisphosphate 3‑kinase (PI3K)/RAC‑alpha serine/threonine‑protein kinase(AKT), were determined. CoQ10 significantly increased the proliferation and osteogenic differentiation of BMSCs in a dose‑dependent manner, with an increased expression of osteogenic markers. CoQ10 significantly decreased bone resorption but exhibited no effect on serum E2 levels invivo. CoQ10 markedly enhanced bone formation. Furthermore, the abundance of p‑PI3K and p‑AKT increased while PTEN levels decreased in a dose‑dependent manner following administration of CoQ10. CoQ10 stimulates the proliferation and differentiation of BMSCs and is effective for the treatment of OVX‑induced osteoporosis in rats. The above effects of CoQ10 may be mediated by activation of the PTEN/PI3K/AKT pathway.

Site-Specific Variations in Bone Mineral Density under Systemic Conditions Inducing Osteoporosis in Minipigs.

Osteoporosis is a systemic bone disease with an increasing prevalence in the elderly population. There is conflicting opinion about whether osteoporosis affects the alveolar bone of the jaws and whether it poses a risk to the osseointegration of dental implants. The aim of the present study was to evaluate the effects of systemic glucocorticoid administration on the jaw bone density of minipigs. Thirty-seven adult female minipigs were randomly divided into two groups. Quantitative computed tomography (QCT) was used to assess bone mineral density BMD of the lumbar spine as well as the mandible and maxilla, and blood was drawn. One group of minipigs initially received 1.0 mg prednisolone per kg body weight daily for 2 months. The dose was tapered to 0.5 mg per kg body weight per day thereafter. The animals in the other group served as controls and received placebo. QCT and blood analysis were repeated after 6 and 9 months. BMD was compared between the two groups by measuring Hounsfield units, and serum levels of several bone metabolic markers were also assessed. A decrease in BMD was observed in the jaws from baseline to 9 months. This was more pronounced in the prednisolone group. Statistically significant differences were reached for the mandible (p < 0.001) and the maxilla (p < 0.001). The administration of glucocorticoids reduced the BMD in the jaws of minipigs. The described model shows promise in the evaluation of osseointegration of dental implants in bone that is compromised by osteoporosis.