Bone Alkaline Phosphatase Levels Research Articles

Association of low testosterone with changes in non-cardiovascular biomarkers in adult men

Testosterone has effects on many organs and systems. The purpose of this study was to test the hypothesis that low testosterone is associated with changes in various non-cardiovascular biomarkers in men older than 40 who were tested for possible hypogonadism. We extracted data from 9939 outpatient men who were over 40 years old (median age 56) and who also had concurrent laboratory measurements of total testosterone and one or more biomarkers of interest: estradiol, uric acid, prostate-specific antigen (PSA), sex-hormone binding globulin (SHBG), luteinizing hormone, creatinine, bone alkaline phosphatase (BAP), creatine kinase, hemoglobin A1c, and 25-hydroxy-vitamin D, and body mass index (BMI). In a smaller exploratory study of 19 otherwise healthy men presenting for evaluation of possible hypogonadism, pre-albumin (a.k.a.transthyretin, a marker of anabolism) and testosterone were measured. Men with lower levels of testosterone had significantly (p < 0.001) lower mean levels of PSA, SHBG, luteinizing hormone, and estradiol. Overall, men with low levels of testosterone also had significantly (p < 0.001) higher mean levels of LDH and BAP, but these associations varied between men who were younger or older than 56 years. There was a moderate but statistically significant positive correlation (r = 0.63, p < 0.05) between testosterone levels and pre-albumin. These results confirm our hypothesis that testosterone deficiency is associated with a broad range of systemic changes demonstrable in hormonal and non-hormonal serum assays in men over 40 years old being tested for possible hypogonadism.

A distinct bone phenotype in ADPKD patients with end-stage renal disease

Autosomal dominant polycystic kidney disease (ADPKD) is among the most common hereditary nephropathies. Low bone turnover osteopenia has been reported in mice with conditional deletion of the PKD1 and PKD2 genes in osteoblasts, and preliminary clinical data also suggest suppressed bone turnover in patients with ADPKD. The present study compared the bone phenotype between patients with end stage renal disease (ESRD) due to ADPKD and controls with ESRD due to other causes. Laboratory parameters of bone mineral metabolism (fibroblast growth factor 23 and sclerostin), bone turnover markers (bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b) and bone mineral density (BMD, by dual energy x-ray absorptiometry, DXA) were assessed in 518 patients with ESRD, including 99 with ADPKD. Bone histomorphometry data were available in 71 patients, including 10 with ADPKD. Circulating levels of bone alkaline phosphatase were significantly lower in patients with ADPKD (17.4 vs 22.6 ng/mL), as were histomorphometric parameters of bone formation. Associations between ADPKD and parameters of bone formation persisted after adjustment for classical determinants including parathyroid hormone, age, and sex. BMD was higher in skeletal sites rich in cortical bone in patients with ADPKD compared to non-ADPKD patients (Z-score midshaft radius -0.04 vs -0.14; femoral neck -0.72 vs -1.02). Circulating sclerostin levels were significantly higher in ADPKD patients (2.20 vs 1.84ng/L). In conclusion, patients with ESRD due to ADPKD present a distinct bone and mineral phenotype, characterized by suppressed bone turnover, better preserved cortical BMD, and high sclerostin levels.

Activity and morphologic changes in the mandible after mandibular osteotomy.

Orthognathic surgery accelerates orthodontic tooth movement, and tooth movement accelerates with demineralized bone and accelerated bone remodeling. The purpose of this study was to ascertain whether orthognathic surgery induces accelerated bone remodeling. The research design included a human model and an animal model. The levels of serum tartrate resistant acid phosphatase-5b (TRAP) and bone alkaline phosphatase (BALP) were measured in 15 patients after sagittal split ramus osteotomy. For the animal study, 18 rabbits were divided into 6 groups: a control group and 5 surgery groups. The rabbits in the surgery groups had osteotomies in the molar regions of the mandible. Changes in bone mass of the anterior mandibles were examined by microcomputed tomography, and changes in osteoblast and osteoclast numbers were analyzed by real-time polymerase chain reaction, hematoxylin and eosin staining, TRAP staining, and alkaline phosphatase staining. In the 15 patients, TRAP-5b increased from 1 to 8weeks postoperatively, and BALP increased significantly in 2weeks postoperatively. In the rabbits, the levels of mRNA expression of TRAP were increased at 3weeks, and matrix metalloproteinase 9 was increased at 4 and 8weeks, whereas mRNA expression of BALP and bone morphogenetic protein 2 were increased at 4weeks. Bone loss was detected from 1week postoperatively and reached the maximum at 3weeks; and bone mass and mechanical structure did not recoverer to preoperative levels until 8weeks postoperatively. These findings show active bone remodeling induced by osteotomy.

Bone microstructure is significantly altered in CRPS-affected distal tibiae as detected by HR-pQCT: a retrospective cross-sectional study.

In the course of complex regional pain syndrome (CRPS), local osteopenia in the subchondral/subcortical areas of the affected limb represents a central manifestation. Mechanistic aspects of CRPS-associated pathologies remain unclear, and knowledge about bone morphology in CRPS-affected areas is rare. The aim of this study was to assess trabecular and cortical bone microstructure in patients with CRPS of the distal tibiae. We retrospectively analysed 14 women diagnosed with unilateral CRPS type I of the lower limb whose affected and unaffected distal tibiae were examined by high-resolution peripheral quantitative computed tomography (HR-pQCT). Laboratory tests included serum levels of calcium, phosphate, 25-hydroxyvitamin D, bone alkaline phosphatase, parathyroid hormone, osteocalcin and urinary levels of deoxypyridinoline (DPD). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and both proximal femurs. Average urinary DPD levels, a biochemical marker of bone resorption, were elevated in the examined patient cohort (7.1 ± 1.9nmol/mmol, reference 3.0-7.0nmol/mmol). According to HR-pQCT, CRPS-affected distal tibiae showed significantly lower values of cortical BMD and cortical thickness compared to the unaffected contralateral side. Also, bone volume relative to total volume was significantly lower. Trabecular number and trabecular thickness tended to be lower in the affected tibiae. CRPS is associated with significant alterations in bone microstructure of the affected tibiae. Increased bone resorption seems to play a crucial role within a multifactorial process of CRPS-mediated bone atrophy. HR-pQCT could possibly serve as a diagnostic tool in specific CRPS therapy.

Diagnostic value of biochemical markers of bone metabolism in treatment of generalized periodontitis in patients with age-related osteoporosis

The topicality of the problem of periodontal diseases is due to their significant prevalence. The purpose of this work is to study the dynamics of markers of bone metabolism in the process of treatment of generalized periodontitis of the II–III levels of severity in patients with age-related osteoporosis and without osteoporotic changes in the skeleton. The examination and treatment of 104 patients, aged 63–78, equal ratio of men and women, was conducted. Among the selected patients, 49 persons had normal bone mineral density, while the remaining 55 had osteoporotic changes in the bone tissue of involutory genesis. All subjects were assessed for the following indicators ; mineral density of jaw bone tissue (BMD) according to the results of the computer tomography, the concentration of C-Propeptide of Type I Procollagen (CICP) in blood plasma, the activity of tartrate-resistant acid phosphatase (TRAP), bone alkaline phosphatase (BAP), osteocalcin, parathyroid hormone in blood serum, concentration of β-CrossLaps in urine, total calcium and inorganic phosphorus content in blood with calculation of the Ca/P index. It was established that in patients with periodontitis of the II–III degree there was a decrease in the BMD of the alveolar bone in comparison with the control values (P ˂ 0.05), whereas the presence of systemic osteopenia worsened the indices (P ˂ 0.001). The least osteoregenerative activity, which was characterized by the decrease in BAP, TRAP and CICP levels, was registered in patients with generalized periodontitis of the III degree on the background of age-related osteoporosis (P ˂ 0.05). In the patients with generalized periodontitis of the III degree of severity, at the beginning of treatment, a weak negative correlation was found between BMD and TRAP activity (r = –0.292, P &lt; 0.05) and mean strength correlation – with β-CrossLaps in urine (r = –0.348, P &lt; 0.01). The concentration of CICP positively correlated with the mineral density of bone tissue from the third month after the start of treatment (r = 0.312, P &lt; 0.05). As a conclusion, the mineral density of alveolar bone in the process of treatment varies unevenly depending on the severity of generalized periodontitis and the character of osteoporotic changes in the skeleton. The biochemical markers of bone metabolism allow the balance of processes of bone resorption and formation to be determined in order to correct treatment of generalized periodontitis.

Protective Effects of 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside on Ovariectomy Induced Osteoporosis Mouse Model.

2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG), an active polyphenolic component of Polygonum multiflorum, exhibits many pharmacological activities including antioxidant, anti-inflammation, and anti-aging effects. A previous study demonstrated that TSG protected MC3T3-E1 cells from hydrogen peroxide (H2O2) induced cell damage and the inhibition of osteoblastic differentiation. However, no studies have investigated the prevention of ovariectomy-induced bone loss in mice. Therefore, we investigated the effects of TSG on bone loss in ovariectomized mice (OVX). Treatment with TSG (1 and 3 μg/g; i.p.) for six weeks positively affected body weight, uterine weight, organ weight, bone length, and weight change because of estrogen deficiency. The levels of the serum biochemical markers of calcium (Ca), inorganic phosphorus (IP), alkaline phosphatase (ALP), and total cholesterol (TCHO) decreased in the TSG-treated mice when compared with the OVX mice. Additionally, the serum bone alkaline phosphatase (BALP) levels in the TSG-treated OVX mice were significantly increased compared with the OVX mice, while the tartrate-resistant acid phosphatase (TRAP) activity was significantly reduced. Furthermore, the OVX mice treated with TSG showed a significantly reduced bone loss compared to the untreated OVX mice upon micro-computed tomography (CT) analysis. Consequently, bone destruction in osteoporotic mice as a result of ovariectomy was inhibited by the administration of TSG. These findings indicate that TSG effectively prevents bone loss in OVX mice; therefore, it can be considered as a potential therapeutic for the treatment of postmenopausal osteoporosis.

A pivotal peptide (Val-Ser-Glu-Glu) from duck egg white promotes calcium uptake and structure-activity relationship study

The effects of desalted duck egg white peptides (DPs) and Val-Ser-Glu-Glu (VSEE) on calcium absorption were investigated in calcium-deficient diets rat model. Six-week oral administration results indicated DPs + CaCO3 and VSEE + CaCO3 were significantly higher than CaCO3 group in calcium absorption, serum osteocalcin, bone calcium content and max load, but lower in serum bone alkaline phosphatase level (P < 0.05). Additionally, in the 0.5% calcium diets groups, the rats fed with DPs showed notably increases in calcium absorption, length of tibias and bone max load than those without DPs. The structure-activity relationship results demonstrated the importance of amino acid units like Glu-Glu and Ser-Ser. Homology modeling and molecular docking results provided two possible active sites of TRPV6 in the promotion of calcium uptake by DPs. The present study expands the understanding of the mechanism of calcium uptake in vivo by DPs, as well as highlights the structure-activity relationship and the potential active sites of TRPV6.

Is it possible to predict a risk of osteoporosis in patients with juvenile idiopathic arthritis? A study of serum levels of bone turnover markers.

Low bone mineral density is a common finding in children with systemic connective tissue diseases, including juvenile idiopathic arthritis (JIA). The influence of the ongoing process of bone remodeling on the disease course merits further investigation. The aim of this study was to assess the clinical relevance of markers of bone turnover and their potential role as predictors of higher fracture risk and, by extension, risk of osteoporosis. Blood samples were collected from 59 patients diagnosed with JIA in order to determine serum levels of the following markers of bone turnover: Beta-Crosslaps, osteocalcin, bone alkaline phosphatase, osteoprotegerin and receptor activator for nuclear factor kappa-B ligand. The values were analyzed with laboratory parameters and results of dual X-ray absorptiometry (DXA). Osteoprotegerin and bone alkaline phosphatase levels were age-dependent. Beta-Crosslaps values were significantly higher in patients with positive JADAS27 score (p=0.0410). Osteoprotegerin levels were higher in patients treated with biological agents than only with disease-modifying anti-rheumatic drugs (p=0.0273). There was no relation between markers of bone turnover and sex, DXA results, dosage of glucocorticosteroids and disease duration. The authors postulate performing DXA measurements every 6 months in patients with higher disease activity. The potential lower fracture risk in children with JIA within biological treatment needs further assessment. Age- and sex-adjusted reference rates of bone turnover markers need to be developed for Central European patients in order to assess individual values properly.

One-year adolescent bone mineral density and bone formation marker changes through the use or lack of use of combined hormonal contraceptives

ObjectiveThe objective of this study was to evaluate the effects of two low-dose combined oral contraceptives on bone metabolism in adolescents for one year. MethodsThis was a quasi-experimental study. The adolescents were divided into three groups: oral contraceptives 1 (n=42) (20μg EE/150μg desogestrel), oral contraceptives 2 (n=66) (30μg EE/3mg drospirenone), and a control group (n=70). Adolescents underwent anthropometric assessment and densitometry (dual-energy X-ray). Bone age and bone formation markers (osteocalcin and bone alkaline phosphatase) were evaluated. The oral contraceptives users were evaluated again after 12 months. Linear regression analysis was used to indirectly study the effect of each additional year of chronological age on anthropometric and densitometric variables as well as on bone markers in the control group. ResultsAt study entry, no significant differences were observed between the oral contraceptives 1, oral contraceptives 2, and controls in the analyzed variables. Linear regression analysis showed an increase in bone mineral density and bone mineral content for each additional year. There was a significant reduction in bone alkaline phosphatase levels; no significant difference was observed for osteocalcin in control individuals. Comparison of dual-energy X-ray variables at baseline and after one year showed no significant differences in the oral contraceptives 1 or oral contraceptives 2 groups. A significant reduction in bone alkaline phosphatase and osteocalcin levels was observed in both the oral contraceptives 1 and oral contraceptives 2 groups. ConclusionAdolescent women gain peak bone mass during this phase of life. Two low-dose combined oral hormonal contraceptives were associated with lower bone gain and lower bone formation markers than in untreated controls.

Effects of curcumin and melatonin on bone formation in orthopedically expanded suture in rats: A biochemical, histological and immunohistochemical study.

To investigate the effects of curcumin (CUR) and melatonin (MEL) on new bone formation following rapid maxillary expansion (RME) in rats. For this study, 24 12-week-old adult male Wistar albino rats from the Animal Laboratory at Adnan Menderes University, Faculty of Medicine, were used. The rats were randomly divided into the following 3 groups (n=8 each): only expansion (OE), expansion plus MEL (MEL) and expansion plus CUR (CUR). CUR and MEL were given to the rats during the study period. After the sacrifice of the animals, biochemical, histological and immunohistochemical examinations were performed. Serum bone alkaline phosphatase levels in the MEL group were statistically (P=.007) higher than in the OE group. Serum glutathione peroxidase and catalase activities in the CUR and MEL groups were significantly higher than in the OE group (P=.007 and P=.021, respectively). Inflammatory cell infiltration, new bone formation and capillary intensity parameters did not demonstrate statistically significant differences between the groups (P=.865, P=.067 and P=.055, respectively). The immunohistochemical findings revealed that IL-1, IL-6 and TNF-α H scores showed considerable differences between the groups (all P<.001). The highest IL-1, IL-6 and TNF-α H scores were found in the OE groups rather than in the other groups (P<.001). CUR and MEL treatments may be effective in accelerating new bone formation and beneficial in preventing relapse following the RME procedures.

Effects of Lowering Dialysate Calcium Concentration on Bone Metabolic Markers in Hemodialysis Patients With Suppressed Serum Parathyroid Hormone: A Preliminary Study.

Although the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend a dialysate calcium concentration between 2.5 and 3.0 mEq/L, its optimal concentration remains unclear. A total of 53 hemodialysis patients with intact parathyroid hormone (PTH) levels <150 pg/mL were enrolled in this prospective observational study. A dialysate calcium concentration was converted from 3.0 to 2.75 mEq/L and bone metabolic markers including bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase-5b (TRACP-5b) were examined. After 3 months, serum corrected calcium levels decreased (P < 0.001), while serum intact PTH, BAP and TRACP-5b levels increased (P < 0.05, P < 0.05 and P < 0.001, respectively). Multiple regression analyses showed that the amount of change in BAP was significantly associated with dialysis vintage (P < 0.01). In conclusion, the lowering of dialysate calcium concentration stimulated parathyroid gland and bone remodeling in hemodialysis patients with suppressed PTH, particularly with longer dialysis vintage.

PR625: Effects of smoking on the implant stability quotient measurements and the level of bone alkaline phosphatase in peri‐implant crevicular fluid around implants before functional loading

PR625: Effects of smoking on the implant stability quotient measurements and the level of bone alkaline phosphatase in peri‐implant crevicular fluid around implants before functional loading

The Levels of Bone Alkaline Phosphatase (BALP) and Soluble Epidermal Growth Factor Receptor-2 (ECD/HER-2) in Pediatric Patients with Osteosarcoma During Clinical Treatment

AimThe aim of this study was to assess the usefulness of bone-specific alkaline phosphatase (BALP) and the extracelluar domain of human epidermal growth factor receptor 2 (ECD/HER-2) measurements in pediatric patients with osteosarcoma as prospective prognostic and predictive markers for monitoring the treatment and early detection of disease recurrence.Material and methodsWe studied 22 patients (5 girls, 17 boys) aged 7-20 years with osteosarcoma (OS) treated at the Institute of Mother and Child in Warsaw. All the patients were evaluated for the serum levels of BALP and ECD/HER-2 before treatment, during pre- and postoperative chemotherapy and after the completion of treatment. Healthy children (n=22) were the reference group. The levels of BALP and ECD/HER-2 were measured using immunoenzymatic methods.ResultsThe values of BALP and ECD/HER-2 proteins were higher (p<0.01; p<0.05, respectively) in patients with osteosarcoma at the time of diagnosis compared with the control group. The values of both markers significantly decreased during chemotherapy in most patients with remission. In contrast to ECD/HER-2, the value of BALP after therapy was higher in patients with progression than with remission (p<0.001).ConclusionsOur results demonstrate the different pattern of BALP and ECD/HER-2 proteins during clinical treatment in patients with osteosarcoma. Higher values of BALP may characterize the progression of the disease and unfavourable prognosis. Further longitudinal studies are necessary to confirm the prognostic values of BALP and ECD/HER-2 proteins in this group of patients.

Physical Fitness, Adiposity, and Diets as Surrogate Measures of Bone Health in Schoolchildren: A Biochemical and Cross-Sectional Survey Analysis

This study aimed to investigate the associations between adiposity, muscular fitness (MF), diet, sun exposure, and physical activity profiles as surrogate measures with bone health status in a sample of schoolchildren aged 8–18 yr old. A total of 250 Egyptian schoolchildren aged 8–18 yr were randomly invited to participate in these cross-sectional survey analyses. Calcaneal broadband ultrasound attenuation (c-BUA), bone mineral density (BMD), and bone formation markers (total calcium, serum bone alkaline phosphatase, and osteocalcin) were measured as markers of bone health. Adiposity profile, MF, physical activity (PA), sun exposure, Ca, and vitamin D dietary intake as related cofactors of bone health were measured by using prevalidated questionnaires and standard analytical techniques. A total of 85% (n = 213) of the study population showed normal bone health and 14.8% (n = 37) had abnormal bone health; most of them are girls (67.6%) classified according to BMD and c-BUA Z-scores into osteopenia (9.6%) and osteoporosis (5.2%). Compared with boys, higher correlations between c-BUA, bone mineral content, and BMD measures in the femoral neck, lumbar spine, whole body, and bone markers were reported in girls with lower bone mass. There was a positive significant correlation between body mass index, adiposity, sun exposure, MF, PA status, Ca and vitamin D intake, and c-BUA and BMD score analyses. These parameters were shown to be associated with about ~57.3%–88.4% of bone health characteristics of children and adolescents with osteopenia and osteoporosis. In children and adolescents, sun exposure, Ca and vitamin D diets, adiposity, PA, and changes in the levels of Ca, osteocalcin, and serum bone alkaline phosphatase were shown to be associated with bone health. Also, a significant correlation was reported between c-BUA score, dual-energy X-ray absorptiometry-BMD measures, and bone markers at clinically important bone sites of girls and boys. However, further clinical trials should be studied to consider c-BUA and bone markers as the benchmark estimates of bone mass for diagnostic purposes in young ages.

Abstract P031: Effect of Exercise on Function and Differentiation of Adipose Tissue Derived Mesenchymal Stromal Cells (MSCs)

Approximately 422 million people have diabetes worldwide (2014) and it is predicted that diabetes will rise by nearly 54% by 2030. Aerobic exercise is known to show positive effect on health of diabetic and pre diabetic patients. The effect of exercise has been studied extensively using plasma biochemistry but cellular data is scares. Previously, we have shown endothelial progenitor cells (EPCs) can act as a strong cellular biomarker of endothelial function following aerobic exercise as an intervention. In this study, we are examining the effect of aerobic exercise on adipocyte derived MSCs to study stromal cell differentiation and as a cellular surrogate of fat metabolism. Methods: Overweight and obese subjects (n=5) were enrolled in a 12 week exercise intervention study. The biweekly exercise sessions were supervised by a trained exercise physiologist and consisted of a 1 hour sessions that included warm-up and cool-down and 30 min of combined aerobic and resistance training at an exercise intensity of 50-80% of heart rate reserve. Physical and biochemical parameters were tested pre and post exercise. Subcutaneous abdominal fat biopsies were obtained and fat derived stromal cells were cultured in vitro for 2-3 weeks. MSCs were analyzed for mRNA gene expression (qRT-PCR) and cellular oxygen consumption rate (OCR), pre and post 12 week exercise. Results: With exercise, A1C reduced significantly. An increase of METs was also noticed post exercise. Both basal and maximal respiration increased significantly post exercise when compared with commercially obtained MSCs. Simultaneously, mitochondrial genes COX4 and ATP5B (p= 0.01, 1.4 fold, 0.02, 1.5 fold respectively), Glucose transporter, GLUT1 (p=0.04, 1.8 fold), antioxidants GPX3 and CAT (p= 0.01, 3.2 fold and p=0.04, 1.5 fold respectively) upregulated whereas pro-inflammatory cyclo-oxygenase-2 (p=0.04, 2.5 fold) gene reduced significantly, post exercise. Regarding differentiation potential of multipotent MSCs, post exercise, we noted enhanced expression of bone markers such Alkaline Phosphatase (p= 0.03, 2.7 fold) BGLAP and RUNX2 (1.3 and 1.2 fold) and also for collagen marker COL2 (2.4 fold) expression. For adipogenic differentiation potential PPARG mRNA expression was reduced. Interestingly, serum value of osteocalcin increased significantly from 15.0 (5.5) to 16.3(6.1) ng/ml (9% increase, p=0.03) with 1% increase in bone alkaline phosphatase level, post exercise. Conclusion: We conclude that exercise augments cellular glucose transporters (GLUT1), anti-oxidants and reduce MSC inflammation and up-regulates mitochondrial function and gene expression profile of MSCs. Increased serum value of osteocalcin complement increased gene expression of bone formation markers indicating a cross talk between fat derived MSCs and bone formation, post exercise.

Changes in bone mineral density after kidney transplantation: 2-year assessment of a French cohort.

In renal transplant patients, bone loss may be related to the drugs patients are taking but also to their past history of chronic kidney disease. The purpose of this study was to assess changes in BMD 2years after an initial assessment (performed 9months post transplantation) and the factors associated with these changes. This longitudinal study included patients who had undergone a renal transplantation between 2005 and 2011, and who were followed up at the Lille Regional University Hospital. Patients were included if they had a first bone evaluation (including bone densitometry, spine X-rays and biological assessment) and at least another BMD assessment. The first assessment was performed on average 9months post transplantation. A second assessment was performed at 2years. Two hundred fifty-nine out of 366 patients satisfied the inclusion criteria. The population included 96 women. Mean age at transplantation was 49.7 ± 12.1years. Mean duration of dialysis was 3.2 ± 3.3years. For 75 patients (29.0%), corticosteroid treatment was discontinued 7days after transplantation without subsequent resumption during follow-up. Vertebral fractures assessed by X-rays at baseline were found in 28 patients (10.8%). According to the WHO classification, 106 patients (40.9%) patients had osteoporosis and 111 patients (42.8%) had osteopenia at the first assessment. Oral bisphosphonates were prescribed for 95 patients. The decision to prescribe bisphosphonates was taken jointly by rheumatologists and nephrologists based on BMD assessment, past history of fracture and corticosteroid management. In all patients, BMD gains at the second evaluation (2.2 ± 0.79years) compared with baseline were significant (3.9 ± 6.6, 2.6% ± 7.6, 3.0 ± 7.2% at the lumbar spine, femoral neck and total hip respectively; p < 0.0001). The difference in gain between bisphosphonate-treated and untreated patients was significant (+ 5.0 ± 0.8% (p < 0.0001), + 2.5 ± 1.0% (p = 0.01) and + 2.7 ± 0.9% (p < 0.01) at the lumbar spine, femoral neck and total hip respectively. The patients who benefited early corticosteroid discontinuation had higher gains in BMD at the lumbar spine (+ 2.1 ± 0.9%; p = 0.02) and total hip (+ 2.0 ± 1.0%; p = 0.04) compared to those for whom corticosteroid therapy was maintained. Stepwise regression analysis (patients without bisphosphonates) showed associations between change in BMD (femoral neck) and duration of corticosteroid therapy, bone alkaline phosphatase level at baseline, and absence of vertebral fracture. No correlation was found between change in BMD and duration of dialysis or renal function. Kidney transplant recipients have an increased risk of bone fragility in the year following transplantation. Bisphosphonates and early corticosteroid discontinuation can improve BMD.

Markov chain based simulation analysis of bone mineral density and changes in the level of biochemical markers of bone transformation in postmenopausal women

The changes in biochemical marker level of bone turnover of women before and after menopause and the relationship between it and bone mineral density (BMD) are analyzed. At the same time, the level of biochemical markers of bone metabolism of women with decreased BMD at premenopause and postmenopause is discussed. In this paper, the lumbar vertebrae (L1–L4) and femoral neck BMD of 225 female outpatients with osteoporosis were measured by dual-energy X ray bone sonometer. Among them, 185 menopause women at age of 45–65 were selected, and they were divided into normal bone mass group (50), decreased bone mass group (35) and osteoporosis group (100) according to BMD; in addition, 45 menopause women with decreased BMD at age of 51–70 were selected as postmenopause decreased-BMD group, and 25 non-menopause decreased-BMD women at age of 42–50 were selected as premenopause decreased-BMD group. Enzyme-linked immunosorbent assay was carried out to measure the level of serum cathespin K (Cathe K), bone alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase (TRAP) of all patients; and electrochemiluminescence immunoassay is used to detect the level of osteocalcin, β-crosslaps and type-I procollagen N-terminal propeptide(PINP). The Cathe K, PINP, β-crosslaps, osteocalcin and TRAP level of postmenopausal women with osteoporosis are obviously higher than those of normal bone mass group (P 0.05). The Cathe K and TRAP level of serum in postmenopause decreased-BMD group were significantly lower than those in premenopausal women (P 0.05). Osteoporosis of postmenopausal women is high turnover. The changes in the levels of serum osteocalcin, β-crosslaps, PINP, B-ALP, TRAP and Cathe K could reflect the bone metabolism activity. The joint detection of BMD and bone-turnover biochemical marker is beneficial to the prevention, treatment and efficacy observation of the patients with osteoporosis.

Effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism in children with chronic kidney disease.

We investigated the effects of nutritional vitamin D supplementation on markers of bone and mineral metabolism, i.e. serum levels of fibroblast growth factor 23 (FGF23), Klotho, bone alkaline phosphatase (BAP) and sclerostin, in two cohorts with chronic kidney disease (CKD). In all, 80 vitamin D-deficient children were selected: 40 with mild to moderate CKD from the ERGO study, a randomized trial of ergocalciferol supplementation [estimated glomerular filtration rate (eGFR) 55 mL/min/1.73 m2], and 40 with advanced CKD from the observational Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study (eGFR 24 mL/min/1.73 m2). In each study, vitamin D supplementation was started in 20 children and 20 matched children not receiving vitamin D served as controls. Measures were taken at baseline and after a median period of 8 months. Age- and gender-related standard deviation scores (SDSs) were calculated. Before vitamin D supplementation, children in the ERGO study had normal FGF23 (median 0.31 SDS) and BAP (-0.10 SDS) but decreased Klotho and sclerostin (-0.77 and -1.04 SDS, respectively), whereas 4C patients had increased FGF23 (3.87 SDS), BAP (0.78 SDS) and sclerostin (0.76 SDS) but normal Klotho (-0.27 SDS) levels. Vitamin D supplementation further increased FGF23 in 4C but not in ERGO patients. Serum Klotho and sclerostin normalized with vitamin D supplementation in ERGO but remained unchanged in 4C patients. BAP levels were unchanged in all patients. In the total cohort, significant effects of vitamin D supplementation were noted for Klotho at eGFR 40-70 mL/min/1.73 m2. Vitamin D supplementation normalized Klotho and sclerostin in children with mild to moderate CKD but further increased FGF23 in advanced CKD.

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.

Effect of TAK1 on osteogenic differentiation of mesenchymal stem cells by regulating BMP-2 via Wnt/β-catenin and MAPK pathway

ABSTRACTMesenchymal stem cells (MSCs) have the ability to differentiate into osteoblasts and chondrocytes. In vitro osteogenic differentiation is critical but the molecular mechanism has yet to be further clarified. The role of TGF-β activated kinase 1 (TAK1) in MSCs osteogenesis differentiation has not been reported. By adding si-TAK1 and rhTAK1, the osteogenic differentiation of MSCs was measured. Expression levels of the osteoblastic marker genes during osteogenic differentiation of MSCs were checked. As well as molecules involved in BMP and Wnt/β-catenin signaling pathways. The phosphorylation of p38 and JNK was also checked. TAK1 is essential for mineralization of MSCs at low concentration, but excessive rhTAK1 inhibits mineralization of MSCs. It up regulates the expression levels of bone sialoprotein (BSP), osteocalcin (OSC), Alkaline phosphatase (ALP), and RUNX2 during osteogenic differentiation of MSCs. It can also promote TGF-β/BMP-2 gene expression and β-catenin expression, and down regulate GSK-3β expression. Meanwhile, TAK1 promotes the phosphorylation of p38 and JNK. Additionally, TAK1 up regulates the expression of BMP-2 at all concentration under the inhibition of p38 and JNK. Our results suggested that TAK1 is essential in MSCs osteogenesis differentiation, and functions as a double-edged sword, probably through regulation of β-catenin and p38/JNK.