Bone Alkaline Phosphatase Levels Research Articles

Effects of Low-Phosphorus Diets Supplemented with Phytase on the Production Performance, Phosphorus-Calcium Metabolism, and Bone Metabolism of Aged Hy-Line Brown Laying Hens

This study was conducted to evaluate the effects of phytase supplementation in low-phosphorus diets on the production performance, phosphorus-calcium metabolism, and bone metabolism in laying hens from 69 to 78 weeks of age. Hy-Line Brown laying hens (n = 1350) were assigned randomly to six treatments with five replicates of 45 birds. A corn-soybean meal-based diet with no inorganic phosphates was formulated to contain 0.12% non-phytate phosphorus (NPP) and 1470 FTU/kg phytase (Released phytate phosphorus content ≥ 0.1%). Inorganic phosphorus (dicalcium phosphate) was supplemented into the basal diet to construct five test diets (level of NPP supplementation = 0.10%, 0.15%, 0.20%, 0.25%, and 0.30%). The level of calcium carbonate was adjusted to ensure that all six experimental diets contained the same calcium percentage (3.81%). The feeding trial lasted 10 weeks (hens from 69 to 78 weeks of age). Upon supplementation with phytase (1470 FTU/kg), supplemental inorganic phosphates (dicalcium phosphate) had no significant effects (p > 0.05) on the production performance or egg quality. Significant differences in serum levels of calcium, phosphorus, copper, iron, zinc, or manganese were not detected across treatments (p > 0.05). Hens fed NPP (0.15%, 0.20%, 0.25%, and 0.30%) had higher levels (p < 0.0001) of tibial ash, calcium, and phosphorus than those not fed inorganic phosphates. The tibial breaking strength of the group without inorganic phosphates was significantly lower than that of the other groups (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of calcitonin (CT) and 1,25-dihydroxy-vitamin D3 (1,25-(OH)2D3). Hens that did not receive supplementation with inorganic phosphates had higher serum levels of parathyroid hormone (PTH), osteoprotegerin (OPG), type-I collagen c-telopeptide (CTX-I), and tartrate-resistant acid phosphatase 5b (TRACP-5b) compared with those in the other groups (p < 0.01). Serum levels of CTX-I and TRACP-5b were significantly lower in the NPP-supplementation groups of 0.25% and 0.30% than in the 0.10% NPP-supplementation group (p < 0.01). Dietary supplementation with inorganic phosphates had no effect (p > 0.05) on serum levels of bone-alkaline phosphatase (BAP), osteocalcin (OCN), or osteopontin (OPN). Hens not fed inorganic phosphate had the highest renal expression of phosphorus transporter type IIa Na/Pi cotransporter (NaPi-Ⅱa). Renal expression of NaPi-Ⅱa was increased significantly in NPP-supplementation groups of 0.10-0.20% compared with that in NPP-supplementation groups of 0.25% and 0.30% (p < 0.0001). The results indicated that a reduction in NPP supplementation to 0.15% (dietary NPP level = 0.27%) with phytase inclusion did not have an adverse effect on the production performance or bone health of laying hens from 69 to 78 weeks of age, which might be attributed to renal phosphorus reabsorption and bone resorption. These findings could support the application of low-phosphorus diets in the poultry industry.

340 Dupilumab treatment of children with moderate-to-severe atopic dermatitis increases bone alkaline phosphatase, a marker of bone mineralization

Abstract Children with atopic dermatitis (AD) are at risk for low bone mineral density (BMD), which is associated with an increased prevalence of osteopenia, osteoporosis, and fracture risk.1,2 Factors such as restricted nutrition, vitamin D deficiency, poor sleep and corticosteroid use contribute to lower bone alkaline phosphatase (BALP) levels, a marker of bone mineralization, seen in children with moderate-to-severe AD compared with healthy children.3 A major determinant for the lifetime risk of fractures and osteoporosis is the magnitude of peak bone mass achieved during prepubescent years. Low BALP and BMD in children with moderate-to-severe AD could contribute to a higher prevalence of osteopenia and osteoporosis. The objective of this analysis is to report the impact of dupilumab treatment on markers of bone formation in children aged ≥ 6 to &amp;lt; 12 years with moderate-to-severe AD. The analysis was performed retrospectively on sera from participants in LIBERTY AD PEDS (NCT03345914) and LIBERTY AD PED-OLE (NCT02612454). In LIBERTY AD PEDS, a double-blind, 16-week, phase 3 trial, children aged 6 to &amp;lt; 12 years were randomized 1 : 1 : 1 to 300 mg dupilumab every 4 weeks (300 mg q4w), a weight-based regimen of dupilumab every 2 weeks (100 mg q2w for patients with baseline weight &amp;lt;30 kg, and 200 mg q2w for those with baseline weight ≥30 kg), or placebo; with concomitant medium-potency topical corticosteroids (TCS). After the initial 16-week trial, children aged 6 to &amp;lt;12 years were enrolled in the open-label extension study LIBERTY AD PED-OLE. Patients received dupilumab 300 mg q4w, which could be titrated up in case of inadequate clinical response at week 16 (200 mg q2w for patients with baseline weight &amp;lt;60 kg, and 300 mg q2w for those with baseline weight ≥60 kg); with concomitant medium-potency TCS. Bone biomarkers including BALP, procollagen type 1 N-terminal propeptide, C-terminal crosslinking telopeptide of type 1 collagen, osteocalcin, and insulin-like growth factor 1 were analysed at baseline, 8, 12, 16 and BALP only at 52 weeks. Dupilumab treatment led to a rapid and significant increase in geometric mean (standard error) levels of BALP in children with moderate-to-severe AD at 16 weeks compared with patients in the placebo group (77.7(1.02) μgL−1 vs. 65.0(1.04) μgL−1; P &amp;lt; 0.0001). As well as a rapid and significant increase in BALP levels in children from the placebo group once they joined the OLE trial. BALP levels increased over 52 weeks in all treated children, reaching a level of 78–84 μgL−1 which constitutes a significant improvement compared with baseline, and is comparable to healthy reference intervals. An increasing trend from baseline to 16 weeks of dupilumab treatment was observed for other biomarkers, however, there was a limited number of data points due to insufficient volumes of serum available for analysis. These placebo-controlled results show, for the first time, a rapid and significant increase in BALP, and a possible trend in other biomarkers, in children with AD during treatment with dupilumab. These results suggest increased bone mineralization during the treatment period.

Measuring of Specific Bone Alkaline phosphatase ( BAP ) Bone Remodeling biomarker for Post-COVID Iraqi Patient

Background: There are several diseases in the body following recovery from COVID-19 infection because this virus operates on human genes in various types of peripheral tissue in the human body. It penetrates host cells via Angiotensin-converting enzyme-2 receptors and may have effects on bone remodeling, leading to osteopenia or osteoporosis, which are characterized by low bone mineral density, resulting in diminished bone strength. Bone Alkaline Phpsphatase is an enzyme released into the bloodstream as a soluble homodimer after being cleaved by a phospholipase and can be utilized as a biomarker of bone development. Objective: This research was designed to investigate the alteration of bone homeostasis balance in Iraqi post-COVID-19 infection patients. Cases and Methods: This is a case control study. The study has received approval from the ethical committee at the Faculty of Medicine, Baghdad University, established on November 20, 2021–March 2, 2022. A hundred and thirty individuals were enrolled in this study. The subjects were divided into two groups; the first group (80) post-COVID-19 infection patients and the second group (50) non-COVID-19 individuals. Also, measuring markers like serum Angiotensin-converting enzyme-2 and Bone Alkaline Phosphatase by using the ELISA technique. The bone mineral density was measured by a DEXA scan. Results:This study found that there is an effect of coronavirus infection on the bone strength measured by the mean ± SD Bone Alkaline Phosphatase level, which was found to be highly significant in the serum of post-COVID-19 patients when compared with non-COVID-19 individuals (P-value = 0.001), but the mean ± SD of Angiotensin-converting enzyme-2 level was statistically non-significant between the two groups (P-value = 0.13). who had recovered from a coronavirus infection for 3 months or more. Also, the bone mineral density of Post COVID-19 patients that was measured by DEXA scan had a highly significant T-score% when compared between the two groups. Conclusions:This research found that COVID-19 has an impact on the bone remodeling process, leading to osteopenia or osteoporosis, which may be identified by checking the blood levels of the bone biomarker BAP and the bone mineral density (by DEXA scan) at least three months following coronavirus recovery. This investigation also discovered that some of the individuals had osteopenia rather than osteoporosis.

Perilla seed oil improves bone health by inhibiting bone resorption in healthy Japanese adults: A 12-month, randomized, double-blind, placebo-controlled trial.

Accumulating evidence suggests the beneficial effect of omega-3 polyunsaturated fatty acids (PUFAs) on bone mineral density (BMD). However, the effects of perilla (Perilla frutescens) seed oil (PO), a rich source of α-linoleic acid (LNA), on human bone have not yet been elucidated. This randomized, double-blind, placebo-controlled trial investigated the effects of long-term PO intake on bone health in Japanese adults. After screening for eligibility, 52 participants (mean age 54.2 ± 6.4 years) were randomly assigned to placebo (n=25) and PO (n=27) groups, which received 7.0 ml of olive oil and PO daily, respectively. At baseline and 12-month, quantitative ultrasound of the right calcaneus was measured with an ultrasound bone densitometer and percentage of the Young Adult Mean (%YAM) was calculated. Serum levels of tartrate-resistant acid phosphatase 5b (TRACP-5b), and bone alkaline phosphatase (BALP) were evaluated. In addition, PUFA levels in the erythrocyte plasma membrane (RBC-PM), serum biological antioxidant potential (BAP), and diacron reactive oxygen metabolites (d-ROM) were evaluated. Compared with the placebo group, %YAM levels increased and serum TRACP-5b levels decreased significantly in the PO group at 12-month, while serum BALP levels remained unchanged. Moreover, RBC-PM LNA levels and BAP/d-ROM ratios increased significantly in the PO compared with the placebo group. These results suggest that long-term PO intake may improve age-related BMD decline by suppressing bone resorption and increasing LNA levels.

Characteristics of the state of bone tissue in genetically modified mice with impaired enzymatic regulation of steroid hormone metabolism

Introduction: The aim was to evaluate the structural and functional changes of bone tissue in mice with null expression of 11β-HSD2 or both 11β-HSD2 and Apolipoprotein E.&#x0D; Materials and methods: The experimental study was performed in 60 male mice, weighting 24–30 g. The animals were kept in accordance with the rules of laboratory practice for preclinical studies on the territory of the Russian Federation. Mice lacking 11β-HSD2 (Hsd2-/-) and male mice lacking 11β-HSD2 and Apolipoprotein E (Hsd2-/-/Apoe-/-) were used in the study. We studied and characterized the state of bone tissue, indicators of bone density, microcircu­lation in bone tissue, endothelial dysfunction coefficient, width of bone trabeculae, as well as serum concentrations of bone alkaline phosphatase, hydroxyproline, deoxyprinoline and expression levels of p53, Bcl2, Bax, eNOS genes.&#x0D; Results and discussion: We showed that mice with the Hsd2-/- genotype with no expression of 11ß-HSD2 by the 6th month of life showed a statistically significant decrease in bone density, which progresses to the 7th and 8th months of life. At the 8th month of animal life, a decrease in bone density is accompanied by a statistically significant decrease in the level of microcirculation in the bone and an increase in the coefficient of endothelial dysfunction. Taking into account the relationship of endothelial dysfunction, atherogenesis and disorders in the processes of bone remodeling, in the framework of this study, we also assessed the state of bone tissue in double transgenes with the genotype Hsd2-/-/Apoe-/-, which lack the expression of both 11ß-HSD2 and Apolipoprotein E. In this study, we also saw increased acti­vation of processes leading to disruption of bone remodeling processes. In the group of the animals with the genotype Hsd2-/-/Apoe-/-, we found statistically significant differences from the mice with no expression of 11ß-HSD2 in bone density and microcirculation, and the width of bone trabeculae. Also, a statistically significant increase in hydroxypro­line and deoxyprinoline was found in the group of double transgenes, in the absence of significant changes in the con­centration of bone alkaline phosphatase. This fact indicates a pronounced activation of bone resorption processes in the absence of activation of osteosynthesis processes, which leads to the detected violation of bone remodeling processes.&#x0D; Conclusion: Thus, we have shown that a violation of the metabolic regulation of steroid hormone metabolism in ani­mals with null expression of the 11ß-HSD2 (Hsd2-/- genotype) leads to the development of signs of osteoporosis – bone density decreases, which is accompanied by a decrease in the width of bone trabeculae, the level of microcirculation in bone tissue decreases simultaneously with an increase in the coefficient of endothelial dysfunction. The additional null expression of ApoE gene in double transgenes with the genotype Hsd2-/-/Apoe-/- leads to an increase in the severity of changes associated with a violation of bone remodeling processes and, in addition to a more pronounced change in bone tissue density, bone trabecular width, microcirculation and the coefficient of endothelial dysfunction leads to an increase in the concentration of biochemical markers of bone resorption. These changes indicate the important role of the enzyme 11ß-hydroxysteroid dehydrogenase type 2 in the processes of bone remodeling disorders.&#x0D; Graphical abstract:

125I brachytherapy: a useful treatment to control painful osteoblastic bone metastases

Backgrounds125I brachytherapy is effective in relieving cancer pain due to osteolytic bone metastases. However, fewer studies focused on painful osteoblastic bone metastases (OBMs), we conducted a retrospective study to evaluate the efficacy of 125I brachytherapy for the treatment of painful OBMs.MethodsFrom April 2017 to April 2019, clinical data of a total of 65 patients with OBMs who underwent CT/cone beam CT -guided 125I brachytherapy were collected and analyzed. The primary study endpoints were technical success, relief of pain (RoP), and quality of life (QoL). The secondary study endpoints were treatment-related complications, local tumor control (LCR), and overall survival (OS). The logistic regression analysis was performed to predict RoP.ResultsTechnical success rate was 100%. Visual analog scale scores and daily morphine consumption continuously decreased significantly at 2 weeks, 6 weeks, and 10 weeks (all P < 0.05). The RoP at 6 weeks was 84.62%. QoL presented improvement at 6 and 10 weeks. Only minor complications occurred in 12 patients (18.46%). LCR was 93.85% at 10 weeks. The OS was 29.80 months. Two factors were significantly associated with the RoP: max diameter (MD, < 3 cm vs. ≥ 3 cm, P = 0.019) and serum levels of bone alkaline phosphatase (B-ALP, ≥ 100 U/L vs. < 100 U/L, P = 0.016).Conclusions125I brachytherapy is an effective treatment in relieving painful OBMs and improving patients’ QoL.

Acceleration of Bone Fracture Healing through the Use of Bovine Hydroxyapatite or Calcium Lactate Oral and Implant Bovine Hydroxyapatite-Gelatin on Bone Defect Animal Model.

Bone grafts a commonly used therapeutic technique for the reconstruction and facilitation of bone regeneration due to fractures. BHA-GEL (bovine hydroxyapatite-gelatin) pellet implants have been shown to be able accelerate the process of bone repair by looking at the percentage of new bone, and the contact between the composite and bone. Based on these results, a study was conducted by placing BHA-GEL (9:1) pellet implants in rabbit femoral bone defects, accompanied by 500 mg oral supplement of BHA or calcium lactate to determine the effectiveness of addition supplements. The research model used was a burr hole defect model with a diameter of 4.2 mm in the cortical part of the rabbit femur. On the 7th, 14th and 28th days after treatment, a total of 48 New Zealand rabbits were divided into four groups, namely defect (control), implant, implant + oral BHA, and implant + oral calcium lactate. Animal tests were terminated and evaluated based on X-ray radiology results, Hematoxylin-Eosin staining, vascular endothelial growth Factor (VEGF), osteocalcin, and enzyme-linked immunosorbent assay (ELISA) for bone alkaline phosphatase (BALP) and calcium levels. From this research can be concluded that Oral BHA supplementation with BHA-GEL pellet implants showed faster healing of bone defects compared to oral calcium lactate with BHA-GEL pellet implants.

The antibiotics supplemented bone cement improved the masquelet's induced membrane in a rat femur critical size defect model

BackgroundMasquelet technique is a two-stage surgical procedure used in the treatment of critical-size bone defects (CSD). Adding antibiotics to polymethylmethacrylate (PMMA) is still questionable to create higher quality induced membrane (IM). The aim of the study was to evaluate the effects of three antibiotic-supplemented cement, fusidic acid, teicoplanin, and gentamicin, on osteogenesis and IM progression applied to rat femur CSD model by comparing histopathological, biochemical, and immunohistochemical findings. MethodsTwenty-eight male rats were divided into four groups control, gentamicin (G), teicoplanin (T), and fusidic acid (FA). A 10 mm CSD was created in rat femurs. In the postoperative 4th week, intracardiac blood samples were collected for biochemical analysis of bone alkaline phosphatase (BALP), osteocalcin (OC), and tumor necrosis factor-alpha (TNF-α) levels. IMs obtained in secondary operation were fixed and prepared for histopathological scoring of membrane progression and immunohistochemical evaluation of rat-specific Transforming Growth Factor-Beta (TGF-β), Runt-related Transcription Factor 2 (Runx2), and Vascular Endothelial Growth Factor (VEGF) expressions. ResultsLevels of BALP and OC in serum didn't change among groups significantly while serum TNF-α levels significantly decreased in all antibiotic groups compared to the control group (P = 0.017). Histological scores of groups FA and T were significantly higher than those of groups Control and G (P = 0.0007). IMs of groups T and FA showed good progression while those of groups Control and G were also moderately progressed. A significant increase in TGF-β expression was observed in group G and FA (P = 0.001) while a significant increase in the expression of VEGF was observed in groups G and T compared to the control group (P = 0.036). ConclusionsThe bone cement impregnated with thermostable and safe antibiotics, gentamicin, fusidic acid, and teicoplanin can increase osteogenesis and support IM progression by increasing the expressions of TGF-β and VEGF. Anabolic effects of induced membranes used in the treatment of critical-size bone defects can be enhanced by antibiotic-supplemented PMMAs applied by altering the original technique.

Tubiechong patching promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway

Ethnopharmacological relevanceThe external use of traditional Chinese medicine (TCM) to treat fractures has a long history of clinical application and theoretical basis, and is also one of the characteristic treatment methods of TCM with significant efficacy and many advantages. Among the commonly used external Chinese medicines, Tubiechong is noteworthy. Aim of the studyTo elucidate whether local patching of Tubiechong can promote fracture healing and explore its mechanism of action. Materials and methodsA rat tibia fracture model was constructed by the modified Einhorn modeling method. X-ray films were taken to evaluate the progress of fracture healing. Serum bone alkaline phosphatase (BALP), osteocalcin (BGP) and the C-terminal content of collagen type I (CTX-I) were analyzed by ELISA. CD31 immunohistochemistry was used to evaluate angiogenesis in the tibia segment. The effects of Tubiechong decoction (TD) on HUVEC proliferation, migration and invasion were detected by MTT assay, wound healing assay and Transwell migration assay, respectively. RNA-seq was performed to identify differentially expressed genes (DEGs). Enrichment of functions and signaling pathway analysis were performed based on the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Quantitative real time polymerase chain reaction (qRT-PCR) was used to study gene expression levels. Western blotting (WB) was used to detect the expression of relevant regulatory proteins. ResultsThe healing time of rat tibia fractures in the three TD dose groups was shortened. The serum levels of BALP, BGP and CTX- I in the TD-treated group were higher than those in the NC group. The X-ray results showed that on the 7th day after surgery, the fracture healing degree of the high-dose TD group was significantly better than that of the NC group, and the fracture healing degrees of each TD treatment group were significantly higher than those of the NC group on the 14th, 17th, and 21st days after the operation. The CD31 immunohistochemistry results showed that the number of blood vessels and the vascular area in the TD treatment group were higher than those in the NC group. In vitro, TD promoted the proliferation, wound healing and migration of HUVECs. GO analysis of transcriptome sequencing results showed that TD significantly altered the expression of genes related to cell growth, metabolism, and motility. According to KEGG annotations, VEGFA was upregulated. Eight DEGs were enriched in the VEGFA-VEGFR2 signaling pathway, of which six were upregulated. KEGG signaling pathway analysis showed that the most abundant DEGs were in mitogen-activated protein kinase (MAPK) signaling pathway. qRT-PCR showed that VEGFA gene expression in HUVECs was 7.8 times that of the control group after 1 mg/mL TD treatment for 24 h, and WB experiments showed that its protein expression was 3 times that of the control group. WB results showed that the phosphorylated ERK gene was highly expressed, while the expression levels of phosphorylated P38 and phosphorylated JNK protein remained unchanged. ConclusionTubechong patching therapy promotes tibia fracture healing in rats by regulating angiogenesis through the VEGF/ERK1/2 signaling pathway.

Antiosteoporosis and bone protective effect of nimbolide in steroid-induced osteoporosis rats.

Osteoporosis is a metabolic, hereditary, progressive disease characterized by unusual bone production across the skeleton and a loss the bone tissue microstructure and mass. In this experimental study, we scrutinized the antiosteoporosis effect of nimbolide against glucocorticoid (GCs) induced osteoporosis in rats. Swiss albino female rats were employed for the current experiment study and the rats were divided into different groups. Dexamethasone (0.1 mg/kg/day) was used for induction the osteoporosis and the rats were received the different doses of nimbolide (2.5, 5, and 7.5 mg/kg) for the estimation of bone protective effects. The body weight was estimated (initially and finally). Hormones, bone metabolic markers, bone turnover markers, bone structure, biomechanical, histomorphometric dynamic, biochemical markers, and histomorphometric static parameters were analyzed. The body weight of GCs group rats considerably suppressed and nimbolide treatment remarkably improved the body weight. Nimbolide treated group exhibited the enhancement of bone metabolic, bone structure markers, and histomophometric dynamic markers, which was suppressed during the GCs-induced osteoporosis. GCs-induced osteoporosis rats exhibited the enhancement of procollagen type 1 C-terminal propeptide (P1CP), carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1), Dickkopf-1 (DKK1), tartrate-resistant acid phosphatase 5b (TRACP 5b), and suppressed the level of bone alkaline phosphatase (BAP), which was reversed by the nimbolide treatment. Nimbolide treatment remarkably improved the level of estradiol and suppressed the level of parathyroid hormone (PTH), which was altered during the osteoporosis. Nimbolide treatment significantly (p < 0.001) improved the level of calcium, magnesium, and phosphorus in the serum and bone tissue. Nimbolide treatment also altered the level of bone metabolic markers and suppressed the level of inflammatory cytokines. Based on the findings, we may conclude that nimbolide has antiosteoporosis properties via balancing the bone mass and improving vitamin and hormone levels.

P8.033: Teriparatide in Kidney Transplant Patients With Bisphosphonate-Resistent Osteoporosis

Introduction: Bisphosphonates increase Bone mineral density (BMD) by suppressing bone turnover inhibiting osteoclastic function with risk of inducing adynamic bone disease. Teriparatide is a fragment of the natural human parathyroid hormone (PTH) consisting of the first 34 amino acids counting from the N-terminus end of the natural PTH. Is anabolic drugs stimulate bone formation by increasing osteoblast activity and regulates both bone formation and resorption reducing the risk of vertebral and nonvertebral fractures. Arm: Teriparatide (Parathormone 1-34) treatment in renal trasplant patients with bisphosphonate-resistent osteoporosis.Metods: observational describe study of cases series of 10 kidney transplant patients with bone fragility without response to prolonged treatment with bisphosphonates (greater than 3 years). They were treated with daily subcutaneous injections of 20 microg teriparatide (PTH 1-34) by 18 months. All the patients had 6 months of bisphosphonate wash out. Measurements: we investigated bone turnover markers and effect of teriparatide over BMD of the femoral neck and lumbar spine as well also fractures, graft rejection, cardiovascular events, death and drug related adverse event. Results: 10 patients 9 women, mean age 64.4±14.15 years, BMI 24.3 ±2.64, etiology 3GMN, 3 PKD, 3 unknown, 1 NDBT, HD 9, preempive 1, transplant Time 10.12±5.21 years, 1 preemptive, 8 DBD and 1 LRD, Induction: 8 thymoglobulin, 2 basiliximab, Maintenance 5 belatacept/mycophenolate/MTP, 2 rapamune/mycophenolate/MTP, 3 tacrolimus/mycophenolate/MTP, 6 patients with fractures prior to treatment. Mean of treatment with bisphosphonates 4.1±1.79 years. It is observed at 18 months of treatment with 1-34 PTH increased levels of bone alkaline phosphatase (13.26 UI/L ± 5.75 vs 17.90 ± 7.28, p = 0.045), with NS changes in the rest of the analytes (Table 1) and increase of lumbar bone density of 11.27% (0.8816 gr/cm2 (TS-2.6) vs 0.9941 gr/cm2 (TS-1.38)) and femoral neck of 7.07% (0.6752 gr/cm2(TS-2.5) vs 0.7230 gr/cm2(TS-2.19)). 2 patients presented wrist fractures during treatment with low response(lumbar BMD) to treatment. No cardiovascular events, rejections, deaths were reported. Adverse Events: 1 patient presented hypotension during the first month of treatment. Conclusion: In this group of patients, and adequate response to teriparatide treatment was observed however our limitation were small number of patients and bone biopsy prior teriparatide treatment.

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

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. 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. 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). 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.

Antiosteoporosis and bone protective effect of dieckol against glucocorticoid-induced osteoporosis in rats

BackgroundGlucocorticoids (GCs) induce osteoporosis, which results in fractures in the bond, causing significant morbidity. In the conducted study, we examined the antiosteoporosis effect of dieckol against GC-induced osteoporosis in rats.MethodsSprague–Dawley (SD) rats were used for the current study and dexamethasone (2.5 mg/kg) induced osteoporosis in the rats that received the dieckol (test) and alendronate (standard) for 20 weeks. Bone turnover parameters, microCT, antioxidant, inflammatory cytokines, nutrient, and hormones parameters.ResultsDieckol noticeably suppressed the body weight and boosted the uterine and vagina weight. Dieckol considerably altered the level of trabecular number (Tb. N), the bone volume to total volume (BV/TV), trabecular separation (Tb.Sp), bone surface to bone volume (BS/BV), and t​r​a​b​e​c​u​l​a​r thickness (Tb.Th). Dieckol noticeably (P < 0.001) elevated the level of osteocalcin (OC) and alleviated the level of bone Gla protein (BGP), acid phosphatase (ACP), alkaline phosphatase (ALP), and β-CTx. Dieckol markedly boosted the level of malondialdehyde (MDA) and suppressed the level of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) along with the suppression of inflammatory cytokines like TNF-α, IL-1β, and IL-6. Dieckol remarkably increased the level of calcium, potassium, magnesium, and 25 (OH) vitamin D. Dieckol substantially (P < 0.001) boosted the level of estradiol and alleviated the level of parathyroid hormone and tartrate-resistant acid phosphatase (TRAP). Dieckol also suppressed the level of receptor activator of nuclear factor κB ligand (RANKL) and boosted the level of osteoprotegerin (OPG).ConclusionTaken together, our data suggest that dieckol demonstrated the anti-osteoporosis effect against GC-induced osteoporosis in rats.

Effect of nHA-Coated Femoral Stem Prosthesis Combined with Platelet-Rich Plasma in Hemi Hip Replacement of Femoral Neck Fracture in the Elderly.

Purpose This study investigated the efficacy of nanohydroxyapatite- (nHA-) coated biological prosthesis combined with platelet-rich plasma (PRP) in hemi hip replacement of femoral neck fracture (FNF) in the elderly. Methods From September 2018 to September 2021, 102 elderly patients with FNF treated in our hospital were chosen and divided into two groups according to different intervention methods. Fifty-one patients in the bone cement group were treated with bone cement prosthesis, and the rest 51 patients in the observation group were treated with nHA biological prosthesis combined with PRP in hemi hip replacement. In order to explore the osteogenic effect of nHA and PRP, osteoblasts were cultured. Results It was found that nHA and PRP could both effectively promote the proliferation of osteoblasts and improve their mineralization ability, especially when used in combination. In the course of clinical therapy, we found that the use of biological prosthesis combined with PRP could effectively reduce the level of serum procollagen type I carboxy terminal peptide (PICP) and better improve the levels of bone alkaline phosphatase (BALP) and bone Gla protein (BGP), so as to reduce the bone conversion rate and promote the formation of new bone around the prosthesis. In addition, no significant difference was found in intraoperative bleeding, operation time, hospital stay, 48 h drainage volume, partial weight-bearing time, and complete weight-bearing time between two groups. Otherwise, the use of biological prosthesis could effectively avoid the occurrence of adverse reactions such as bone cement crisis and fracture around femoral prosthesis, so as to better restore the hip function and improve patients' life quality. Conclusions Therefore, in hemi hip replacement of FNF in the elderly, nHA biological prosthesis combined with PRP can effectively promote the formation of new bone around the prosthesis stem, so as to obtain good initial stability, enable patients to carry out early weight-bearing exercise, and effectively avoid adverse reactions caused by bone cement prosthesis, thus improving patients' hip function and life quality.

Effect of Vitamin D Combined with Recombinant Human Growth Hormone in Children with Growth Hormone Deficiency.

Objective Growth hormone deficiency (GHD) refers to the complete or partial lack of pituitary growth hormone synthesis and secretion. This study is aimed at investigating the efficacy of vitamin D and recombinant human growth hormone (rhGH) in children with GHD. Methods A total of 100 children with GHD at our hospital were included between 1st January 2018 and 31st October 2020. The patients were divided into a study group (n = 70, received vitamin D combined with rhGH) and a control group (n = 30, received rhGH). The growth and development (bone age, growth rate, and height), bone metabolism (bone alkaline phosphatase (BAP), β-collagen degradation product (β-CTX), osteocalcin (OC), and amino-terminal propeptide type I procollagen (PINP)), insulin-like growth factor 1 (IGF-1), ghrelin, and adverse reactions in the two groups were measured before and 12 months after treatment. Results There were no significant differences in the bone age, growth rate, and height between the two groups before treatment. After 12 months of treatment, the bone age, growth rate, and height of the study group were significantly higher than those of the control group. After 12 months of treatment, the levels of serum BAP, PINP, and OC in the study group were significantly higher than those in the control group, while the levels of β-CTX in the study group were significantly lower than those in the control group. The serum IGF-1 level in the study group was significantly higher than that in the control group, while the ghrelin level in the study group was lower. There was no significant difference in the incidence of adverse reactions between the two groups. Conclusion Combined rhGH and vitamin D treatment can promote growth and development, improve bone metabolism, and regulate IGF-1 and ghrelin levels.

Correlation of Serum Estradiol with Bone Mineral Density and Bone Metabolism in Patients of Postmenopausal Type 2 Diabetes Mellitus Complicated with Osteoporosis.

Type 2 diabetes mellitus (T2DM) complicated with osteoporosis, is a systemic metabolic disease that affects postmenopausal women. This disease is closely related to the lack of estrogen. This study aims to demonstrate the correlation between serum estradiol (E2) levels and osteoporosis, bone mineral density, and bone metabolism indicators in postmenopausal women with T2DM complicated with osteoporosis (T2DM-OP). 130 postmenopausal women with T2DM were divided into the T2DM group (n=62) and the T2DM-OP group (n=68) according to bone mineral density (BMD). In addition, 80 postmenopausal women with average blood glucose and bone density were selected as the healthy control group. We compare the serum levels of E2, bone metabolism indicators, and biochemistry indexes among the three groups of participants. Compared with the healthy control and T2DM groups, the BMD and serum level of E2 in T2DM-OP patients were significantly decreased, while the serum levels of bone alkaline phosphatase, type I procollagen amino-terminal propeptide, osteocalcin, and β-collagen C-terminal collagen cross-links were significantly increased. The serum levels of E2 in the postmenopausal T2DM-OP patients are positively correlated with BMD and negatively correlated with bone resorption indicators.

The Effect of BMI, Age, Gender, and Pubertal Stage on Bone Turnover Markers in Chinese Children and Adolescents

ObjectivesTo ascertain the associations of serum bone turnover markers (BTMs) levels with body mass index (BMI) in Chinese children and adolescents, and whether the influence of BMI, age, pubertal stage on BTMs varied by gender.MethodsA total of 500 students (180 controls and 320 children and adolescents with overweight/obesity) aged 9–14 years were randomly selected from the Chinese National Survey on Students Constitution and Health Cohort. Serum levels of BTMs, including bone formation marker bone alkaline phosphatase (BAP), collagen type 1 C-terminal propeptide (CICP), and bone resorption markers C-terminal telopeptide of type-I collagen (CTX) were determined by commercial enzyme-linked immunosorbent assay kits. The associations among BMI, age, gender, pubertal stage, and BTMs were analyzed.ResultsSerum levels of CICP and CTX in overweight/obese children and adolescents were lower than those in controls (p<0.05). Moreover, after subgroup analysis stratified by gender, the decreased serum CICP and CTX levels in overweight/obese children and adolescents were observed only in boys (p<0.05). After adjustment of age and pubertal stage, there was a negative correlation between serum BAP and BMI in both boys and girls (p<0.05). However, the correlations between serum CICP, CTX levels, and BMI were significant in boys but not in girls. Serum BAP and CICP levels were independently correlated with BMI, age, gender, and pubertal stage, while CTX levels were independently correlated with BMI, age, and gender (p<0.05). BAP, CICP, and CTX levels showed a clear age, gender, and pubertal stage dependence with significantly higher values in boys (p<0.05).ConclusionsOur findings support the associations between serum BTMs levels and BMI in Chinese children and adolescents, and suggest age, gender, and pubertal stage differences in this relationship that warrant future studies.

MO554: Roxadustat Improves Renal Osteodystrophy by Dual Regulating Bone Remodeling

Abstract BACKGROUND AND AIMS Renal osteodystrophy (ROD) is a complication of chronic kidney disease (CKD) resulting in increased susceptibility to fractures. Therefore, developing effective drugs to prevent and treat ROD is vital. Accumulating evidence suggested stabilization of hypoxia-inducible factor-1α (HIF-1α) could promote bone formation. Roxadustat is a novel HIF stabilizer to treat renal anemia in CKD patients. This study aims to investigate the effects of roxadustat on bone remodeling using a CKD rat model. METHOD A total of 24 8-week-old male Sprague–Dawley rats were divided into three groups (n = 8/group): the normal group (Normal), CKD group and CKD + Roxadustat group. For induction of CKD, the diet containing 0.5% (w/w) adenine was given to the rats for the first 4 weeks. Roxadustat (10 mg/kg, by gavage) was given every other day from the third week of CKD induction for 4 weeks. Then blood was collected to test hemoglobin (Hb) concentrations, serum levels of creatinine (Cr), calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and bone turnover markers including bone alkaline phosphatase (BAP), osteocalcin (OCN) and tartrate-resistant acid phosphatase 5b (TRACP-5b). Left femurs were subjected to micro-computed tomography (micro-CT) to evaluate bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp). Left tibiae were collected to calculate osteoclast surface/bone surface (Oc.S/BS), osteoclast number/bone surface (N.Oc/BS), osteoblast surface/bone surface (Ob.S/BS) and osteoblast number/bone surface (N.Ob/BS). One-way analysis of variance followed by Tukey HSD post hoc test was used for comparisons. P &amp;lt; 0.05 was statistically significant. RESULTS CKD rats exhibited remarkably higher serum Cr, P, iPTH, TRACP-5b levels and obviously lower Hb and serum Ca levels compared with the normal group. Whereas roxadustat treatment significantly decreased iPTH, TRACP-5b and increased Hb, BAP and OCN levels in CKD rats. CKD induced remarkably decreased BMD, BV/TV, Tb.N, Tb.Th and dramatically increased Tb.Sp compared with the normal group. However, roxadustat treatment improved these changes in CKD rats. CKD rats had increased Oc.S/BS, N.Oc/BS, Ob.S/BS and N.Ob/BS compared with the normal group. Roxadustat decreased Oc.S/BS, N.Oc/BS but further increased Ob.S/BS and N.Ob/BS in CKD rats. CONCLUSION Roxadustat alleviated bone loss and bone microstructure deterioration of CKD rats by promoting bone formation and inhibiting bone resorption.

Free and Bioavailable Vitamin D Levels of Patients with Type 1 Diabetes Mellitus and Association with Bone Metabolism.

Vitamin D deficiency is known to be associated with metabolic bone diseases. The aim of this study is to evaluate vitamin D and calculated free and bioactive vitamin D levels of type 1 diabetic patients and to evaluate the association with bone turnover markers. This cross-sectional study includes 60 patients admitted to endocrinology outpatient clinic with diagnosis of type 1 diabetes mellitus and 60 controls. Weight, height and waist circumference were recorded and blood samples were taken for measurement of 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP), osteocalcin, bone alkaline phosphatase (bone-ALP), c-telopeptide. Free and bioavailable vitamin D levels were calculated with formula. Vitamin D levels of type 1 diabetic patients were significantly higher (p = 0.01). Parathormone levels of the group with vitamin D level under 20ng/ml was significantly higher (p = 0.029). VDBP levels were similar in both groups. Correlation analysis of free and bioavailable vitamin D level with osteocalcin, c-telopeptide, bone alkaline phosphatase revealed only a weak significant correlation between free vitamin D and osteocalcin (r = -0.201; p = 0.028). A negative correlation was determined between 25(OH)D and parathormone levels (r = -0.294; p < 0.005). Serum osteocalcin, bone alkaline phosphatase and c-telopeptide levels of control group were significantly higher. 25(OH)D levels of the study population was extremely low. The measurement of VDBP and calculated free and bioactive vitamin D levels did not show a better correlation with bone turnover markers according to 25(OH)D levels.

Efficacy of Duhuo Jisheng Decoction in Treating Ankylosing Spondylitis: Clinical Evidence and Potential Mechanisms.

Background Duhuo Jisheng Decoction (DHJSD) is an ancient compound widely used in the treatment of ankylosing spondylitis (AS). However, its efficacy is controversial, and its mechanism of action is not clear enough. Using meta-analysis and network pharmacology, our study evaluated the clinical efficacy of DHJSD in the treatment of AS and explored its mechanisms of action. Methods We searched medical databases, including Embase, PubMed, the China National Knowledge Infrastructure databases, Wanfang, and the Chinese Scientific Journal Database, to identify studies that met the inclusion criteria. RevMan 5.3 software was used for the meta-analysis. The compounds and the potential protein targets of DHJSD were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and analysis platform. AS was treated as a search query in the NCBI, PharmGKB, TTD, DrugBank, and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and AS were identified, and then Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed. Cytoscape was employed to construct a drug-compound-target network and a protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. Results A total of 10 studies involving 860 participants were included in the meta-analysis. Compared with the control, DHJSD treatment significantly improved clinical symptoms; reduced the erythrocyte sedimentation rate (ESR), the C-reactive protein (CPR), and interleukin 6 (IL-6) levels; increased the degree of motion of the chest; reduced the visual analog scale (VAS) pain score; reduced Schober's test values; reduced the finger-to-floor distance; reduced the duration of morning stiffness. However, the differences were not statistically significant in the Bath Ankylosing Spondylitis Functional Index scores, the Bath Ankylosing Spondylitis Disease Activity Index scores, the bone Gla-containing protein (BGP) levels, or the bone alkaline phosphatase (BALP) levels. In terms of adverse events, DHJSD treatment of AS reduced the incidence of gastrointestinal events, the incidence of skin events, and the incidence of abnormal liver function; however, there was no statistically significant reduction in the incidence of adverse renal function events. Subgroup analysis showed that in the treatment of AS, the clinical effect of DHJSD for AS was better than that of the controls for both treatment durations, ≤2 months and >2 months. A total of 178 active compounds and 47 related potential targets were identified for DHJSD in the treatment of AS, including four hub genes (CXCL8, PTGS2, VEGFA, and STAT3). The core active ingredients of DHJSD in the treatment of AS were mainly quercetin, kaempferol, licochalcone A, and isorhamnetin. DHJSD treatment of AS-related pathways mainly involved the IL-17 signaling pathway, the TNF signaling pathway, and the rheumatoid arthritis signaling pathway. Conclusion The above results suggest that DHJSD acts on AS through multiple targets, components, and pathways with significant clinical efficacy. Future studies may further explore the active components of DHJSD.