Osteocalcin Concentrations Research Articles

Osteoprotegerin and receptor activator of the nuclear factor kappa B ligand (RANKL) in healthy pubertal girls - relationships with physical growth and classical bone turnover markers.

Osteoprotegerin (OPG) is a trap receptor for the receptor activator of the nuclear factor kappa B ligand (RANKL). We aimed to determine the OPG and free soluble RANKL (sRANKL) concentrations in girls during puberty and their relationships with pubertal stage, growth rate and serum concentrations of estradiol, as well as classical bone formation (N-terminal propeptide of type I collagen (PINP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC)) and bone resorption (C-terminal telopeptide of type I collagen (CTX)) markers. The semi-longitudinal study involved 88 healthy girls, aged 11.8-13.2 years. Their weight and height were measured twice at one-year intervals. Pubertal stages were assessed using the Tanner (T) scale. Blood samples were taken at the first examination. Serum concentrations of OPG, sRANKL, CTX and BALP were determined by enzyme-linked immunosorbent assay, estradiol and PINP by radioimmunoassay and osteocalcin by immunoradiometric assay. The one-year increase in height and weight of girls in the T2 and T3 pubertal stages was greater than that of girls in the T4 stage (p=0.000, p<0.03). OPG concentrations (T2: 4.04±0.62; T3: 4.31±0.79; T4: 4.46±0.84 pmol/L) sRANKL concentrations (T2: 0.22 (IQR 0.09-0.54); T3: 0.42 (IQR 0.22-0.79); T4: 0.35 (IQR 0.16-1.04) pmol/L) and sRANKL/OPG ratios (T2: 0.05 (IQR 0.03-0.13); T3: 0.11 (IQR 0.05-0.19); T4: 0.09 (IQR 0.05-0.19) did not differ significantly between pubertal stages. Concentrations of PINP, CTX, BALP and OC were higher in girls at T3 stage than at the T4 stage (p=0.000, p=0.001, p=0.046, p=0.038; respectively). Concentrations of sRANKL and OPG did not correlate with body weight, height, growth rate, or concentrations of estradiol, PINP, CTX, BALP and OC. There were correlations between the increase in height over one year and the concentrations of PINP (r=0.499, p=0.000), CTX (r=0.311, p=0.003) and BALP (r=0.224, p=0.036), as well as of estradiol (r=-0.473, p=0.000). Unlike PINP, OC, BALP, CTX or estradiol concentrations, sRANKL and OPG concentrations do not change in girls during puberty. Neither OPG nor sRANKL concentrations correlate with somatic characteristics and classical bone turnover markers concentrations.

Effect of acute resistance exercise on bone turnover in young adults before and after concurrent resistance and interval training.

Weight-bearing physical activity can stimulate bone adaptation. This investigation explored the effect of an acute bout of resistance exercise before and after resistance+interval training on circulating biomarkers of bone metabolism and muscle-bone crosstalk. Healthy young male and female participants (n = 21 male, 28 ± 4 years; n = 17 female, 27 ± 5 years) performed a 6 × 10 squat test (75% 1RM) before and after a 12-week resistance+interval training program. Before and after completion of the training program, blood samples were collected at rest, immediately postexercise, and 2 h postexercise. Blood samples were analyzed for βCTX, P1NP, sclerostin, osteocalcin, IGF-1, and irisin. Significant effects of acute exercise (main effect of time) were observed as increases in concentrations of IGF-1, irisin, osteocalcin, and P1NP from rest to postexercise. A sex*time interaction indicated a greater decline in βCTX concentration from rest to 2 h postexercise and a greater increase in sclerostin concentration from rest to immediately postexercise in male compared with female participants. Sex differences (main effect of sex) were also observed for irisin and P1NP concentrations. In summary, changes in concentrations of biochemical markers of bone metabolism and muscle-bone crosstalk were observed in males and females after an acute bout of resistance exercise and following 12 weeks of resistance+interval training.

Effects of negative dietary cation-anion difference and calcidiol supplementation in transition diets fed to sows on piglet survival, piglet weight, and sow metabolism.

Diets that provide a negative dietary anion cation difference (DCAD) and supplement with a vitamin D metabolite 25-OH-D3 (calcidiol) may increase calcium availability at parturition, and enhance piglet survival and performance. This factorial study assessed the effects of DCAD, calcidiol (50 µg/kg), and parity (parity 1 or >1) and their interactions. Large White and Landrace sows (n = 328), parity 1 to 8 were randomly allocated in blocks to treatment diets from day 103 of gestation until day 3 postfarrow: 1) negative DCAD without calcidiol (negative DCAD + no CA), n = 84, 2) negative DCAD with calcidiol (negative DCAD + CA) n = 84, 3) positive DCAD without calcidiol (negative DCAD + no CA), n = 81, and 4) positive DCAD with calcidiol (positive DCAD + CA), n = 79. Negative DCAD diets were acidified with an anionic feed (2kg/t) and magnesium sulfate (2kg/t). All treatment diets contained cholecalciferol at 1,000 IU/kg. Dry sow diets contained 14.8% crude protein (CP), 5.4% crude fiber (CF), 0.8% Ca, and 83 mEq/kg DCAD. Treatment diets 1 and 2 contained 17.5% CP, 7.3% CF, 0.8% Ca, and -2 mEq/kg DCAD. Treatment diets 3 and 4 contained 17.4% CP, 7.4% CF, 0.8% Ca, and 68 mEq/kg DCAD. Before farrowing, all negative DCAD sows had lower urine pH than all sows fed a positive DCAD (5.66 ± 0.05 and 6.29 ± 0.05, respectively; P < 0.01); urinary pH was acidified for both DCAD treatments indicating metabolic acidification. The percentage of sows with stillborn piglets was not affected by DCAD, calcidiol, or parity alone but sows fed the negative DCAD + CA diet had a 28% reduction in odds of stillbirth compared to the negative DCAD + no CA diet and even lesser odds to the positive DCAD + CA diet. At day 1 after farrowing, blood gas, and mineral and metabolite concentrations were consistent with feeding a negative DCAD diet and that negative DCAD diets influence energy metabolism, as indicated by increased glucose, cholesterol, and osteocalcin concentrations and reduced nonesterified free fatty acids and 3-hydroxybutyrate concentrations. In the subsequent litter, total piglets born and born alive (14.7 ± 0.3 and 13.8 ± 0.3 piglets, respectively; P = 0.029) was greater for positive DCAD diets compared to negative DCAD diets; and there was an interaction between DCAD, calcidiol, and parity (P = 0.002). Feeding a negative DCAD diet influenced stillbirth, subsequent litter size, and metabolic responses at farrowing. More studies are needed to define optimal diets prefarrowing for sows.

Lumbar vertebral bone density is decreased in horses with pituitary pars intermedia dysfunction.

Pathological fractures have been reported in equids with pituitary pars intermedia dysfunction (PPID) but their prevalence and pathogenesis is unknown. To compare: (1) bone mineral density (BMD) in weight bearing and nonweight bearing bones in PPID+ equids and aged and young PPID- controls; and (2) biomechanical properties of the fourth lumbar vertebral body in PPID+ equids and aged PPID- equids. Case-control study: five PPID+ equids and six aged and four young PPID- control horses. PPID status was based on clinical signs and necropsy examination of the pituitary gland (PG). The lumbar vertebral column, right front third metacarpus (MC3), left hind third metatarsus (MT3), and PG were removed after euthanasia. BMD was determined by quantitative computed tomography of regions of interest (ROI) in each bone and biomechanical testing was performed on the fourth lumbar vertebral body. Serum concentrations of parathormone (PTH), ionised Ca++ , 25-hydroxyvitamin D, and osteocalcin (OC) were also measured. Data were analysed using one-way ANOVA and correlation analyses. BMD of trabecular and cortical regions of interest (ROI) of the third, fourth (L4), and fifth lumbar vertebrae were significantly lower in PPID+ equids as compared with aged (p < 0. 001) and young (p < 0.01) PPID- controls. In contrast, no differences were found in BMD of trabecular or cortical ROIs of MC3 and MT3 between groups. No differences were detected in force at fracture, displacement at fracture, Young's modulus or strain of L4 between PPID+ and aged PPID- horses. No differences were found in serum PTH, ionised Ca++ , 25-hydroxyvitamin D, or OC concentrations between groups. Limited number of equids studied and variation in test results. BMD of nonweight bearing bones can be decreased with PPID and could increase risk of developing pathological fractures.

Morphological and biochemical characteristics of osteogenesis during drug therapy of experimental osteoporosis

Relevance. Osteoporosis is a clinical and economic problem on a global scale. A significant contribution to solving the problem of effective treatment of osteoporosis can be the creation of drugs based on unique biologically active compounds.The aim of the study was the morphological substantiation of the experimental model of osteoporosis and a comprehensive (multifactorial) assessment of the effectiveness of its drug therapy.Materials and methods. The study was carried out on 40 mature female Wistar rats, which comprised 6 groups. A model of osteoporosis was formed in animals of four experimental groups (6 animals in each): the first and second groups (respectively) consisted of young rats, the third and fourth — old ones. Animals of the second and fourth groups were injected with a drug tested for its ability to activate the process of osteosynthesis. Rats of the fifth and sixth groups (young and old, 8 animals each), subjected to sham surgery, served as controls. As a result of the use of the histo-morphometric method and atomic absorption spectroscopy in the diaphysis of the femur, the thickness of the layers of the compact substance, the number of bone plates and osteocytes, as well as the amount of collagen, calcium and phosphorus were determined. Using enzyme immunoassay, bone remodeling markers — osteocalcin, sclerostin, osteoprotegerin, fibroblast growth factor-23 and nuclear factor kappa-β activator ligand (RANKL) — were determined in the blood serum. Statistical processing of the data was carried out using the GraphPad PRISM (USA) program to determine the median, upper and lower quartiles. Differences were considered significant at p &lt; 0.01.Results. Modeling of osteoporosis induces atrophic thinning of the compact substance, a decrease in the number of osteocytes and bone plates in the diaphysis of the femur, a decrease in the content of collagen, calcium and phosphorus in them, a decrease in the concentration of osteocalcin, sclerostin, fibroblast growth factor, osteoprotegerin and an increase in the concentration of RANKL in the blood plasma, more pronounced in old animals. As a result of the use of the drug X3 for the treatment of osteoporosis, the following were revealed: a significant increase in the thickness of the compact substance, the number of osteocytes and bone plates in the diaphysis, the content of collagen, calcium and phosphorus in them, an increase in the concentration of biochemical markers of osteosynthesis, and a mild imbalance of RANKL. The increase in plasma levels of markers of bone remodeling was most pronounced when the drug X3 was combined with vitamin D3.Conclusion. 1. The used surgical-endocrine method of modeling osteoporosis leads to pronounced degenerative changes in osteocytes and their derivatives in all parts of the compact bone substance, and also causes significant disturbances in the mineral composition and an imbalance of bone remodeling markers, more pronounced in senile rats. 2. The tested drug X3, used for the treatment of osteoporosis, has a high degree of effectiveness, since it stimulates regenerative osteogenesis, restores the damaged structure of bone tissue elements, its organic and mineral components. 3. The restorative effect of the drug is more pronounced in senile rats.

Determinants of Bone Mineral Density in Iranian Women with Polycystic Ovary Syndrome.

Whether the endocrine aberrations caused by polycystic ovary syndrome (PCOS) might influence bone density in women of reproductive age is controversial. The present study aimed to compare PCOS women to a control group matched in terms of age and body mass index (BMI) regarding bone indices and to clarify the potential relationship between their hormonal changes and bone density. This case-control study consisted of 61 PCOS patients, and 35 women with normal ovulatory function served as controls. Bone parameters, including bone mineral content (BMC) and bone mineral density (BMD) in addition to T- and Z-scores, were measured at the lumbar vertebrae, neck of the left femur, hip, and distal part of the radial bone, using dual-energy X-ray absorptiometry. Blood samples were taken to be tested for biochemical parameters and serum concentrations of insulin, osteocalcin, parathyroid hormone (PTH), vitamin D, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, dehydroepiandrosterone sulfate (DHEAS), and estradiol were measured. Insulin resistance was evaluated through the homeostatic model assessment of insulin resistance (HOMA-IR). The results revealed greater levels of HOMA-IR and total testosterone in PCOS women than in controls. Nevertheless, the two groups were comparable in terms of bone parameters. In the control group, BMI was the only determinant of bone density at most of the skeletal sites. Nonetheless, BMI and HOMA-IR were independently and positively associated with bone indices at the femoral neck (FN) and total hip in the PCOS group. Parathyroid hormone and vitamin D concentrations were not different in the two groups. However, phosphate levels were higher in PCOS patients (P = 0.025). Osteocalcin was inversely correlated to BMI, and both groups had a negative correlation between DHEAS and PTH. Serum phosphate was inversely and independently associated with estrogen in the PCOS group (r = -0.377, P = 0.004). Body mass index and HOMA-IR were independent and positive determinants of FN and total hip bone density in the PCOS subjects. Nonetheless, in the non-PCOS women, BMI was the only independent determinant of bone density at most of the skeletal sites. Additionally, osteocalcin was inversely correlated with BMI in both groups.

Analysis of changes in serum high t-PINP/β-CTX ratio and risk of re-fracture after vertebral osteoporotic fracture surgery.

This study's aim was to investigate the expression changes of total type I procollagen amino-terminal peptide (t-PINP) and type I collagen C-terminal peptide (β-CTX) in serum after vertebral osteoporotic fracture surgery and the clinical value of predicting the risk of refracture. The clinical data of 100 patients with vertebral osteoporotic fractures treated in our hospital from January 2019 to January 2020 were retrospectively analyzed, and the patients were divided into the control group (patients without re-fracture, n = 68) and the observation group (patients with re-fracture, n = 32) according to whether they had re-fracture at 2-year follow-up. The risk factors of postoperative re-fracture were analyzed using Multivariate logistic regression analysis. The serum contents of t-PINP, β-CTX, osteocalcin (BGP), and calcium (Ca) were measured. Bone mineral density (BMD) was measured by bone densitometer. The correlation between the t-PINP/β-CTX ratio and the bone metabolic index was analyzed by Pearson correlation. The area under the curve (AUC), sensitivity, and specificity of t-PINP/β-CTX in predicting the risk of re-fracture were determined by the receiver operating characteristic (ROC) curve. There was a significant difference in age, the number of vertebral bodies with initial fracture, and whether there was leakage of bone cement between the two groups (p < 0.05). Age, the number of vertebral bodies with primary fracture, and the leakage of bone cement were risk factors affecting re-fracture after operation (p < 0.05). Compared with those in the control group, the level of t-PINP and the ratio of t-PINP/β-CTX were higher, and the β-CTX level was lower in the observation group (p < 0.05). The BGP level was higher, and the levels of BMD and Ca were lower in the observation group than those in the control group (p < 0.05). Pearson correlation analysis showed that t-PINP had a positive correlation with BGP (r = 0.222, p < 0.05). β-CTX was positively correlated with BMD and Ca (r = 0.230, 0.269, p < 0.05). The ratio of t-PINP/ β-CTX was negatively correlated with BMD and Ca (r = -0.621 and -0.660, p < 0.05), but positively correlated with BGP (r = 0.517, p < 0.05). ROC curve analysis showed that the AUC of t-PINP, β-CTX, and the ratio of t-PINP/β-CTX in predicting the risk of re-fracture after vertebral osteoporotic fracture surgery was 0.724, 0.736, and 0.838, respectively. The t-PINP/β-CTX ratio was significantly correlated with the bone metabolic indexes in patients with vertebral osteoporotic fractures. The detection of the changes in its index can help predict the risk of postoperative re-fracture, providing a new idea for clinical assessment of the risk of postoperative re-fracture.

THU603 Bone Fragility In Mild Autonomous Cortisol Secretion: A Cross-Sectional Cohort Study

Abstract Disclosure: C.D. Zhang: None. S. Singh: None. J. Saini: None. M. Suresh: None. K. Thangamuthu: None. R. Nathani: None. A.L. Ebbehøj: None. V. Fell: None. S.J. Achenbach: None. E.J. Atkinson: None. S. Khosla: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have higher rates of fractures compared to patients with non-functioning adrenal nodules, but bone mass is typically only modestly reduced. We hypothesized that chronic exposure to mild levels of cortisol excess may lead to a deterioration in bone quality. Objective: To characterize the effect of MACS on bone metabolism and bone microarchitecture, as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In this cross-sectional single-center study, patients with MACS were matched by age, sex, and gonadal status to referent subjects without adrenal nodules. MACS was defined as serum cortisol concentration &amp;gt;1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (1-mg DST), in the absence of a classic Cushingoid phenotype. Those with other known secondary causes of osteoporosis and/or on pharmacologic treatment for low bone mass were excluded. All study participants underwent a bone health interview, blood draw for bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan with trabecular bone score (TBS), and HR-pQCT of the non-dominant radius and tibia. Participants with a recent fracture within 12 months were excluded from the analysis of bone turnover markers. The Kruskal-Wallis test was used to compare measurements between groups. Results: A total of 82 patients with MACS and 82 referent subjects were prospectively enrolled between 1/2019 and 7/2022. The median age of study participants at the time of enrolment was 57 years (interquartile range [IQR], 47-65), and 57 (70%) were women. In the MACS cohort, the median cortisol following 1-mg DST was 3.2 mcg/dL (IQR, 2.3-6.5) with median ACTH of 8.7 pg/mL (IQR, 6.0-14.0) and median DHEA-S of 42.0 mcg/dL (IQR 23.0-68.0). While no differences in bone mineral density (BMD) were observed at any site (lumbar spine, total hip, femoral neck, or distal radius) between the two groups, patients with MACS had decreased TBS (1.374 vs 1.467, P &amp;lt;0.001) and lower osteocalcin concentrations (16.9 vs. 19.7 ng/mL, P = 0.005) than referent subjects without adrenal nodules. On HR-pQCT at the tibia, patients with MACS had significantly reduced trabecular volumetric BMD (151.6 vs 167.4 mg hydroxyapatite/cm3, P = 0.002), trabecular bone volume/tissue volume ratio (0.219 vs 0.237, P = 0.011), and number of trabeculae (1.428 vs 1.506 1/mm, P = 0.045), while trabecular separation (0.707 vs 0.656, P = 0.023) was increased compared to referent subjects. Conclusions: Patients with MACS have altered bone metabolism and microstructural deterioration that is not evident on routine DXA BMD testing. These changes may mediate their increased fracture risk and could serve as biomarkers of cortisol-induced changes in the bone. Presentation: Thursday, June 15, 2023

The Effects of Dairy Product Supplementation on Bone Health Indices in Children Aged 3 to 18 Years: A Meta-Analysis of Randomized Controlled Trials.

Childhood and adolescence are critical periods for optimizing skeletal growth. Dairy products are valuable sources of bone-beneficial nutrients, particularly calcium and protein. A random-effects meta-analysis of published randomized controlled trials was performed to quantitatively assess the effects of dairy supplementation on bone health indices in children and adolescents. The PubMed and Web of Science databases were searched. Dairy supplementation increased whole-body bone mineral content (BMC) (+25.37 g) and areal bone mineral density (aBMD) (+0.016 g/cm2), total hip BMC (+0.49 g) and aBMD (+0.013 g/cm2), femoral neck BMC (+0.06 g) and aBMD (+0.030 g/cm2), lumbar spine BMC (+0.85 g) and aBMD (+0.019 g/cm2), and height (0.21 cm). When expressed as a percentage difference, whole-body BMC was increased by 3.0%, total hip BMC by 3.3%, femoral neck BMC by 4.0%, lumbar spine BMC by 4.1%, whole-body aBMD by 1.8%, total hip aBMD by 1.2%, femoral neck aBMD by 1.5%, and lumbar spine aBMD by 2.6%. Dairy supplementation increased serum insulin-like growth factor I concentrations (19.89 nmol/L) and reduced concentrations of urinary deoxypyridinoline (-1.78 nmol/mmol creatinine) and serum parathyroid hormone (-10.46 pg/mL) but did not significantly affect the serum concentrations of osteocalcin, bone alkaline phosphatase, and C-terminal telopeptide of type 1 collagen. Serum 25-hydroxyvitamin D concentrations (+4.98 ng/mL) increased with vitamin D-fortified dairy supplementation. The positive effects on bone mineral mass parameters and height were generally consistent across subgroups defined by sex, geographical region, baseline calcium intake, calcium from the supplementation, trial duration, and Tanner stages. In summary, dairy supplementation during growth leads to a small but significant increase in bone mineral mass parameters, and these findings are generally supported by the changes in several biochemical parameters related to bone health.

Metabolic activity of bone tissue osteoblasts in patients with chronic pancreatitis

Objective — to investigate the level and role of osteocalcin in patients with chronic pancreatitis, to determine the dependence of changes in this indicator on the vitamin D receptor gene. Materials and methods. Examinations involved 70 patients with chronic pancreatitis (CP), who formed the main group. Women (46 or 66.4%) prevailed in this group. The age of the patients was from 29 to 43 years, the mean age 33.2±2.1 years. Control group consisted of 78 practically healthy subjects. The groups were comparable in terms of age and gender ratio. The diagnostic search included the study of the polymorphism of vitamin D receptor (VDR) gene and the biochemical marker of bone tissue, osteocalcin. Their possible effects on the course of the disease and the formation of complications have been investigated. Results. In the process of determining the VDR gene polymorphism, the significant difference was found in the distribution of gene alleles (χ2=30.08, df=4; p &lt;0.01). According to the results of genetic testing, both groups of patients were divided into three subgroups: 1st subgroup (bb‑genotype carriers), 2nd subgroup (Bb‑genotype carriers), 3rd subgroup (BB‑genotype carriers). In the control group, the distribution was as follows: 27 (38.6%), 34 (48.6%) and 9 (12.8%) patients, in the main group — 13 (18.5%), 30 (42.8%) and 27 (38.7%) patients. With the presence of CP, there was a change in the distribution of alleles towards the BB genotype of the VDR gene, which was associated with a higher risk of osteoporosis. 35 (50.0%) patients with CP and 3 (3.8%) individuals from the control group had a history of bone fractures (p &lt;0.01). In CP, the average osteocalcin level was 22.20±2.53 ng/ml, 27 (38.6%) patients had normal levels, 15 (55.6%) of them had the Bb genotype, 7 (25.9%) — genotype BB, in 5 (18.5%) — genotype bb. A decrease in the level of osteocalcin below the norm (to 12.7±1.87 ng/ml) was registered in 4 (5.7%) patients, of which 2 (50.0%) had the BB genotype, 1 (25.0%) — Bb genotype, another 1 (25.0%) — bb genotype. A higher than normal level of osteocalcin (45.1±23.24 ng/ml) was recorded in 39 (55.7%) patients of the main group, of which 18 (43.6%) had the BB genotype, 14 (35.9%) — Bb genotype, 7 (20.5%) — bb genotype. Conclusions. The course of CP in most cases is accompanied by an increase in osteocalcin levels, which can be considered as an indicator of a violation of the mineral density of bone tissue. Changes in the ratio of genotypes of the VDR gene are registered in patients with CP, which gives reason to assume a violation of the absorption of vitamin D due to genetic aberrations. In the majority of patients with CP, in the presence of an unfavorable genotype (BB) of the VDR gene, an increase in the content of osteocalcin is observed, which can be explained by one of the ways of the formation of osteoporotic conditions — a violation of the differentiation of osteoblasts. Chronic pancreatitis can be considered as an unfavorable nosology that provokes interference in bone metabolism with a high probability of formation of osteoporotic conditions, which requires early diagnosis and prevention of complications.

Effect of Compound Supplement on the Bone Health of Rats with Osteoporosis Induced by Ovariectomy

Background: The World Health Organization (WHO) has recognized osteoporosis as the second most serious epidemic in the world. There are many factors in the occurrence of osteoporosis, among which amenorrhea and aging are major causes, therefore the risk of osteoporosis increases with age. Moreover, osteoporosis influences personal health and mobility, and in turn, greatly increases national healthcare expenses. It is known that chicken sternal cartilage (CSC) hydrolysate, salmon nasal cartilage extract, turmeric (Curcuma longa L.) extract, mangosteen (Garcinia mangostana) extract, soybean extract, calcium citrate, vitamin C, and vitamin D have the potential to reduce bone loss and protect bones. However, this novel combination for improving bone loss has not yet been studied or discussed. Objective: This study discussed the effect of a CSC formula containing chicken sternal cartilage hydrolysate, salmon nasal cartilage extract, turmeric extract, mangosteen extract, soybean extract, calcium citrate, vitamin C, and vitamin D on improving the osteoporosis of rats which had received ovariectomy. Their body weight, body length, serum biochemical value, bone tissue, and biomechanics were analyzed. Design: The 10-week-old female Sprague-Dawley (SD) rats used in this study were randomly divided into six groups for the experiment, including the sham group (10 rats) and five ovariectomy (OVX) groups (53 rats). Two weeks after the ovariectomy, the following doses were administered to the corresponding groups respectively every day: carboxymethyl cellulose (CMC) solvent group (represented by OVX+CMC), and CSC 339 mg/kg (represented by OVX+CSC-L), CSC 678 mg/kg (represented by OVX+CSC-M), CSC 1356 mg/kg (represented by OVX+CSC-H). The positive control (alendronate, 2.5 mg/kg represented by OVX+AD) was administered three times weekly. The rats were sacrificed 14-weeks after administration of the experimental materials. Results: According to the experimental results, in comparison to the OVX+CMC group, the OVX+CSC-L group, OVX+CSCM group, and OVX+CSC-H group could significantly reduce the N-terminal telopeptides of type I collagen, the N-telopeptide (NTX) concentration, and the osteocalcin concentration in the serum. According to the micro-computed tomography analysis, in comparison to the OVX+CMC group, the femoral bone mineral density, trabecular area percentage, and trabecular thickness of the OVX+CSC-L, OVX+CSC-M, and OVX+CSC-H groups increased significantly, and the trabecular separation decreased significantly. According to the biomechanical analysis, in comparison to the OVX+CMC group, the OVX+CSC-L, OVX+CSC-M, and OVX+CSC-H groups could increase the maximum load, hardness, absorbed energy, and Young’s modulus of the femur significantly. Conclusion: CSC can increase the bone mineral density, trabecular area percentage, and trabecular thickness significantly; it can reduce the trabecular separation, NTX and osteocalcin (OCN) concentrations in serum significantly, and it can retard the bone loss induced by ovariectomy effectively, as well as protect bones. It can be used as a mild and long-term dietary supplement; however, the result of long-term administration to the human body should be observed in the future.

Diagnostic and prognostic value of indicators of markers of bone metabolism in type 2 diabetes mellitus patients with UV functionalised dental implants

BackgroundDiabetes mellitus affects many organ systems, including bone tissue.In diabetic patients, the activity of osteoblasts is suppressed and the activity of osteoclasts in the bone matrix increases, bone formation decreases, which can disrupt the process of osseointegration and ultimately lead to disintegration and failed implants. Based on the foregoing, with diabetes, it is very important to study bone metabolism to predict and dynamically control dental implants. ObjectivesTo assess the indicators of bone metabolism markers Osteocalcin and β-Cross-Laps in blood serum in patients with type 2 diabetes mellitus with intraosseous dental implants. MethodsThe study included 86 patients, diagnosed type 2 diabetes mellitus in period 2018 - 2023 with partially or complete edentulous.Implant surgery was performed after periodontal therapy using 367 UV functionalized dental implants in patients 1 group. Patients 2 group was performed implant surgery using 54 dental implants that were not UV functionalization.Final dental prosthetics was performed 4–5 months. UV functionalization of the implant surface was carried out using a UV Activator YWJ-QSY001 (Foshan, Wenjian Medikal Enstriman) for 20 s. The content biochemical markers of bone Osteocalcin and β-Cross-Laps serum was determined by enzyme-linked immunosorbent assay ELISA (ELISA, IFA Roche Diagnostics, Basel, Switzerland) before and after dental implantation according to the manufacturers’ protocols. Outcomes assessed included; implant survival, men MBL, PPD, BOP, RFA, prosthetic success. ResultsThere were no clinical examinations of serious biological or prosthetic complications. There is a correlation between different concentrations of Osteocalcin or β-Cross- Laps and the success rate of implants. Implants were shown to be unsuccessful low concentrations of Osteocalcin and high concentrations β-Cross- Laps in serum compared with average mean biochemical markers of bone in 2 group patients. In patients of the 2nd group, the indicators of biochemical bone markers were within the normal range; no correlation was found between osseointegration failers and the complication of peri-implatitis.Short implants success rate was 96,7 %, standart implants success rate was after 97,5 after 5 years. ConclusionImplant therapy can be successfully used in diabetic patients with UV photofunctionalized implants, blood glucose levels should be constantly maintained at a normal level. Monitoring of bone metabolism markers in patients with type 2 diabetes mellitus may have prognostic value for implants and will encourage the practitioner to apply corrective drug therapy in case of violation of markers.

Free Radical Oxidation and Metabolic Processes of Cartilage and Bone Tissues in Animals with Surgical Model of Posttraumatic Osteoarthrosis

INTRODUCTION: Posttraumatic osteoarthrosis (PTOA) resulting from injuries of connective-tissue components of the joint, is accompanied by formation of free radicals activating chondro- and osteoresorption, which leads to fragmentation of biopolymers of the extracellular matrix of the joint tissues.&#x0D; AIM: To study the peculiarities of free radical oxidation and metabolic processes of cartilage and bone tissues in animals with a surgical model of PTOA of the knee joint.&#x0D; MATERIALS AND METHODS: The study was conducted on 31 rats (11 intact animals and 20 animals with PTOA model). The metabolic processes of the connective tissue were evaluated by the changes in the content of biomarkers of the cartilage (hyaluronan, aggrecan) and bone (fibroblast growth factor-23, osteprotegerin, sclerostin, osteocalcin) tissues. The condition of the free radical oxidation processes was evaluated by the level of lipid hydroperoxides, and the activity of antioxidant system by the parameters of the total antioxidant and thiol statuses.&#x0D; RESULTS: In rats with the PTOA model, an increase in cartilage tissue biopolymers aggrecan and hyaluronan (p 0.001) was noted with a negative change in the marker of bone formation (a tendency to increase in the content of osteocalcin) and markers of regulation of bone homeostasis (increased fibroblast growth factor-23, p 0.001), with a tendency to decrease in the content of osteoprotegerin and sclerostin, in comparison with intact animals of the control group. In parallel with this, an increase in lipid hydroperoxides (p 0.01) in the systemic bloodstream was detected with a decrease in the thiol status index (p 0.01) with preserved normal total antioxidant activity (p 0.05).&#x0D; CONCLUSION: The data of the conducted study evidences intensification of free radical oxidation and derangement of metabolic processes in the bone and cartilage tissues in animals with a surgical model of PTOA of the knee joint. A negative change in the metabolism of the bone tissue was manifested by the loss of balance of remodeling processes, and metabolic disorders in the cartilage tissue consisted in the destruction of its biopolymers in conditions of intensification of free radical oxidation processes and relative tension of the thiol system with the total antioxidant activity remaining within the physiological norm. The established facts are promising from the point of view of using the studied biomarkers both for the identification of pathogenetic triggers of PTOA of the knee joint, and for the determination of the direction of therapeutic measures.

Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD-induced menopausal mice.

As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone-derived hormone osteocalcin has been reported to be necessary to prevent anxiety-like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin. Menopausal mouse model was induced by intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light-dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co-localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis-related proteins. The VCD mice showed obvious anxiety-like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL-2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons. Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD-induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.

Children with severe acute malnutrition have high rates of bone resorption: A cross-sectional comparative study

Malnutrition in under-5 children (i.e., children younger than age 5 years) remains a major public health problem. Because of the reductive adaptation in children with severe acute malnutrition (SAM), changes in bone health are often subtle. We hypothesized that children with SAM have higher rates of bone resorption than bone formation, which can be assessed using bone turnover markers. In this cross-sectional comparative study, we evaluated the status of bone turnover markers, serum osteocalcin and serum tartrate-resistant acid phosphatase-5b (TRAP-5b) in under-5 children with SAM. Thirty children (6-59 months) with SAM (defined as per World Health Organization criteria) were enrolled as cases and another 30 children (age and sex matched) with normal nutritional status (weight for height -1 standard deviation [SD] to +1 SD) were enrolled for comparison of bone turnover markers. Serum TRAP-5b concentrations were significantly higher in children with SAM compared with children with normal nutritional status (mean [SD] 22.6 [15.3] vs. 11.3 [9.6], P=.009), whereas serum osteocalcin concentrations were comparable between the 2 groups (mean [SD] 40.6 [17.9] vs. 36.0 [12.5], P=.344). Frequency of hypocalcemia and vitamin D deficiency were also significantly high in children with SAM (P < .05). An inverse correlation was found between serum calcium and serum osteocalcin (r=-0.383, P < .05). Our results indicate that children with SAM have a higher bone resorption rate than children with normal nutrition status indicating compromised bone health.

Immunological, hormonal and hemostasis parameters in cosmonauts’ blood after long-term orbital missions

The extreme factors associated with space flight influence pronouncedly various physiological systems of the human body. The current study focuses on the impact of factors associated with prolonged space missions lasting up to 6 months on cellular innate immunity, hormonalregulation, and hemostasis in Russian cosmonauts. Immune system adaptation to the conditions of long-term space flight was shown to be accompanied by a significant increase in the level of monocytes and granulocytes, along with a decreased number of cells expressing adhesion molecules. The coagulation cascade, main anticoagulant and fibrinolysis proteins were also evaluated. The early post-flight period was characterized by elevated D-dimer levels compared to baseline values, indicative of blood clotting and fibrinolysis activation caused by a damage of endothelium during landing. aAlterations in blood rheology during re-adaptation to Earth conditions was also observed. The blood concentrations of aldosterone, cortisol, estradiol, testosterone, osteocalcin, and erythropoietin were analyzed, and their correlation with the parameters of hemostasis was assessed.The summary findings indicate an adaptive physiological reaction in cosmonauts associated with 6 months duration of spaceflight. The observations may be related to endothelium damage, which manifested in the activation of certain components of the immune system, along with the activation of fibrin clot formation and subsequent fibrinolysis.

Diagnostic and Prognostic Value of Indicators of Bone Metabolism Markers in Patients Following Mandibulectomy and Free Fibula Flap Reconstruction with Endosteal Implants.

To evaluate and assess the indicators of bone metabolism markers osteocalcin and β-Cross-Laps in blood serum as a tool for monitoring bone regeneration and determining the time of implantation in patients after mandibulectomy and reconstruction of a free fibular flap with subsequent endosteal implants. Forty-eight patients in a 6-year period participated in this study, due to resection for tumors. All patients underwent reconstruction with fibula free flap after tumor resection, 4-6months after osteoectomy, dental implants were installed with further orthopedic rehabilitation. To assess the rate of bone remodeling after transplantation, the content biochemical markers of bone remodeling osteocalcin and β-Cross-Laps serum were determined by enzyme immunoassay. All 46 fibular free flaps were healed without complications and were survived. A total 326 implants installed, 8 implants failed to osseointegrate, and 6 implants failed after 5years of loading (peri-implantitis). Success rate of implants after 5years was 95,7%. In patients before surgery, the mean of osteocalcin levels was 8.5ng/ml, two months later, there was a sharp increase in the content of osteocalcin by 15.4ng/ml, after four months reached 24.7ng/ml, after six months of 28.6ng/ml, then the indicator began to decrease and after 12months it was approaching the norm of 14.7ng/ml. In patients before surgery, the mean level of β-Cross-Laps was 0.76ng/ml, after two months bone transplantation the mean level of β-Cross-Laps decreased to - 0.65ng/ml, after four months the indicator increased and reached of 0.98ng/ml, after six months the indicator was - 1.56ng/ml, then these indicators began to decrease and after 12months, approaching normal values of - 0.87ng/ml. There is a correlation between different concentrations of osteocalcin or β-Cross- Laps and the success rate of implants. Implants were shown to be unsuccessful low concentrations of osteocalcin and high concentrations of β-Cross-Laps in serum. Studies have shown that the long-term survival and success rates of implants placed in the reconstructed areas may guarantee an excellent prognosis of implant-supported prostheses. Bone markers in blood serum osteocalcin and β-Cross-Laps can be used to evaluate the rate of bone remodeling, which allows you to determine the time of implantation.

CHANGES IN MARKERS OF BONE TISSUE REMODELING AND THE INFLAMMATORY PROCESS IN THE BLOOD SERUM OF WHITE RATS IN CASE OF DEFECT FILLING OF THE FEMUR WITH IMPLANTS BASED ON POLYLACTIDE AND TRICALCIUMPHOSPHATE WITH MESENCHYMAL STEM CELLS

Objective. Based on the analysis of markers of inflammation and metabolism of bone tissue in the blood serum of laboratory rats, to evaluate the course of bone remodeling after filling the defect in the distal metaphysis of the femur with 3D-printed implants based on polylactide and tricalcium phosphate (3D-I) alone or in combination with mesenchymal stromal cells (MSCs). Methods. 53 white rats were used, which were divided into groups: intact (5 animals) — the operation was not performed; Control (15) — 3D-I; Experiment I (15) — 3D-I + cultured alloMSCs; Experiment II (15) — 3D-I + introduction of alloMSCs into the area of surgical intervention 7 days after implantation. The following were studied: the content of glycoproteins (GP), interleukin-6 (IL-6), osteocalcin, chondroitin sulfates (CS), total protein, calcium, alkaline (AlP) and acid phosphatase (AP) activity, and their ratio, mineralization indices were calculated. Results. Compared with intact animals, higher indicators were determined in the rats of the Control group: the content of GP by 39.73; 32.88; 23.29 %; CS — 250.00; 222.09 and 196.51 %, AlP activity — 81.67, 51.03, 39.36 %, on the 15th, 30th, and 90th days of the experiment; IL-6 — 44.89; 60.06 % on the 15th and 30th days. In the rats of the Experiment I g roup: the content of GP — by 82.19; 65.75, 57.53 %, IL-6 — 72.14; 96.59; 79.88 %, CS — 306.98; 276.74; 253.49 %; AlP activity — 63.73; 129.70; 51.28 %, on the 15th, 30th and 90th days of the experiment. In the Experiment II group: on the 15th, 30th and 90th days, the content of GP was higher by 27.40; 26.03; 129.18 %; CS — by 175.58; 137.21 and 115.12 %; AlP activity — 192.99; 178.02, 76.31 %; on the 15th and 30th days: IL-6 — by 37.46; 20.74 %. Conclusions. In the case of filling the defect with 3D-printed implants, biochemical signs of moderate inflammation were determined; 3D-printed implants together with MSCs — pronounced inflammation, slowing of bone formation, formation of connective tissue; 3D-printed implants with postoperative injection of MSCs — moderate inflammation and optimal conditions for healing the defect with bone tissue.

Effects of Donepezil on the Musculoskeletal System in Female Rats.

The extension of human life makes it more and more important to prevent and treat diseases of the elderly, including Alzheimer's disease (AD) and osteoporosis. Little is known about the effects of drugs used in the treatment of AD on the musculoskeletal system. The aim of the present study was to investigate the effects of donepezil, an acetylcholinesterase inhibitor, on the musculoskeletal system in rats with normal and reduced estrogen levels. The study was carried out on four groups of mature female rats: non-ovariectomized (NOVX) control rats, NOVX rats treated with donepezil, ovariectomized (OVX) control rats and OVX rats treated with donepezil. Donepezil (1 mg/kg p.o.) was administered for four weeks, starting one week after the ovariectomy. The serum concentrations of CTX-I, osteocalcin and other biochemical parameters, bone mass, density, mineralization, histomorphometric parameters and mechanical properties, and skeletal muscle mass and strength were examined. Estrogen deficiency increased bone resorption and formation and worsened cancellous bone mechanical properties and histomorphometric parameters. In NOVX rats, donepezil decreased bone volume to tissue volume ratio in the distal femoral metaphysis, increased the serum phosphorus concentration and tended to decrease skeletal muscle strength. No significant bone effects of donepezil were observed in OVX rats. The results of the present study indicate slightly unfavorable effects of donepezil on the musculoskeletal system in rats with normal estrogen levels.

Modern glucose-lowering treatment effect on bone remodeling in experimental diabetes mellitus and surgical menopause

BACKGROUND: Diabetes mellitus (DM) is an independent risk factor for low-traumatic fractures. On the other hand, hypoglycemic drugs can have both positive and negative effects on bone remodeling.THE AIM: Тo investigate bone metabolism parameters during surgical menopause and experimental DM under the treatment with glucagon-like peptide receptor agonist type 1 (arGLP-1) liraglutide (LIRA) and sodium-glucose cotransporter type 2 inhibitor (iSGLT-2) canagliflozin (CANA).MATERIALS AND METHODS: Female Wistar rats have been subjected to bilateral ovariectomy at the beginning of the experiment. Diabetes mellitus (DM) was modelled using a high-fat diet and streptozotocin+nicotinamide. Four weeks after the following groups were formed: “OE+DM” (females after ovariectomy with DM and without any therapy, n=4) «OE+DM+CANA» (females after ovariectomy with DM under treatment with CANA, n=4), «OE+DM+LIRA» (females after ovariectomy with DM under treatment LIRA, n=5). The treatment or observation period were continuing for 8 weeks. Calcium, phosphorus and bone turnover markers (fibroblast growth factor-23 (FGF-23), osteocalcin, sclerostin, osteoprotegerin (OPG), nuclear factor-kappa-B receptor activator ligand (RANKL), were measured in the end of experiment. Bone histomorphometry was performed after euthanasia.RESULTS: Treatment with both CANA and LIRA did not significantly affect the phosphorus-calcium metabolism, sclerostin and osteocalcin concentrations. At the same time, the level of OPG was the highest in «OE+DM ‘’ group (9.1 [7.81; 10.045] pmol/l). The differences were significant compared with «OE+DM+CANA’’ (2, 33 [1.84; 5.84] pmol/l, p = 0.003) and «OE+DM+LIRA» (1.7 [1; 2] pmol/l, p = 0.003) groups. There were no differences in OPG levels between animals treated with different drugs. Similarly, the OPG/RANKL ratio was similarly reduced with both types of treatment. In “OE+DM+CANA’’ group the bone trabeculae number of the femur epiphysis (p=0.042) were decreased in comparison to «OE+DM» group. LIRA did not change the histoarchitectonic parameters.CONCLUSION: Bone metabolism markers did not differ when using as canagliflozin as liraglutide. Besides, canagliflosin can lead to the activation of bone resorption, which is expressed in the femur epiphyseal trabeculae number decreasing.