Terminal Telopeptide Research Articles

The Effects of Increasing Doses of Nigella Sativa and Conjugated Estrogen on Bone-Specific Alkaline Phosphatase (B-ALP), Procollagen Type 1 N-Terminal Propeptide (P1NP), Carboxy Terminal Crosslinked Telopeptide of Type 1 Collagen (CTX-1), and Osteoprotege

The Effects of Increasing Doses of Nigella Sativa and Conjugated Estrogen on Bone-Specific Alkaline Phosphatase (B-ALP), Procollagen Type 1 N-Terminal Propeptide (P1NP), Carboxy Terminal Crosslinked Telopeptide of Type 1 Collagen (CTX-1), and Osteoprotege

Bone Health Assessment in Patients with Methylmalonic Acidemia

Abstract Background Methylmalonic acidemia (MMA) is a genetically heterogeneous disorder of methylmalonate and cobalamin metabolism. Isolated MMA is a rare inherited disorder of organic acid metabolism associated with elevated methylmalonic acid concentration in the blood and urine without elevation of homocysteine level or malonic acid. Nutritional intervention for MMA patients includes dietary restriction of proteins along with medical food and dietary supplements. Decreased bone mineral density (BMD) is a widely accepted complication of the life-long protein restricted diet in addition to accumulation of acids and toxic metabolites in those patients. Aim of the Study To investigate the effect of restricted and modified diet on bone health in a sample of patients with MMA. Subject and Methods Clinical, nutritional, selected laboratory parameters of bone health and bone mineral density (BMD) assessment by Dual-energy X-ray absorptiometry (DXA) scan of bones were carried out on Egyptian MMA patients from Genetics Clinic, Medical Genetic Department, Ain Shams University. Bone formation was assessed by measurement of serum osteocalcin level while bone resorption was evaluated by serum carboxy terminal telopeptide of collagen type 1 (S-CTX). Results The study included 24 patients from 14 families (13 males and 11 females). Their ages ranged between 5.2 to 26 years with median age of 10 years (IQR: 6.5-14). Consanguineous marriage was present in 91.67 of families. Median age of symptoms was 140 days (IQR: 3.5-332.5) while median age of diagnosis was 12 months (IQR (2.5-40). History of fractures was present in 5 patients (20.83%). Decreased total body BMD was detected in 14 patients (54.5 %) with mean Z score of -1.31 ± 1.38 SD. Decreased spine BMD was present in 21 patients (79.16%) with mean Z score of -1.9 ± 1.1 SD. This decrease was significantly related to non-compliance, chronic acidosis, low serum copper. There was no significant relation between BMD and creatinine, calcium, vitamin D, zinc, selenium, osteocalcin or S-CTX levels. Conclusion MMA patients have decreased BMD related to copper deficiency, poor compliance and chronic acidosis. This resulted in defective bone formation and increased bone resorption.

The Evolution of the Bone Turnover Marker in Patients Following Recovery from Diabetic Ketoacidosis.

The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and β-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and β-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (β=0.58, p=0.003) and recovery (β=0.447, p=0.025), although sex was significant in pre-treatment (β=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers.

Prenatal but not continued postpartum vitamin D supplementation reduces maternal bone resorption as measured by C-terminal telopeptide of type 1 collagen without effects on other biomarkers of bone metabolism

Vitamin D is a key regulator of bone mineral homeostasis and may modulate maternal bone health during pregnancy and postpartum. Using previously-collected data from the Maternal Vitamin D for Infant Growth (MDIG) trial in Dhaka, Bangladesh, we aimed to investigate the effects of prenatal and postpartum vitamin D3 supplementation on circulating biomarkers of bone formation and resorption at delivery and 6 months postpartum. MDIG trial participants were randomized to receive a prenatal;postpartum regimen of placebo or vitamin D3 (IU/week) as either 0;0 (Group A), 4200;0 (B), 16,800;0 (C), 28,000;0 (D) or 28,000;28,000 (E) from 17 to 24 weeks' gestation to 6 months postpartum. As this sub-study was not pre-planned, the study sample included MDIG participants who had data for at least 1 biomarker of interest at delivery or 6 months postpartum, with a corresponding baseline measurement (n = 690; 53 % of 1300 enrolled trial participants). Biomarkers related to bone turnover were measured in maternal venous blood samples collected at enrolment, delivery, and 6 months postpartum: osteoprotegerin (OPG), osteocalcin (OC), receptor activator nuclear factor kappa-B ligand (RANKL), fibroblast growth factor 23 (FGF23), procollagen type 1 N-terminal propeptide, (P1NP) and carboxy terminal telopeptide of type 1 collagen (CTx). Supplementation effects were expressed as percent differences between each vitamin D group and placebo with 95 % confidence intervals (95 % CI). Of 690 participants, 64 % had 25-hydroxyvitamin D concentrations (25OHD) <30 nmol/L and 94 % had 25OHD < 50 nmol/L at trial enrolment. At delivery, mean CTx concentrations were 27 % lower in group E versus placebo (95 % CI: −38, −13; P < 0.001), adjusting for enrolment concentrations. However, at 6 months postpartum, CTx concentrations were not statistically different in group E versus placebo (14 %; 95 % CI: −5.3, 37; P = 0.168), adjusting for delivery CTx concentrations. Effects on other biomarkers at delivery or postpartum were not statistically significant. In conclusion, prenatal high-dose vitamin D supplementation reduced bone resorption during pregnancy, albeit by only one biomarker, and without evidence of a sustained effect in the postpartum period. However, further evidence is needed to substantiate potential maternal bone health benefits of vitamin D in the postpartum period.

The Effects of Obesity on Bone Turnover Markers in Diabetic Patients with Diabetic Ketosis or Ketoacidosis.

Despite the fact that diabetes individuals are often associated with a higher risk of bone fracture, our previous research demonstrated that Diabetic ketosis (DK) or ketoacidosis (DKA) induced significant alterations in bone biomarkers. It is unknown whether there is a difference in bone metabolism between obese and non-obese diabetic populations while they are in DK or DKA; hence the current study will investigate this further to aid in the prognosis and prediction of bone fracture risk in patients with different BMIs. We categorized patients into four groups based on their BMI utilizing data from our hospital's medical record system from 2018 to 2020 in the Department of Endocrinology: obese DK or DKA patients (OB+DK/DKA, n=41), non-obese DK or DKA patients (DK/DKA, n=201), obese type 2 diabetes patients without DK or DKA (OB+T2D, n=93), and patients with type 2 diabetes only (T2D only, n=304). The comparisons were made on glycosylated hemoglobin (HbA1c), body mass index (BMI), fasting plasma C-peptide (FPCP), and plasma lipids, in addition to bone metabolism indicators such as total 25-OH-VitD3 (25-OH-VitD3), N-terminal middle molecular fragment of osteocalcin (NMID), -C terminal cross-linking telopeptide of type 1 collagen (-CTX), parathyroid hormone (PTH), and blood calcium (Ca2+). The OB+DK/DKA group had a lower average age (p<0.05) than the DK/DKA group, while the DK/DKA group had a significantly lower FPCP (p<0.05). The 25-OH-VitD3 levels of DK/DKA patients were considerably lower than those of the T2D-only group (p< 0.05). In contrast, NMID and Ca2+ levels were significantly lower than those of non-ketosis or acidosis patients (p<0.05), and PTH levels in the DK/DKA group were significantly lower than those of OB+ T2D patients (p<0.05). In contrast, the β-CTX of the DK or DKA group (OB+DK/DKA and DK+DKA) was significantly greater than that of the non-DK or DKA group (p<0.05), although there was no significant difference in blood phosphorus between OB+DK/DKA and DK/ DKA (p>0.05). The levels of thyroid-stimulating hormone (TSH) and free T4 (FT4) did not differ significantly among the four groups (p>0.05); however, the levels of total T3 (TT3), T4 (TT4), and free T3 (FT3) were significantly lower in the DK/DKA group (p<0.05); the ratio of TT3 to TT4 (TT3/TT4) was significantly decreased in the DK/DKA group, whereas the ratio of FT3/FT4 was significantly lower (p<0.05). Obese patients with DK or DKA have a younger onset age, superior pancreatic function, and better blood glucose management than non-obese patients with DK/DKA. Despite having higher bone absorption signals than non-DK/DKA patients, OB+DK/DKA patients have stronger bone formation markers than non-obese DK/DKA patients, according to a recent study. Changes in markers of bone metabolism may be linked to non-thyroidal illness syndrome in cases of DK or DKA.

Denosumab biosimilar (LY01011) in the treatment of bone metastases in patients with solid tumors: A multicenter, randomized, double-blind, active comparator-controlled phase 3 study.

12126 Background: The study was to evaluate the equivalence of LY01011 to the reference product denosumab in terms of reduction of bone metabolism markers. Methods: Eligible patients were randomized at 1:1 ratio to receive 120 mg LY01011 injection or 120 mg denosumab every four weeks subcutaneously. Following the completion of three doses of 120 mg LY01011 or denosumab in a 12-week double-blind treatment period (DBTP), all enrolled patients would continue to receive LY01011 administration until the week 53 of follow-up period. The primary end point was the natural logarithm change at week 13 from baseline in urinary cross-linked N terminal telopeptide of type I collagen, corrected for urine creatinine (uNTx/uCr). The equivalence between LY01011 and denosumab would be concluded if the 90% CI was completely inside the pre-defined equivalence boundary between -0.135 and 0.135. A formal blinded sample-size re-estimation (BSSR) was planned to take place once 60% of the planned participants had completed the Week 13 assessments. After BSSR, the sample size increased from 560 to 850 according to prespecified procedure based on pooled standard deviationfrom the blinded data, which was set as a cap to ensure a feasible sample size for the study and no need to do any multiplicity adjustment. Results: All eligible 850 patients, included in the full analysis set, were randomized into the LY01011 group (n = 424) and denosumab group (n = 426). The samples from the 12-week DBTP were collected for analysis in both groups. The least square mean (LSM) (SE) of the natural logarithm change of uNTX/uCr at week 13 from baseline was -1.740 (0.0420) in the LY01011 group and -1.745 (0.0421) in denosumab group. The LSM difference was 0.005 between LY01011 and denosumab groups with 90% CI of [-0.088, 0.097] (p &gt; 0.05). Skeletal related events occurring in the LY01011 and denosumab groups were 3.5% and 2.8%, respectively. The mean (SD) percentage changes of serum bone-specific alkaline phosphatase (s-BALP) from baseline to week 13 were -31.154% (39.6790) and -33.021% (37.3826) in the LY01011 and denosumab groups, respectively. The median was -36.866% and -37.457% (p &gt; 0.05). The incidence of treatment-emergent adverse events (TEAEs) of any grade was 91.7% and 90.8% in LY01011 and denosumab groups(p &gt; 0.05). Both groups had 38.4% of Grade ≥3 TEAEs, of which 5.4% (LY01011) and 4.5% (denosumab) were judged to be related to the study drug. Immunogenicity analysis showed that no participant (0/399) had a positive ADA test in denosumab group and only one participant (0.2%, 1/401) was tested ADA positive in LY01011 group. Conclusions: The study demonstrated the equivalent efficacy of LY01011 in the reduction of bone metabolism biomarker NTX to reference product, denosumab, which met the primary endpoint. It had a good safety profile with no unexpected adverse reactions in the study. Clinical trial information: NCT04859569 .

Impact of Skeletal Maturation on Bone Metabolism Biomarkers and Bone Mineral Density in Healthy Brazilian Adolescents

This study was conducted to evaluate the behavior of biomarkers in the bone formation and resorption in Brazilian adolescents according to their biological maturation. Eighty-seven volunteers were selected and divided into three groups according to their bone age (BIA); 10-12 years (n=25), 13-15 years (n=36) and 16-18 years (n=26). Few parameters and biomarkers such as, the weight (kg), height (m), body mass index (kg/m2), 3-day calcium intake (mg/day), assessment of pubertal events by Tanner criteria, levels of the biomarkers [osteocalcin (OC) (ng/mL), bone alkaline phosphatase (FAO) (U/L), and serum carboxy–terminal telopeptide (S–CTx) (ng/mL)] and their correlation with bone mineral density (BMD) (g/cm2) were measured by dual–energy X–ray attenuation of the lumbar spine, proximal femur and total body in each volunteer. The results showed that, all the biomarkers have similar behaviors, showing a higher median value for 13 to 15 years (FAO=154.71 U/L, OC=43.0 ng/mL, S–CTx=2.09 ng/mL; p&lt;0.01) at the pubertal stage G4, and the median is decreased with the advancing IO and sexual maturation level. Additionally, the biomarker levels showed a parallelism with a peak velocity in the stature level, and interestingly, the training biomarkers indicated a negative correlation with BMD where high BMD values correlated with the low biomarker values. In conclusion, this is the first study were conducted in Brazilian adolescents with strict, and careful inclusion and exclusion criteria to assess the correlation between the bone markers and BMD against the indicators of biological maturation. The results of this study may help to understand and monitor the bone turnover and bone metabolism respectively.

Assessment of bone mineral density and bone turnover markers in patients with juvenile idiopathic arthritisy

Juvenile idiopathic arthritis (JIA) is one of the most common chronic inflammatory diseases occurring in childhood, associated with decreased bone mineral density (BMD) and increased risk of osteopenia and osteoporosis, which increases the fracture risk. Aim of the work: to assess BMD and bone turnover markers (serum osteocalcin for bone formation and C terminal telopeptide of type 1 collagen for bone resorption) in JIA patients and their relation to disease activity. This study included 50 patients with JIA (female:male – 20:30). The study was approved by the Ethical Research Committee and Institutional Review Board of the Faculty of Medicine, Menoufia University, Egypt (Approval number: 19519INTPH48). Written informed consent was obtained from each patient or the parents. These patients were diagnosed with JIA according to the criteria of classification of the International League of Associations for Rheumatology. BMD was measured by Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine using the Z-score. The results were correlated with JIA disease duration, disease activity, bone turnover markers and serum level of vitamin D. Clinical disease activity was evaluated by juvenile arthritis disease activity score (JADAS-27). There was a significant negative correlation between DEXA Z-score and disease activity (p-value &lt; 0.001), bone turnover markers (p-value &lt; 0.001), and duration of JIA (p-value &lt; 0.05). There was a significant difference between vitamin D level and DEXA Z-score; DEXA Z-score was lower in vitamin D deficient patients. JIA patients with higher disease activity are at a higher risk of osteopenia and osteoporosis. Well-timed and efficient treatment of JIA and proper control of disease activity may help to improve the bone status and reduce the incidence of osteoporosis. Consequently, valuable targeted interventions are essential to preserve bone health during JIA.

Effect of Odanacatib on the release of NTX (Amino Terminal Telopeptide) from LPS contaminated type I dentin collagen.

To evaluated the Odanacatib inhibitor treatment on lipopolysaccharide (LPS) contamination effect on cathepsin-K mediated dentin degradation by analysis of type I collagen C- and N-termini telopeptides. Pulverized and disks of human dentin were demineralized and LPS contaminated, or stored in deionized water (DW) for 12h. Samples were challenged with lactic acid (LA). Aliquots of dentin powder were treated with 1mL Odanacatib or stored in DW for 30min. Dentin collagen degradation was determined by sub-product release of C-terminal (ICTP and CTX) and N-terminal (NTX) telopeptides, normalized to total protein (tp) concentration (n=3). Dentin matrix was evaluated for gravimetric (n=8) and ultrastructural changes. Data were analyzed by Student t-test, one-way ANOVA and Tukey's test (α=5 %). LA incubation significantly increased telopeptide release compared with DW (p<0.05). In untreated groups, significantly higher CTXtp, NTXtp telopeptide rates were observed for LA+LPS samples compared with DW (p<0.01). Odanacatib significantly reduced ICTPtp, CTXtp, and NTXtp telopeptide release for LPS, LA, and LA+LPS conditions. In untreated groups, LPS and LA+LPS challenge significantly increased dentin weight loss (p=0.02). Within each storage condition, Odanacatib treatment did not affect weight change (p>0.05) of dentin disks. This study showed that LPS contamination resulted in significantly higher rates of NTX than CTX from dentin matrix. Odanacatib significantly reduced telopeptide release rates of LPS contaminated dentin matrix.

Serum bone resorption markers and 25-hydroxyvitamin D level in women of the Trans-Baikal region of the Russian and Buryat nationalities

Osteoporosis (OP) is a metabolic bone disease , characterized by a decrease of bone mineral density , leading to the development of low-energy fractures . Serum pyridinoline (PYD) and C- terminal cross-linking telopeptide type I (β- CrossLaps ) are among the specific markers of bone resorption . Vitamin D is involved in the metabolism of bone tissue , its deficiency accelerates the processes of bone tissue breakdown . Material and methods . 60 women with osteoporosis were studied (30 Russian and 30 Buryat nationalities ) aged 50 to 80 years ; the control group included 20 women (10 Russian and 10 Buryat nationalities ). Serum bone resorption markers , namely pyridinoline a nd β- C rossLaps , 25-hydroxyvitamin D (25(OH)D) w ere m easured u sing i mmunoassays . R esults a nd d iscussion . The l evel o f β- C rossLaps w as h igher a nd t he c ontent o f 25(OH)D w as l ower i n w omen w ith o steoporosis c ompared t o t he c ontrol g roup . T here w as a p ositive r elationship b etween β- C rossLaps c oncentration a nd b ody m ass i ndex &lt; 20 k g / cm 2 , f requent f alls , a nd a h ip f racture , b etween t he l evel o f 25(OH)D a nd h ereditary h istory o f o steoporosis i n Russian w omen . T here w as a p ositive r elationship b etween S erum p yridinoline a nd s moking , b etween 25(OH)D a nd l ow p hysical a ctivity , β- C rossLaps a nd t he m ajor o steoporotic f ractures i n B uryat w omen . It w as f ound t hat t he β- C rossLaps i s a n i ndependent p redictor o f t he d evelopment o f f ractures i n Russian w omen (β = 0.678, p = 0.04). In B uryat w omen , i ndependent p redictors o f f ractures a re p yridinoline (β = –0.38, p = 0.04) a nd β- C rossLaps (β = 0.671, p = 0.01). C onclusions . The s ystemic m arkers o f b one r esorption ( p yridinoline , β- C rossLaps ) a nd 25(OH)D c an b e u sed i n t he d iagnosis o f o steoporosis a nd f ractures i n r esidents o f t he Trans- B aikal R egion i n a ddition t o r isk f actor a ssessment a nd b one m ineral d ensity m easurement .

Severe Zinc Deficiency Impairs Accrual of Bone in Rapidly Growing Rats That Is Partially Corrected Following Short-term Zinc Repletion.

Zinc (Zn) deficiency impairs bone growth. However, the precise skeletal effects of varying levels of Zn deficiency and response to subsequent Zn repletion on the growing skeleton are incompletely understood. To address this gap in knowledge, we investigated the effects of dietary Zn ((severe deficiency (< 0.5mg Zn/kg diet) and short-term Zn repletion (30mg/kg diet), marginal deficiency (6mg Zn/kg diet)) on bone mass, density, and cortical and cancellous bone microarchitecture in growing male Sprague Dawley rats. Marginal Zn intake for 42days had no effect on bone mass or cortical and cancellous bone microarchitecture. Twenty-one days of severe Zn deficiency lowered serum osteocalcin and C terminal telopeptide of type I collagen (CTX-1), decreased tibial bone mineral content and density, and lowered cross-sectional volume, cortical volume, and cortical thickness in tibial diaphysis as compared to both Zn-adequate (30mg/kg diet) and pair-fed controls. Severe Zn deficiency similarly lowered cancellous bone volume in proximal tibial metaphysis. Zn repletion (10days) accelerated weight gain, indicative of catch-up growth, normalized CTX-1 and osteocalcin, but did not normalize bone mass (unadjusted and adjusted for body weight) or cortical and cancellous bone microarchitecture. In summary, severe but not marginal Zn deficiency in rapidly growing rats impaired acquisition of cortical and cancellous bone, resulting in abnormalities in bone microarchitecture. Zn repletion accelerated weight gain compared to Zn-adequate controls but absence of a compensatory increase in serum osteocalcin or bone mass suggests Zn repletion may be insufficient to fully counteract the detrimental effects of prior Zn deficiency on skeletal growth.

Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.

The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (tartarate-resistant acid phosphatase 5b (TRAP), C terminal telopeptide (CTX)), and osteocyte markers (intact fibroblast growth factor 23 (iFGF23), sclerostin) and soluble klotho were measured at baseline and after 3months of intensive replacement therapy. The change in biomarkers and ratio of markers of bone formation to resorption were compared between treatment arms. BAP and TRAP were expressed as age- and sex-specific z-scores. 25OHD levels increased with cholecalciferol supplementation, with 85% achieving normal levels. There was a significant increase in the BAP/TRAP ratio (p = 0.04), iFGF23 (p = 0.004), and klotho (p = 0.002) with cholecalciferol therapy, but this was comparable across all three therapy arms. The BAPz was significantly higher in the weekly arm (p = 0.01). The change in 25OHD (Δ25OHD) inversely correlated with ΔPTH (r = - 0.4, p < 0.001). Although cholecalciferol supplementation was associated with a significant increase in bone formation, the three dosing regimens of cholecalciferol supplementation have a comparable effect on the bone biomarker profile, suggesting that they can be used interchangeably to suit the patient's needs and optimize adherence to therapy. A higher resolution version of the Graphical abstract is available as Supplementary information.

Vibration therapy as an effective approach to improve bone healing in diabetic rats.

ObjectiveTo investigate the effects of vibration therapy on fracture healing in diabetic and non-diabetic rats.Methods148 rats underwent fracture surgery and were assigned to four groups: (1) SHAM: weight-matched non-diabetic rats, (2) SHAM+VT: non-diabetic rats treated with vibration therapy (VT), (3) DM: diabetic rats, and (4) DM+VT: diabetic rats treated with VT. Thirty days after diabetes induction with streptozotocin, animals underwent bone fracture, followed by surgical stabilization. Three days after bone fracture, rats began VT. Bone healing was assessed on days 14 and 28 post-fracture by serum bone marker analysis, and femurs collected for dual-energy X-ray absorptiometry, micro-computed tomography, histology, and gene expression.ResultsOur results are based on 88 animals. Diabetes led to a dramatic impairment of bone healing as demonstrated by a 17% reduction in bone mineral density and decreases in formation-related microstructural parameters compared to non-diabetic control rats (81% reduction in bone callus volume, 69% reduction in woven bone fraction, 39% reduction in trabecular thickness, and 45% in trabecular number). These changes were accompanied by a significant decrease in the expression of osteoblast-related genes (Runx2, Col1a1, Osx), as well as a 92% reduction in serum insulin-like growth factor I (IGF-1) levels. On the other hand, resorption-related parameters were increased in diabetic rats, including a 20% increase in the callus porosity, a 33% increase in trabecular separation, and a 318% increase in serum C terminal telopeptide of type 1 collagen levels. VT augmented osteogenic and chondrogenic cell proliferation at the fracture callus in diabetic rats; increased circulating IGF-1 by 668%, callus volume by 52%, callus bone mineral content by 90%, and callus area by 72%; and was associated with a 19% reduction in circulating receptor activator of nuclear factor kappa beta ligand (RANK-L).ConclusionsDiabetes had detrimental effects on bone healing. Vibration therapy was effective at counteracting the significant disruption in bone repair induced by diabetes, but did not improve fracture healing in non-diabetic control rats. The mechanical stimulus not only improved bone callus quality and quantity, but also partially restored the serum levels of IGF-1 and RANK-L, inducing bone formation and mineralization, thus creating conditions for adequate fracture repair in diabetic rats.

Influence of Iguratimod on Bone Metabolism in Patients with Rheumatoid Arthritis: A Meta-analysis.

Background Influence of iguratimod on bone mineral density (BMD) and biomarkers of bone metabolism in patients with rheumatoid arthritis (RA) remains not determined. Accordingly, a meta-analysis was performed for systematical evaluation. Methods Relevant randomized controlled trials (RCTs) were retrieved by searching of PubMed, Embase, Cochrane's Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases. A random-effect model was used to pool the results. Results In total, 24 RCTs including 2439 patients with RA contributed to the meta-analysis. Pooled results showed that compared to methotrexate alone, additional use of iguratimod 25 mg Bid for 12∼24 weeks significantly improved lumbar-spine BMD (mean difference [MD]: 0.12, 95% confidence interval [CI]: 0.04 to 0.20, p=0.002, I2 = 39%) in patients with RA. Moreover, treatment with iguratimod was associated with increased serum osteoprotegerin (MD: 180.36 pg/ml, 95% CI: 122.52 to 238.20, p < 0.001, I2 = 48%), and decreased serum receptor activator for nuclear factor kappa-B ligand (MD: −10.65 pmol/l, 95% CI: −15.59 to −5.72, p < 0.001, I2 = 53%). In addition, iguratimod was associated with increased bone formation markers such as the serum N-terminal middle molecular fragment of osteocalcin (MD: 4.23 ng/ml, 95% CI: 3.74 to 4.71, p < 0.001, I2 = 35%) and total procollagen type I amino-terminal propeptide (MD: 9.10 ng/ml, 95% CI: 7.39 to 10.80, p < 0.001, I2 = 86%), but decreased the bone resorption marker such as serum β-C terminal cross-linking telopeptide of type 1 collagen (MD: −0.18 pg/ml, 95% CI: −0.21 to −0.14, p < 0.001, I2 = 70%). Conclusions Iguratimod could prevent the bone loss and improve the bone metabolism in patients with RA.

The Comparative Study on the Status of Bone Metabolism and Thyroid Function in Diabetic Patients with or without Ketosis or Ketoacidosis.

PurposeThis study aims to identify changes in bone turnover markers and thyroid function in diabetic ketosis (DK) and diabetic ketoacidosis (DKA).Materials and MethodsWe compared data from the Department of Endocrinology at Shanghai Pudong Hospital from 2018 to 2020 on the pancreatic status and previous glucose control, bone transformation, calcium homeostasis, and thyroid function in groups with diabetes (DM alone, n=602), DK (n=232), and DKA (n=60). Similar comparisons were made in recurrent DK (A) (n=17) and single DK (A) (n=272).ResultsThe fasting C-peptide level decreased significantly, but hemoglobin A1c (HbA1c) levels were higher in DK or DKA (p<0.05). Blood calcium and 25-hydroxyvitamin D3 (25-OH-VitD3) levels were significantly lower in DKA (p<0.05), but parathyroid hormone (PTH) levels remained constant across all three groups. The N-terminal middle molecular fragment of osteocalcin (N-MID) and β-C terminal cross-linking telopeptide of type 1 collagen (β-CTX) showed significant inverse alterations in DKA, regardless of gender or age (p<0.05). Otherwise, DKA significantly inhibited thyroid function (p<0.05). Furthermore, Spearman correlation analyses revealed a relationship between N-MID and HbA1c in DM alone (r=−0.27, p<0.01), while total triiodothyronine (TT3, r=0.62, p<0.01) or free T3 (FT3, r=0.61, p<0.01) in DK, and DKA (TT3, r=0.45, p<0.01; FT3, r=0.43, p<0.01). Multilinear regression analyses revealed that β-CTX (β=0.564), HbA1c (β=−0.196), TT3 (β=0.183), and 25-OH-VitD3 (β=−0.120) were the only independent determinants of N-MID in DM, whereas FT3 (β=0.491), β-CTX (β=0.315) in DK, and FT3 (β=0.420), β-CTX (β=0.367), TG (β=−0.278) in DKA. Only 25-OH-VitD3 was found to be significantly lower in recurrent DK (A) than in single onset DK (A) (p<0.05), and β-CTX (β=0.745) was found to be significantly independently associated with N-MID.ConclusionOur preliminary findings show a dramatic change in bone turnover markers in DM patients with DK and DKA, and this change may be related to thyroid function.

POS-249 BONE BIOMARKERS IN RESPONSE TO DIFFERENT DOSING REGIMEN OF CHOLECALCIFEROL THERAPY IN CHILDREN WITH CHRONIC KIDNEY DISEASE

The effect of cholecalciferol (25OHD) therapy on parathormone levels (PTH) have been well studied in CKD. However, the endocrine effect of daily vs weekly or monthly treatment regimens of 25OHD supplementation on biomarkers of bone formation and resorption are not known. We investigated the effect of 25OHD supplementation on the bone biomarkers (Bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP), C terminal telopeptide of type 1 collagen (CTX), N terminal propeptide of type 1 procollagen (PINP), sclerostin) in children with CKD stages 2-4.

Indices of connective tissue metabolism, their interconnection in patients with 5D stage chronic kidney disease and in patients with anterior abdominal wall hernias

Objective. To study the interconnection between the indices of matrix metalloproteinases (MMPs) of type I collagen terminal telopeptides in patients with end-stage chronic kidney disease (CKD) and in patients with anterior abdominal wall hearnias.Materials and methods. 39 patients with CKD stage 5D, 24 patients with primary anterior abdominal wall hernias and 25 patients of the comparison group without visual signs of connective tissue dysplasia were included into the prospective study. The concentrations of the levels of MMP-1, MMP-2, MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-3, N-terminal telopeptide NTX-N, C-terminal telopeptide CTX-C were determined in plasma using the enzyme immunoassay (ELISA).Results. The end-stage patients with CKD and the patients with anterior abdominal wall hernias showed no statistically signifcant biochemical indices of ongoing bone tissue destruction based on the levels of terminal telopeptides NTX-N and CTX-C. There are statistically signifcant increases in the levels of MMP-1, MMP-2, MMP-9 (p ˂ 0.001) in the CKD stage 5D patients and major TIMP-1 and TIMP-3 (p ˂ 0.001) in relation to the comparison group. These indices were comparable with the changes in the connective tissue of the patients with primary anterior abdominal wall hernias.Conclusion. The obtained results indicate disturbances in the regulation of the synthesis and structural relationships of connective tissue in CKD stage 5D patients and in patients with primary anterior abdominal wall hernias. CKD stage 5D patients and primary anterior abdominal wall hernias reveal identical direct correlations in the indices of connective tissue metabolism according to NTX-N, MMP-1 and MMP-9, TIMP-1, which indicates similar disturbances in the regulation of the synthesis and structural disorders in connective tissue.

Role of food fortification with vitamin D and calcium in the bone remodeling process in postmenopausal women: a systematic review of randomized controlled trials

Foods containing vitamin D reduce the deficiency of this vitamin and improve bone turnover. To discuss effects of the intake of vitamin D-fortified foods in isolated form or associated with calcium on bone remodeling in postmenopausal women. PubMed, Lilacs, Scopus, and Bireme databases. OpenThesis and Google Scholar were searched as "grey literature". Medical subject headings or similar terms related to food fortified with vitamin D and bone in postmenopausal women were used. Information was collected on study methodology and characteristics of studied populations; dosage; the food matrix used as the fortification vehicle; duration of intervention; dietary intake; 25-hydroxyvitamin D [25(OH)D] levels; serum parathyroid hormone (PTH) concentrations; bone resorption and/or formation markers (ie, carboxy terminal cross-linked telopeptide of type I collagen [CTX], tartrate-resistant acid phosphatase isoform 5b [TRAP5b], and procollagen type 1 N-terminal propeptide [P1NP]); main results; and study limitations. Five randomized controlled trials involving postmenopausal women were included. The mean ages of participants ranged from 56.1 to 86.9 years. Daily consumption of soft plain cheese fortified with 2.5 µg of vitamin D3 and 302 mg of calcium for 4 weeks resulted in a mean increase of 0.8 ng/mL in 25(OH)D and 15.9 ng/mL in P1NP levels compared with baseline, and decreased CTX, TRAP5b, and PTH values. A similar intervention for 6 weeks, using fortified cheese, showed a reduction only in TRAP5b values (-0.64 U/L). Yogurt fortified with 10 µg of vitamin D3 and 800 mg of calcium did not change P1NP values after 8 weeks of intervention, but was associated with decreases of 0.0286 ng/mL and 1.06 U/L in PTH and TRAP5b, respectively. After 12 weeks of eating the fortified yogurt, 25(OH)D levels increased by a mean of 8.8 ng/mL and PTH levels decreased in by a mean of 0.0167 ng/mL. The interventions contributed toward the improvement of the bone resorption process but not to the bone formation process in postmenopausal women. CRD42019131976.

Effect of cachexia on bone turnover in cancer patients: a case-control study

BackgroundIncreased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients.MethodsIn this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio.ResultsBased on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis.ConclusionsCTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer.

Influence of hyperbaric oxygen therapy on bone metabolism in patients with neoplasm.

Hyperbaric oxygen therapy (HBOT) is useful in the treatment of complications due to radiotherapy in patients with neoplasm. Its effects on bone metabolism are unclear. In our study, we analyzed the effects of HBOT on bone remodeling in oncological patients with radiotherapy. Prospective clinical study in 23 patients with neoplasms undergoing treatment with HBOT due to complications of radiotherapy (hemorrhagic cystitis, proctitis or radionecrosis) and 25 patients with chronic anal fissure. The average number of HBOT sessions was 20 ± 5 (100% oxygen, 2.3 atmospheres and 90 min per day). Serum levels of aminoterminal propeptide of type I collagen (P1NP), C terminal telopeptide of type I collagen (CTX), alkaline phosphatase (AP), 25hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), were measured at 3 time points: T0 (before beginning HBOT), T1 (at the end of HBOT) and T2 (6 months after HBOT). At baseline, the patients with neoplasm have higher bone turnover than those with anal fissure. These differences were 41% in CTX (0.238 ± 0.202 ng/mL in neoplasm and 0.141 ± 0.116 ng/mL in fissure; p = 0.04), 30% for PTH (46 ± 36 pg/mL in neoplasm and 32 ± 17 pg/mL in fissure; p = 0.04) and 15% for alkaline phosphatase (80 ± 24 U/L in neoplasm and 68 ± 16 U/L in fissure; p = 0.04). In the group with neoplasm, the values of P1NP decreased 6% after HBOT (T0: 49 ± 31 ng/mL, T2: 46 ± 12 ng/mL; p = 0.03). Also, there were non-significant decreases in PTH (-34%) and CTX (-30%). Patients with neoplasm and complications with radiotherapy have an increase in bone remodeling that may be diminished after HBOT.