C-terminal Cross-linking Telopeptide Of Type Research Articles

Determinants of joint effusion in tarsocrural osteochondrosis of yearling Standardbred horses

Tarsocrural osteochondrosis (OCD) is a developmental orthopedic disease commonly affecting young Standardbreds, with different fragment localization and size. Clinically, it is characterized by variable synovial effusion in the absence of lameness, whose determinants are ill-defined. We hypothesized that localization and physical characteristics of the osteochondral fragments like dimensions, multifragmentation, and instability influence joint effusion and correlate with synovial markers of cartilage degradation and inflammation. Clinical data, synovial fluid and intact osteochondral fragments were collected from 79 Standardbred horses, aged between 12 and 18 months, operated for tarsocrural OCD. The severity of tarsocrural joint effusion was assessed semi-quantitatively. The osteochondral fragment site was defined radiographically at the distal intermediate ridge of the tibia (DIRT), medial malleolus (MM) of the tibia, and/or lateral trochlear ridge (LTR) of the talus. Size, stability, and arthroscopic appearance (unique or multi-fragmented aspect) of the fragments were determined intra-operatively. Synovial concentrations of C-terminal cross-linked telopeptides of type II collagen (CTX-II), leukotriene B4 (LTB4), and prostaglandin E2 (PGE2) were quantified. Tarsocrural synovial effusion was significantly affected by localization and stability of the fragments, with MM-located and unstable fragments being associated with highest joint effusion. Concentrations of CTX-II, LTB4, and PGE2 positively correlated with the severity of synovial effusion. This study underlines characteristics of the osteochondral fragments determining higher synovial effusion in OCD-affected tarsocrural joints and suggests both inflammation and extra-cellular matrix degradation are active processes in OCD pathology.

Association between osteocalcin and residual β-cell function in children and adolescents newly diagnosed with type 1 diabetes: a pivotal study.

This pivotal study aimed to evaluate circulating levels of bone remodeling markers in children and adolescents at the onset of type 1 diabetes (T1D). Additionally, we assessed their correlation with glucose control, residual β-cell function, and the severity of presentation. In this single-center cross-sectional study, we recruited children and adolescents newly diagnosed with T1D at our tertiary-care Diabetes Centre. Anamnestic, anthropometric, clinical, and biochemical data at T1D diagnosis were collected. Basal and stimulated C-peptide levels were assessed, along with the following bone remodeling biomarkers: osteocalcin (OC), alkaline phosphatase (ALP), parathormone (PTH), 25-OH Vitamin D (25OH-D), and the C-terminal cross-linked telopeptide of type 1 collagen (CTX). We enrolled 29 individuals newly diagnosed with T1D, with a slight male prevalence (51.7%). The mean age was 8.4 ± 3.7 years. A positive correlation between OC and stimulated C-peptide (R = 0.538; p = 0.026) and between PTH and serum HCO3- (R = 0.544; p = 0.025) was found. No other correlations between bone remodeling biomarkers and clinical variables were detected. Our data showed a positive correlation between OC levels and residual β-cell function in children and adolescents at T1D presentation. Further longitudinal studies evaluating OC levels in pediatric subjects with T1D are needed to better understand the complex interaction between bone and glucose metabolisms.

Blood and urine biomarkers for the diagnosis of early stages of knee osteoarthritis: A systematic review.

To identify biomarkers in human blood or urine at an early stage of knee osteoarthritis (OA) and to elucidate if any can accurately differentiate between healthy controls and early knee OA patients and be considered as a candidate for widespread clinical use for early diagnosis of the disease. Medline, Embase and Web of Science were screened to identify comparative studies measuring differences in blood or urine biomarkers between healthy controls and knee OA patients at an early stage (grade 1 or 2 Kellgren-Laurence). Two independent reviewers screened the abstracts for eligibility, reviewed the full texts, assessed the methodological quality and extracted the data. The Joanna Briggs Institute critical appraisal tool for diagnostic test accuracy studies was used to assess the quality of the included studies. Due to relevant heterogeneity, meta-analysis was not appropriate. Five studies met the eligibility criteria. The examined biomarkers were adropin, collagen type II metabolite, C-terminal cross-linked telopeptide of type II collagen, C-terminal cross-linked telopeptide of type I collagen, cartilage oligomeric matrix protein, matrix metalloproteinase 3, N-terminal propeptide of procollagen type IIA, type I procollagen N-terminal propeptides, N-terminal osteocalcin, angiopoietin-2, follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, interleukin-8, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, vascular endothelial growth factor and calprotectin and totalling 19 biomarkers. All of the biomarkers were studied only once in the selected papers. There is no reliable biomarker available to differentiate between early knee OA in patients and healthy controls, but a potential role of a cluster of biomarkers to close this gap. There are several limitations, including inappropriate study designs, small sample sizes, nonconsecutive patient groups and inadequate statistical methods for evaluating biomarker performance in studies included. Level III.

Markers of Bone Mineral Metabolism in Thyroid Disorders

Abstract Background and Aim: Thyroid hormones are essential for normal skeletal development and bone metabolism. Despite various studies, the effect of thyroid hormone on bone metabolism has not been clearly understood. We studied the bone formation markers (procollagen type 1 N-propeptide [P1NP] and osteocalcin [OC]) and bone resorption markers (C-terminal cross-linking telopeptide of type 1 collagen [CTX] and tartrate-resistant acid phosphatase [TRAP]) in patients with thyroid disorders and the effect of treatment on them. Furthermore, a study correlating these markers with thyroid-stimulating hormone (TSH) levels was done. Materials and Methods: This cross-sectional study recruited 60 cases (40 – hypothyroid and 20 – hyperthyroid) and 20 controls based on inclusion and exclusion criteria. To evaluate the effect of treatment, cases were further subdivided based on the duration of treatment received into 0-month (newly diagnosed), 1–6-month, and >6-month treatment subgroups. Both the cases and control underwent a thorough history, clinical examination, and detailed investigation based on a predesigned proforma. Results: In hyperthyroidism with 0-month treatment subgroup, both formation (OC, P1NP) and resorption (CTX) markers were significantly increased compared to control (P < 0.05), which became insignificant on treatment (1–6 months) with antithyroid medication despite low TSH value. Contrarily, in hypothyroidism, a statistically significant (P < 0.05) lower mean value of markers (OC, P1NP, and CTX) was observed only in the subgroup with levothyroxine supplementation. In hyperthyroidism, both the formation (OC and P1NP) and resorption markers (CTX and TRAP) showed a strong negative (P < 0.001) correlation with TSH, the strength of correlation decreased, and became insignificant on treatment. In hypothyroidism, only P1NP and CTX showed an overall significant positive (P < 0.05) correlation with TSH. Conclusion: Hyperthyroidism has high bone turnover markers, which showed early reversibility of markers on treatment with antithyroid medication despite low TSH, whereas in hypothyroidism, significantly lower mean value of markers is seen only in the subgroup with levothyroxine supplementation, probably owing to the suppressive effect of TSH. P1NP and CTX showed high sensitivity in both hypothyroidism and hyperthyroidism. The pattern of correlation between TSH and bone metabolism markers in hyperthyroidism suggests a direct negative effect of TSH on bone turnover, whereas in hypothyroidism, it either suggests TSH showing a positive correlation at a very high level which becomes negative as the TSH value decreases or TSH is not a dominant hormone regulating bone metabolism in hypothyroidism.

Metformin as adjuvant therapy in obese knee osteoarthritis patients.

This study aimed at investigating the efficacy of metformin as adjuvant therapy for obese knee osteoarthritis (OA) patients, considering its anti-inflammatory and cartilage-protective effects. In this randomized, double-blind, placebo-controlled study, 50 obese knee OA patients were assigned randomly to two groups, the metformin group (n = 25) which was treated with metformin 500mg orally BID plus celecoxib 200mg orally once daily, and the placebo group (n = 25) which was treated with placebo tablets BID plus celecoxib 200mg orally once daily for 12weeks. Cartilage Oligomeric Matrix Protein (COMP), C-terminal cross-linked telopeptide of type I collagen (CTX-1), and Interleukin 1-beta (IL-1β) serum levels were measured, while Western Ontario and McMaster Universities Arthritis Index (WOMAC) score assessed knee pain, stiffness, and physical function at baseline and after 12weeks. Following a 12-week treatment, the metformin group exhibited significantly reduced levels of COMP, CTX-1, and IL-1β in the serum compared to the placebo group (p = 0.0081, p = 0.0106, and p = 0.0223, respectively). Furthermore, metformin group produced significant improvements in WOMAC total scale (p < 0.0001), specifically in knee pain, stiffness, and physical function compared to placebo group (p < 0.0001, p < 0.0001, and p < 0.0001, respectively). Metformin as an adjuvant therapy in obese knee OA patients may have beneficial effects on cartilage degradation and inflammation, as evidenced by the significant decreases in serum COMP, CTX-1, and IL-1β levels. Additionally, metformin may improve clinical outcomes, as shown by the significant improvements in WOMAC scores. NCT05638893/Registered December 6, 2022 - Retrospectively.

Bone turnover markers and muscle decay indicator in patients with proximal femur fracture - a case-control study.

Fracture of the proximal femur is common in elderly patients, in fact threatening their lives. Age-related sarcopenia may be involved in the imbalance resulting in the injury. Handy and readily accessible biochemical tests would be useful to assess the musculoskeletal system condition in daily practice. The aim of the study was to determine whether there is any relation between muscle decay and fracture of the proximal femur and to assess bone quality in elderly patients. In the study 22 patients who represented the treatment group were hospitalized due to proximal femur fracture. Eighteen patients from the control group with no fracture in their history were admitted to the Internal Medicine Department. Anyone treated for osteoporosis, immune disease affecting protein balance, neoplasm, mental illness, heart failure, or myocardial infarction was excluded from the study. In every case a blood sample from an elbow vein was drawn, collected in EDTA-K2 tubes, and then centrifuged to separate plasma from the whole blood. Subsequently, the concentrations of C-terminal cross-linked telopeptide of type I collagen (CTX-I), sex hormone binding globulin (SHBG) and creatine kinase (CK) in plasma were determined using commercial enzyme-linked immunosorbent assays. The CK plasma concentration differed between the patient groups (p = 0.011). The SHBG plasma concentration was significantly higher in the treatment group (p = 0.006), whereas a slight difference in CTX-I plasma concentration between the groups was found (p = 0.038). No significant correlations between plasma CK, SHBG or CTX-I were found (p > 0.05). Creatine kinase is actually not an appropriate marker for the clinical assessment of muscle tissue quality in patients with or at risk of proximal femur fracture. Analyzing the quality of bone tissue, we can conclude it was poorer in patients with proximal femur fracture than in the control group.

Three-year effect of bisphosphonates on bone mineral density after denosumab withdrawal: observations from a real-world study.

Data on long-term treatment regimens for preventing bone mineral density (BMD) loss that occurs after denosumab (Dmab) withdrawal are scarce. Our aim was to evaluate the long-term changes (12-36months) in BMD and bone turnover markers in a group of postmenopausal women who had been treated with Dmab and received subsequent treatment with bisphosphonates. Secondary objectives were to evaluate factors associated with BMD loss, to compare the BMD change in patients who received oral vs intravenous bisphosphonates, and to assess the frequency of fragility fractures after Dmab discontinuation. The clinical data of 54 patients, 26 of whom had clinical and DXA assessments at 36months, were analyzed. After 12months, the mean LS BMD had decreased by 2.8% (±5.0), FN BMD by 1.9% (±5.8), and TH BMD by 1.9% (±3.7). After 36months, LS BMD had decreased by 3.7% (±6.7), FN BMD by 2.5% (±7.1), and TH BMD by 3.6% (±5.2). C-terminal cross-linked telopeptide of type I collagen significantly increased during the first 12months after Dmab withdrawal but then decreased at 36months. BMD loss at 12months was higher in patients with more than 30months of Dmab treatment, but this difference was only statistically significant at FN (-3.3% vs -0.3%, P = .252 at LS, -3.3% vs 0.3%, P = .033 at FN, and -2.1% vs 0.9, P = .091 at TH). There were no statistically significant differences regarding the change in BMD at 12 and 36months between oral and intravenous treatment. Seven patients suffered incidental vertebral fractures (clinical vertebral fractures: n = 6, morphometric fractures: n = 1) three of which were multiple. None of these patients were treated following international or institutional guidelines or recommendations. In summary, our study suggests that bisphosphonates can help maintain BMD for 36months after Dmab discontinuation.

S-Allylmercapto-N-Acetylcysteine (ASSNAC) Attenuates Osteoporosis in Ovariectomized (OVX) Mice.

Osteoporosis is a bone-debilitating disease, demonstrating a higher prevalence in post-menopausal women due to estrogen deprivation. One of the main mechanisms underlying menopause-related bone loss is oxidative stress. S-allylmercapto-N-acetylcysteine (ASSNAC) is a nuclear factor erythroid 2-related factor 2 (Nrf2) activator and cysteine supplier, previously shown to have anti-oxidation protective effects in cultured cells and animal models. Here, we studied the therapeutic potential of ASSNAC with and without Alendronate in ovariectomized (OVX) female mice. The experimental outcome included (i) femur and L3 lumbar vertebra morphometry via Micro-Computed Tomography (μCT); (ii) bone remodeling (formation vs. resorption); and (iii) oxidative stress markers in bone marrow (BM) cells. Four weeks after OVX, there was a significant bone loss that remained evident after 8 weeks, as demonstrated via µCT in the femur (cortical and trabecular bone compartments) and vertebra (trabecular bone). ASSNAC at a dose of 50 mg/Kg/day prevented bone loss after the four-week treatment but had no significant effect after 8 weeks, while ASSNAC at a dose of 20 mg/Kg/day significantly protected against bone loss after 8 weeks of treatment. Alendronate prevented ovariectomy-induced bone loss, and combining it with ASSNAC further augmented this effect. OVX mice demonstrated high serum levels of both C-terminal cross-linked telopeptides of type I collagen (CTX) (bone resorption) and procollagen I N-terminal propeptide (P1NP) (bone formation) after 2 weeks, and these returned to control levels after 8 weeks. Alendronate, ASSNAC and their combination decreased CTX and increased P1NP. Alendronate induced oxidative stress as reflected by decreased glutathione and increased malondialdehyde (MDA) levels, and combining it with ASSNAC partially attenuated these changes. These results portray the therapeutic potential of ASSNAC for the management of post-menopausal osteoporosis. Furthermore, ASSNAC ameliorates the Alendronate-associated oxidative stress, suggesting its potential to prevent Alendronate side effects as well as improve its bone-protective effect.

Abstract 2920: In vitro assays for investigating the effects of cancer therapeutics on bone

Abstract Bone microenvironment is an important factor in regulating bone metastasis. When cancer cells home to bone they secrete factors that stimulate osteoclast activity leading to increased bone resorption. Stimulatory factors released from the resorbed bone matrix in turn promote proliferation of cancer cells and this process, referred as the vicious cycle, often leads to osteolytic lesions in bone when osteoclastic bone resorption exceeds osteoblastic bone formation. The vicious cycle observed in osteolytic disease occurs also in osteoblastic metastases, and in addition cancer cells produce osteoblast-stimulating factors. Cancers with bone metastases often include both osteolytic and osteoblastic lesions. Our aim was to establish in vitro cell culture models to study the effects of cancer therapeutics on osteoblast and osteoclast differentiation and activity. In the osteoclast differentiation assay, human osteoclast precursor cells (Lonza) were cultured on bovine bone slices for 7 days. Denosumab was added in the cultures at day 0, and tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) activity was measured from the culture medium collected at day 7. Osteoclast activity was studied by allowing osteoclasts resorb bone after 7 days’ maturation period for additional 3 days in the presence of odanacatib. The amount of C-terminal cross-linked telopeptides of type I collagen (CTX-I) was measured in the culture medium collected at day 10 to quantitate osteoclast activity. Denosumab and odanacatib showed strong concentration dependent inhibition of osteoclast differentiation and activity, respectively. A mouse osteoblast progenitor cell line KS483 (Pharmatest Services) was used to study differentiation and activity of osteoblasts with test compounds bone morphogenetic protein 2 (BMP-2) and estradiol (E2). In the osteoblast differentiation assay, the activity of cellular alkaline phosphatase (ALP), a marker of osteoblast differentiation, was measured at day 8. In the osteoblast activity assay, the cells were cultured for 13 days. N-terminal propeptide of type I procollagen (PINP) secreted into the culture medium was determined at day 11 to indicate the effects on organic bone formation and calcium deposition was determined at the end of the study as a marker of inorganic bone formation. BMP-2 and E2 stimulated osteoblast differentiation and activity indicated by the increase in ALP activity, PINP and calcium levels. We conclude that these culture systems can be used for studying the effects of cancer therapeutics and identifying new potential compounds affecting the disease process of bone metastases with different mechanisms of action. Citation Format: Jenni H. Mäki-Jouppila, Mervi Ristola, Jukka Rissanen, Katja Fagerlund. In vitro assays for investigating the effects of cancer therapeutics on bone [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2920.

Effects of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion.

The effect of anti-osteoporosis treatment in elderly patients with osteoporosis and lumbar discectomy and fusion (LIF) for lumbar degenerative diseases is not well known. This study aimed to evaluate the effect of perioperative anti-osteoporosis treatment in the patients with osteoporosis and LIF. From January to December 2022, patients were divided into three groups according to the inclusive criteria: the normal group (Group A), the osteopenia group (Group B) and the osteoporosis group (Group C). Quantitative computed tomography (QCT), height of the intervertebral space (HIS), segmental sagittal angle (SSA), visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were compared between the groups at the follow-up time. The serum Ca2 + , osteocalcin (OC), propeptide of type I procollagen (PINP) C-terminal cross-linking telopeptide of type I collagen (β-CTX) and 25-OH vitamin D (25-OH VD) levels were compared between the groups at the time of follow-up. Interbody fusion was graded on the X-ray and CT images at the follow-up time. There were 165 patients in this study. There were significant differences in the mean age, mean score, HIS and SSA between the groups at the different follow-up times. There were significant differences in the concentrations of serum Ca2 + , OC, β-CTX, 25-OH VD and PINP at the sixth month after surgery between the groups. There were significant differences in the concentrations of serum Ca2 + , β-CTX and 25-OH VD between the pre-surgery and at six months after surgery in Group B and β-CTX and 25-OH VD in Group C. There was a significant difference in the degree of fusion between Group B and C (χ2= 5.6243, P< 0.05). In elderly patients with LIF and osteoporosis, anti-osteoporosis therapy could reduce bone resorption and thus facilitate fusion. Anti-osteoporosis medication tends to enhance radiological, functional, and fusion short-term outcomes.

Osteoporosis and low bone mass among schizophrenia and bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve subjects

BackgroundA growing body of data shows that schizophrenia (SCZ) and bipolar disorder (BD) have substantial metabolic risks; however, few studies have focused on bone metabolism. This study aimed to assess the prevalence and associated influencing factors of low bone mass and osteoporosis in SCZ and BD before pharmacological effects occur. Methods108 healthy controls (HCs) and drug-naïve individuals with SCZ (n = 56) and BD (n = 130) had their lumbar spine (L1–L4) and left femur (Neck/Trochanter/Ward's triangle) bone mineral density (BMD) determined using dual-energy X-ray absorptiometry. Besides, we measured bone turnover markers (BTMs) levels, including procollagen I N-terminal propeptide, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen in different groups. ResultsIndividuals with SCZ and BD had significantly lower BMD and significantly higher prevalence of low bone mass and osteoporosis compared with HCs. In the main observation regions of the total lumbar (F = 18.368, p < 0.001) and left femur (F = 14.790, p < 0.001), BMD was lower in individuals with SCZ and BD than HCs, with SCZ showing lower BMD than BD. The osteocalcin (H = 11.421, p = 0.003) levels were significantly higher in SCZ and BD than HCs.Binary regression analysis showed that SCZ or BD was an independent risk factor for low bone mass and osteoporosis. In addition, sex, age, and BTMs also influenced the occurrence of low bone mass and osteoporosis. LimitationsCross-sectional study. ConclusionThe results findings of the study might contribute to our understanding of the increased risk of bone metabolism in SCZ and BD. Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR1900021379.

Demographic and disease-related factors impact bone turnover and vitamin D in children with hemato-oncological diseases.

Children with hemato-oncological diseases may have significant skeletal morbidity, not only during and after treatment but also at the time of diagnosis before cancer treatment. This study was designed to evaluate the vitamin D status and circulating bone metabolic markers and their determinants in children at the time of diagnostic evaluation for hemato-oncological disease. This cross-sectional study included 165 children (91 males, median age 6.9yr range 0.2-17.7yr). Of them, 76 patients were diagnosed with extracranial or intracranial solid tumors, 83 with leukemia, and 6 with bone marrow failure. Bone metabolism was assessed by measuring serum 25OHD, PTH, bone alkaline phosphatase, intact N-terminal propeptide of type I procollagen, and C-terminal cross-linked telopeptide of type I collagen. Vitamin D deficiency was found in 30.9% of children. Lower 25OHD levels were associated with older age, lack of vitamin D supplementation, season outside summer, and a country of parental origin located between latitudes -45° and 45°. Children diagnosed with leukemia had lower levels of markers of bone formation and bone resorption than those who had solid tumors or bone marrow failure. In conclusion, vitamin D deficiency was observed in one-third of children with newly diagnosed cancer. Bone turnover markers were decreased in children with leukemia, possibly because of the suppression of osteoblasts and osteoclasts by leukemic cells. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid in the development of supportive treatment to reduce the adverse effects of cancer and its treatment.

Association of biochemical markers with bone marrow lesion changes on imaging—data from the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium

BackgroundTo assess the prognostic value of short-term change in biochemical markers as it relates to bone marrow lesions (BMLs) on MRI in knee osteoarthritis (OA) over 24 months and, furthermore, to assess the relationship between biochemical markers involved with tissue turnover and inflammation and BMLs on MRI.MethodsData from the Foundation for the National Institutes of Health OA Biomarkers Consortium within the Osteoarthritis Initiative (n = 600) was analyzed. BMLs were measured according to the MRI Osteoarthritis Knee Score (MOAKS) system (0–3), in 15 knee subregions. Serum and urinary biochemical markers assessed were as follows: serum C-terminal crosslinked telopeptide of type I collagen (CTX-I), serum crosslinked N-telopeptide of type I collagen (NTX-I), urinary CTX-Iα and CTX-Iβ, urinary NTX-I, urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II), serum matrix metalloproteinase (MMP)-degraded type I, II, and III collagen (C1M, C2M, C3M), serum high sensitivity propeptide of type IIb collagen (hsPRO-C2), and matrix metalloproteinase-generated neoepitope of C-reactive protein (CRPM). The association between change in biochemical markers over 12 months and BMLs over 24 months was examined using regression models adjusted for covariates. The relationship between C1M, C2M, C3M, hsPRO-C2, and CRPM and BMLs at baseline and over 24 months was examined.ResultsIncreases in serum CTX-I and urinary CTX-Iβ over 12 months were associated with increased odds of changes in the number of subregions affected by any BML at 24 months. Increase in hsPRO-C2 was associated with decreased odds of worsening in the number of subregions affected by any BML over 24 months. C1M and C3M were associated with BMLs affected at baseline.ConclusionsShort-term changes in serum CTX-I, hsPRO-C2, and urinary CTX-Iβ hold the potential to be prognostic of BML progression on MRI. The association of C1M and C3M with baseline BMLs on MRI warrants further investigation.

Management and Amelioration of Knee Joint Osteoarthritis in Adults Using a Novel High-Functional Bovine Collagen Peptide as a Nutritional Therapy: A Double-Blind, Prospective, Multicentric, Randomized, Active and Placebo Controlled, Five-Arm, Clinical Study to Evaluate the Efficacy, Safety, and Tolerability.

The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional "Wellnex" Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial (n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied. Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician's Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored. Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy. The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.

Fermented calcium butyrate supplementation in post-peak laying hens improved ovarian function and tibia quality through the “gut-bone” axis

The compromised egg quality and leg abnormality during the end of the laying cycle (after 40 weeks) have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium (Ca) butyrate, produced by fermentation by Clostridium butyricum, on production, eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at 50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength (P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet (both P < 0.05). The birds that received fermented Ca butyrate diets exhibited higher villus height (P < 0.05) and upregulated expression of tight junction proteins, whereas it did not alter the composition of cecal microbiota (P > 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker (P < 0.05), whereas it tended to increase the concentration of the procollagen type I N-terminal propeptide that reflects bone formation marker in serum. Moreover, the layers fed fermented Ca butyrate diets possessed higher (P < 0.05) bone area and trabecular number of the proximal tibia, yield load, and ultimate load than those that consumed basal diets. Collectively, dietary fermented Ca butyrate supplementation in post-peak layer diets improved the ovarian function and tibia quality, which might be related to enhancing intestinal integrity and consequently decreasing inflammation mediated bone resorption.

Bone protective effect of sinomenine against monosodium iodoacetate induced knee and hip injury in rat model: an inflammatory pathway.

Osteoarthritis (OA) is a degenerative joint disease which is categorized via destruction of joint cartilage and it also affects the various joints, especially knees and hips. Sinomenine active phytoconstituents isolated from the stem of Sinomenium acutum and already proof anti-inflammatory effect against the arthritis model of rodent. In this experimental protocol, we scrutinized the anti-osteoarthritis effect of sinomenine against monosodium iodoacetate (MIA) induced OA in rats. MIA (3 mg/50 μL) was used for inducing the OA in the rats, and rats received the oral administration of sinomenine (2.5, 5 and 7.5 mg/kg body weight) up to the end of the experimental study (four weeks). The body and organs weight were estimated. Aggrecan, C-terminal cross-linked telopeptide of type II collagen (CTX-II), glycosaminoglycans (GCGs), monocyte chemoattractant protein-1 (MCP-1), Interferon gamma (IFN-γ), antioxidant, inflammatory cytokines, inflammatory mediators and matrix metalloproteinases (MMP) were analyzed. Sinomenine significantly (P < 0.001) boosted the body weight and reduced the heart weight, but the weight of spleen and kidney remain unchanged. Sinomenine significantly (P < 0.001) reduced the level of nitric oxide, MCP-1 and improved the level of aggrecan, IFN-γ and GCGs. Sinomenine remarkably upregulated the level of glutathione, superoxide dismutase and suppressed the level of malonaldehyde. It effectually modulated the level of inflammatory cytokines and inflammatory mediators and significantly (P < 0.001) reduced the level of MMPs, like MMP-1, 2, 3, 9 and 13. Sinomenine is a beneficial active agent for the treatment of OA disease.

Comparing the effects of two different vitamin regimens on bone metabolism for meat ducks at starting phase

Objective Leg problems including lameness and tibial dyschondroplasia (TD) are one of the most important factors affecting health and animal welfare in meat-type poultry, which are considerably impacted by dietary vitamin regimens. The present study was conducted to investigate the effects of dietary vitamin levels on growth performance and tibia quality in 14-d-old meat ducks. Methods One-d-old Cherry Valley meat-type male ducks were allocated to two vitamin regimens for 14 d, which was formulated according to the recommendation of the National Research Council (NRC, 1994) or China Agricultural Industry Standards (NY/T 2122-2012). Each group included 8 replicates with 16 birds per replicate. Results There was no significant difference in the growth performance of ducks, whereas dietary NY/T vitamin supplementation decreased leg abnormalities as compared to the NRC group, along with similar tibia length, perimeter, and the relative weight of tibia. The tibia from the birds that received the NY/T vitamin diet exhibited markedly higher (p < 0.05) ash level, calcium (Ca) content, and bone strength when compared with the bone of NRC vitamin-treated birds. In the tibia proximal end, the increased trabecular area and a number of bone trabeculae were observed in the NY/T vitamin diet (p < 0.05). Moreover, a pronounced increase (p < 0.05) in the serum Ca, alkaline phosphatase activity, and C-terminal cross-linked telopeptide of type I collagen level as the indicators of bone formation were found in NT/T vitamin diet than them in NRC diet. Dietary supplementation with NY/T vitamin regimen also significantly upregulated the relative gene expression of phosphate regulating endopeptidase homolog x linked (Phex), an osteoblastic gene, as compared to the NRC vitamin diet (p < 0.05). However, the concentration of serum bone resorption markers and the transcription of osteoclast-related genes were comparable between the NRC and NY/T vitamin groups (p > 0.05). Conclusion NY/T vitamin diet improved tibia quality and subsequently decreased leg abnormalities in 14-d-old ducks, which was probably linked with the promoted bone formation.

Osteoporosis: Investigations and Monitoring.

Osteoporosis is characterized by microarchitectural disruption of the bone, decrease in bone mineral density, and increased skeletal fragility and risk of fracture. Osteoporosis occurs due to the decoupling of bone formation and bone resorption, with a significant increase in resorption. This review article focuses on the role of laboratory investigations in the diagnosis and monitoring of treatment in patients with osteoporosis. This review article collected literature from various databases using keywords such as 'Laboratory investigations', 'Osteoporosis', 'Diagnosis', 'Monitoring', and 'Bone turnover markers'. Laboratory investigations, including serum calcium, alkaline phosphatase, vitamin D, and parathormone, are commonly performed tests to exclude secondary causes of osteoporosis and monitor the response to therapy. The biochemical markers of bone turnover are newly emerged tests for monitoring individual patients with osteoporosis. These markers are classified as bone formation and resorption markers, measurable in both serum and urine. The use of these markers is limited by biological and analytical variability. The International Federation of Clinical Chemistry and Laboratory Medicine and the International Osteoporosis Foundation recommend serum procollagen type 1 amino-terminal propeptide as the bone formation marker and β-form of C-terminal cross-linked telopeptide of type I collagen (β-CTx-1/β-CrossLaps) as the marker of choice, using standardized procedures. However, in specific cases, such as patients with chronic renal disease, CTx-1 is replaced by the resorption marker tartrate-resistant acid phosphatase 5b, as its levels are not affected by renal excretion. Bone turnover markers have emerged as tools for the assessment of osteoporosis, using standardized procedures, and are useful in monitoring therapy and treatment compliance.

Isolation and Characterization of an Anti-Osteoporotic Compound from Melia toosendan Fructus.

Melia toosendan fructus, traditionally employed in traditional Chinese and Korean herbal medicine, exhibits diverse biological properties encompassing anti-tumor, anti-inflammatory, and anti-viral effects. However, its influence on bone metabolism remains largely unexplored. In this study, we investigated the impact of an ethanolic extract of Melia toosendan fructus (MTE) on osteoclast differentiation and characterized its principal active constituent in osteoclast differentiation and function, as well as its effects on bone protection. Our findings demonstrate that MTE effectively inhibits the differentiation of osteoclast precursors induced by receptor activator of nuclear factor κB ligand (RANKL). Utilizing a bioassay-guided fractionation approach coupled with UHPLC-MS/MS analysis, we isolated and identified the triterpenoid compound toosendanin (TSN) as the active constituent responsible for MTE's anti-osteoclastogenic activity. TSN treatment downregulated the expression of nuclear factor of activated T cells c1, a pivotal osteoclastogenic transcription factor, along with molecules implicated in osteoclast-mediated bone resorption, including tumor necrosis factor receptor-associated factor 6, carbonic anhydrase II, integrin beta-3, and cathepsin K. Furthermore, treatment of mature osteoclasts with TSN impaired actin ring formation, acidification, and resorptive function. Consistent with our in vitro findings, TSN administration mitigated trabecular bone loss and reduced serum levels of the bone resorption marker, C-terminal cross-linked telopeptides of type I collagen, in a mouse bone loss model induced by intraperitoneal injections of RANKL. These results suggest that TSN, as the principal active constituent of MTE with inhibitory effects on osteoclastogenesis, exhibits bone-protective properties by suppressing both osteoclast differentiation and function. These findings imply the potential utility of TSN in the treatment of diseases characterized by excessive bone resorption.

Structural and functional state of bone in patients with arteriovenous malformations of the lower extremities

Background. Disruption of regional blood flow in patients with arteriovenous malformations (AVMs) of the lower extremities changes the conditions of bone tissue functioning. The purpose was to study the structural and functional state of bone tissue and its metabolism in patients with AVMs of the lower extremities using dual-energy X-ray absorptiometry and the markers of bone turnover. Materials and methods. Fifteen patients with AVMs had been examined. The clinical class of chronic venous disease (CVD) was evaluated according to CEAP; patients were divided into 2 subgroups: the first one was with CVD C1-C3 and the second one was with CVD C4-C6. Bone mineral density (BMD) was studied based on the X-ray absorptiometry. The level of bone metabolism markers, such as procollagen type 1 N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (β-CTx) and osteocalcin, 25-hydroxyvitamin D (25(ОН)D) and parathyroid hormone were studied. Results. Disturbances of the bone tissue indices of the affected limb were found in 70 % of the patients. Also, the statistically significant difference in BMD of the affected limb compared to the healthy limb was established (р = 0.005). A multidirectional level of P1NP was detected; β-CTx exceeded norm in 80 % of the patients; osteocalcin exceeded norm in 33 % of the cases. In 67 % of the patients, a decrease in serum level of 25(OH)D was noted. Increase of the β-CTx level in the first subgroup and its decrease in the second one was associated with stabilization of the AVMs course and age-related changes in the hormonal background of the patients. Conclusions. Disturbances in the structural state of bone tissue of the affected limb were found in 70 % of the patients; statistically significant difference between the BMD of the affected and healthy limb obviously caused by the influence of regional hemodynamic disturbances. Various deviations of the metabolism markers were found, which indicates the need to develop a system of drug therapy.