Pyridinoline Research Articles

Effects of isoflavone interventions on bone turnover markers and factors regulating bone metabolism in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

This study aimed to assess the impact of isoflavone interventions on bone turnover markers and various biochemical markers of bone metabolism through systematic review and meta-analysis. Four electronic databases, including PubMed, Embase, Scopus, and Cochrane Library, were searched in September 2023 for investigating the effects of isoflavones on bone turnover markers as well as signaling molecules regulating osteoclast differentiation, bone minerals, and hormones regulating bone metabolism in postmenopausal women. The main effect estimates, obtained using a random-effects model, were summarized using the mean difference (MD) or standardized mean difference (SMD), as appropriate. A total of 73 randomized controlled trials were included, comparing an isoflavone intervention to a placebo. Our findings demonstrated that isoflavone interventions significantly reduced bone resorption markers, that is, β cross-linked C-telopeptide of type 1 collagen (β-CrossLaps) (MD = - 0.0943ng/mL; P = 0.0071) and pyridinoline (PYD) (SMD = - 0.9111; P = 0.0247). Moreover, isoflavone interventions positively affected bone mineral parameters by increasing serum calcium levels (MD = 0.3430mg/dL; P = 0.0267) and decreasing serum phosphorus levels (MD = - 0.0648mg/dL; P = 0.0435). Hormones involved in regulating bone metabolism, particularly insulin-like growth factor type 1 (IGF-1), exhibited significant increases following isoflavone interventions (MD = 9.8163ng/mL; P < 0.0001). Subgroup analysis suggested that the effects of isoflavones on bone turnover markers are influenced by factors such as the duration since menopause and the intervention duration. This systematic review and meta-analysis highlight the potential of isoflavone interventions to rectify imbalances in bone remodeling, enhance bone mineral homeostasis, and optimize hormones regulating bone metabolism in postmenopausal women.

Markers of bone metabolism and overall survival in men with bone-metastatic hormone sensitive prostate cancer (HSPC): A subset analysis of SWOG S1216, a phase III trial of androgen deprivation with or without orteronel.

Circulating biomarkers of bone metabolism are significantly associated with overall survival (OS) in men with advanced prostate cancer. In the SWOG S1216 phase III trial, we showed that elevated bone biomarkers are significantly associated with an increased risk of death in hormone-sensitive prostate cancer (HSPC) regardless of the status of bone metastases, identifying three risk groups with differential OS outcomes based on bone biomarker status. Here we report the association of bone biomarkers with OS in men with HSPC and documented skeletal metastases as part of a planned subset analysis of S1216. Bone resorption [C-telopeptide (CTx); Pyridinoline (PYD)] and bone formation markers [C-terminal collagen propeptide (CICP); bone alkaline phosphatase (BAP)] were assessed in blood from men with bone metastatic HSPC. Patients were randomly divided into training (n = 238) and validation (n = 475) sets. In the training set, recursive partitioning that maximizes discrimination of OS was used to identify the dichotomous cut-point for each biomarker and for a combination of biomarker split points to define prognostic groups. In the validation set, Cox proportional hazards models were used to assess the impact of biomarkers on OS, adjusted for patient and tumor characteristics. Of 1279 men, 713 had both baseline bone metastases and evaluable bone biomarkers. Patient characteristics were similar between the overall population and the subset with bone metastases. Elevated levels of CICP, CTX, and PYD were strongly prognostic for OS. Hazard ratios (95% CI) for OS adjusted for treatment arm and baseline clinical variables were: BAP-1.31 (0.93, 1.84), p = 0.12; CICP-1.58 (1.09, 2.29), p < 0.02; CTx - 1.55 (1.12, 2.15), p = 0.008; and PYD-1.66 (1.27, 2.217), p = 0.0002. There was no evidence of interaction between elevated biomarkers and treatment (all p > 0.2). Recursive partitioning algorithms identified four groups of patients with differential OS outcomes based on bone biomarkers, adjusted for baseline clinical variables, with median OS ranging from 2.3 years (highest risk group) to 7.5 years (lowest risk group). In this planned S1216 subset analysis of men with HSPC and bone metastases, elevated serum markers of bone metabolism were significantly associated with worse OS. Bone biomarker levels alone and in combination with patient and tumor characteristics identify unique subsets of men with differential OS outcomes. NCT01809691.

Textural dynamic crisping mechanism of crisp grass carp: Oxidative stress, apoptosis, collagen filling, and cross‐linking

AbstractFeeding faba beans to freshwater fish could crisp its muscle texture to avoid softening. However, the dynamic crisping mechanism was unclear. Herein, a 120‐day feeding trial was conducted to systemically investigate the textural crisping mechanism of crisp grass carp (CGC) via molecular‐level, gene/protein expression analysis. In the early crisping stage (0–30 days), the total antioxidant capacity significantly decreased (by 16.79%), TUNEL staining and qRT‐PCR results revealed that apoptosis occurred, which was induced by oxidative stress validating by proteomics. Meanwhile, the content of dityrosine and hydroxylysyl pyridinoline rose, thereby substantially increasing the hardness and chewiness of CGC by 37.51% and 40.84%, respectively. With further crisping (30–90 days), Masson staining exhibited collagen gradually filling the gap between myofibrils, the content and cross‐linking degree of collagen further increased, finally elevating the hardness and chewiness of CGC. This study laid a theoretical foundation for producing and supplying aquatic raw materials with different texture characteristics.

Uterine Collagen Cross-Linking: Biology, Role in Disorders, and Therapeutic Implications.

Collagen is an essential constituent of the uterine extracellular matrix that provides biomechanical strength, resilience, structural integrity, and the tensile properties necessary for the normal functioning of the uterus. Cross-linking is a fundamental step in collagen biosynthesis and is critical for its normal biophysical properties. This step occurs enzymatically via lysyl oxidase (LOX) or non-enzymatically with the production of advanced glycation end-products (AGEs). Cross-links found in uterine tissue include the reducible dehydro-dihydroxylysinonorleucine (deH-DHLNL), dehydro-hydroxylysinonorleucine (deH-HLNL), and histidinohydroxymerodesmosine (HHMD); and the non-reducible pyridinoline (PYD), deoxy-pyridinoline (DPD); and a trace of pentosidine (PEN). Collagen cross-links are instrumental for uterine tissue integrity and the continuation of a healthy pregnancy. Decreased cervical cross-link density is observed in preterm birth, whereas increased tissue stiffness caused by increased cross-link density is a pathogenic feature of uterine fibroids. AGEs disrupt embryo development, decidualization, implantation, and trophoblast invasion. Uterine collagen cross-linking regulators include steroid hormones, such as progesterone and estrogen, prostaglandins, proteoglycans, metalloproteinases, lysyl oxidases, nitric oxide, nicotine, and vitamin D. Thus, uterine collagen cross-linking presents an opportunity to design therapeutic targets and warrants further investigation in common uterine disorders, such as uterine fibroids, cervical insufficiency, preterm birth, dystocia, endometriosis, and adenomyosis.

The Effects of Polyphenols on Bone Metabolism in Postmenopausal Women: Systematic Review and Meta-Analysis of Randomized Control Trials.

Osteoporosis is a condition favored by the postmenopausal decline in estrogen levels and worsened by oxidative stress (OS). Polyphenols are natural compounds abundantly found in fruits and vegetables, and they exert antioxidant and hormonal effects that could be useful in osteoporosis prevention, as suggested by epidemiological studies showing a lower incidence of fractures in individuals consuming polyphenol-rich diets. The aim of our meta-analysis is to evaluate the effects of polyphenols on bone mineral density (BMD, primary endpoint) and bone turnover markers (BTMs, secondary endpoint) in postmenopausal women. Twenty-one randomized control trials (RCTs) were included in our analysis after in-depth search on PubMed, EMBASE, and Scopus databases. We found that supplementation with polyphenols for 3-36 months exerted no statically significant effects on BMD measured at lumbar spine (sMD: 0.21, 95% CI [-0.08 to 0.51], p = 0.16), femoral neck (sMD: 0.16, 95% CI [-0.23 to 0.55], p = 0.42), total hip (sMD: 0.05, 95% CI [-0.14 to 0.24], p = 0.61), and whole body (sMD: -0.12, 95% CI [-0.42 to 0.17], p = 0.41). Subgroup analysis based on treatment duration showed no statistical significance, but a significant effect on lumbar BMD emerged when studies with duration of 24 months or greater were analyzed separately. On the other hand, we found a significantly slight increase in bone-specific alkaline phosphatase (BALP) levels (sMD: 1.27, 95% CI [1.13 to 1.42], p < 0.0001) and a decrease in pyridinoline (PD) levels (sMD: -0.58, 95% CI [-0.77 to -0.39], p < 0.0001). High heterogeneity among studies and unclear risk of bias in one third of the included studies emerged. A subgroup analysis showed similar effects for different duration of treatment and models of dual-energy X-ray absorptiometry (DXA) scanner. More robust evidence is needed before recommending the prescription of polyphenols in clinical practice.

Validation of Fourier Transform Infrared Microspectroscopy for the Evaluation of Enzymatic Cross-Linking of Bone Collagen.

Enzymatic cross-linking of the bone collagen is important to resist to crack growth and to increased flexural strength. In the present study, we proposed a new method for assessment of enzymatic cross-link based on Fourier transform infrared (FTIR) microspectroscopy that takes into account secondary structure of type I collagen. Briefly, femurs were collected from sham or ovariectomized mice and subjected either to high-performance liquid chromatography-mass spectrometry or embedded in polymethylmethacrylate, cut and analyzed by FTIR microspectroscopy. FTIR acquisition was recorded before and after ultraviolet (UV) exposure or acid treatment. In addition, femurs from a second animal study were used to compare gene expression of Plod2 and Lox enzymes and enzymatic cross-links determined by FTIR microspectroscopy. We evidenced here that intensities and areas of subbands located at ~1660, ~1680, and ~1690cm-1 were positively and significantly associated with the concentration of pyridinoline (PYD), deoxypyridinoline, or immature dihydroxylysinonorleucine/hydroxylysinonorleucine cross-links. Seventy-two hours exposure to UV light significantly reduced by ~86% and ~89% the intensity and area of the ~1660cm-1 subband. Similarly, 24h of acid treatment significantly reduced by 78% and 76% the intensity and area of the ~1690cm-1 subband. Plod2 and Lox expression were also positively associated to the signal of the ~1660 and ~1690cm-1 subbands. In conclusion, our study provided a new method for decomposing the amide I envelope of bone section that positively correlates with PYD and immature collagen cross-links. This method allows for investigation of tissue distribution of enzymatic cross-links in bone section.

Bone biomarkers and subsequent survival in men with bone-metastatic hormone sensitive prostate cancer (HSPC): Results from the phase III SWOG S1216 trial of androgen deprivation +/- orteronel.

5048 Background: We previously reported that circulating serum biomarkers of bone metabolism were significantly associated with overall survival (OS) in men with advanced prostate cancer, either in the hormone sensitive (Lara, et al. ASCO 2022) or castration resistant state (Lara, et al. JNCI 2016). In S1216, we showed that elevated bone biomarkers were significantly associated with an increased risk of death in HSPC regardless of bone metastases (mets). We also identified three risk groups (low, intermediate, and poor) with differential OS outcomes (median OS: 8.2, 5.1, and 2.1 years, respectively) based on combinations of bone biomarkers in these patients. Here we report the association of bone biomarkers with OS in men with HSPC and documented skeletal mets as part of a planned analysis of S1216. Methods: Bone resorption [C-telopeptide (CTx) and Pyridinoline (PYD)] and bone formation markers [C-terminal collagen propeptide (CICP) and bone alkaline phosphatase (BAP)] were assessed from patient sera. Patients were randomly divided into training (n=238) and validation (n=475) sets. In the training set, recursive partitioning that maximizes discrimination of OS was used to identify the dichotomous cut-point for each biomarker and for a combination of biomarker split points to define prognostic groups. In the validation set, Cox proportional hazards models were used to assess the impact of biomarkers on OS, adjusted for patient and tumor characteristics. Results: Of 1,279 men in S1216, 713 had both baseline bone mets and evaluable bone biomarkers. Patient characteristics were similar between the overall population and the subset with bone mets. Elevated levels of CICP, CTX, and PYD were strongly prognostic for OS, but not for BAP. Hazard ratios (95% CI) for OS adjusted for treatment arm and baseline clinical variables were: BAP – 1.31 (0.93, 1.84), p=0.12; CICP – 1.58 (1.09, 2.29), p&lt;0.02; CTx – 1.55 (1.12, 2.15), p=0.008; and PYD – 1.66 (1.27, 2.217), p=0.0002. There was no evidence of interaction between elevated biomarkers and treatment (all p&gt;0.2). Recursive partitioning algorithms identified four groups of patients with differential OS outcomes based on bone biomarkers, adjusted for baseline clinical variables, with median OS ranging from 2.3 years (highest risk group) to 7.5 years (lowest risk group). Conclusions: In this subset analysis of men with HSPC and bone mets in S1216, elevated serum markers of bone metabolism were significantly associated with worse OS. Bone biomarker levels alone and in combination with patient and tumor characteristics identify unique subsets of men with differential OS outcomes. Clinical trial information: NCT01809691 .

Evaluation of Bone Turnover Markers in Patients with Acute and Chronic Leukemia.

This study investigated different bone biomarkers (cross-linked carboxy-terminal telopeptide of type 1 collagen (CTX-1), pyridinoline (PYD), osteocalcin (OC), interleukin-6 receptor (IL-6R), calcium (Ca), and magnesium (Mg)) in terms of their metabolism in 4 different leukemia subtypes (ALL, AML, CLL and CML). The design was case control study with 30 controls and 60 cases of leukemia patients. Authors have reported many results regarding decrease as well as increase of specific bone biomarker under investigation with each leukemia subtype when compared to control. In addition, Authors reported correlations between each biomarker level and leukemia subtypes.

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 .

Organic Bone Matrix Component Type I and V Collagen Are Not Destructed in Bisphosphonate-Associated Osteonecrosis of the Jaws.

Background and objectives: The investigation of the pathophysiology behind medication-related osteonecrosis (MRONJ) of the jaw mostly focuses on alterations in osteoclast and osteoblast cell activity, but changes in the organic and inorganic bone matrix have rarely been studied. The aim of this study was to investigate whether collagen, the main organic component of extracellular bone matrix, is destructed in osteonecrosis of the jaw secondary to antiresorptive medication. Material and methods: Bone samples of patients with MRONJ (n = 15, control group n = 3) were demineralized, and collagen fragments were separated from intact collagen pellets by ultrafiltration. The quantification of mature collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in pellets and ultrafiltrates was performed by high-performance liquid chromatography (HPLC). The detection of hydroxyproline (Hyp) was carried out using a spectrophotometric assay. In addition, collagen chains were analyzed by sodium dodecylsulfate-polyacrylamide gel (SDS-PAGE). Results: The results revealed significantly higher concentrations of HP, LP and Hyp in pellet samples. In addition, there were no significant differences between samples from MRONJ patients and those of the control group. These results were paralleled by SDS- PAGE. Conclusion: These findings suggest that MRONJ does not involve the destruction of type I and V collagen molecules, in contrast to previously reported destruction by osteoradionecrosis.

Influence of Canadian beef quality grade and method of intramuscular connective tissue isolation on collagen characteristics of the bovine longissimus thoracis

Forty-eight bovine longissimus thoracis (LT) muscles, twelve from each Canada quality grade (Canada A, AA, AAA, and Prime) were used to test the hypotheses that intramuscular total collagen and collagen solubility decreased with increased quality grade and intramuscular fat, and that alkali isolation of intramuscular connective tissue (IMCT) does not reduce Ehrlich Chromogen (EC) or Pyridinoline (PYR) concentrations. Total collagen increased as intramuscular fat increased when estimated using lyophilized meat but did not when estimated using isolated IMCT. Beef quality grades and their concomitant intramuscular fat did not affect collagen heat solubility or mature collagen cross-link concentrations. Use of alkali for IMCT isolation did not degrade EC or PYR collagen cross-links, suggesting it is an excellent method for isolating IMCT for further characterization. The EC cross-link was most related to WBSF in the LT muscles from youthful cattle (< 30 months), confirming that EC is the most influential collagen cross-link on WBSF of low IMCT content muscles when cattle are young.

Immunoblotting identification of jumbo squid (Dosidicus gigas) LOX isoforms and in vitro crosslinking assay over selected collagenous materials

Jumbo squid (Dosidicus gigas) muscle hardness has been related to hydroxylysyl-pyridinoline (HP) formation (collagen fibre stabilization) via condensation of oxidized ε-amino groups of lysine and/or hydroxylysine by lysyl oxidase (LOX). Previously published literature has suggested the presence of LOX isoforms in squid muscle. Thus, the objective of the present research was to test the hypothesis that squid LOX isoforms exist in fresh mantle muscle. A semi-pure LOX extract (SPLE) was used to perform an immunoblotting assay using two commercial human-LOX antibodies. Furthermore, SPLE (specific activity of 20 mU/mg of protein) was tested in vitro for possible HP formation using several collagenous materials. Immunoblotting assay confirmed the presence of squid LOX at 32 kDa and its isoforms at 34 kDa and 24 kDa. Although LOX oxidized ε-amino groups on collagenous materials, no HP formation was detected. However, the latter could promote interesting collagen functional modifications.

The Interpretation of Biochemical Investigations in the Management of Metabolic Bone Disorders

A bone is basically a combination of the organic matrix, inorganic minerals (calcium phosphate), and vitamins that make the structural framework. The two counteracting processes, bone formation and bone resorption, make the bone a metabolically active tissue that undergoes continuous remodeling. The laboratory evaluation of serological and urinary markers is important in the diagnosis of suspected bone disease such as osteoporosis, rickets/osteomalacia, fluorosis, and primary hyperparathyroidism, which are common metabolic bone diseases (MBD), whereas a few rare MBDs include Paget’s disease, fibrous dysplasia, osteogenesis imperfecta, tumor-induced osteomalacia, etc. Calcium and phosphate level in serum and urine reflects the status of metabolism of bone. Markers of one formation include: alkaline phosphatase (ALP), osteocalcin (OCn), and procollagen I peptides: the amino (N-) terminal propeptide (PINP) and the carboxy (C-) terminal propeptide (PICP). Markers of bone resorption include hydroxyproline (OHP), hydroxylysine (HYL), deoxypyridinoline (DPD), pyridinoline (PYD), bone sialoprotein (BSP), osteopontin (OP), tartrate-resistant acid phosphatase 5b (TRAP 5b), carboxy-terminal crosslinked telopeptide of type 1 collagen (CTX-1), amino-terminal crosslinked telopeptide of type 1 collagen (NTX-1), cathepsin K (CTSK), urinary calcium, and acid phosphatase. Novel biochemical markers such as periostin, cathepsins, RANK-L, secreted frizzled-related proteins (sFRP), Wnt inhibitory factor-1 (WIF1), Dickkopfs (Dkk) 1–4, sphingosine-1-phosphate (S1P), sclerostin, fibroblast growth factor (FGF)-23, and miRNA are also the markers of bone metabolism. Biochemical markers of bone metabolism provide a potentially important clinical tool for assessing and monitoring MBD. These markers are quick to appear after any derangement in physiology. Still, we must keep in mind that the characteristics of any marker are at present primarily a function of the assay used for the assessment of the marker. That continued efforts aimed at improving the analysis and interpretation of markers that are known today must continue.

Predictive and Prognostic Biomarkers for Lung Cancer Bone Metastasis and Their Therapeutic Value

Lung cancer is the leading cause of cancer-related death worldwide. Bone metastasis, which usually accompanies severe skeletal-related events, is the most common site for tumor distant dissemination and detected in more than one-third of patients with advanced lung cancer. Biopsy and imaging play critical roles in the diagnosis of bone metastasis; however, these approaches are characterized by evident limitations. Recently, studies regarding potential biomarkers in the serum, urine, and tumor tissue, were performed to predict the bone metastases and prognosis in patients with lung cancer. In this review, we summarize the findings of recent clinical research studies on biomarkers detected in samples obtained from patients with lung cancer bone metastasis. These markers include the following: (1) bone resorption-associated markers, such as N-terminal telopeptide (NTx)/C-terminal telopeptide (CTx), C-terminal telopeptide of type I collagen (CTx-I), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), pyridinoline (PYD), and parathyroid hormone related peptide (PTHrP); (2) bone formation-associated markers, including total serum alkaline phosphatase (ALP)/bone specific alkaline phosphatase(BAP), osteopontin (OP), osteocalcin (OS), amino-terminal extension propeptide of type I procollagen/carboxy-terminal extension propeptide of type I procollagen (PICP/PINP); (3) signaling markers, including epidermal growth factor receptor/Kirsten rat sarcoma/anaplastic lymphoma kinase (EGFR/KRAS/ALK), receptor activator of nuclear factor κB ligand/receptor activator of nuclear factor κB/osteoprotegerin (RANKL/RANK/OPG), C-X-C motif chemokine ligand 12/C-X-C motif chemokine receptor 4 (CXCL12/CXCR4), complement component 5a receptor (C5AR); and (4) other potential markers, such as calcium sensing receptor (CASR), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2), cytokeratin 19 fragment/carcinoembryonic antigen (CYFRA/CEA), tissue factor, cell-free DNA, long non-coding RNA, and microRNA. The prognostic value of these markers is also investigated. Furthermore, we listed some clinical trials targeting hotspot biomarkers in advanced lung cancer referring for their therapeutic effects.

Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases.

Objectives In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern.Patients and methods A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT.Results A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements.Conclusion Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

High-intensity Interval Training Elicits Superior Benefits On Bone Metabolism In Sedentary Young Women

PURPOSE: The objective of the present study was to investigate the effects of 8-week high-intensity interval training (HIIT) on bone metabolism in sedentary college women. METHODS: Twenty-six healthy, sedentary female participants were randomly assigned into either HIIT (n = 13, age 23.2 ± 2.9 yr, weight 59.2 ± 7.2 kg, height 162.9 ± 3.3 cm; 90% VO2max run for 3 min interspersed with 40% VO2max run for 2 min, 6 bouts in one session) or moderate-intensity continuous training (MICT) group (n = 13, age 21.9 ± 1.7 yr, weight 59.3 ± 6.6 kg, height 160.9 ± 4.4 cm; 60% VO2max continuous run for 30 min) with 3 sessions per week for 8 weeks. The bone mineral density (BMD), quantitative ultrasound of the calcaneus (CUS), serum bone turnover markers, jump abilities and body composition were measured pre and post HIIT and MICT interventions. RESULTS: After 8-week interventions, 1) The total body BMD (pre vs post: 0.94 ± 0.05 vs 1.01 ± 0.05, p < 0.01 in HIIT; 0.95 ± 0.05 vs 1.00 ± 0.05 g/cm2, p < 0.01 in MICT), lower limb BMD (1.01 ± 0.08 vs 1.06 ± 0.06, p < 0.01 in HIIT; 1.00 ± 0.08 vs 1.04 ± 0.10 g/cm2, p < 0.01 in MICT), pyridinoline (PYD) (29.93 ± 7.00 vs 25.42 ± 6.79, p < 0.01 in HIIT; 31.64 ± 6.22 vs 25.13 ± 5.39 nmol/L, p < 0.01 in MICT) and %body fat (31.43 ± 5.65 vs 28.85 ± 5.52, p < 0.01 in HIIT; 33.15 ± 4.48 vs 31.48 ± 4.73, p < 0.05 in MICT) were significantly changed without differences between two groups. 2) The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (12.10 ± 2.59 vs 17.19 ± 3.44, p < 0.01 in HIIT; 12.08 ± 2.11 vs 14.80 ± 2.01 ug/L, p < 0.01 in MICT), standing long jump (1.61 ± 0.78 vs 1.77 ± 0.83, p < 0.01 in HIIT; 1.59 ± 0.13 vs 1.65 ± 0.14 m, p < 0.01 in MICT) and vertical jump (2.30 ± 0.05 vs 2.42 ± 0.05, p < 0.01 in HIIT; 2.33 ± 0.04 vs 2.37 ± 0.04 m, p < 0.01 in MICT) were increased in both groups with significantly higher changes in HIIT group (p < 0.05). 3) The calcaneus stiffness index (CSTI) (108.77 ± 10.47 vs 126.38 ± 11.92 %, p < 0.01 in HIIT), calcaneus broadband ultrasound attenuation (CBUA) (121.70 ± 9.47 vs 140.40 ± 9.17 dB/MHz, p < 0.01 in HIIT) and osteocalcin (OC) only significantly increased after HIIT intervention (p < 0.01). CONCLUSIONS: It suggested that 8-week HIIT and MICT intervention could improve BMD and body composition. Compared with similar workload MICT, HIIT elicited superior benefits on bone formation and related jump abilities.

Effects of Soy Isoflavones on Biochemical Markers of Bone Metabolism in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

This systematic review and meta-analysis of randomized controlled trials was performed to more completely assess potential changes in bone turnover marker levels in postmenopausal women during the intake of soy isoflavones. PubMed (Medline) and EMBASE were searched for relevant studies, and their quality was evaluated according to Cochrane criteria. The levels of markers were evaluated in a total of 1114 women who ingested mean daily doses of 98.2 mg (30.9 to 300) of soy isoflavones for 3 to 24 months, in comparison to those of 1081 subjects who used a placebo. Ten, eighteen, eight, and fourteen comparison studies were finally selected for an estimation of the effects on osteocalcin (OC), bone alkaline phosphatase (BAP), pyridinoline (PYD), and deoxypyridinoline (DPD), respectively. A summary of the results of intervention was as follows: 4.16%, 95% CI: −7.72–16.04, p = 0.49 for OC; 5.50%, 95% CI: −3.81–14.82, p = 0.25 for BAP; −12.09%, 95% CI: −25.37–1.20, p = 0.07 for PYD; and −7.48%, 95% CI: −15.37–0.41, p = 0.06 for DPD. The meta-analysis of the included studies revealed some statistically insignificant observations that soy isoflavones intake is associated with a trend in increased levels of OC and BAP, as well as a trend in reduced levels of PYD and DPD. Soy isoflavones may have a beneficial effect on bone formation markers, but this requires extensive multi-center research.

Biochemical Factors Affecting East Asian Consumers’ Sensory Preferences of Six Beef Shank Cuts

The objective of this study was to evaluate biochemical factors affecting Warner-Bratzler shear force (WBSF) and East Asian consumers’ eating preferences of 6 different beef shank cuts cooked by moist heat. Six different beef shank muscles were collected from 12 USDA Choice beef carcasses (N = 72). Shank cuts from the left sides were cooked with moist heat and used for East Asian consumer sensory evaluation and WBSF, and shank cuts from the right sides were left uncooked and used for biochemical analysis and visual panels utilizing the same group of consumers. A correlation analysis was conducted to determine the driving factors that contributed to WBSF and East Asian consumers’ overall liking for beef shanks. Biceps brachii and flexor digitorum superficialis-pelvic received the greatest sensory overall liking, with deep digital flexor from the foreshank having the lowest scores (P &amp;lt; 0.01). Deep digital flexor from the foreshank had the greatest WBSF value, most cooked collagen content, and greatest insoluble collagen percentage as well as the greatest raw and cooked pyridinoline (PYD) densities among all the beef shank cuts (P &amp;lt; 0.05). For visual overall liking, shank cuts at approximately 700–750 g such as biceps brachii and extensor carpi radialis received the highest ratings (P &amp;lt; 0.01), and consumers indicated that there was no visual difference in surface color among the shank cuts (P &amp;gt; 0.10). Correlation analysis showed that cooked collagen content and insoluble collagen percentage as well as raw PYD densities had positive correlations with WBSF (P &amp;lt; 0.05) and negative correlations with consumer overall liking (P &amp;lt; 0.01). Surprisingly, collagen content from uncooked shank cuts did not have a direct relationship with consumers’ overall liking nor with WBSF. The results demonstrated that raw PYD density may be a great indicator for cooked beef tenderness in beef cuts with a high concentration of connective tissue prepared with moist heat cookery.

A floppy infant without lingual frenulum and kyphoscoliosis: Ehlers Danlos syndrome case report

BackgroundEhlers-Danlos syndrome (EDS) represents a group of connective tissue disorders characterized by the fragility of the soft connective tissues resulting in widespread skin, ligament, joint, blood vessel and internal organ involvement. The clinical spectrum is highly variable in terms of clinical features, complications, severity, biochemical characteristics and genes mutations.The kyphoscoliotic type EDS (EDS VIA) is a rare variant of the disease, with an incidence of 1:100.000 live births. EDS VIA presents at birth as severe muscular hypotonia, early onset of progressive kyphoscoliosis, marked hyperelasticity and fragility of the skin with abnormal scarring, severe joint hypermobility, luxations and osteopenia without a tendency to fractures. This condition is due to a mutation in the PLOD1 gene, and less commonly in FKBP14 gene, which results in the erroneous development of collagen molecules with consequent mechanical instability of the affected tissue.Case presentationA female newborn, found to be floppy at birth, presented a remarkable physical examination for joint hypermobility, muscle weakness, hyperelastic skin, a slight curve of the spine, the absence of the inferior labial and lingual frenulum. Due to severe hypotonia, neuromuscular disorders such as Spinal Muscular Atrophy (SMA), genetic diseases such as Prader Willi syndrome (PWS), myopathies and connective tissue disorders were considered in the differential diagnosis. Targeted gene sequencing were performed for SMN1, PLOD1, FKBP14, COL6A1, COL6A2, COL6A3. The urinary lysyl and hydroxy-lysyl pyridinoline ratio was diagnostic before discovering the homozygous duplication in the PLOD1 gene, which confirmed kyphoscoliotic EDS diagnosis.ConclusionIn front of a floppy infant, a large variety of disorders should be considered, including some connective diseases. The presence at the birth of kyphoscoliosis, associated with joint hypermobility and the absence of the lingual and lower lip frenulum, should suggest an EDS.

Serum changes in pyridinoline, type II collagen cleavage neoepitope and osteocalcin in early stage male brucellosis patients

Musculoskeletal changes are the most common clinical manifestation of brucellosis. The main objective of this study was to provide a better understanding of this disease, while also attempting to identify potential markers that can identify the early stage musculoskeletal changes associated with human brucellosis. In this case–control study, 41 male early-stage brucellosis patients (within 6 months of diagnosis) who had not received drug therapy and 44 matched controls were examined. Venous blood samples were collected and serum pyridinoline (PYD), type II collagen cleavage neoepitope (C2C) and osteocalcin (OC) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). In the brucellosis group, the median serum levels of PYD (278.53 µg/L), C2C (82.23 µg/L) and OC (8.41 µg/L) were significantly elevated relative to the control group (Z = 5.686, 3.997, 3.579; P = 0.000). Serum PYD, C2C, and OC levels were increased in early-stage male brucellosis patients, and these factors appear to have promise as potential indicator biomarkers that can reflect the osteoarticular changes that occur in the early stage of human brucellosis.