Collagen Telopeptide Research Articles

The Association Between Osteocalcin and Chronic Inflammation in Patients with Type 2 Diabetes Mellitus

Osteocalcin acts as an endocrine hormone to regulate energy homeostasis. Although several in vivo and in vitro studies suggest that osteocalcin is involved in chronic inflammation, the association between osteocalcin and chronic inflammation in humans is unknown. In this cross-sectional study, 246 patients with type 2 diabetes mellitus (T2DM) were recruited to investigate the association of bone turnover markers with chronic inflammation parameters such as high-sensitive C-reactive protein (hsCRP), ferritin, and leukocyte subtype counts. Bone-specific alkaline phosphatase (BAP), total osteocalcin (OC), undercarboxylated OC (ucOC), and urinary N-terminal cross-linked telopeptide of type-I collagen (uNTX) were measured. Multiple regression analysis adjusted for age, duration of diabetes, body mass index, estimated glomerular filtration rate, and hemoglobin A1c showed that serum OC levels were significantly and negatively associated with hsCRP, ferritin, basophil count, and monocyte count (β = - 0.18, p = 0.013; β = - 0.22, p = 0.031; β = - 0.14, p = 0.038; and β = - 0.17, p = 0.012, respectively). Moreover, serum ucOC levels were significantly and negatively associated with hsCRP, ferritin, total leukocyte count, neutrophil count, and monocyte count (β = - 0.24, p = 0.007; β =- 0.37, p = 0.003; β = - 0.21, p = 0.007; β = - 0.24, p = 0.002; and β = - 0.20, p = 0.011, respectively). The ratio of ucOC to OC was significantly and negatively associated with ferritin (β = - 0.31, p = 0.014). However, neither BAP nor uNTX was associated with any chronic inflammation parameters. This is the first study to show that serum OC and ucOC levels were negatively associated with chronic inflammation parameters such as hsCRP, ferritin, and leukocyte subtypes in patients with T2DM. Therefore, OC could be a therapeutic target for protecting against chronic inflammation.

Isosteviol Derivative Inhibits Osteoclast Differentiation and Ameliorates Ovariectomy-Induced Osteoporosis

NC-8 (ent-16-oxobeyeran-19-N-methylureido) is an isosteviol-derived analogue with multiple biological effects, including anti-inflammation and anti-bacterial activities and inhibition of HBV viral surface antigen gene expression. In this study, we explored the effects of NC-8 on the formation of osteoclasts from RAW 264.7 cells. We found that NC-8 exerts the novel effect of inhibiting osteoclast-like cell formation. Our experiments showed that RANKL-induced ERK, p38, and JNK phosphorylation were inhibited by NC-8. An ovariectomy-induced osteoporosis animal model was used to examine the protective effects of oral treatment with NC-8. Serum analysis was used to examine markers of osteoblasts, osteoclasts, and renal and hepatic function in rats. Micro CT scanning and histological analysis were used to measure bone loss in ovariectomized rats. Oral administration of NC-8 effectively decreased excess bone resorption and significantly antagonized trabecular bone loss in ovariectomized rats. Serum analysis of C-terminal telopeptide of type-I collagen, an osteoclast marker, also showed that NC-8 administration inhibited excess bone resorption. Furthermore, serum analysis showed that renal and liver function were not affected by these doses of NC-8 during long-term treatment. Our results demonstrate that NC-8 inhibits osteoclast differentiation and effectively ameliorates ovariectomy-induced osteoporosis.

The Changes of CTX, DPD, Osteocalcin, and Bone Mineral Density During the Postmenopausal Period.

ObjectiveTo investigate appropriate treatment time and useful bone turnover markers (BTMs) for monitoring bone turnover during the postmenopausal period, we analyzed changes of two bone resorption markers; serum carboxyterminal telopeptide of collagen I (s-CTX), urine deoxypyridinoline (u-DPD), one bone formation marker; serum osteocalcin (s-OC), and bone mineral density (BMD) in Korean postmenopausal women.MethodsSeventy-eight menopausal women were divided into three groups according to postmenopausal period: group I (0–5 years), group II (6–10 years), group III (≥10 years). All groups were subdivided into an osteoporosis group (T-score≤-2.5) and a non-osteoporosis group (T-score>-2.5). BTMs such as s-CTX, u-DPD, s-OC, and BMD (g/cm2) were measured by dual-energy X-ray absorptiometry (DXA) in all patients. Analysis of variables among groups based on the postmenopausal period was performed using ANOVA.ResultsThere was significant negative correlation between BMD and postmenopausal period. The levels of all BTMs including s-CTX, u-DPD, and s-OC were highest in group II and the increased levels of all BTMs subsequently declined in group III. The levels of BTMs were higher in the osteoporosis groups than in the non-osteoporosis groups in all subjects. It was statistically significant that the level of s-CTX in group I was higher in the osteoporosis group than in the non-osteoporosis group.ConclusionThis study showed that bone resorption and bone formation were the highest 5–10 years after menopause, and s-CTX is more useful than u-DPD among the bone resorption markers. It’s important to measure serially both BMD and BTM within 10 years after menopause for accurate diagnosis and management for postmenopausal osteoporosis.

Combination therapy with BMP-2 and psoralen enhances fracture healing in ovariectomized mice.

The advantages of combining local delivery of bone morphogenetic protein (BMP)-2 with systemic or local anti-osteoporosis treatments have also been studied for enhancing osteoporotic fracture healing. The aim of the present study was to evaluate the effect of combination therapy with BMP-2 and psoralen on fracture repair in ovariectomized mice. At 6 weeks after bilateral ovariectomy, mice (n=30) underwent unilateral transverse osteotomy on the femur and were divided into 3 groups. In the model group (n=10), animals were implanted with an absorbable collagen sponge (ACS) alone and administered physiological saline intragastrically (i.g.). In the recombinant human (rh)BMP-2 group (n=10), animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered physiological saline i.g. In the psoralen + rhBMP-2 group (n=10) animals were implanted with an ACS loaded with 2.5 µg rhBMP-2 and administered psoralen i.g. The mice were euthanized after 21 days and their fractured femurs were assessed by micro computed tomography, histological analysis and biomechanical testing. Furthermore, the serum of the animals was analyzed. Psoralen + rhBMP-2 exerted more beneficial effects on callus consolidation and biomechanical strength. In addition, increased bone-specific alkaline phosphatase levels and decreased C-terminal telopeptide of type-1 collagen were observed in the Psoralen + rhBMP-2 group. However, no difference in estrogen levels was detected between the groups. In conclusion, the present study demonstrated that in ovariectomized mice, combination of locally delivered BMP-2 and systemically administered psoralen improved bone healing compared with BMP-2 alone.

Performance Assessment of Interdigital Sensor for Varied Coating Thicknesses to Detect CTX-I

Two most important features of a sensor are selectivity and sensitivity. In this paper, the role of the coating thickness on the sensitivity of the planar interdigital sensors has been investigated. The sensor had been coated with two different types of materials: acrylic lacquer as a protective layer and molecular imprinted polymer (MIP) as a selective layer. The performance of the coated-sensor was studied by estimating the sensitivity of the sensor with various coating thicknesses. C-terminal telopeptide of type-I collagen (CTX-I) sample was used for this study. It was concluded that the MIP-coated sensor exhibited more sensitivity compared with the acrylic-coated one for CTX-I measurement. The Dip-coating method was employed to coat the sensor. The effect of the two important parameters, withdrawal speed and immersion time, on the thickness of the coating layer was studied. This investigation concluded that the faster the withdrawal speed, the thicker the coating layer. Moreover, the thickness of the coating layer was increased by increasing the dipping time. However, the results show that increasing the thickness enhances the saturated level. Depending on the application you need to have a trade-off between the saturation level and the sensitivity obtained by varying the coating thickness.

Abstract #550 Use of C-Terminal Telopeptide of Type-I Collagen (CTX) in Clinical Decision-making

Abstract #550 Use of C-Terminal Telopeptide of Type-I Collagen (CTX) in Clinical Decision-making

Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial.

There is increasing recognition that, in men, some biological actions attributed to testosterone (TS) are mediated by estradiol (E2). This study used two low doses of daily transdermal E2 gel to assess the effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen deprivation therapy (ADT). Secondarily, we aimed to assess short-term biological effects of E2 add-back without increasing circulating TS. 28-day randomised, placebo-controlled trial. 37 participants were randomised to either 0.9 or 1.8 mg of 0.1% E2 gel per day or matched placebo gel. Fasting morning serum hormones, quality of life questionnaires, and treatment side effects were evaluated at baseline, days 14 and 28. Hot flush diaries and other biochemical measurements were completed at baseline and study end. Transdermal E2 significantly raised serum E2 from baseline to day 28 compared to placebo in the 0.9 mg dose group (median: 208 pmol/L; interquartile range: 157-332) and in the 1.8 mg dose group (median: 220 pmol/L; interquartile range: 144-660). E2 treatment reduced hot flush frequency and severity as well as beta carboxyl-terminal type 1 collagen telopeptide. In men with castrate levels of E2 and TS, daily transdermal E2: 0.9-1.8 mg increased median serum E2 concentrations into the reference range reported for healthy men, but with substantial variability. E2 treatment reduced hot flushes and bone resorption. Larger studies will be required to test whether low-dose E2 treatment can mitigate ADT-associated adverse effects without E2-related toxicity.

Vitamin D and Calcium Addition during Denosumab Therapy over a Period of Four Years Significantly Improves Lumbar Bone Mineral Density in Japanese Osteoporosis Patients.

This study investigated whether or not vitamin D and calcium supplementation affected bone metabolism and bone mineral density (BMD) over a period of four years of denosumab therapy in patients with primary osteoporosis. Patients were divided into a denosumab monotherapy group (22 cases) or a denosumab plus vitamin D and calcium supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b, urinary N-terminal telopeptide of type-I collagen (NTX), and BMD of the lumbar 1–4 vertebrae (L-BMD) and bilateral hips (H-BMD) at baseline and at 12, 24, 36, and 48 months of treatment. There were no significant differences in patient background. Serum BAP, TRACP-5b, and urinary NTX were significantly and comparably inhibited in both groups from 12 to 48 months versus baseline values. L-BMD was significantly increased at every time point in both groups, while H-BMD was significantly increased at every time point in the combination group only. There were significant differences between the groups for L-BMD at 24, 36, and 48 months (P < 0.05) and for H-BMD at 12 months (P < 0.05). Compared with denosumab monotherapy, combination therapy of denosumab plus vitamin D and calcium significantly increased H-BMD at 12 months and L-BMD from 24 to 48 months. These findings indicate that continuous vitamin D and calcium supplementation is important, especially for 12 months to improve H-BMD and from 24 to 48 months to improve L-BMD.

Circulating Dkk1 and TRAIL Are Associated With Cognitive Decline in Community-Dwelling, Older Adults With Cognitive Concerns.

Osteoporosis and Alzheimer's disease are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The aim of the current study is to investigate the relationship between circulating levels of bone-related biomarkers and cognition. The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18 months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging. Baseline plasma concentrations of bone-related biomarkers, including undercarboxylated, carboxylated, and total osteocalcin, parathyroid hormone, C-terminal telopeptide of collagen 1 (CTX-1), procollagen type 1 amino-terminal propeptide, osteoprotegrin, osteopontin, Dickkopf WNT signaling pathway inhibitor 1 (Dkk1), sclerostin, and amyloid β peptides (Aβ40 and Aβ42), were measured. Using sex, age, and education-adjusted mixed-effects models, we found that baseline levels of TNF-related apoptosis-inducing ligand (TRAIL; p < .001), Dkk1 (p = .014), and CTX-1 (p = .046) were related to the annual rate of change of global cognition over the 18 month follow-up. In cognitive domain-specific analysis, baseline TRAIL was found to be positively related to the annual rate of change in episodic (p < .001) and working memory (p = .016), and baseline Dkk1 was positively related to semantic memory (p = .027) and negatively related to working memory (p = .016). These results further confirm the link between bone and brain health and suggest that circulating levels of bone-related biomarkers may have diagnostic potential to predict worsening cognition.

Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial.

BackgroundAdjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis.MethodsMarkers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided.ResultsWhen considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell’s c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid.ConclusionsSerum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study.

Beneficial effects of natural eggshell membrane versus placebo in exercise-induced joint pain, stiffness, and cartilage turnover in healthy, postmenopausal women.

PurposeDespite its many health benefits, moderate exercise can induce joint discomfort when done infrequently or too intensely even in individuals with healthy joints. This study was designed to evaluate whether NEM® (natural eggshell membrane) would reduce exercise-induced cartilage turnover or alleviate joint pain or stiffness, either directly following exercise or 12 hours post exercise, versus placebo.Patients and methodsSixty healthy, postmenopausal women were randomly assigned to receive either oral NEM 500 mg (n=30) or placebo (n=30) once daily for two consecutive weeks while performing an exercise regimen (50–100 steps per leg) on alternating days. The primary endpoint was any statistically significant reduction in exercise-induced cartilage turnover via the biomarker C-terminal cross-linked telopeptide of type-II collagen (CTX-II) versus placebo, evaluated at 1 and 2 weeks of treatment. Secondary endpoints were any reductions in either exercise-induced joint pain or stiffness versus placebo, evaluated daily via participant questionnaire. The clinical assessment was performed on the per protocol population.ResultsNEM produced a significant absolute treatment effect (TEabs) versus placebo for CTX-II after both 1 week (TEabs −17.2%, P=0.002) and 2 weeks of exercise (TEabs −9.9%, P=0.042). Immediate pain was not significantly different; however, rapid treatment responses were observed for immediate stiffness (Day 7) and recovery pain (Day 8) and recovery stiffness (Day 4). No serious adverse events occurred and the treatment was reported to be well tolerated by study participants.ConclusionNEM rapidly improved recovery from exercise-induced joint pain (Day 8) and stiffness (Day 4) and reduced discomfort immediately following exercise (stiffness, Day 7). Moreover, a substantial chondroprotective effect was demonstrated via a decrease in the cartilage degradation biomarker CTX-II. Clinical Trial Registration number: NCT02751944.

The relationship among serum lipocalin 2, bone turnover markers, and bone mineral density in outpatient women.

We aimed to investigate associations among serum levels of LCN2, bone resorption marker carboxy-terminal cross-linking telopeptide of type-1 collagen (CTx), bone formation marker osteocalcin (OCN), and bone mineral densities (BMDs) in ambulatory healthy women. This cross-sectional study analyzed 1012 previously enrolled outpatient Han Chinese women. BMDs of the lumbar spine and femoral neck were measured using dual energy X-ray absorptiometry. Serum levels of LCN2, CTx, OCN, and creatinine (Scr) were measured. Circulating LCN2 was inversely correlated with BMDs at the lumbar spine and femoral neck (Spearman's r = -0.08, P = 0.010 and r = -0.14, P < 0.001; respectively). A significant positive correlation between LCN2 and CTx (r = 0.11, P < 0.001), OCN (r = 0.06, P = 0.047), age (r = 0.21, P < 0.001), and Scr (r = 0.24, P < 0.001) was also observed. After adjusting for age and Scr, the correlation among LCN2, BMDs and OCN disappeared, but LCN2 was still positively associated with CTx (r = 0.08, P = 0.010). The circulating concentration of LCN2 showed no significant difference between subjects with and without osteoporotic fractures (43.63 (35.29, 53.66) vs. 42.25 (34.43, 51.46) ng/ml, respectively, P = 0.111). Serum CTx concentrations rose with serum LCN2 increasing from the lowest to the highest quartile (P for trend = 0.005), even after adjusting for age and Scr (P for trend = 0.040). In multivariate regression analysis, LCN2 was one of the main determinants for changes in serum CTx (standard β = 0.061, P = 0.005). In ambulatory healthy women, the relationships among serum LCN2 level, BMDs, and OCN were confounded by age and Scr. Although LCN2 was positively related with CTx, the correlation was very weak and may not be physiologically relevant.

Influence of Apelin-13 on osteoporosis in Type-2 diabetes mellitus: A clinical study

Objective:To investigate the relationship between serum level of Apelin-13 and bone mineral density (BMD) as well as other parameters, and determine the influence of Apelin-13 on osteoporosis in patients with Type-2 diabetes mellitus.Methods:Seventy-six patients with Type-2 diabetes mellitus were recruited from Department of Endocrinology of our hospital between January 2013 and July2017. The clinical data, including age, gender, height, weight, body mass index (BMI) and disease duration were recorded for all patients. Blood sample was collected for measurement of Apelin-13, Procollagen type-I N propeptide (PINP) and Cross-linked carboxy terminal telopeptide of type-I collagen (ICTP), and BMD was tested with a dual-energy X-ray absorptiometry scanner.Results:The patients were divided into three groups, in which 19 patients were assigned in osteoporosis group, 25 in osteopenia group and 32 in normal group. The level of Apelin-13 in osteoporosis group was significantly lower than that in osteopenia and normal groups (p<0.05), and the value in osteopenia group was significant lower than that in normal group (p<0.05). Correlation analysis showed in the included patients the level of Apelin-13 was positively correlated to the value of BMD and PINP (p<0.05), but negatively correlated to age and ICTP (p<0.05).Conclusion:In conclusion, this study demonstrated that there was a close relationship among Apelin-13, BMD, ICTP and PINP, and Apelin-13 plays an important role in the occurrence of osteoporosis in patients with Type-2 diabetes mellitus.

Serum 25-hydroxyvitamin D, bone turnover markers and bone mineral density in postmenopausal women with hip fractures

BackgroundVitamin D and bone turnover markers (BTMs) might have an effect on the occurrence of acute hip fracture, while the current results are conflicting. The purpose of this study is to explore the relationship between serum 25(OH)D, bone turnover markers and bone mineral density in Chinese postmenopausal women with hip fracture. MethodsA total of 277 patients with hip fractures and 272 patients without fractures were included in this study. The serum 25(OH)D, bone formation markers, including N-terminal extension propeptide of type-I collagen (P1NP), alkaline phosphatase (ALP) and osteocalcin(OC), bone resorption markers, including C-terminal telopeptide of type-I collagen (CTX-1), and bone mineral density were collected and analyzed. ResultsWomen with hip fractures had significantly lower concentrations of serum 25(OH)D, higher concentrations of serum CTX-1, P1NP and OC, lower concentrations of femoral neck and total hip bone mineral density (P<0.05). After adjustment for age and other confounding factors, multiple logistic regression analysis showed that serum 25(OH)D (OR=0.878, 95%CI=0.855–0.902, P<0.001), CTX-1 (OR=4.884, 95%CI=2.419–9.861, P<0.001)and total hip BMD (OR=0.141, 95%CI=0.034–0.577, P=0.006) were independent risk factors for hip fractures in postmenopausal women. The receiver operating characteristics curves showed that serum 25(OH)D had a good AUC value (0.830). ConclusionsIn this study, lower concentrations of serum 25(OH)D and total hip bone mineral density were widely existed in Chinese postmenopausal women with hip fractures. Furthermore, bone resorption was more active than bone formation in senile postmenopausal women. Therefore, monitoring the alteration of serum CTX-1 in clinically might be useful for fracture prevention.

Connection between bone remodeling and inflammatory markers in obstructive sleep apnea in relation to disease severity: a preliminary study

INTRODUCTION There is growing evidence that obstructive sleep apnea (OSA) influences both bone metabolism and structure. Chitinase‑3‑like protein 1 (YKL‑40) is a novel inflammatory and remodeling marker, the levels of which were shown to increase in OSA. YKL‑40 can probably alter the bone turnover. OBJECTIVES The aim of the study was to assess a possible interplay between YKL‑40 and bone turnover markers in patients with different stages of OSA, and to evaluate the relation between bone mass, severity of OSA, and YKL‑40 levels. PATIENTS AND METHODS The study involved 72 male patients with OSA. They were divided into 3 groups according to disease severity, using the apnea-hypopnea index (AHI): group 1 (n = 18; 5≤ AHI <15), group 2 (n = 25; 15≤ AHI <30), and group 3 (n = 29; AHI ≥30). All patients underwent polysomnography and densitometry. Fasting blood samples were collected for YKL‑40, C‑terminal telopeptide of typeI collagen (CTX), procollagen type 1 N‑terminal propeptide (P1NP), and other markers. RESULTS P1NP differed between groups 1 and 2, as well as groups 1 and 3 (P = 0.02). Group 2 had higher CTX levels than group 1 (borderline significance, P = 0.05). A simple linear regression analysis showed that serum YKL‑40 levels were associated with the levels of CTX (P <0.0001, β = 0.9871) and P1NP (P <0.0001, β = 0.9780). CONCLUSIONS Our study might suggest that YKL‑40 is associated with bone turnover in OSA. We may assume that this marker influences both bone formation and destruction; thus, OSA could be characterized by preserved bone mineral density.

Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment

To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group (18 cases) or a denosumab plus vitamin D supplementation group (combination group; 23 cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density (BMD) of L1–4 lumbar vertebrae (L)-BMD and bilateral hips (H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months (except at 12 months for NTX). In the combination group, TRACP-5b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months (P<0.05). BAP was significantly suppressed in both groups at 2–12 months. L-BMD significantly increased at 8 and 12 months (8.9%) in the combination group and at 4, 8 and 12 months (6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group (3.6%) compared with the denosumab group (1.2%) at 12 months (P<0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD (especially at the hips).

123CMRI-assessed left ventricular extra-cellular volume fraction, not left atrial late gadolinium uptake, is related to higher left atrial pressure and increased type 1 collagen telopeptide levels in pre-ablation AF patients

123CMRI-assessed left ventricular extra-cellular volume fraction, not left atrial late gadolinium uptake, is related to higher left atrial pressure and increased type 1 collagen telopeptide levels in pre-ablation AF patients

Paradoxical elevation of serum TRACP5b levels despite increase in lumbar spine bone mineral density during anti-TNFα therapy in patients with inflammatory rheumatic disease: a 2-year prospective assessment of bone mass, bone metabolism, and the trabecular bone score.

To examine the impact of long-term anti-TNFα therapy on bone mass, bone metabolism, and the trabecular bone score (TBS) in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). In eight patients with RA and 12 with AS, bone mineral densities (BMDs) of the lumbar spine (LS), left and right femoral neck, and total skeleton were measured using dual X-ray absorptiometry at baseline and then at 6, 12, and 24 months after anti TNFα therapy. The TBS was also calculated. At baseline and at 1, 3, 6, 12, 18, and 24 months, bone metabolism was assessed by measurements of pro-collagen-I carboxyterminal propeptide (PICP), osteocalcin, and bone alkaline phosphatase levels in the serum, which are indicative of bone formation and β-isomerized carboxy-terminal telopeptide of type-I collagen (β-CTX-I) and serum isoform 5b of tartrate-resistant acid phosphatase (TRACP5b) levels in the serum, which are indicative of bone resorption. In patients with RA, the LS T-score increased (3.2%, p<0.001) and the TBS progressively decreased (-3.9%, p=0.03). In patients with AS, the LS BMD and T-score increased (4.3% and 6.2%, respectively; p<0.001) with no significant change in the TBS. Serum TRACP5b levels dramatically increased in both groups (227% in patients with RA and 150% in those with AS, p<0.001), while β-CTX-I levels did not change. Serum osteocalcin and PICP levels showed a transitory increase in patients with AS. Long-term anti-TNFα therapy increased LS bone mass and affected bone quality (TBS) with little impact on bone remodeling. Conversely, TRACP5b levels dramatically increased during anti-TNFα therapy but without any detrimental effect on bone mass.

Bone health in long-term gastric cancer survivors: A prospective study of high-dose vitamin D supplementation using an easy administration scheme

Bone disease in long-term survivors after gastric cancer resection has received little research attention. This study aimed to investigate bone health after curative resection of gastric cancer and the consequences of high-dose vitamin D supplementation in patients with low levels of 25-(OH)-vitamin D. Disease-free patients at least 24months after gastric cancer resection represented the study cohort. Serum markers of bone metabolism were assessed at baseline and at 3 and 12months. Bone mineral density and presence of fractures were assessed by X-ray at baseline. Patients with 25-(OH)-vitamin D ≤30ng/mL at baseline received 16,000IU of vitamin D3 every 10days during the 1-year follow-up. Forty patients were included in the study. Mean time from surgery was 48.9 (24-109)months. Vitamin D insufficiency and secondary hyperparathyroidism were observed in 38 and 20 patients, respectively. Densitometry showed osteoporosis in 14 women and seven men and prevalent fractures in 12 women and six men at baseline. After 3months of vitamin D supplementation, 35 patients reached values of 25-(OH)-vitamin D over 30ng/mL. After 12months, 38 patients were in the normal range of 25-(OH)-vitamin D. At the same time, iPTH levels and markers of bone turnover (C-terminal cross-linked telopeptide of type-I collagen, serum concentrations of bone-specific alkaline phosphatase and osteocalcin) significantly decreased after vitamin D intervention. Oral administration of high doses of vitamin D is easily implemented and restored 25-(OH)-vitamin D and iPTH values, which are frequently disturbed after gastric cancer resection.

Effect of pH on dentin protease inactivation by carbodiimide.

A water-soluble crosslinking agent, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), has been used as a pretreatment of acid-etched dentin to inactivate matrix-bound endogenous dentin proteases. The aim of this study was to evaluate the effect of pH on the inactivation capacity of EDC. Demineralized dentin beams (1×2×6mm) were divided into six groups (n=8 per group). Then, EDC (0.3M) was solubilized in distilled water with pH of 2, 4, 6, 7, 9, or 11. Control EDC was solubilized in 0.1M 2-(N-morpholino) ethanesulfonic acid (MES) buffer and its pH was adjusted to 6. The dentin beams were pretreated for 1min with EDC at each pH or with EDC in MES buffer at pH6.0 and then incubated in 1ml of simulated body fluid (pH7.2) for 1, 3, 7, or 14d. Untreated beams served as controls. At each study time-point, the dry mass of dentin beams was assessed and the incubation media were analyzed for carboxyterminal telopeptide of type-I collagen (ICTP) and C-terminal telopeptide of type I collagen (CTX) using specific ELISAs. Data were subjected to repeat-measures anova. The results of the study indicated that specimens pretreated with EDC in MES buffer showed the lowest collagen degradation in terms of mass loss and release of telopeptides, while specimens pretreated in alkaline media showed the highest collagen degradation. This study indicates that the pH of the EDC solution plays an important role in the stability of dentin protease inactivation.