Collagen C-terminal Telopeptide Research Articles

Biochemical predictors of cartilaginous tissue metabolic disorders for early osteoarthrosis evidence diagnostics.

The complete laboratory and clinical instrumental examination was conducted, it included serum COMP test, circadian excretion of type II collagen C-terminal telopeptides Urine CartiLaps (СТХ II) and Т2 relaxometry in 29 patients of both sexes of the main group with early (0-I) X-ray osteoarthrosis stages, 30 subjects of comparison group with no X-ray osteoarthrosis evidences aged 44.7±5.9 years and 25 healthy subjects aged 26.3±2.6 years of the control group. The increase (р<0,05) of COMP and Urine CartiLaps levels as well as the increase of Т2 relaxation signal was found at early osteoarthrosis evidences. It was proven that there was (р<0.01) a connection (R=0.8) between COMP and Urine CTX II levels as well as (р<0.05) results of Т2 relaxometry (R=0.8). It was proven that collagen anisotropy and formation of chondromalacia areas as Т2 relaxometry showed in patients with early OA evidences were connected with accumulation of serum COMP and increase of type II collagen circadian renal excretion. The combination of laboratory and radiological methods of articular hyaline cartilage assessment may be used for finding early osteoarthrosis stages.

Biological variation in serum bone turnover markers

Background Serum total N-terminal propeptide of type I collagen (P1NP) and serum C-terminal telopeptide of type I collagen (CTX) are used as reference analytes of bone turnover in clinical application. Biological variation is important for clinical application of these biomarkers. However, the biological variation data of these biomarkers are not consistent. The present study determined biological variations of total P1NP and CTX and their confidence intervals in China using electrochemiluminescence. Methods We collected samples from 25 healthy individuals (17 women and 8 men, ranging from 22 to 49 years of age) at weekly intervals for six weeks. Samples were analysed in a single run in duplicate. Biological variations and their related parameters, such as reference change value and index of individuality (II) were calculated. The results were compared with individual studies in the EFLM database. Results Within-subject and between-subject biological variations were 8.0% and 32.5% for total P1NP and 11.4% and 38.7% for CTX, respectively. The index of individuality for total P1NP and CTX was 0.25 and 0.30, while the reference change value for P1NP values and CTX was 22.4% and 31.9%, respectively. Conclusions No difference was found in weekly biological variation of bone turnover markers between men and premenopausal women. Compared with daily and monthly variation, the present study based on weekly variation provided additional support for clinical application.

Effects of maternal intake restriction during early pregnancy on fetal growth and bone metabolism in goats

• Effect of maternal intake restriction on bone metabolism of goats was investigated. • Maternal intake restriction during early gestation decreased the INTP and CTX-1 in fetal umbilical blood. • Nutritional restriction during early gestion regulated the femur metabolic activity of fetal goats. The objective of this study was to investigate the effects of maternal nutritional restriction on fetal growth and bone metabolism in early pregnancy. Twelve twin-bearing goats (Xiangdong black goats) in second pregnancy, with similar weight (31.2 ± 8.1 kg) and age (2.0 ± 0.3 year) were assigned to two dietary treatments in early gestation (26–65 days): control group (CON, 100% feed) and intake restriction group (IR, 60% of CON intake). The umbilical blood, right femur and liver of the fetuses were sampled on day 65 to determine the bone metabolism indicators and expression of genes involved in bone development. Maternal intake restriction did not affect the growth performance of pregnancies ( P > 0.05), increased ( P < 0.05) the body weight, body length, thoracic circumference and umbilical circumference of fetal goats, but decreased ( P < 0.05) the concentrations of cross-linked N-terminal telopeptides of type I collagen and cross-linked C-terminal telopeptides of type I collagen, which involved in bone metabolic activity, in the fetal umbilical blood of the IR. In fetal femurs, the mRNA expression of bone gamma-carboxyglutamate protein, osteoprotegerin and mothers against decapentaplegic homolog 1 both participating in osteoclast differentiation were increased ( P < 0.05), whereas transcript of the low density lipoprotein receptor related protein 5 involved in osteoblast differentiation was decreased ( P < 0.05), compared with the fetuses from the CON. These results indicate that nutrition restriction in early pregnancy regulated the fetal growth and promoted formative activity of femur. The molecular mechanism of maternal intake restriction on bone metabolism needs further investigation.

Antiretroviral Therapy-Induced Bone Loss Is Durably Suppressed by a Single Dose of Zoledronic Acid in Treatment-Naive Persons with Human Immunodeficiency Virus Infection: A Phase IIB Trial.

Human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are associated with bone loss leading to increased fracture rate among persons with HIV (PWH). We previously showed long-acting antiresorptive zoledronic acid (ZOL) prevented ART-induced bone loss through 48 weeks of therapy and here investigate whether protection persisted. We randomized 63 nonosteoporotic, treatment-naive adult PWH initiating ART to ZOL (5 mg) versus placebo in a double-blinded, placebo-controlled, phase IIb trial. Here we analyzed the long-term outcome data (144 weeks). Plasma bone turnover markers and bone mineral density (BMD) were quantified at weeks 0, 12, 24, 48, 96, and 144. Primary outcome was change in bone resorption marker C-terminal telopeptide of collagen (CTx). Repeated-measures analyses using mixed linear models were used to estimate and compare study endpoints. At 96 weeks, mean CTx was 62% lower with ZOL relative to placebo (n = 46; CTx = 0.123 vs 0.324 ng/mL; P < .001); at 144 weeks a 25% difference between arms was not statistically significant. At 48 weeks, lumbar spine BMD with ZOL was 11% higher than placebo (n = 60; P < .001) and remained 9-11% higher at 96 (n = 46) and 144 (n = 41; P < .001) weeks. 144 weeks after ZOL infusion, BMD did not change at the lumbar spine (P = .22) but declined at the hip (P = .04) and femoral neck (P = .02). A single dose of ZOL administered at ART initiation blunts bone resorption and BMD loss at key fracture-prone anatomical sites in treatment-naive PWH for 3 years. A multicenter randomized phase III clinical trial validating these results in a larger population is needed. NCT01228318.

Monocyte Chemoattractant Protein-1-Induced Protein in Age-Related Atrial Fibrillation and Its Association with Circulating Fibrosis Biomarkers

Background: Atrial fibrillation (AF), for which age is an independent risk factor, is the most common persistent arrhythmia. Monocyte chemoattractant protein-1-induced protein (MCPIP), a transcription factor that induces a series of inflammation and cell death procedures, has been indicated to cause cardiomyocyte death in ischemic cardiomyopathy. The objective of this research was to investigate the relationship between age-related AF and MCPIP. Methods: A total of 1,084 participants were included in this study, including 542 AF patients and 542 non-AF controls. Their medical histories were collected and analyzed. Moreover, blood samples were collected, and ELISA tests for expression of the inflammatory factor MCPIP and the fibrosis biomarkers pro-collagen type III N-terminal peptide (PIIINP) and type I collagen C-terminal telopeptide (ICTP) were conducted. Finally, a correlation analysis of these inflammatory factors and biomarkers was performed based on the ELISA results. Results: We compared the echocardiography results of AF patients and found that the left ventricular ejection fraction and left atrial appendage velocity decreased with age (p < 0.05). Moreover, ELISA analysis of these samples showed that the expression of MCPIP was the highest in elderly patients with AF (p < 0.05), and there was no significant difference in expression between adult AF patients and elderly controls (p > 0.05). Finally, the correlation analysis demonstrated that the expressions of MCPIP, PIIINP, and ICTP were positively correlated in the elderly AF patient group, the adult AF group, and the elderly control group (p < 0.05). Conclusion: MCPIP expression was higher in age-related AF than in the other patient groups and it was associated with AF-induced fibrosis.

Docosahexaenoic Acid Inhibits Inflammation-Induced Osteoclast Formation and Bone Resorption in vivo Through GPR120 by Inhibiting TNF-α Production in Macrophages and Directly Inhibiting Osteoclast Formation.

Docosahexaenoic acid (DHA) is an n-3 fatty acid that is an important structural component of the cell membrane. DHA exerts potent anti-inflammatory effects through G protein-coupled receptor 120 (GPR120), which is a functional receptor for n-3 fatty acids. DHA also regulates osteoclast formation and function. However, no studies have investigated the effect of DHA on inflammation-induced osteoclast formation in vivo. In the present study, we investigated whether DHA influences osteoclast formation, bone resorption and the expression of osteoclast-associated cytokines during lipopolysaccharide (LPS)-induced inflammation in vivo, and then we elucidated the underlying mechanisms by using in vitro experiments. In vitro experiments revealed both receptor activator of NF-kB ligand (RANKL)- and tumor necrosis factor-α (TNF-α)-induced osteoclast formation was inhibited by DHA. Supracalvarial administration of LPS with or without DHA was carried out for 5 days and then the number of osteoclasts, ratio of bone resorption pits and the level of type I collagen C-terminal cross-linked telopeptide were measured. All measurements were significantly lower in LPS+DHA-co-administered mice than LPS-administered mice. However, this DHA-induced inhibition was not observed in LPS-, DHA-, and selective GPR120 antagonist AH7614-co-administered mice. Furthermore, the expression of RANKL and TNF-α mRNAs was lower in the LPS+DHA-co-administered group than in the LPS-administered group in vivo. TNF-α mRNA levels were decreased in macrophages co-treated with LPS+DHA compared with cells treated with LPS in vitro. In contrast, RANKL mRNA expression levels from osteoblasts co-treated with DHA and LPS in vitro were equal to that in cells treated with LPS alone. Finally, the inhibitory effects of DHA on osteoclast formation in vitro were not observed by using osteoclast precursors from GPR120-deficient mice, and inhibition of LPS-induced osteoclast formation and bone resorption by DHA in vivo was not observed in GPR120-deficient mice. These results suggest that DHA inhibits LPS-induced osteoclast formation and bone resorption in vivo via GPR120 by inhibiting LPS-induced TNF-α production in macrophages along with direct inhibition of osteoclast formation.

3159 Bone Turnover Biomarkers May Discriminate Low Bone Mineral Density in HIV-Infected Adults

OBJECTIVES/SPECIFIC AIMS: Persons living with HIV (PLWH) are at increased risk for fragility bone disease. Current osteoporosis screening guidelines do not account for HIV status, and clinical risk assessment tools are not sensitive in PLWH. We examined the value of traditional osteoporosis risk factors, HIV-specific indices, and bone turnover biomarkers in predicting low bone mineral density (BMD) in PLWH. METHODS/STUDY POPULATION: Demographic and clinical characteristics, dual energy x-ray absorptiometry (DXA)-derived BMD, HIV indices (viral load, CD4 count, antiretroviral therapy [ART]), and biomarkers of bone turnover (C-terminal telopeptide of collagen [CTx], osteocalcin [OCN]) were evaluated in a cross-sectional analysis of PLWH (n=248) and HIV- controls (n=183). The primary outcome was low BMD, defined as osteopenia or osteoporosis by WHO criteria. Multivariable logistic and modified Poisson regression models were used to assess associations between low BMD and covariates of interest. RESULTS/ANTICIPATED RESULTS: Overall, median age was 44 years, 48% were male, 88% were black, median body mass index (BMI) was 28 kg/m2, 72% smoked cigarettes, and 53% used alcohol; characteristics did not differ by HIV status. PLWH had a mean CD4 of 408 cells/mm3, 55% were ART-naïve, and 45% had viral suppression on ART. Overall, 25% (109/431) had low BMD, including 31% of PLWH compared to 16% of HIV- controls. In multivariable models, HIV was significantly associated with low BMD (aOR 2.46, 95%CI 1.39-4.34; aRR 1.90, 95%CI 1.18-3.07). Adjusting for HIV, three traditional risks– age, race, and BMI– were independently associated with low BMD in the full cohort. However, bone turnover markers, CTx and OCN, were better able to discriminate low vs. normal BMD in PLWH compared to HIV- controls. In PLWH, mean serum CTx was 23% higher in low vs. normal BMD (mean CTx difference=0.06 ug/mL); in HIV- controls, no association with BMD was observed (mean CTx difference=0 ug/mL). In PLWH, mean serum OCN was 38% higher in those with low vs. normal BMD (mean OCN difference=2.48 ug/mL); in HIV- controls, mean serum OCN was only 16% higher in those with low vs. normal BMD (mean OCN difference=1.08 ug/mL). DISCUSSION/SIGNIFICANCE OF IMPACT: In PLWH as opposed to HIV- controls, serum biomarkers reflecting a high bone turnover state, may discriminate individuals with low versus normal BMD. Because changes in biomarkers precede changes in BMD, these markers should be explored further either alone or in combination with traditional risk assessment tools to improve early screening for osteoporosis in PLWH.

Bone metabolism markers are associated with neck circumference in adult Arab women.

Body fat distribution is associated with decreased bone resorption and neck circumference (NC), a surrogate measure for upper body fat, has never been tested as a marker that can reflect bone turnover. This is the first study aimed to analyze the associations between NC and several bone biomarkers among adult Saudi women. This cross-sectional study included a total of 265 middle-aged Saudi women [86 non-obese (mean age 52.7 ± 8.1; mean BMI 26.9 ± 2.3) and 179 obese (mean age 50.6 ± 7.5; mean BMI 35.7 ± 4.5)] recruited from primary care centers in Riyadh, Saudi Arabia. Anthropometrics included BMI, NC, waist and hip circumferences, total body fat percentage (%), and blood pressure. Biochemical parameters included glucose and lipid profile which were measured routinely. Serum levels of 25(OH) D, parathyroid hormone, RANKl, sclerostin, C-terminal telopeptide of collagen I (CTX-I), Dkk1, IL1β, osteoprotegerin, osteopontin, and osteocalcin were measured using commercially available assays. In all groups, NC was inversely associated with PTH (R = - 0.22; p < 0.05) and positively associated with osteoprotegerin (R = 0.20; p < 0.05) even after adjustments for age and BMI. Using all anthropometric indices as independent variables showed that only NC explained the variance perceived in CTX-I (p= 0.049). In the non-obese, waist-hip ratio (WHR) was significantly associated with sclerostin (R = 0.40; p < 0.05) and body fat was significantly associated with osteopontin (R = 0.42; p < 0.05). NC is modestly but significantly associated with bone biomarkers, particularly the bone resorption markers, among adult Arab women. The present findings highlight the importance of NC as measure of upper body subcutaneous fat in influencing bone biomarker expression in adult females.

Longitudinal 5-Year Evaluation of Bone Density and Microarchitecture After Roux-en-Y Gastric Bypass Surgery.

Bone health declines in the initial years after Roux-en-Y gastric bypass (RYGB), but long-term skeletal effects are unclear. To document longitudinal changes in bone mineral density (BMD) and microarchitecture 5 years after RYGB. Prospective 5-year observational study of 21 adults with severe obesity receiving RYGB at an academic medical center. Spine and hip areal BMD were measured by dual-energy X-ray absorptiometry, and trabecular volumetric BMD (vBMD) of the spine was assessed by quantitative CT (QCT). We measured vBMD and microarchitecture of the distal radius and tibia by high-resolution peripheral QCT in a subset of subjects. Serum type I collagen C-terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (P1NP) were also measured. Areal BMD declined by -7.8% ± 7.6% at the spine and -15.3% ± 6.3% at the total hip by 5 years after RYGB (P ≤ 0.001), although the rate of bone loss slowed in later years. Trabecular spine vBMD decreased by -12.1% ± 12.3% by 5 years (P ≤ 0.001). At peripheral sites, vBMD continued to decrease steadily throughout 5 years, with parallel declines in cortical and trabecular microarchitecture, leading to decreases in estimated failure load of -20% and -13% at the radius and tibia, respectively (P < 0.001). Five years after RYGB, CTX and P1NP were 150% and 34% above baseline (P < 0.001 and P = 0.017, respectively). Sustained high-turnover bone loss and bone microarchitectural deterioration occur in the 5 years after RYGB. Adults receiving RYGB warrant assessment of bone health.

Immediate implant placement following 1-year treatment with oral versus intravenous bisphosphonates: a histomorphometric canine study on peri-implant bone.

Bisphosphonates (BPs) are anti-resorptive medications with inhibitory effects on osteoclasts which decrease bone turnover. The present study aimed to assess the early effects of BPs on peri-implant bone. Twelve female mongrel dogs were assigned to one control and two experimental groups as follows: 12months of oral alendronate (ALN, 3.5mg/kg/week) or intravenous (IV) pamidronate (PAM, 1mg/kg/week) for experimental groups. Following 8weeks after implant insertion, the specimens were sacrificed, histological evaluation was performed, and C-terminal telopeptide of collagen I (CTx) analysis was performed on serums. PAM demonstrated the greatest marginal bone level (MBL), 2.64 ± 0.48, followed by ALN and control, 2.5 ± 0.4 and 0.66 ± 0.5 respectively. The least bone-implant contact was observed in PAM group (%39 ± 0.03) while it was significantly greater in the control group (p < 0.05). PAM and ALN demonstrated < 10 CTx levels versus > 300 in controls. It is assumed that long-term oral or IV BP therapy decreases marginal bone resorption and osseointegration. These changes were more accentuated in IV BP administration. CTx does not seem to be a precise predictor for bisphosphonate-related osteonecrosis of the jaw. BPs impair peri-implant bone remodeling and this phenomena may be effective for reducing resorption at esthetic zone implants; however, decrease in osseointegration may be a concern for implant treatment in patients receiving BPs.

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.

Hyperglycemia is associated with increased bone mineral density and decreased trabecular bone score in elderly Japanese men: The Fujiwara-kyo osteoporosis risk in men (FORMEN) study

PurposePatients with type 2 diabetes mellitus (T2DM) have an increased fracture risk despite having higher areal bone mineral density (aBMD). This study aimed to clarify the association between glycemic and insulin resistance status and bone microarchitecture, and whether pentosidine and bone turnover markers play any roles in the association. MethodsA total of 2012 community-dwelling men aged ≥65years completed baseline measurements of spine aBMD, fasting plasma glucose (FPG) and serum insulin, hemoglobin A1c (HbA1c), osteocalcin, type I procollagen N-terminal propeptide, type I collagen C-terminal crosslinking telopeptide, tartrate-resistant acid phosphatase isoenzyme 5b, pentosidine, height and weight and an interview regarding past disease history. Homeostasis model assessment-insulin resistance (HOMA-IR) was also calculated. T2DM was defined as physician-diagnosed middle age or elderly-onset diabetes mellitus, or according to biochemical test results. To evaluate bone microarchitecture, trabecular bone score (TBS) was calculated at the same vertebrae as those used for aBMD measurement. ResultsAfter excluding participants who had a disease history and/or were taking medications affecting bone metabolism, 1683 men (age, 72.9±5.2years) were analyzed. Men with T2DM had significantly higher aBMD compared to those without T2DM. There was no significant difference in TBS. However, FPG, HbA1c and HOMA-IR levels were significantly inversely correlated with TBS after adjusting for age, BMI and aBMD. Multivariate linear regression analyses revealed that glycemic indices (FPG and HbA1c) were significantly associated with increased aBMD and decreased TBS, and that HOMA-IR was associated only with TBS. These associations did not change after further adjusting for bone turnover makers and pentosidine levels. ConclusionsHyperglycemia and elevated insulin-resistance were associated with low TBS independently of bone turnover and pentosidine levels.

Interrelationship of clinical, radiographic and haematological features in patients under bisphosphonate therapy.

To analyze the clinical, radiographic and haematological aspects of patients under bisphosphonate therapy. A retrospective study was conducted where the records of patients taking bisphosphonates were analyzed considering the occurrence of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Evaluation included panoramic and periapical radiographies, haematological examinations and clinical features. Radiographies were analyzed determining the presence or absence of bone sclerosis, osteolysis, persisting alveolar socket, narrowing of the mandibular canal, widening of the periodontal ligament space, periradicular radiolucency, sequestrum and thickening of the lamina dura. Laboratory tests consisted of complete blood count, fasting serum glucose, erythrocyte sedimentation rate (ESR) and serum levels of calcium, phosphorus, alkaline phosphatase, parathormone (PTH) and C-terminal telopeptide of collagen I (CTX). Alkaline phosphatase and ESR were significantly higher in the BRONJ group, whereas fasting serum glucose, CTX, PTH, calcium and phosphorus did not significantly differ. BRONJ showed association with smoking, tooth extraction, anaemia and leukocytosis. On radiographic analysis, persisting alveolar socket, osteolysis, bone sclerosis and narrowing of the mandibular canal were significantly more prevalent in the BRONJ group. Thickening of the lamina dura, periapical radiolucencies, widening of the periodontal ligament space and sequestrum did not significantly differ between the groups. BRONJ is a multifactorial disease with high morbidity, which requires experimental studies to clarify the role of the reported risk factors and clinical radiographic signs to improve its diagnosis.

Monthly Oral Ibandronate Reduces Bone Loss in Korean Women With Rheumatoid Arthritis and Osteopenia Receiving Long-term Glucocorticoids: A 48-week Double-blinded Randomized Placebo-controlled Investigator-initiated Trial

PurposeOur aim was to investigate the efficacy of monthly oral ibandronate in Korean women with rheumatoid arthritis and reduced bone mineral density (BMD) receiving long-term glucocorticoids. MethodsPatients (n = 167 women) were randomly assigned (1:1) to receive ibandronate 150 mg or placebo every 4 weeks. Patients had taken glucocorticoid (equivalent of daily prednisolone ≥5 mg) for 3 or more consecutive months before enrollment, and had a lumbar spine 1 to 4 (L1–L4) T-score of < −1.0 and ≥ −2.5. Both groups were provided with daily calcium carbonate and cholecalciferol. The primary end point was the L1 to L4 BMD percent changes at 48 weeks compared with baseline. FindingsBaseline characteristics were comparable between the 2 groups. BMD percent changes in L1 to L4 at 48 weeks were significantly different between the ibandronate versus the placebo group (+3.7% [5.1%] vs −1.9% [4.4%], respectively; P < 0.0001). BMD percent changes at 48 weeks in femur neck and total hip also had similar results (P = 0.0073 and P = 0.0031, respectively). Decrease of serum type 1 collagen C-terminal telopeptide was significant at both 24 and 48 weeks in the ibandronate group. There was no incident of fragility fracture in both groups during the study period. Safety profiles, including adverse events, were comparable between the 2 groups. ImplicationsMonthly oral ibandronate for 48 weeks is well tolerated and effective in reducing bone mineral loss in women with rheumatoid arthritis on long-term glucocorticoid therapy. Longer follow-up studies are needed to investigate the benefit of ibandronate on fracture rate reduction in this subset of patients. ClinicalTrials.gov identifier: NCT01287533.

Physical activity may be a potent regulator of bone turnover biomarkers in healthy girls during preadolescence.

This study investigated the effects of different levels of habitual physical activity (PA) assessed by pedometry on bone turnover markers of preadolescent girls according to a cross-sectional experimental design. Sixty prepubertal girls of similar chronological age, bone age, maturity level, and nutritional status were assigned to a low PA (LPA; n=25), a moderate PA (MPA; n=17), or a high PA (HPA; n=18) group. Dual-energy X-ray absorptiometry was used to measure areal bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine (L2-L4) and dominant hip (femoral neck and trochanter). Blood was collected for the measurement of alkaline phosphatase (ALP), bone-specific ALP (BSAP), procollagen typeIN-terminal propeptide (PINP), C-terminal telopeptide of collagen I (CTX), parathyroid hormone (PTH), osteocalcin, thyroid-stimulating hormone, estradiol, testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. ANOVA revealed that the HPA group (18,695±1244 steps per day) had a lower daily energy intake and body mass than the MPA group (10,774±521steps per day) and the LPA group (7633±1099 steps per day). The HPA group had higher (P<0.05) lumbar and hip BMD and hip BMC than the LPA group and higher (P<0.05) lumbar BMD than the MPA group. The MPA group had higher (P<0.05) hip BMC than the LPA group. The HPA group had greater (P<0.05) values of BSAP, PINP, and ALP and lower (P<0.05) values of PTH and CTX than the LPA group but not the MPA group. A partial correlation analysis (adjusted for body mass index) revealed a positive correlation of steps per day with BMD and BSAP concentration and a negative correlation with PTH and CTX concentration. In conclusion, PA increases BMD and BMC of premenarcheal girls by favoring bone formation over bone resorption.

Clinical significance of combined detection of urine NTX and serum ICTP for breast cancer patients with bone metastases

To study the clinical significance and prognostic value of combined detection of urinary N-terminal telopeptide of type Ⅰ collagen (NTx) and serum C-terminal telopeptide of type Ⅰ collagen (ICTP) in breast cancer patients with bone metastases. Serum and urine samples from 68 women with advanced breast cancer who received the treatment in Jilin Cancer Hospital between October 2012 and October 2008 were collected before and 2 months after treatment. Among them, 35 patients had bone metastases (group A), including 12 cases with single bone metastasis and 23 cases with multiple bone metastases. 33 out of the 68 patients had other organ metastases (group B). 30 healthy females were included as the control group (group C). The levels of urine NTX and serum ICTP were measured by ELISA. The levels of NTx and ICTP of group A were significantly higher than those of groups B and C [NTx: (7.17±1.11) nmol/L vs. (2.08±0.22) nmol/L and (2.09±0.24) nmol/L, respectively, (P<0.05); ICTP: (7.75±1.14) ng/ml vs. (2.15±0.34) ng/ml and (2.22±0.31) ng/ml, respectively, (P<0.05)], while no significant difference was found between the groups B and C. Compared with the patients with single bone metastasis, the patients with ≥2 bone metastases had significantly higher NTx and ICTP levels [NTx: (7.69±0.93) nmol/L vs. (6.16±0.62) nmol/L, P<0.05; ICTP: (8.21±1.00) ng/ml) vs. (6.88±0.81) ng/ml (P<0.05)]. At two months after treatment, 40.0%(14/35) of patients with bone metastasis had partial remission (PR), 42.9%(15/35) of patients had stable disease (SD), and 6 patients with progressive disease (PD). Both urinary NTx and serum ICTP of the patients with PR and SD were significantly decreased compared with those before treatment (P<0.05). 10 cases of patients (28.6%) with bone metastases had skeletal-related events (SREs) during the treatment, including one PR patient (1/14, 7.1%), 5 SD patients (5/15, 33.3%) and 4 PD patients (4/6, 66.7%). The combined detection of urinary NTx and serum ICTP is of important significance for early diagnosis and efficacy evaluation and to control skeletal-related adverse events in breast cancer patients with bone metastases.

Dietary Silicon Intake of Korean Young Adult Males and Its Relation to their Bone Status.

Accumulated data suggests a positive effect of silicon on bone health; however, limited research exists on the silicon content of foods. To further the understanding of the relationship between dietary silicon intake and bone health, a food composition database of commonly consumed foods in Korea is required. For quantitative data on the intake levels of silicon, we analyzed the silicon content of 365 food items commonly consumed in Korea using inductively coupled plasma-atomic emission spectrometry following microwave-assisted digestion. To investigate the dietary silicon intake status and to examine the potential role of dietary silicon intake in the bone status of men, a total of 400 healthy Korean adult males aged 19-25 were observed for their diet intake and calcaneus bone density using the 24-h recall method and quantitative ultrasound, respectively. Clinical markers reflecting bone metabolism such as serum total alkaline phosphatase, N-mid osteocalcin, and type 1 collagen C-terminal telopeptide concentrations were also analyzed. Silicon intake of the subjects was estimated as 37.5 ±22.2mg/day. Major food sources of dietary silicon in the Korean male were cereal and cereal products (25.6% of total silicon intake), vegetables (22.7 %), beverages and liquors (21.2 %), and milk and milk products (7.0%). Silicon intake correlated positively with age, weight, energy intake, protein intake, calcium intake, and alcohol intake. After adjusted for age, weight, energy intake, protein intake, calcium intake, alcohol intake, smoking cigarettes, and regular exercise status, daily total silicon intake had no correlation with calcaneus bone density and the bone metabolism markers, but silicon intake from vegetables had a positive correlation with serum total alkaline phosphatase activity, a bone formation maker. These findings show the possible positive relationship between dietary silicon intake from vegetables and the bone formation of young adult males. Further investigation in a larger (Korean) population and correcting for additional nutritional confounders is required to confirm these findings.

Serum Matrix Metalloproteinases as Quantitative Biomarkers for Myocardial Fibrosis and Sudden Cardiac Death Risk Stratification in Patients With Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is associated with an increased risk of sudden cardiac death due to ventricular tachycardia (VT), and myocardial fibrosis reflects an important risk factor. Several matrix metalloproteinases (MMPs) and procollagen N-terminal propeptides (PNPs) are involved in collagen turnover and discussed as fibrosis biomarkers. We aimed to identify biomarkers that correlate with myocardial fibrosis in late-gadolinium-enhancement cardiac magnetic resonance imaging (LGE-CMR) and/or cardiac events (syncope, VT) in HCM patients. Methods and ResultsIn 54 HCM patients (age 55.9 ± 14.3 y, 50% female) fibrosis was quantified by LGE-CMR. Serum concentrations of MMP-1, -2, -3, -9, and tissue inhibitor of MMP (TIMP) 1 were analyzed by means of enzyme-linked immunosorbent assay and PINP, PIIINP, and type I collagen C-terminal telopeptide (ICTP) concentrations by radioimmunoassay. MMP-9 was associated with fibrosis in LGE-CMR (mean increase 0.66 g/unit MMP9 [95% confidence interval [CI] 0.50–0.82]; P < .001) and with cardiac events in women (odds ratio [OR] 1.07 [1.01–1.12], P = .01) but not in men. Increased MMP-2 levels in women were associated with lower fibrosis (0.05 [−0.09 to −0.01]; P = .015). MMP-3 levels were positively associated with cardiac events (OR 1.13 [1.05–1.22]; P = .001) independently from fibrosis and sex. No association was detected for MMP-1, TIMP-1, PNPs, and ICTP. ConclusionsThese data suggest that MMP-9 is a useful biomarker for fibrosis and cardiac events in female HCM patients, whereas MMP-3 is associated with a higher event rate independent from fibrosis and sex.

Marcadores de recambio óseo en mujeres postmenopáusicas: utilidad clínica

Bone metabolism is a dynamic process, which includes formation and resorption. Osteoblast and osteoclast are responsible of replacing 20% of bone each year. Bone Markers are fragments of bone matrix; these peptides are released in the process of formation and resorption, later accumulated in body compartments (bone and blood) and finally excreted in the urine, reflecting bone dynamic. The international Federation of Osteoporosis and the International Federation of Laboratory and Clinical Chemistry recommend the use of these two markers (one representing bone formation and the other bone resorption) to evaluate bone turnover, especially in high-risk groups such as postmenopausal women. The collagen C-terminal telopeptide or carboxi-terminal collagen crosslinking (CTX) is one of the most used, among different bone markers. This is a blood biomarker that can be measured to assess bone turnover; this marker increases when the bone resorption is accelerated. On the other hand, osteocalcin (a non-collagen protein) is a bone formation marker, which has been widely studied and can be measured in venous blood during bone formation. Both markers are important&#x0D; for monitoring anti-resorptive therapy, and they have been validated to predict fracture risk complementing densitometry in osteoporosis diagnosis. Main disadvantages are variability of the laboratory techniques and lack of information about normal reference values in different populations. Therefore it is necessary to establish normal reference values for each population&#x0D; before its incorporation as a clinical tool.

The Association between Coffee Consumption and Bone Status in Young Adult Males according to Calcium Intake Level.

The purpose of this study was to investigate the association between coffee consumption and bone status (bone mineral density and bone metabolism-related markers) according to calcium intake level in Korean young adult males. Healthy and nonsmoking males (19-26 years, n = 330) participated in this study. Anthropometric measurements, dietary habits, and nutrient intakes were surveyed. Bone status of the calcaneus was measured by using quantitative ultrasound (QUS). Bone metabolism-related markers including serum total alkaline phosphatase activity (TALP), N-mid osteocalcin (OC), and type 1 collagen C-terminal telopeptide (1CTP) were analyzed. The subjects were divided into two groups based on daily calcium intake level: a calcium-sufficient group (calcium intake ≥ 75% RI, n = 171) and a calcium-deficient group (calcium intake < 75% RI, n = 159). Each group was then further divided into three subgroups based on daily average coffee consumption: no-coffee, less than one serving of coffee per day, and one or more servings of coffee per day. There were no significant differences in height, body weight, body mass index, energy intake, or calcium intake among the three coffee consumption subgroups. QUS parameters and serum 1CTP, TALP, and OC were not significantly different among either the two calcium-intake groups or the three coffee consumption subgroups. Our results may show that current coffee consumption level in Korean young men is not significantly associated with their bone status and metabolism according to the calcium intake level.