Bone metastasis is common in lung cancer patient and the diagnosis of bone metastasis is usually made by using imaging techniques, especially bone scintigraphy. However, the diagnostic yield from bone scintigraphy is limited. The aim of this study is to assess the clinical usefulness of urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), urinary deoxypyridinoline (DPD), and serum alkaline phosphatase (ALP) in the assessment of bone metastasis in patients with lung cancer. Urinary NTx, DPD, and serum ALP were measured in 151 lung cancer patients (33 with and 118 without bone metastasis). Lung cancer patients with bone metastasis had a higher urinary excretion of NTx and DPD, and a higher serum ALP than those without bone metastasis. NTx had a better receiver operating characteristic (ROC) curve than DPD and ALP, since the areas under the ROC curve were 0.82, 0.79, and 0.71, respectively. Although correlation coefficients among NTx, DPD and ALP were significantly positive (p < 0.005), the strongest relationship was appeared between NTx and DPD (R=0.616). In conclusion, our results showed the utility of the new bone markers in detecting bone metastasis and suggested that measurement of urinary NTx was valid diagnostic method of bone metastasis from lung cancer.
Adult ; Aged ; Aged, 80 and over ; Alkaline Phosphatase/blood ; Amino Acids/urine ; Bone Neoplasms/blood/*secondary/urine ; Collagen/urine ; Humans ; Lung Neoplasms/*pathology ; Middle Aged ; Peptides/urine ; Predictive Value of Tests ; Research Support, Non-U.S. Gov't ; Tumor Markers, Biological/blood/*urine

Biomarkers ; urine ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; pathology ; urine ; Enzyme-Linked Immunosorbent Assay ; Hepatitis A Virus Cellular Receptor 1 ; metabolism ; Humans ; Intracellular Signaling Peptides and Proteins ; urine ; Kidney Diseases ; pathology ; urine ; Lipocalin-2 ; urine ; Membrane Proteins ; urine ; Sialoglycoproteins ; urine ; Tissue Inhibitor of Metalloproteinase-2 ; urine

Tongluo Xingnao effervescent tablet (TLXNET) is a patented prescription, which comes from modified Xionggui decoction and can improve cognitive function. However, its effect on the urine metabolites and anti-dementia mechanism in the dementia model rats induced by hippocampal injection with Aβ25-35 remains unclear. The experiment focused on the changes in trajectory and inter-relationship among the urinary metabolite of rats in the blank group, Aβ25-35 hippocampal injection dementia model group and the TLXNET intervention group, in order to determine theirs characteristic metabolic markers and explain the anti-dementia effect of TLX-NET base on the change of metabolic trajectory of these bio-markers. According to the experimental results, 5, 6-indolequinone, 4-hydroxyphenyl pyruvic acid (4-HPPA), cortisol and 3-thiosulfate lactic were preliminarily identified as the characteristic metabolic markers. They mainly participate in dopamine system, glucocorticoids and energy metabolic pathways. TLXNET can apparently downregulate the disturbances of metabolic trajectory of the four bio-markers. The experiment indicates that the dementia model induced by injecting Aβ25-3 into hippocampus has its characteristic endogenous metabolic markers in urine, and ELXNET can ameliorate dementia by down-regulating the disturbances of metabolic trajectory.
Amyloid beta-Peptides ; metabolism ; toxicity ; Animals ; Biomarkers ; urine ; Dementia ; drug therapy ; urine ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hippocampus ; drug effects ; metabolism ; Humans ; Male ; Metabolomics ; Peptide Fragments ; metabolism ; toxicity ; Rats ; Rats, Sprague-Dawley ; Tablets ; administration & dosage ; Urine ; chemistry

OBJECTIVEThe aim of this study was to access the relationship of osteolytic bone metabolic markers such as serum type I collagen carboxy-terminal telopeptide (sICTP), N-terminal cross-linked telopeptides of type I collagen (uNTx), urinary pyridinoline (uPyd) with the therapeutic effect in breast cancer patients with bone metastases.

METHODS120 patients with breast cancer were included in this study. The levels of sICTP, uNTx and uPYD were measured by ELISA assay. The differences were compared between patients with and without bone metastasis. The patients with bone metastasis were treated and followed up as clinically indicated.

RESULTSThe levels of all above mentioned biomarkers in patients with bone metastasis were significantly higher than that in patients without bone metastasis (P < 0.01). A significant correlation was found between each two markers (r > 0.5, P < 0.01). The biomarkers were examined again in 45 patients with bone metastasis after treatment to evaluate the treatment response. The median follow-up was 10 months. Based on clinical evaluation criteria, 25 patients were responders and 20 were non-responders. For responders, after 3 months treatment, the levels of the three bone markers were significantly reduced (P = 0.025, P < 0.001, P < 0.001). But for non-responders, with progression of bone lesions, the levels of the three markers were significantly raised (P = 0.011, P = 0.002, P = 0.002). By means of multiple logistic regression with stepwise selection, the uPyd and uNTx activities were closely correlated with treatment response (OR = 17.0, P = 0.019; OR = 16.7, P = 0.015), however, the sICTP did not show any correlation with treatment response P = 0.841).

CONCLUSIONThe levels of sICTP, uNTx and uPyd may be used as indicators in assessment of the effect of antiresorptive treatment and evaluation of prognosis in breast cancer patient with bone metastases.

Adult ; Aged ; Amino Acids ; urine ; Biomarkers, Tumor ; metabolism ; Bone Neoplasms ; drug therapy ; metabolism ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Collagen ; urine ; Collagen Type I ; blood ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Peptides ; blood ; Remission Induction

OBJECTIVEThis report aims to describe the oxidative damage profile in brain of presenilin1 and presenilin2 conditional double knockout mice (dKO) at both early and late age stages, and to discuss the correlation between oxidative stress and the Alzheimer-like phenotypes of dKO mice.

METHODSThe protein level of Abeta(42) in dKO cortex and free 8-OHdG level in urine were measured by ELISA. Thiobarbituric acid method and spectrophotometric DNPH assay were used to determine the lipid peroxidation and protein oxidation in cortex, respectively. SOD and GSH-PX activities were assessed by SOD Assay Kit-WST and GSH-PX assay kit, separately.

RESULTSSignificant decrease of Abeta(42) was verified in dKO cortex at 6 months as compared to control mice. Although lipid peroxidation (assessed by MDA) was increased only in dKO cortex at 3 months and protein oxidation (assessed by carbonyl groups) was basically unchanged in dKO cortex, ELISA analysis revealed that free 8-OHdG, which was an indicator of DNA lesion, was significantly decreased in urine of dKO mice from 3 months to 12 months. Activities of SOD and GSH-PX in dKO and control cortices showed no statistical difference except a significant increase of GSH-PX activity in dKO mice at 9 months.

CONCLUSIONOxidative damage, especially DNA lesion, was correlated with the neurodegenerative symptoms that appeared in dKO mice without the deposition of Abeta(42). Triggers of oxidative damage could be the inflammatory mediators released by activated microglia and astrocytes.

Age Factors ; Alzheimer Disease ; genetics ; metabolism ; physiopathology ; Amyloid beta-Peptides ; urine ; Animals ; Deoxyguanosine ; analogs & derivatives ; urine ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; methods ; Glutathione ; metabolism ; Hydrazines ; metabolism ; Lipid Peroxidation ; genetics ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred CBA ; Mice, Knockout ; physiology ; Oxidation-Reduction ; Oxidative Stress ; physiology ; Peptide Fragments ; urine ; Presenilin-1 ; deficiency ; Presenilin-2 ; deficiency ; Spectrophotometry, Atomic ; methods ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the effects of Migu tablet(MG) on bone mineral density (BMD), serum matrix metalloproteinase-2 (MMP-2) and bone metabolic markers in Chinese postmenopausal women.

METHODAccording to the criteria of osteoporosis, 192 Chinese postmenopausal female of the aged 55-62 were randomized into 4 groups, such as the normal, MG group, XLGB group and Leli group. The serum MMP-2, bone alkaline phosphates (sBAP), osteocalcin (sOC), bone cross-linked C-telopeptides of type I collagen (sCTx) and urine bone cross-linked N-telopeptides of type I collagen (uNTx) were measured using ELISA. BMD were measured using dual energy X-ray absorptiometry before and after medication at 12 and 24 weeks.

RESULTAfter treatment, the values of BMD were significantly higher in MG and XLGB groups separately, otherwise lower in Leli and normal control groups. At the same time, serum MMP-2, sCTx, uNTx/Cr concentrations were significantly lower and sBAP, sOC concentrations were higher, but the concentrations in Leli and normal control groups were basically same to the value of before treatment.

CONCLUSIONThe effects of MG tablet to treat the PMO were notable, just same to XLGB. But calcium tablet cannot play a role in the treatment of osteoporosis and do not prevent the loss of bone.

Aged ; Alkaline Phosphatase ; blood ; Biomarkers ; blood ; urine ; Bone Density ; drug effects ; Collagen Type I ; blood ; urine ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; therapeutic use ; Female ; Humans ; Matrix Metalloproteinase 2 ; blood ; Middle Aged ; Osteocalcin ; blood ; Osteoporosis, Postmenopausal ; blood ; physiopathology ; prevention & control ; Peptides ; blood ; urine ; Phytotherapy ; Plants, Medicinal ; chemistry ; Tablets ; Treatment Outcome

OBJECTIVETo evaluate the efficacy and safety of zoledronic acid in the treatment of bone pain in patients with bone metastasis from solid tumor or multiple myeloma.

METHODSA randomized, double-blind, double-simulated and multi-center phase III clinical trail with pamidronate as control was conducted. Patients with moderate to severe bone pain (VAS > 50 mm) induced by solid tumor or multiple myeloma were randomized to receive intravenous zoledronic acid 4 mg or pamidronate 90 mg. Then the change of VAS and urinary NTX/Cr and CTX/Cr were observed in two groups.

RESULTSFrom July 2005 to September 2006, 228 patients with bone pain induced by bone metastasis from 15 cancer centers were randomize into two groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. Significant improvement in bone pain after treatment were observed both in zoledronic acid group and the control group when compared with baseline VAS on D8 (-11.77% vs. -10.87%), D15 (-24.60% vs. -21.06%) and D28 (-32.37% vs. -31.26%) (P< or =0.0001), but no significant difference existed between two groups (P =0.6587). Compared with baseline, urine NTX/Cr and CTX/Cr level were decreased rapidly after treatment in both groups, the nadir was on D8, the median decreased on D28, which was -36.9% vs. -32.1% for NTX/Cr (P = 0.7922) and -63.2% vs. -47.9% for CTX/Cr (P =0.834). The frequently observed adverse events were pyrexia (19.0% vs. 31.3%), vomiting (6.0% vs. 8.9%), nausea (4.3% vs. 4.5%), fatigue (3.4% vs. 2.7%) and constipation (2.6% vs. 1.8%) in the two groups. Compared with baseline, the serum creatinine level was not significantly increased throughout the study.

CONCLUSIONIntravenous injection of 4 mg zoledronic acid can significantly reduce bone pain and bone resorption marker in urine in the Chinese patients with bone metastasis from solid tumor or multiple myeloma, which is tolerable and also comparable to pamidronate in the efficacy and safety.

Adult ; Aged ; Analgesics ; adverse effects ; therapeutic use ; Bone Density Conservation Agents ; adverse effects ; therapeutic use ; Bone Neoplasms ; complications ; secondary ; Breast Neoplasms ; pathology ; Collagen Type I ; urine ; Colorectal Neoplasms ; pathology ; Creatinine ; urine ; Diphosphonates ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Fever ; chemically induced ; Humans ; Imidazoles ; adverse effects ; therapeutic use ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Multiple Myeloma ; complications ; Pain Measurement ; Pain, Intractable ; drug therapy ; etiology ; urine ; Peptides ; urine ; Prospective Studies ; Vomiting ; chemically induced

OBJECTIVETo explore the dynamic change in biochemical markers of bone turnover in preterm infants and the effect of early parenteral calcium supply.

METHODSForty preterm infants were divided into parenteral calcium supply group and control group. Blood and urine samples were collected at 24 h and 11 d after birth. Serum osteocalcin (OC) was measured with ELISA, serum carboxyterminal telopeptide type I collagen (ICTP) with radioimmunoassay, serum alkaline phosphatase (AKP), calcium, phosphate, and urine calcium, phosphate, creatinine with automatic biochemical analyzer. Blood samples were also collected from 22 term infants as control. Calcium gluconate (10%, 4 ml/kg x d(-1)) was administered intravenously in parenteral calcium supply group.

RESULTAt 24 h, serum AKP, ICTP [(147.86+/- 44.87)IU, (57.36+/- 6.34)micro g/L] in preterm infants were significantly higher than those [(147.86+/- 44.87)IU, (57.36+/- 6.34)micro g/L] in term infants, and negatively correlated with gestational age and birth weight (r =-0.528, P<0.01; -0.614, P< 0.01), but serum OC [(648.77+/- 238.89) nmol/L] in preterm infants was lower than that [(851.68+/- 238.69)nmol/L] of term infants, and positively correlated with gestational age and birth weight (r=0.359, P< 0.05; 0.376, P< 0.01). At 11 day, serum OC [947.25+/- 335.47)nmol/L] in preterm infants was markedly elevated and reached the level of term infants [(941.65+/- 297.28)nmol/L], but serum ICTP [(65.44+/- 6.24)micro g/L] in preterm infants was higher than that [(57.10+/- 3.48)micro g/L] in term infants all along. Serum AKP [(246.00+/-66.64)IU] in parenteral calcium supply group was higher than that [(206.53+/- 53.9)IU] in the control group. There were no significantly differences in serum OC and ICTP between parenteral calcium supply group and the control group. Calcium in serum and urine was elevated, phosphate in serum and urine was reduced in the parenteral calcium supply group. Urine analysis and kidney ultrasounds were normal.

CONCLUSIONThere is active bone formation and bone resorption in preterms as compared with terms. Alone parenteral calcium supply during early life can not increase formation of bone protein or decrease degradation of bone collagen, but can elevate serum calcium and urine calcium levels. Hematuria and renal calcification were not found in short duration.

Alkaline Phosphatase ; blood ; Bone and Bones ; metabolism ; Calcium ; administration & dosage ; blood ; urine ; Collagen Type I ; Female ; Humans ; Infant, Newborn ; Infant, Premature ; Injections, Intravenous ; Male ; Osteocalcin ; blood ; Peptide Fragments ; blood ; Peptides ; Procollagen ; blood

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p< 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p< 0.05 and R2=0.103, p< 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p< 0.001), serum ALP level, and urinary NTX level (R2=0.074, p< 0.05 and R2=0.160, p< 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.
Aged ; Aged, 80 and over ; Alendronate/*administration & dosage ; Alkaline Phosphatase/blood ; Bone Density/*drug effects ; Calcium/blood ; Collagen/urine ; Densitometry, X-Ray ; Female ; Humans ; Incidence ; Japan ; *Lumbar Vertebrae/radiography ; Middle Aged ; Osteoporosis, Postmenopausal/*drug therapy/epidemiology/radiography ; Peptides/urine ; Phosphorus/blood ; Spinal Fractures/epidemiology/prevention & control

OBJECTIVETo evaluate the clinical efficacy of zoledronic acid combined with chemotherapy in the management of skeletal metastasis of non-small cell lung cancer (NSCLC) and investigate the value in urine amino-terminal telopeptide of type I collagen (uNTX) and serum bone specific alkaline phosphatase (sBALP) in monitoring skeletal metastasis of NSCLC.

METHODSFrom February, 2007 to January, 2009, 32 NSCLC patients with bone metastases received treatment with zoledronic acid at the dose of 4 mg given every 3 weeks and platinum-based chemotherapy (each cycle lasting for 3 weeks). Before and during the treatments, uNTX and sBALP were measured in these patients using ELISA and precipitation with wheat germ lectin, respectively. The patients were followed up for skeletal-related events (SREs) and status of survival.

RESULTSA significant decrease occurred in the pain scores and analgesic use in the patients after the therapy. SREs were not observed during the treatment. Serum creatinine and calcium levels underwent no significant variation during the treatment. Eleven patients reported 14 possible zoledronic acid-related adverse events. The concentration of uNTX and sBALP in patients with bone metastases was above the upper limit of the normal range. A positive correlation was observed between the levels of the markers and the extent of bone metastases. At the third month, uNTX and sBALP were significantly lowered, but radionuclide whole-body bone imaging showed no obvious changes. Of the 32 patients, 24 had elevated uNTX values, which became normal after the treatment in 15 patients and remained elevated in the other 9 patients. SREs occurred in these two subgroups at the rates of 53% and 89% (P=0.039), respectively. Twenty-six patients had elevated sBALP level, and 16 of them exhibited normal sBALP level after the treatment. The incidences of SREs in the patients with elevated and normal sBALP level were 50% and 90% (P=0.038), respectively. The levels of uNTX/Cr and sBALP were not correlated to the survival of the patients.

CONCLUSIONSZoledronic acid combined with chemotherapy is an effective treatment for NSCLC with bone metastases. Zoledronic acid is safe and well tolerated. Urinary NTX and serum BALP have a high value in the diagnosis, therapeutic effect monitoring and SRE prediction of NSCLC with bone metastases.

Adult ; Aged ; Alkaline Phosphatase ; blood ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biomarkers, Tumor ; metabolism ; Bone Density Conservation Agents ; therapeutic use ; Bone Neoplasms ; drug therapy ; metabolism ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; metabolism ; pathology ; Collagen Type I ; urine ; Diphosphonates ; therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Imidazoles ; therapeutic use ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Peptides ; urine