Estimation of N‑terminal telopeptides of type I collagen in periodontal health, disease and after nonsurgical periodontaltherapy in gingival crevicular fluid: A clinico ‑ biochemical study.

Aim: This study explored gingival crevicular fluid (GCF) N‑terminal telopeptides of type I collagen (NTx) levels in periodontal health, disease and after nonsurgical periodontal therapy along with its association with the clinical parameters. Materials and Methods: Study comprised of three groups of 10 subjects each: Healthy (Group I), gingivitis (Group II), and periodontitis (Group III), while Group III patients after scaling and root planning (SRP) constituted Group IV. Gingival index (GI), probing pocket depth (PPD), clinical attachment loss (CAL), and radiological parameters were recorded. GCF samples were analyzed by competitive‑enzyme‑linked immunosorbent assay. Results: Samples in Group III and Group IV tested positive for NTx whereas in Group I and Group II, NTx was not detected. Mean NTx levels were higher in Group III (6.79 ± 0.94 nanomole bone collagen equivalents per liter [nm BCE/L]) compared to Group IV (5.73 ± 0.95 nm BCE/L) which was statistically significant. Positive correlation was seen between the clinical parameters and the NTx levels in Group III and IV. Conclusion: As NTx is specific bone turnover marker, it is detected only in periodontitis Group and the values decline after SRP. Failure to detect NTx in Group I and II, relates to the minimum or no resorption at the sample sites.

Biomarcadores óseos y su relación con la densidad mineral ósea en adultas jóvenes y adolescentes en su primer año posparto / Bone biomarkers and its relation with bone mineral density in adults and adolescents during the first year postpartum

La información sobre biomarcadores óseos en adolescentes y adultas durante el periodo posparto es incierta, por lo que el objetivo de este artículo fue analizar el patrón de biomarcadores óseos en adolescentes y adultas a 15, 90, 180 y 365 días posparto (dpp) y su asociación con la densidad mineral ósea (DMO) y lactancia materna. Se realizó un estudio de cohorte en 32 madres adolescentes ≤17 años y 41 adultas de 18 a 29 años de edad en el primer año posparto. Se realizaron medidas antropométricas, DMO y biomarcadores óseos y así como datos del tipo y la duración de lactancia. Como resultados se encontró asociación entre la concentración basal de N-telopéptidos ≤24 μg/L y mayor aumento de DMO. Las adolescentes tuvieron mayor concentración de N-telopéptidos (p≤0.004) y menor concentración de osteocalcina (5±3 vs13±4, p <0.001) que las adultas. La lactancia no afectó el cambio de DMO (p>0.050), ni de biomarcadores óseos. La osteocalcina se asoció con el cambio en DMO (p<0.040). La prolactina fue mayor entre las que practicaron lactancia materna exclusiva (p<0.001). A menor edad menores concentraciones de osteocalcina (p<0.001) y mayores concentraciones de N-telopéptidos (p<0.001). Se concluyó que a menor concentración de N-telopéptidos y mayor de osteocalcina hubo un mayor aumento de DMO, lo cual implica menor aumento de ésta en el grupo de adolescentes. La lactancia no afectó la DMO.

The objective of this study was to describe the trend of bone biomarkers in adults and adolescents women at 15, 90, 180 and 365 postpartum days (ppd) and its relation with bone mineral density (BMD). It was a prospective cohort of 32 teenager’s ≤17 and 41 women from 18 to 29 years old. We evaluated diet, anthropometry, BMD, bone biomarkers and hormonal profile. In all, the concentration of N-telopeptide was higher at 15 days postpartum decreasing during first year postpartum, but adolescents had the highest concentration. The lowest N-telopeptide concentration was associated with highest increasing of the BMD. Osteocalcin concentration was lower in adolescents than in adults women (5 ± 3 vs 13 ± 4 ng/mL, p<0.001) during first year postpartum. Exclusive breastfeeding did not affect the BMD (p>0.050) or bone biomarkers. Osteocalcin concentration was positively associated with bone BMD (p<0.040), breastfeeding did not affect osteocalcin concentrations. Prolactin was higher among women who breastfed exclusively (p<0.001). Age and breastfeeding inversely correlated with bone biomarkers (p<0.001) N-telopeptide and PTHi respectively. We concluded that a lower N-telopeptide concentration and a higher osteocalcin concentration were associated with a higher increasing of BMD, so then, adolescents showed the lowest recovery of the BMD. Breastfeeding does not affect the BMD.

Ancillary value of urinary N-terminal telopeptide of type Ⅰ collagen to bone scintigraphy in the diagnosis of bone metastases / 中华核医学与分子影像杂志

Objective To explore the value of urinary N-terminal telopeptide of type Ⅰ collagen (uNTX) combined with bone scintigraphy (BS) for the diagnosis of bone metastases.Methods A total of 227 patients suspected of bone metastases by BS were selected from Jan to May of 2012.UNTX was tested for each subject.The threshold of uNTX was chosen as 65 nmol bone collagen equivalents (BCE)/mmol creatinine (Cr) for the diagnosis of bone metastasis.Patients with uNTX greater than 65 nmol BCE/mmol Cr would be diagnosed as having bone metastasis.Other examinations (CT,MRI,PET/CT or bone biopsy) were also performed to confirm the diagnosis.The uNTX values of benign and malignant bone lesions were compared using two-sample t test.The diagnostic efficacy of uNTX combined with BS was evaluated.A ROC curve was analyzed to evaluate the cut-off value of uNTX for the diagnosis of bone metastasis.Results The mean value of uNTX of all 227 patients was (84.30± 13.29) nmol BCE/mmol Cr,which was significantly higher than the upper limit of normal range (t =21.875,P＜0.01).Using 65 nmol BCE/mmol Cr as the threshold,197 cases were diagnosed as with and 30 without bone metastases,in which 188 and 27 were respectively confirmed by other examinations.The mean uNTX was (88.73 ± 8.37) and (60.76± 9.14) nmol BCE/mmol Cr in patients with and without bone metastases,respectively (t =-18.134,P＜0.01).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index of uNTX combined with BS were 98.4％ (188/191),75.0％ (27/36),95.4％ (188/197),90.0％ (27/30),94.7％ (215/227) and 73.4％ respectively.The cut-off value by ROC curve analysis was 78.88 nmol BCE/mmol Cr and the area under the curve was 0.982.Using 78.88 nmol BCE/mmol Cr as threshold,the corresponding sensitivity,specificity,positive predictive value,negative predictive value,accuracy and Youden index were 97.4％(186/191),94.4％(34/36),98.9％(186/188),87.2％(34/39),96.9％(22/227) and 91.8％ respectively.Conclusions Using the cut-off value of 78.88 nmol BCE/mmol Cr,uNTX may have clinical value in helping the differential diagnosis of bone scintigraphy for patients suspected of metastatic bone disease.

Bone turnover and its related molecular mechanism in STZ-induced diabetic rats / 中华内分泌代谢杂志

Objective To study the bone turnover and its related molecular mechanism in STZ-induced diabetic rats. Methods Of 30 male SD rats studied, 15 were induced diabetics by intravenous injection of streptozotocin (50 mg/kg)and fed for 8 weeks. After the sacrifice of both the diabetic and control groups, serum Ca, P, alkaline phosphatase (ALP), and osteocalcin were determined, and 24 h urinary Ca and urinary cross-linked N-telopeptide of type Ⅰ collagen (NTx)and creatinine (Cr)ratio were also determined. The left tibia was dissected for bone histomorphometry analysis. Right femur and lumbar vertebrae (L1-L4) were reserved for bone mineral density (BMD) determination. The right tibia was separated for the study of bone tissue RANKL/osteoprotegerin, Core binding factor 1 (Cbfa1) ,osterix and osteocalcin mRNA level which was performed by real-time quantitative reverse transcription polymerase chain reaction assay. Results No significant difference was found in serum Ca, P, and ALP levels between 2 groups of rats. ST-Z-induced diabetic rats were characterized by extreme hyperglycemia, marked weight loss, polyuria, and hypercalciuria. A low-turnover osteopenia was evidenced in diabetic rats by decreased BMD in both femur [(0. 099±0.013) vs (0. 139 ± 0.013 g/cm~3) , P < 0.01] and lumbar vertebrae [(0. 107±0.011)vs (0. 149±0.009) g/cm~3, P<0.01] , reduced serum osteoealcin level [a marker of formation, (3.03±0.52) vs (6. 18±0.71) ng/ml ,P<0. 01]) ,decreased urine NTx/Cr ratio [(5. 67±0.86) vs (5.23±0.98) nmol/g Cr, P<0. 05], decreased trabeeular volume and thickness, and reduced bone label surface and bone formation rate [(0. 44±0. 11) vs (0. 78±0. 14) μm/d,P<0. 01] by bone dynamic study. The RANKL/ osteoprotegerin [(0.57±0.11)vs (0.89±0.13) ,P<0.01] ,osterix [(1.93×10~(-4)±0.65×10(~-4))vs (4.19×10~(-4)± 0.71×10~(-4)) ,P<0.01] ,Cbfa1 [(26.68×10~(-4)±6.53×10~(-4))vs (37.21×10~(-4)±7.14×10~(-4)) ,P<0.01] ,and osteocalcin [(2.25×10~(-4)±1.19×10~(-4))vs (3.43×10~(-4)±1.63×10~(-4)) ,P<0.01] mRNA expressions were declined in the bone tissue of the tibia in the ST-Z-induced diabetic rats, as compared with the control. Conclusion A low-turnover osteopenia is evidenced in STZ-induced diabetic rats by significant decrease of both osteoclastic marker(RANKL/ osteoprotegerin)and osteoblastic marker (osterix ,Cbfa1 ,osteocalcin)mRNA levels in tibia.

Role of Zoledronic Acid on Bone Loss by Letrozole / 한국유방암학회지

PURPOSE: The aromatase inhibitors cause bone loss by estrogen depletion. Zoledronic acid (ZA) can prevent bone mineral density (BMD) loss associated with the use of aromatase inhibitors. Accordingly interest has arisen in measuring surrogate markers of bone resorption to monitor the response of treatment of BMD loss in place of a radiologic assessment. This study was designed to determine whether ZA would prevent bone loss that is known to occur with letrozole and identified surrogate markers of bone resorption in an animal model. METHODS: In ovariectomized or sham-operated rat, we administrated ZA and letrozole to 5 different groups including: a sham operation control group (OC), a group in which an ovariectomy was performed followed by saline administration (OS), an ovariectomy with ZA treatment group (OZ), an ovariectomy with letrozole treatment group (OL) and an ovariectomy with ZA and letrozole combined treatment group (OZL). The levels of serum osteocalcin, serum bone alkaline phosphatase (BALP), serum calcium and urine N-telopeptide (NTX) and BMD were estimated and compared at the same periods for each group. The distinct microscopic findings of proximal tibia at week sixteen were also compared. RESULTS: Significantly reduced levels of urine NTX and significantly increased BMD were measured in the OZ group. In the OL group no difference was seen in in BMD in comparison to the OS group. However, a significant increase in BMD was measured in the OZL group. Urine NTX levels were measured and found to be lower in the OL group and significantly lower in the OZL group. Serum osteocalcin levels were similar to each other for each group. Levels of serum calcium and BALP were significantly lower in the OZL group than in the OS group. CONCLUSION: The combination treatment with ZA and letrozole is effective in the inhibition of bone resorption and in the preservation of BMD. Measurement of serum osteocalcin, urine NTX, and BMD, levels are recommended as surrogate markers for determining the response for the treatment of bone loss.

Usefulness of Bone Metabolic Markers in the Diagnosis of Bone Metastasis from Lung Cancer

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.

Biochemical Bone Markers in Postmenopausal Women with Hormone Replacement Therapy / 대한산부인과학회잡지

OBJECTIVES: To investigate the patterns of biochemical bone markers, such as urinary deoxypyridinoline (DPD), N-telopeptide of type I collagen (NTX), and serum osteocalcin (OC), bone-specific alkaline pbosphatase (BSAP) in postmenopansal women with hormone replacement therapy (HRT). Materials and METHOD: From July 1997 to January 1998, total 239 postmenopausal women were emolled in the present study, and 198 healthy premenopausal women with regular menstruation were served as control. The postmenopausal women were pouped into the HRT group and the non-HRT group. The women in the HRT poup have received estrogen with continuous or cyclic progestin therapy far more tban 6 months. The biochemical bone markers of all women were assayed. Results were analysed with Students t-test. RESULTS: The urinary DPD of the non-HRT group was sigaificantly higher than both the HRT poup and the premenopausal group(5.51 +/- 2.47 vs. 3.36 +/- 1.02 and 4.01 +/- 3.86 nM/mM, p < 0.05, repectively). The urinary NTX of the non-HRT group was also higher in comparison to the HRT group and the premenopausal group(48.71 +/- 11.54 vs. 33.70 +/- 17.43 and 33.70 +/- 17.43 nM BCE/mmol, p < 0.05, repectively). However, there were no significant differences in the concentrations of serum BSAP and OC among the three poups. CONCLUSION: The urinary DPD and NTX were more sensitive indicators of bone metabolism tban serum BSAP and OC in postmenopausal women undergoing HRT.

Effects of total flavonoids of Herba Epimedii on the metabolism of typeⅠcollagen and the expression of cathepsin K in the bone of ovariectomized rats / 中华内分泌代谢杂志

Objective To investigate the effects of total flavonoids of Herba Epimedii(HEF)on the metabolism of typeⅠcollagen and the expression of cathepsin K in the bone of ovariectomized(OVX)rats. Methods Fifty-four female SD rats were allocated into 6 groups;OVX group,sham operation group,OVX rats followed by three doses of HEF(40,80 and 160 mg?kg~(-1)?d~(-1))and nilestriol(0.1 mg?kg~(-1)?d~(-1))for 12 weeks respectively.Bone mineral density(BMD)of whole body was determined by dual-energy X-ray absoptiometry.The level of cross-linked N-telopeptide of typeⅠcollagen(NTx)in the urine were determined by ELISA.The amounts of typeⅠcollagen protein and cathepsin K protein in bone tissue were detected by immunohistochemical method and Western blotting.Results Compared with OVX group,the total BMD values in the HEF treated groups were increased(all P＜0.05),and the expression levels of typeⅠcollagen in three HEF treated groups rose significantly in a dose-dependent manner after 12 week,and simultaneously,both the expression of cathepsin K in bone and the level of NTx/Cr were reduced markedly(P＜0.05),being most significant(P＜0.01)in the group treated with the highest dose of HEF(160 mg?kg~(-1)?d~(-1)).Conclusion HEF seems to be able to elevate BMD and improve bone quality of rats via promoting synthesis and inhibiting proteolysis and absorption of typeⅠcollagen in the bone.