NTx Values Research Articles

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Calprotectin and N-telopeptide of Type I Collagen (NTx) as Gingival Crevicular Fluid (GCF) Biomarker in Peri-Implantitis Patients

Introduction: Formulation of various preventive and therapeutic strategies is possible only by a better understanding of the immune-inflammatory profile of peri-implant diseases. For understanding the changes and turnover of bone, various markers have been used in the past literature, out of which, N-telopeptide of Type I Collagen (NTx) is acknowledged to be the most reliable marker.Aims and objectives: Assessment of calprotectin and NTx concentration in gingival crevicular fluid (GCF) around the implant sites in subjects suffering from peri-implantitis.Materials and methods: In total, 70 healthy individuals were included in the present study. These patients had opted for dental implants within the last decade. After collecting the peri-implant crevicular fluid (PICF) and GCF, various examinations were carried out. PICF samples were obtained with the help of sterile paper available in the form of strips. The enzyme-linked immunosorbent assay (ELISA) technique was used for measuring the calprotectin and NTx. All the readings were obtained in nanograms per microliter of PICF. All the results were recorded and analyzed.Results: The overall mean calprotectin and NTx values were observed to be in a significantly higher range within the sites suffering from peri-implantitis when compared with healthy locations. The calprotectin values and NTx levels were positively correlated with the mean values of periodontal parameters observed clinically.Conclusion: Both calprotectin and NTx could be used as a biomarker signifying the presence of inflammation as well as bone resorption in patients suffering from peri-implantitis.

A Case control study to determine Macrophage migration inhibitor, and N-telopeptides of type I bone collagen Levels in the sera of osteoporosis patients

This study focused on determining the markers of Macrophage migration inhibitor (MIF), as well as the N-telopeptides of type I bone collagen (NTX), and some other parameters (alkaline phosphatase (ALP), vitamin D (Vit D), calcium (Ca), phosphorus (P), and magnesium (Mg), and their correlation with other parameters in osteoporosis. One hundred ten subjects were involved in the current study. There were two groups of patients: group I (30) women with severe osteoporosis and group II (30) women with mild osteoporosis. For comparison, 50 apparently healthy individuals were included as a control. Serum levels of MIF, and NTX were significantly higher in groups I and II as compared to the control group, which indicate that these two parameters were related to disease. Moreover MIF, and NTX were organized in one cluster when applying cluster analysis test to all the studied groups. This indicates that in most of the studied samples the two parameters were related to each other as well as to osteoporosis. Magnesium showed a significant decrease in its level in both groups as compared to the control. On the other hand, alkaline phosphatase (ALP) showed a significant increase in its activity in both studied groups as compared to the control. Vitamin D level manifested significant difference between group I and group II, with a significant decrease in its level when comparing group II with the control group. The MIF, NTX was highly associated with osteoporosis patients, in addition to Mg and Vit-D. On the other hand, Ca and P levels did not alter in a significant way with osteoporosis which may be considered as a risk factor as long as they are organized in one cluster with MIF, NTX, Mg, and Vit D in all the studied patients. Both markers showed a clear cut-off value using the ROC curve in which the best cutoff value of NTX was 166.8 pg/ml, and the best cutoff value of MIF was 6.6 ng/ml according to ROC analysis.

Modelling cancer outcomes of bone metastatic patients: combining survival data with N-Telopeptide of type I collagen (NTX) dynamics through joint models

BackgroundJoint models (JM) have emerged as a promising statistical framework to concurrently analyse survival data and multiple longitudinal responses. This is particularly relevant in clinical studies where the goal is to estimate the association between time-to-event data and the biomarkers evolution. In the context of oncological data, JM can indeed provide interesting prognostic markers for the event under study and thus support clinical decisions and treatment choices. However, several problems arise when dealing with this type of data, such as the high-dimensionality of the covariates space, the lack of knowledge about the function structure of the time series and the presence of missing data, facts that may hamper the accurate estimation of the JM.MethodsWe propose to apply JM for the analysis of bone metastatic patients and infer the association of their survival with several covariates, in particular the N-Telopeptide of Type I Collagen (NTX) dynamics. This biomarker has been identified as a relevant prognostic factor in patients with metastatic cancer, but only using static information in some specific time points.ResultsWe extended this analysis using the full NTX time series for a larger cohort of patients with bone metastasis, and compared the results obtained by the JM and the extended Cox regression model. Imputation based on fuzzy clustering was used to deal with missing values and several functions for NTX evolution were compared, such as rational, exponential and cubic splines.ConclusionsThe JM obtained confirm the association between NTX values and patients’ response, attesting the importance of this time series, and additionally provide a deep understanding of the key survival covariates.

Elevated N-telopeptide as a potential diagnostic marker for bone metastasis in lung cancer: A meta-analysis.

BackgroundGrowing evidence indicates that the cross-linked N-telopeptide of type I collagen (NTx) is likely to be involved in the development of bone metastasis among lung cancer patients. We perform a meta-analysis to disclose the correlation between bone metastasis and NTx and also to evaluate its value in diagnosis of bone metastasis (BM) in lung cancer.MethodElectronic databases were searched and calculated the weighted mean difference (WMD) with 95% confidence interval (CI) to assess the expression difference of NTx between BM+ and BM- lung cancer patients. Moreover, we conducted a sensitivity and specificity test and drew a summary receiver operating characteristic curve (SROC) to assess the diagnostic value of NTx in discerning bone metastasis.ResultsA total of eleven studies with 1108 individuals were included in this analysis. The results showed an increased NTx was correlated with the incidence of lung cancer (P < 0.001). The overall sensitivity and specificity of serum NTx (sNTx) for discerning bone metastasis was 0.74 (95% CI = 0.67 to 0.79) and 0.85 (95% CI = 0.80 to 0.89), respectively. As for urine NTx (uNTx) the pooled sensitivity and specificity was 0.77(95% CI = 0.67 to 0.86) and 0.81(95% CI = 0.76 to 0.86). The area under the SROC curve was 0.8889(SE = 0.0255) and 0.8655(SE = 0.0254) for sNTx and uNTx respectively.ConclusionsThe elevation of NTx in lung cancer was positively related with the development and progression of bone metastasis. A higher specificity over sensitivity of NTx suggested that it is a more accurate biomarker to distinguish patients without bone metastasis. Regarding SROC curve, sNTx may be a better choice.

Serum cross-linked N-telopeptide of type I collagen for the diagnosis of bone metastases from solid tumours in the Chinese population: Meta-analysis.

ObjectiveA meta-analysis to determine the diagnostic value of serum cross-linked N-telopeptide of type I collagen (NTx) for bone metastasis from solid tumours in the Chinese population.MethodsEligible case–control studies published up until 22 September 2014 were identified by searching the electronic literature databases PubMed®, Web of Science, China National Knowledge Infrastructure and Wanfang using the keyword ‘NTx’ in combination with ‘cancer’. A meta-analysis of the diagnostic value of serum NTx for bone metastasis from solid tumours was undertaken.ResultsThe meta-analysis included 14 studies (1279 patients: 668 with bone metastasis; 611 controls without bone metastasis). There was a significant relationship between serum NTx concentration and bone metastasis from solid tumours in the Chinese population (odds ratio 1.39, 95% confidence intervals 1.26, 1.51). Significant heterogeneity was found in this study, but no publication bias was observed.ConclusionSerum NTx concentration may play an important role in the diagnosis of bone metastasis from solid tumours in the Chinese population.

Urinary N telopeptide levels in predicting the anti-nociceptive responses of zoledronic acid and paclitaxel in a rat model of bone metastases.

The present study investigated the hypothesis that urinary levels of N telopeptide (NTx) can be used to predict the anti-nociceptive responses of zoledronic acid and paclitaxel on bone metastases in a rat model. Rats were implanted with intra-femur Walker 256 carcinoma cells or control solution, and were treated with either normal saline, zoledronic acid or paclitaxel on the 10th day following surgery. Mechanical allodynia was recorded and the urine collagen-crosslinked NTx values were measured prior to, and 7, 14 and 21 days following the injections. Bone sections and osteoclasts were stained on the 14th day (4 days post-injection). Furthermore, the mRNA and protein expression levels of c-fos in the spinal cord and acid-sensing ion channel 3 (ASIC3) in the dorsal root ganglion (DRG) were analyzed. The mechanical allodynia of rats was attenuated from day 14 in the zoledronic acid group and from day 21 in the paclitaxel group. A positive correlation was observed between the anti-nociceptive responses of zoledronic acid and paclitaxel, and the urinary levels of NTx (r=0.619; P<0.001). The mRNA levels of c-fos in the spinal cord and ASIC3 in the DRG in the zoledronic acid group were reduced 14 and 21 days after inoculation, and this reduction was observed in the paclitaxel group 21 days after inoculation. Low dose paclitaxel was observed to have a weaker anti-nociceptive effect on bone cancer pain, with a later-onset, compared with zoledronic acid. The results suggested that urinary levels of NTx may predict the anti-nociceptive responses of zoledronic acid and paclitaxel in a rat model of bone metastases.

D-25 Free Communication/Poster - Physical Activity Correlates

High impact physical training is beneficial for bone structure and mineralization and typically results in increased levels of bone turnover markers. However, the acute effects of a single exercise session on bone markers are unclear. In adults, inconsistent results have been demonstrated following high impact exercise. In children, there is a paucity of data in this area. PURPOSE: To investigate the acute response of bone turnover markers to an exercise session consisting of high mechanical loading in boys and men. METHODS: Participants underwent a protocol of plyometric jumping exercises (total 144 jumps). Venous blood samples were collected pre, 5 minutes post-, 1 hour post- and 24 hours post-exercise session to measure bone-specific alkaline phosphatase (BAP), amino-terminal cross-linking telopeptide (NTx), osteoprotegrin (OPG) and receptor activator of nuclear factor kb ligand (RANKL). RESULTS: Boys had higher BAP levels, with an increase 24 hours post-exercise (111.9±29.2 vs. 137.6±36.3 μg/L, respectively), which was not observed in the men (31.4±11.1 vs. 33.3±10.5 μg/L, respectively). NTx levels were higher in boys, with a greater increase over time in boys than in men (boys: 48.7±13.7 vs. 58.8±16.7 nM BCE pre- and 24 hours post-exercise, respectively; men: 21.7±5.4 vs. 19.4±5.0 NM BCE pre- and 24 hours post-exercise, respectively). OPG and RANKL levels were similar in boys and men before and after exercise, with no change over 24 hours. CONCLUSIONS: These results indicate that even one session of exercise stimulates bone turnover, as reflected in the increase in both BAP and NTx values, in boys (but not men) within 24 hours.

A comparison of the measurements with biochemical markers of bone turnover and bone mineral density in the assessment of the efficiency of osteoporosis treatment

This study aims to compare the measurements using biochemical markers of bone turnover and bone mineral density (BMD) in the assessment of the efficiency of osteoporosis treatment. Between March 2006 and December 2008, 166 patients with osteoporosis in our clinic were included. Patients who were out of contact due to death or other reasons during follow-up were excluded. We compared the measurements of urinary biochemical markers of bone turnover using cross-linked N-telopeptide (Ntx) values and BMD in 60 patients (49 females, 11 males; mean age: 65.7 years; range: 42 to 87 years) with osteoporosis who were treatment-naive and completed study. Twenty-nine (48.3%) of the patients received surgical treatment, while 31 (51.7%) received conservative therapy. Urine NTx values of the patients decreased 38.82% at three months; 51.99% at six months and 66.41% at 12 months. Lumbar vertebra BMD increased by 20.7% and femur neck BMD increased by 11.9% at the end of the first year. Urine NTx values respond to osteoporosis treatment faster than BMD measurements; thereby it may be suitable to use this parameter for the monitorization of the treatment efficiency.

Abstract P1-07-18: Association between Bone Turnover Markers in patients with breast cancer and bone metastases on treatment with bisphosphonates (ZOMAR study)

Abstract Background: The presence of bone metastases (BMe) alters the balance of bone remodeling and consequently, levels of bone turnover markers (BTM). Increased levels of these biomarkers are related to the risk of skeletal-related events (SREs), disease progression and death. Treatment with bisphosphonates reduces the probability of SREs through osteoclastic activity inhibition. The aim of this study was to determine the relation between BTM, bone metastasis development and SREs, disease progression and death in patients with breast cancer (BC) and BMe. Patients and methods: Observational, prospective and multicenter study. Patients with BC and BMe; no previous bone treatment in the last 6 months prior to study entry. Urinary aminoterminal telopeptide of collagen I (NTX, Osteomark NTx Urine, Wampole Laboratories, USA); urinary alpha-alpha-isomer of carboxyterminal telopeptide of collagen I (αα-CTX, ALPHA Crosslaps EIA, ids, UK) and serum bone alkaline phosphatase (BALP, OSTASE BAP, ids, UK) were determined at baseline (V0) and every 3 mo along 18 months (V6). Patients were treated with zoledronic acid (ZA) at inclusion and every 3–4 weeks. Results: 234 patients with BC and BMe were analyzed. BTM results were available for 219 patients at basal visit (V0) and every 3 mo of treatment along 18 months (V6). Population basal characteristics (234 patients): mean age: 59.8 years; ER+: 80.3%; PR+: 64.9%; HER 2+: 18.3%. Patients with pathologic baseline levels were: 49.8% NTX, 39.6% αα-CTX and 83.4% BALP. A significant decrease was observed in BTM at V2 vs V0 after 6 months: 13.7%, 8.4% and 58.4% presented pathologic values of NTX, αα-CTX and BALP respectively. Normalized levels remained steady throughout 18 mo follow-up, finding significant decrease for each BMT for each time point except at V6 for αα-CTX. Regarding association between BTM and SREs, progression and exitus, a significant association was observed between pathologic levels of BTM throughout follow-up: with SRE at V3, V4 for NTX; with disease progression at V3, V4, V5, V6 for NTX, at V2 for αα–CTX and at each follow up visit for BALP; and with death at V1,4,5 for NTX, at V5 for αα–CTX and at V1,2,3,4,5 for BALP. Conclusions: Addition of ZA to standard systemic therapy reduced BTM levels during the first 3 months of treatment and normalized levels remained steady throughout 18 months follow up except at Month 18 for αα-CTX. Pathological levels of BTM were significantly associated with SRE, disease progression and death. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-18.

Usefulness of Biochemical Markers of Bone Turnover in the Evaluation of Venezuelan Patients with Multiple Myeloma

AbstractAbstract 5003Multiple Myeloma is a neoplastic disease of B-lymphocyte that invariably mature into plasma cells, synthesizing abnormal amounts of immunoglobulin or their fragments. Bone destruction is a relevant clinical finding and is responsible for the major signs of the disease. Since the osteolytic lesions of Multiple Myeloma do not heal rapidly, imaging studies and changes in the levels of monoclonal proteins cannot reflect the progress or regression of the bone disease during the anti-myeloma treatment. The purpose of this study is to establish the Profile of Biochemical Markers of Bone Turnover present in Venezuelan patients with Multiple Myeloma. The study was carried out in patients diagnosed with Multiple Myeloma that attended, during the year 2009, the Hematology Service of the “Dr. Miguel Pérez Carreño” General Hospital in Caracas, Venezuela. Methods:A descriptive, transversal, unicentric study was carried out in a single auto-comparable group. Urinary NTx osteoclastic activity biomarkers (Reticulated Collagen-type I N-telopeptides) and serum CTx (C-terminal telopeptide of type I collagen) were processed, as well as the osteoblastic activity biomarkers osteocalcin and bone specific alkaline phosphatase. Results:A total of 34 patients were included: 68% males and 32% females. By the International Staging System (ISS) 45% were stage I; 23 % stage II, 32% stage III. The average value of osteocalcine was the following: 15. 1 ± 9. 5 in stage I; 20. 9 ± 14. 5 in stage II and 25. 2 ± 23. 3 in stage III. The average value of bone specific alkaline-phosphatase was: 19. 1 ± 7. 7 in stage I; 20. 9 ± 8. 4 in stage II and 18. 4 ± 5 in stage III. The average value of CTx was: 2 ± 0. 6 in stage I; 2. 5 ± 0. 7 in stage II and 3. 3 ± 2. 5 in stage III. The average value of urinary NTx was: 48. 3 ± 21. 7 in stage I; 56 ± 22. 9 in stage II and 58. 7 ± 19. 2 in stage III. Discussion:It can be seen that the average value of serum CTx was elevated in all the states of the disease, regardless of the classification used to study the patients. It was also found that this value increases as the disease becomes more severe; that is to say, the more advanced the stage of the patient's disease. This is more significant when using the ISS to study the patients. The value of the urinary NTx osteoclastic activity was never high or outside its reference range. The osteoblastic activity markers osteocalcin and bone specific alkaline-phosphatase never appeared outside their average reference value. Conclusion:Serum CTX osteoclastic activity biomarker is useful to establish the severity of the bone disease in patients with Multiple Myeloma. The urinary NTX osteoclastic activity biomarker and the osteoblastic activity markers osteocalcin and bone specific alkaline-phosphatase do not appear to be useful to establish the severity of the bone disease in patients with Multiple Myeloma. Disclosures:No relevant conflicts of interest to declare.

Randomized trial of marker-directed versus standard schedule zoledronic acid for bone metastases from breast cancer.

511 Background: Zoledronic acid (ZOL) reduces skeletal morbidity associated with metastatic bone disease by 30-50%. Current recommendations are for indefinite administration of intravenous 3-4 weekly (w) ZOL 4mg. Over recent years it has become clear that the risk of skeletal morbidity is related to the rate of bone resorption. We have compared a marker directed schedule of ZOL (M-ZOL), using measurements of urinary n-telopeptide of type I collagen (NTX), to a standard treatment schedule (S-ZOL) in patients with bone metastases from breast cancer. Methods: The primary endpoint was skeletal related events (SRE). A non-inferiority study was designed with 80% power and (one-sided) 5% alpha to demonstrate that M-ZOL retained 67% of the efficacy of S-ZOL. This required 1500 patients, assuming a SRE rate of 0.7/year. Following minimisation for known prognostic factors, patients were randomised to receive S-ZOL 3-4 w or M-ZOL (15-16w; 8-9 w or 3-4w if NTX levels were &lt;50, 50-100, &gt;100 nmol/mmol creatinine respectively), with the schedule adjusted according to NTX measured every 16 weeks. The study duration was 24 months. Results: Due to lower than expected recruitment, the study closed in 2009 following recruitment of 289 patients. 90% of patients had received &gt;4 cycles of ZOL or pamidronate prior to randomisation. The median number of ZOL infusions administered to S-ZOL patients was &gt;2x that received on M-ZOL. 46 (32%) S-ZOL and 55 (38%) M-ZOL patients experienced an SRE. The numbers of SRE were 94 and 138 in the S-ZOL and M-ZOL arms, with the excess in SRE being largely due to more patients on M-ZOL experiencing ≥2 SRE. Multivariate analysis adjusting for key minimisation factors and baseline NTX for all SRE showed a hazard ratio for M-ZOL vs. S-ZOL of 1.41 (90%CI 0.98-2.02, p=.12). NTX levels were significantly higher at all time points in the M-ZOL treated patients. Osteonecrosis of the jaw was uncommon with 3 cases with S-ZOL and 1 with M-ZOL. Conclusions: The study is underpowered to demonstrate non-inferiority in SRE outcome between the treatment strategies. However, the results suggest that the adjustment of ZOL schedule based on NTX values alone may represent sub-optimal management.

25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis

It remains unclear whether vitamin D sufficiency optimizes response to bisphosphonate (BP) treatment in postmenopausal osteoporosis. We evaluated the role and possible mechanisms of vitamin D in adequate response to standard BP treatment for postmenopausal osteoporosis. MethodsWe included 120 postmenopausal osteoporotic women (aged 68±8years) receiving BP (alendronate or risedronate) at their annual follow-up, performing complete anamnesis, including treatment adherence, use of vitamin D supplements, and previous falls and fractures during the last year. We analyzed the evolution of bone mineral density (BMD) during this period and serum PTH and 25 hydroxyvitamin D (25(OH)D) and urinary NTx levels. Patients were classified as inadequate responders to antiosteoporotic treatment based on BMD loss>2% and/or the presence of fragility fractures during the last year. ResultsThirty percent of patients showed inadequate response to BP treatment, with significantly lower levels of 25(OH)D (22.4±1.3 vs. 26.6±0.3ng/ml, p=0.01), a higher frequency of 25(OH)D levels<30ng/ml (91% vs. 69%, p=0.019) and higher urinary NTx values (42.2±3.9 vs. 30.9±2.3 nM/mM, p=0.01). Patients with 25(OH)D>30ng/ml had a greater significant increase in lumbar BMD than women with values <30ng/ml (3.6% vs. 0.8%, p<0.05). The probability of inadequate response was 4-fold higher in patients with 25(OH)D<30 (OR, 4.42; 95% CI, 1.22–15.97, p=0.02). ConclusionsInadequate response to BP treatment is frequent in postmenopausal women with osteoporosis as is vitamin D insufficiency, despite vitamin D supplementation. Maintenance of 25(OH)D levels >30ng/ml is especially indicated for adequate response to BP treatment.

Serum N-Telopeptide and Bone-Specific Alkaline Phosphatase Levels in Patients With Osteonecrosis of the Jaw Receiving Bisphosphonates for Bone Metastases

Oversuppression of bone turnover can be a critical factor in the pathogenesis of osteonecrosis of the jaw (ONJ). We investigated N-telopeptide of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) as potential predictors of ONJ onset. Patients with ONJ and available stored serum were identified retrospectively from the institutional databases. Four approximate points were examined: point of ONJ diagnosis and 12, 6, and 1 month before the diagnosis. NTX and BAP were measured using enzyme-linked immunosorbent assays and examined as possible predictors of ONJ. From March 1998 to September 2009, we identified 122 patients with ONJ. Of these, 56 (46%) had one or more serum samples available. Overall, 55 patients (98%) received bisphosphonates. Using the exact dates, no obvious patterns in either NTX or BAP were noted. Similarly, using the ordinal points, no evidence of suppression of NTX or BAP over time was seen. The consecutive median values were as follows: The median NTX values were 8.0 nmol/L (range 3.8 to 32.9) at 12 months before ONJ; 9.5 nmol/L (range 4.7 to 42.7) at 6 months; 9.5 nmol/L (range 4.5 to 24.6) at 1 month, and 10.4 nmol/L (range 4.4 to 32.5) at the ONJ diagnosis. The median BAP values were BAP 18.0 U/L (range 7.0 to 74) at 12 months before ONJ; 18.0 U/L (range 4.0 to 134) at 6 months; 14.0 U/L (range 4.0 to 132) at 1 month, and 18.0 U/L (range 0.7 to 375) at the ONJ diagnosis. Only 2 patients (4%) had NTX and 17 (30%) had BAP below the normal range at the ONJ diagnosis. In the present large retrospective study, no trends were seen in the NTX and BAP levels before the ONJ diagnosis.

Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n = 23) or who did not develop refractory SHPT (control subjects; n = 25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

Reduction of urinary levels of N-telopeptide correlates with treatment compliance in women with postmenopausal osteoporosis receiving alendronate

The aim of this study was to assess the factors associated with the effectiveness of treatment with alendronate (ALN) quantified by a reduction in urinary excretion of N-telopeptide (NTx). The study is an observational, prospective, multicenter trial, with a 6-month follow-up. Postmenopausal osteoporotic women (densitometric criteria), who initiated treatment with ALN (70 mg/weekly) without previous treatment with antiresorptive agents (12 month) and calcitonin (6 month), were included. The assessment of NTx levels (nmol bone collagen equivalents/mmol creatinine) in the urine was performed at baseline and after completion of follow-up. A logistic regression model included "achieving a reduction in urinary NTx of at least 30% (minimal clinically significant change [MCSC])" as a dichotomous dependent variable and the following as independent variables: baseline urinary NTx levels, treatment compliance, years since diagnosis of menopause, ALN treatment duration, and treatment with calcium and vitamin D. Treatment compliance was assessed as the percentage of days of medication prescribed as a function of the time between the beginning and end of treatment. Good compliance was defined as a percentage between 80% and 120%. The variables that reached statistical significance were baseline urinary NTx values (odds ratio, 1.052; 95% CI, 1.025-1.079) and compliance (odds ratio, 3.9; 95% CI, 1.5-10.1). Therefore, the women with good treatment compliance were almost 4 times more likely to achieve an MCSC in NTx levels, and the raise in one unit of urinary NTx baseline values increased by 5% of the probability of achieving MCSC. Treatment with ALN (70 mg/week) in women with postmenopausal osteoporosis effectively reduces the urinary excretion of the bone turnover biomarker NTx. The probability of achieving a clinically significant reduction is greater in those women with higher baseline levels of NTx and in women who comply with treatment.

Intermediate study: Observational study about levels of biochemical markers of bone turnover in patients with breast cancer and bone metastases (ZOMAR study)

Changes in bone metabolism can be detected through the determination of biochemical markers of bone turnover (BTM). Increased levels of these biomarkers are related to the risk of skeletal events (SREs), disease progression and death in patients with bone metastases associated to cancer. The aim of ZOMAR study is to investigate the relationship among BTM, disease evolution and SREs in patients with breast cancer (BCa) and bone metastases (BMe). An observational, prospective and multicentric study was performed in a cohort of patients with BCa and BMe. Urinary aminoterminal telopeptide of collagen I (NTX, Osteomark NTx Urine, Wampole Laboratories, USA), urinary alpha-alpha-isomer of carboxiterminal telopeptide of collagen I (alpha-alpha-CTX, ALPHA Crosslaps EIA, ids, UK) and serum bone alkaline phosphatase (BALP, OSTASE BAP, ids, UK) were determined in basal conditions (V0, n=133) and after 3 months of treatment (V1, n=66) with zolendronic acid (ZA). 49.4%, 55.6%, and 88.2% of the patients presented elevated values of NTX, alpha-alphaCTX and BALP respectively in V0. Levels of the three BTM studied decreased significantly in V1 with respect to V0. NTX: 92%, p 0.005; BALP: 74%, p<0.005. The above results show that, in basal conditions, the most sensitive, among the studied BTM, in order to detect the presence of bone metastases in BCa is BALP. ZA produced a significant decrease in BTM levels after 3 months of treatment. This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: C. De La Piedra Grant / Research Support from Novartis Laboratories, I. Tusquets: none declared, P. Gomez: none declared, C. Crespo: none declared, L. Calvo: none declared, L. Manso: none declared, P. Martinez: none declared, M. Ruiz-Borrego: none declared, A. Murias: none declared, and A. Barnadas: none declared. doi:10.1016/j.bone.2011.03.614 PP484-S 3D characterization of the vascular bed in bone metastasis of the rat by microcomputed tomography (microCT) H. Nyangoga, H. Marchand-Libouban, M.F. Basle, D. Chappard ⁎ IRIS-IBS Institut de Biologie en Sante, INSERM, U922-LHEA, Angers, France Abstract: Angiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques Angiogenesis contributes to proliferation and metastatic dissemination of cancer cells. Anatomy of blood vessels in tumors has been characterized with 2D techniques (histology or angiography). They are not fully representative of the trajectories of vessels throughout the tissues and are not adapted to analyze changes occurring inside the bone marrow cavities. We have characterized the vasculature of bone metastases in 3D at different times of evolution of the disease. Metastases were induced in the femur of Wistar rats by a local injection of Walker 256/B cells. Microfil®, (a silicone-based polymer) was injected at euthanasia in the aorta 12, 19 and 26 days after injection of tumor cells. Undecalcified bones (containing the radio opaque vascular casts) were analyzed by microCT, and a first 3D model was reconstructed. Bones were then decalcified and reanalyzed by microCT; a second model (comprising only the vessels) was obtained and overimposed on the former, thus providing a clear visualization of vessel trajectories in the invaded metaphysic allowing quantitative evaluation of the vascular volume. Histological analysis of the marrow was possible on the decalcified specimens. Walker 256/B cells induced a marked osteolysis with cortical perforations. The metaphysis of invaded bones became progressively hypervascular. New vessels replaced the major central medullar artery coming from the diaphyseal shaft. They sprouted from the periosteum and extended into the metastatic area. The newly formed vessels were irregular in diameter, tortuous with a disorganized architecture. A quantitative analysis of vascular volume indicated that neoangiogenesis increased with the development of the tumor. This new method evidenced the tumor angiogenesis in 3D at different development times of the metastasis growth. Bone and the vascular bed can be identified by a double reconstruction and allowed a quantitative evaluation of angiogenesis upon time. Image / Graph: This article is part of a Special Issue entitled ECTS 2011. Disclosure of interest: None declared. doi:10.1016/j.bone.2011.03.615 Abstracts / Bone 48 (2011) S251–S260 S252

Early Changes in Bone Specific Turnover Markers During the Healing Process After Vertebral Fracture

Background:The present study measured longitudinal changes in bone turnover markers in elderly patients with vertebral fracture and investigated the relationship among bone turnover markers, duration of bed rest and bone mineral density (BMD).Methods:Criteria for patient selection were 50 years in age and older, and presence of VF. Serum bone-specific alkaline phosphatase (BAP) was measured as a marker of bone formation. Urinary crosslinked N-terminal telopeptides of type I collagen (NTX) was measured as a marker of bone resorption. In principle, samples were collected just after injury, within 24 h, and 1, 2, 3, 5 and 8 weeks after. We also measured duration of bed rest and BMD.Results:The study population consisted of 42 cases. The average BMD of the lumbar vertebrae was 0.670 ± 0.174 g/cm2. Bed rest period was 17.9 ± 8.8 days. BAP showed significantly higher values at 2 and 3 weeks compared with the baseline value. Thereafter, BAP progressively decreased until 8 weeks. Urinary NTX was increased soon after the onset of pain with the same patterns in BAP. Urinary NTX values reached a peak at 3 weeks, and then they kept significantly higher values until 8 weeks. The peak value of serum BAP was affected by the duration of bed rest, although that of the urinary NTX was not. The peak values of serum BAP and urinary NTX showed negative correlations with the initial BMD values.Conclusions:Bone turnover markers remained higher at 8 weeks, even patients symptom was healed after VF. Bone turnover markers were affected on physical activity and BMD.

Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition

The purpose of this study was to determine the longitudinal association between menopausal vasomotor symptoms (VMS) and urinary N-telopeptide level (NTX) according to menopausal stage. We analyzed data from 2283 participants of the Study of Women's Health Across the Nation, a longitudinal community-based cohort study of women aged 42 to 52 years at baseline. At baseline and annually through follow-up visit 8, participants provided questionnaire data, urine samples, serum samples, and anthropometric measurements. Using multivariable repeated-measures mixed models, we examined associations between annually assessed VMS frequency and annual NTX measurements. Our results show that mean adjusted NTX was 1.94 nM of bone collagen equivalents (BCE)/mM of creatinine higher among early perimenopausal women with any VMS than among early perimenopausal women with no VMS (p < .0001). Mean adjusted NTX was 2.44 nM BCE/mM of creatinine higher among late perimenopausal women with any VMS than among late perimenopausal women with no VMS (p = .03). Among premenopausal women, VMS frequency was not significantly associated with NTX level. When NTX values among women with frequent VMS (≥6 days in past 2 weeks) were expressed as percentages of NTX values among women without frequent VMS, the differences were 3% for premenopausal women, 9% for early perimenopausal women, 7% for late perimenopausal women, and 4% for postmenopausal women. Adjustment for serum follicle-stimulating hormone (FSH) level greatly reduced the magnitudes of associations between VMS and NTX level. We conclude that among early perimenopausal and late perimenopausal women, those with VMS had higher bone turnover than those without VMS. Prior to the final menstrual period, VMS may be a marker for risk of adverse bone health. © 2011 American Society for Bone and Mineral Research.

Osteocalcin and specific markers of bone resorption in sickle cell disease

Sickle cell disease commonly causes avascular necrosis of bone. Plain radiographs are not useful if obtained early in the disease. Radionuclide scans do not appear to increase the sensitivity of the diagnosis. Magnetic resonance imaging can detect disease but this is expensive and hard to employ on a routine or regular basis. The determination of the following new biochemical markers of bone metabolism has not been previously performed in sickle cell disease: serum osteocalcin (S-BGP), urinary cross-linked aminoterminal telopeptide of type I collagen (INTP or NTx) and urinary deoxypyridinoline (U∼DPD). As a first step or preliminary study we evaluate the usefulness of these biochemical markers of bone metabolism, by measuring the plasma or serum and urine levels of these markers in 20 adult patients with sickle cell disease. There was no change in S-BGP (p<0.9) a biochemical marker of bone formation. The two markers of bone resorption, urinary NTx (p<0.002) and U-DPD (p<0.001) increased highly significantly. Although the mean values of urinary NTx and U-DPD were significantly elevated in five patients with clinical evidence of bone complications, only two of these subjects had values above mean +2 SD of normal (control) mean values. Hence the sensitivity and specificity of these measures need to be further investigated with a larger sample size. There was significant correlation (P < 0.001) between NTx and U-DPD. These preliminary findings indicate that urinary NTx and U-DPD should be further investigated as possible biochemical markers of skeletal changes in SCD.