Urinary NTX Research Articles

An analysis of osteoporosis in patients with hereditary multiple exostoses.

There are few reports of osteoporosis in hereditary multiple exostoses (HME) patients. Therefore, the purpose of this study was to analyze osteoporosis in HME patients. This retrospective cohort study included 20 patients diagnosed with HME. Patients underwent bone mineral density (BMD) measurement of the lumbar spine (n= 20) and femoral neck (n= 40). Bone metabolic parameters, including serum osteocalcin and urinary cross-linked N-telopeptide of type 1 collagen (NTx), were analyzed in all subjects. EXT1 and EXT2 genes were sequenced using genomic DNA. We also examined the correlation between genotype and BMD Z-score and T-score. The mean BMD values of the lumbar spine were 1.085 ± 0.116g/cm2 (n= 11) in male and 1.108 ± 0.088g/cm2 (n= 9) in female. The mean BMD values of the femoral neck area were 0.759 ± 0.125g/cm2 (n= 22) in male and 0.749 ± 0.115g/cm2 (n= 18) in female. Z-score of most HME patients show < 0, indicating that these patients tend to have low bone mass compared with the age-matched population. According to the T-score of BMD, 30% (6 of 20) and 67.5% (27 of 40) of the patients fell in the range of osteopenia in the lumbar spine and femoral neck areas, respectively. Serum osteocalcin and urinary NTx were in the normal range in most patients. There was no significant correlation between genotypes and Z-score. HME patients have low bone mass, especially in the femoral neck area. They do not have abnormal bone metabolism, and there was no correlation between genotypes and Z-score.

Female Distance Runners Display Altered Bone Remodeling In Fasted Blood And 24 Hour Urine Biomarkers

An increase in underlying bone remodeling is associated with increased fracture risk. The International Osteoporosis Foundation recommend overnight fasted plasma C-terminal cross linked telopeptide type 1 collagen (CTX) and N-terminal propeptide of type 1 procollagen (P1NP) as bone turnover markers (BTM) of homeostatic bone remodeling. Reflected by an increase in plasma CTX, endurance exercise increases bone resorption acutely for a number of hours post-exercise. Female distance runners (FDR) engage in frequent weight-bearing endurance exercise that may alter homeostatic bone remodeling and fracture risk. PURPOSE: To compare bone remodeling in FDR and non-athletic controls (CON). METHODS: Daily 24 h urine samples and fasted morning blood samples were collected for 7 consecutive days of habitual activity in 7 FDR (training volume ≥ 60 km/week; mean ± SD age: 24.1 ± 4.6 y, height: 1.70 ± 0.05 m, mass: 58.5 ± 5.5 kg, fat %: 18 ± 4%) and 11 CON (≤3 h/week intentional vigorous physical activity; mean ± SD age: 23.9 ± 4.1 y, height: 1.67 ± 0.05 m, mass: 64.5 ± 4.4 kg, fat %: 33 ± 6%) who provided prior informed consent for a study which had ethical approval. Plasma CTX and P1NP was measured by automated immunoassay (Roche Diagnostics) and urinary N-terminal cross linked telopeptide type 1 collagen (NTX) by ELISA (Osteomark). Data were pooled and analyzed independent of participant. Data violated the assumption of normality and are reported as the median (IQR). Groups were compared by Mann-Whitney U test. RESULTS: Median CTX was 31.4% lower (0.393(0.147) vs 0.573(0.333) ng/ml; p<0.001; d=0.7) and P1NP was 14.5% lower (55.12(32.39) vs 64.43(16.73) ng/ml; p=0.012; d=0.5) in FDR compared to CON. In contrast, median 24 h NTX was 36.7% higher in FDR (434.2 (572.7) vs 317.6 (302.6) nM bone collagen equivalents; p=0.033; d=0.4) compared to CON. CONCLUSION: Lower overnight fasted CTX and P1NP are deemed devoid of influence exerted by previous exercise or food intake and may indicate an adaptive, regulatory effect of chronic exercise training on systemic (homeostatic) bone remodeling in FDR. By contrast, 24 h urine NTX captures total bone resorptive activity, including response to exercise and diet accrued during the previous 24 h and appear to confirm significantly greater net daily bone resorption in FDR compared to CON.

A Preliminary Study of the Effect of Hyperadrenocorticism on Calcium and Phosphate Concentrations, Parathyroid Hormone and Markers of Bone Turnover in Dogs.

Reports on the effects of hyperadrenocorticism (HAC) on bone turnover in dogs are largely confined to radiographic studies. The aim of this study was to more accurately assess bone turnover in dogs with HAC by measuring circulating total and ionized calcium and phosphate concentrations, both intact and whole parathyroid hormone (PTH) concentrations and markers of both osteoblastic (osteocalcin) and osteoclastic [carboxyterminal cross-linked telopeptide of type 1 collagen (ICTP) and urine aminoterminal telopeptide of type 1 collagen (NTX) activity]. Dogs with HAC and a control group were prospectively enrolled for comparison. Results from 49 dogs with HAC were compared with 39 dogs from a hospital control population. Plasma intact and whole PTH concentrations were determined using a human immunoradiometric assay. Serum osteocalcin and NTX concentrations were measured using human enzyme linked immunosorbent assays. Serum ICTP concentration was measured using a human radioimmunoassay. Total calcium concentrations in dogs with HAC (2.67 ± 0.25 mmol/L) were not significantly different than in the control group (2.67 ± 0.14 mmol/L). By contrast, phosphate concentrations were significantly (P = 0.0143) higher in dogs with HAC (1.46 ± 0.30 mmol/L) compared to the control group (1.28 ± 0.33 mmol/L). The median intact PTH concentration in HAC dogs was 9.25 (range, 1.34–95.45) pmol/L, which was significantly (P < 0.0001) higher than in the control group [median, 3.88 (range, 2.01–10.31) pmol/L]. Whole PTH concentrations were also significantly (P < 0.0001) higher in the HAC group [median, 4.61 (range, 0.56–125.16) pmol/L] compared to the control group [median, 1.83 (range, 0.88–6.81) pmol/L]. Serum osteocalcin and urine NTX concentrations were not significantly different between the two groups of dogs. The median ICTP concentration in dogs with HAC was 2.98 (range, 1.15–6.62) ng/mL which was significantly (P < 0.0001) lower than in the control dogs [median, 7.30 (range, 3.68–21.25) ng/mL]. Both whole and intact PTH concentrations are increased in dogs with HAC compared to a hospital control population. This does not however appear to be associated with a decrease in bone formation (as assessed by osteocalcin) or an increase in bone resorption (as assessed by ICTP and urine NTX).

SUN-412 Graves’ Disease Displayed as a Risk Factor of Vertebral Fracture Even in Premenopausal Women

BackgroundHyperthyroidism is a known risk factor for osteoporosis and fractures especially in older men and postmenopausal women. However, it remains unclear whether younger patients with Graves’ diseases are at a higher risk of fracture compared to healthy individuals.ObjectiveThis study aimed to clarify whether premenopausal women with Graves’ disease represents a risk factor for vertebral fracture (VF).Patients and MethodsWe enrolled 30 premenopausal women (mean age, 32 ± 10 years) who were diagnosed with Graves’ disease at our institution between April 2007 and December 2017. We also enrolled 40 healthy control women who visited our hospital. The control subjects were confirmed to have no endocrine disease or any condition that might affect bone metabolism. None of the study subjects had taken drugs known to influence bone and calcium metabolism such as vitamin D, bisphosphonates, or glucocorticoids. Also, none has taken an oral contraceptive. Serum and urinary biological parameters, alkaline phosphatase (ALP), glycosylated hemoglobin (HbA1c), creatinine, serum calcium, total cholesterol, intact parathyroid hormone, free triiodothyronine (Free T3), free thyroxin (Free T4), thyroid-stimulating hormone (TSH) and urinary type I collagen cross-linked N-telopeptides (NTX; a bone resorption marker) were compared between the groups. Bone mineral density (BMD) of the lumbar spine and femoral neck was determined using dual-energy X-ray absorptiometry and vertebral fractures were diagnosed from lateral X-rays of the thoracic and lumbar spine. The chi-square and unpaired t-tests for two groups comparison were utilized to determine the statistical significance (P < 0.05). Multiple logistic regression analyses were proceeded after adjustments for variables.ResultsPatients with Graves’ disease displayed the higher ALP, eGFR, Ca, free T3, free T4 and urinary NTX levels, and lower body mass index (BMI), Alb, total cholesterol and intact PTH compared to controls.The prevalence of VFs was significantly higher in patients with Graves’ disease (20.0%) than in controls (2.5%, <0.05). Such association remained significant even after adjustment for age, BMI, ALP, eGFR and free T3, but except for BMD. Among premenopausal patients with Graves’ disease, the values of several parameters, such as BMI, ALP, HbA1c, serum Ca, intact PTH and BMD and the prevalence of thyroid related antibodies did not differ significantly between those with and without VF; subjects with VF were older and exhibited lower free T3, free T4 and urinary NTX levels compared to subjects without VF. The mean value of lumbar BMD T score in subjects with VF among premenopausal patients with graves’ disease was -1.0, indicating osteopenia.ConclusionsVF risk could be elevated even in the premenopausal women with Graves’ disease, although the BMD risk levels is not equivalent to that of osteoporosis.

Zoledronik asit osteoporozlu β-talasemi hastalarında kemik mineral yoğunluğunu arttırır: Bir vaka kontrol çalışması

Purpose: This study addresses the efficacy of zoledronic acid treatment in osteoporotic patients with β-thalassemia.Materials and Methods: Thirty-nine thalassemic patients were enrolled in this study. Bone mineral density was measured using Dual energy x-ray absorbtiometry (DEXA), and biochemical markers of osteoporosis in serum and urine were measured at 0, 6, and 12 months of treatment. Patients with thalassemia were randomly received either zoledronic acid 4 mg IV once every six months or calcitriol 0.25 mcg / day for 12 months. A subgroup analysis was also performed according to gonadal status. Results: There were 21 males and 18 females, mean age of 23.1 ± 1.3 and bone age of 16.3±0.35 years. At the end of 12 months, bone mineral densities of the lumbar vertebra and femoral neck significantly increased in the zoledronic acid group. In patients with hypogonadism who received hormone replacement therapy, t-scores significantly increased. Serum NTX levels indicated significant increase in both treatment groups compared with the control group at the end of the treatment. A significant increase was obtained in urinary NTX level in hypogonadal patients who received zoledronic acid, and in serum NTX and IGF-1 levels in normogonadal patients who received calcitriol. Conclusion: In our study, zoledronic acid resulted in significant improvement in bone mineral density and t-scores. This improvement was in correlation with IGF-1 levels.

The Effect of a Low Glycemic Index Pulse-Based Diet on Insulin Sensitivity, Insulin Resistance, Bone Resorption and Cardiovascular Risk Factors during Bed Rest.

We determined the effects of a low glycemic-index pulse-based diet (i.e., containing lentils, chick peas, beans, and split peas) compared to a typical hospital diet on insulin sensitivity assessed by the Matsuda index from the insulin and glucose response to a two-hour oral glucose tolerance test, insulin resistance assessed by the homeostatic model assessment of insulin resistance (HOMA-IR), bone resorption assessed by 24 h excretion of urinary n-telopeptides(Ntx) and cardiovascular risk factors (blood lipids, blood pressure, arterial stiffness and heart rate variability) during bed rest. Using a randomized, counter-balanced cross-over design with one-month washout, six healthy individuals (30 ± 12 years) consumed the diets during four days of bed rest. The Matsuda index, HOMA-IR, urinary Ntx and cardiovascular risk factors were determined at baseline and after the last day of bed rest. Compared to the typical hospital diet, the pulse-based diet improved the Matsuda index (indicating increased insulin sensitivity; baseline to post-bed rest: 6.54 ± 1.94 to 6.39 ± 2.71 hospital diet vs. 7.14 ± 2.36 to 8.75 ± 3.13 pulse-based diet; p = 0.017), decreased HOMA-IR (1.38 ± 0.54 to 1.37 ± 0.50 hospital diet vs. 1.48 ± 0.54 to 0.88 ± 0.37 pulse-based diet; p = 0.022), and attenuated the increase in Ntx (+89 ± 75% hospital diet vs. +33 ± 20% pulse-based diet; p = 0.035). No differences for changes in cardiovascular risk factors were found between the two diet conditions, with the exception of decreased diastolic blood pressure during day three of bed rest in the pulse-based versus hospital diet (61 ± 9 vs. 66 ± 7 mmHg; p = 0.03). A pulse-based diet was superior to a hospital diet for maintaining insulin sensitivity, preventing insulin resistance, attenuating bone resorption and decreasing diastolic blood pressure during four days of bed rest.

Additive effects of eldecalcitol in poorly responding long-term bisphosphonate treatment for osteoporosis

ObjectivesWe examined whether eldecalcitol (ELD) provided additive bone mineral density (BMD) and bone turnover marker gains in patients undergoing long-term bisphosphonate (BP) usage, especially in osteoporotic individuals exhibiting a poor response to BPs. MethodsForty-two post-menopausal patients with primary osteoporosis and low lumbar BMD (L-BMD) and/or bilateral total hip BMD (H-BMD) values receiving long-term BP treatment were prospectively enrolled. Serum bone alkaline phosphatase (BAP) was measured as a bone formation marker and urinary N-terminal telopeptide of type I collagen (NTX) was assessed as a bone resorption marker. L-BMD, H-BMD, and femoral neck BMD (N-BMD) were recorded before, at the commencement of, and during ELD administration. ResultsBAP and urinary NTX were significantly decreased by BP therapy prior to ELD. ELD addition further significantly decreased the bone turnover markers (both p < 0.01). The mean L-BMD increase rate was 0.2% (p = 0.81) from 2 to 1 years before ELD administration, −0.7% (p = 0.30) during the year before ELD, and 2.9% (p < 0.01) during 1 year of ELD. Similar findings were observed for the mean increase rate of H-BMD, with values of 0.2% (p = 0.55), −0.7% (p < 0.01), and 1.2% (p < 0.01), respectively. The mean N-BMD increase rate was significantly increased after ELD administration (1.1%, p = 0.03) despite no gains by BP therapy alone. ConclusionsThis study suggests that ELD addition may be useful for osteoporotic patients exhibiting a diminished long-term BP therapy response.

Changes in bone metabolic profile associated with pregnancy or lactation

Calcium and nutrients are transferred from mothers to fetuses or infants during pregnancy or lactation, respectively, promoting metabolic changes in the mother, many uncharacterized. To evaluate these changes, we undertook two parallel studies. In one we analyzed fourteen clinical cases of vertebral fragility fractures, at or before three months after partum, in mothers who breastfed their infants. In the other, we enrolled 79 additional pregnant subjects, some who chose to breastfeed and others who did not, and analyzed changes in bone metabolic status starting between 34 and 36 weeks of gestation and ending one month after partum. In the larger group, bone-resorbing and bone-forming parameters such as serum TRACP5b and osteocalcin, respectively, significantly increased after partum. Among parameters that changed after partum, serum PTH and the bone-resorbing markers serum TRACP5b and urine NTX were significantly higher in mothers who only breastfed infants compared to mothers who fed infants formula or a mix of both. However, bone-forming parameters were comparable between breastfeeding and non-breast-feeding groups after partum, suggesting that elevated bone-resorption occurs only in the breastfeeding group. Radiographic analysis after partum demonstrated that no subject among the 79 analyzed showed vertebral fractures, even those who breastfed exclusively. Among fracture cases analyzed, subjects exhibited significantly lower bone mineral density than did non-fracture cases in breastfeeding-only subjects. We conclude that bone metabolic status significantly changes over the period between pregnancy and post-partum lactation, and that low bone mineral density seen in a small subset of breastfeeding-only cases likely causes post-partum vertebral fragility fractures.

Tartrate-resistant acid phosphatase 5b, but not periostin, is useful for assessing Paget's disease of bone.

Periostin is a matricellular protein with a preferential location in cortical bone and periosteal tissue, and tartrate-resistant acid phosphatase 5b (TRAP5b) is a marker of osteoclast numbers. In Paget's disease of bone (PDB), there is increased cortical thickening and probably increased periosteal apposition, along with increased osteoclast numbers. To analyse if circulating periostin is a biomarker for PDB, and if it is associated with disease activity and involvement of long bones that represent major cortical contribution. Also, to analyse whether TRAP5b, a scarcely explored bone resorption marker, is useful in the assessment of PDB. We recruited 42 patients with PDB (13F/29M; 71 ± 11.6 yrs). 71.4% had active disease, 66.6% had polyostotic disease and 54.8% had long bone involvement. Blood and urine samples were taken between 8:00 and 10:00 A.M. after an overnight fast. Periostin and TRAP5b were measured in serum, using commercial ELISA assays (Biomedica and IDS, respectively). Serum total ALP, PINP, CTX, bone ALP and urinary NTX were measured. Reference values for periostin and TRAP5b were obtained from 45 healthy subjects. Serum periostin did not differ between patients and controls (989.4 ± 173.2 vs. 966.9 ± 195.4 pMol/L, p = 0.572). No significant differences were observed between patients with and without active disease (964.5 ± 168.8 vs.1051.6 ± 175.6 pMol/L, p = 0.143), involvement or not of long bones (1022.2 ± 145.8 vs 949.7 ± 198.2 pMol/L, p = 0.181) and monostotic or polyostotic disease (963.8 ± 198.7 vs 1002.2 ± 161.4 pMol/L, p = 0.505). There were significant correlations between serum periostin and all bone turnover markers (bone ALP, PINP, uNTX, sCTX and TRAP5b) in PDB patients with active disease, but not in the inactive PDB group. Serum TRAP5b was significantly higher in PDB patients than in controls (4.43 ± 1.76 vs. 3.21 ± 1.02 U/L, p < 0.001), in those with active disease (4.98 ± 1.76 vs. 3.07 ± 0.72 U/L, p < 0.001) and in patients with polyostotic disease than in those with monostotic disease (4.81 ± 1.79 vs 3.68 ± 1.5 U/L, p = 0.005). TRAP5b levels were not influenced by previous bisphosphonate treatment (4.14 ± 1.42 vs. 4.84 ± 2.02 U/L, p = 0.206). Periostin is not useful for assessing PDB, whilst TRAP5b, which has been a scarcely explored bone turnover marker until now, may be useful in the analysis of this disease, providing new information on the resorption process. In addition, periostin levels correlate with all classical BTMs in active PDB, suggesting that this marker may reflect periosteal and cortical metabolism in accelerated bone turnover states.

Calcium and vitamin D supplementation with 3-year denosumab treatment is beneficial to enhance bone mineral density in postmenopausal patients with osteoporosis and rheumatoid arthritis.

BackgroundThis 3-year retrospective study compared the outcomes of bisphosphonate-pretreated denosumab therapy with or without vitamin D and calcium supplementation in postmenopausal osteoporosis (OP) patients with rheumatoid arthritis (RA).Materials and methodsFifty-eight patients under long-term denosumab treatment were divided into groups without (denosumab group; 31 cases) or with (combination group; 27 cases) vitamin D and calcium supplementation. The bone markers of BAP, TRACP-5b, and urinary NTX were measured at baseline and every year for 3 years. We also evaluated bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and bilateral total hips (H-BMD) at the same time points.ResultsThere were no significant differences in the percent changes of serum albumin-corrected calcium between the groups. The percent change in TRACP-5b was significantly higher in the combination group at 2 years. Serum 25-hydroxyvitamin D status was persistently high during therapy in both groups, with significant percent increases over baseline at 2 and 6 months in both groups and at 24 months in the combination group. The percent increase from baseline of serum zinc was significantly higher at 3 years in the combination group over the denosumab group. L-BMD and H-BMD were significantly increased at every time point for 3 years vs pretreatment levels in both groups and were significantly higher in the combination group at all time points.ConclusionCompared with denosumab monotherapy, the combination group displayed significantly increased serum zinc, L-BMD, and H-BMD at 3 years in OP patients with RA. Thus, calcium and vitamin D supplementation may be beneficial to enhance BMD gains, but not necessarily 25-hydroxyvitamin D status, in patients with OP and RA under denosumab.

Maternal type 1collagen N-terminal telopeptide levels in severe hyperemesis gravidarum

BackgroundNausea and vomiting occur 50–90% during the first trimester of pregnancy. However, patients with hyperemesis gravidarum (HG) may be hospitalized at an incidence rate of 0.8–2% before the 20th week of gestational age. The symptoms generally start during the 5–6th gestational weeks, reaching the highest degree during the 9th week, and decline after the 16–20th weeks of gestation. Clinical findings are proportional to the severity of the disease and severe HG is characterized with dehydration, electrolyte imbalance, and nutritional deficiency as a result of vomiting.MethodsThe study population consisted of two groups of pregnant volunteers at 5–12 weeks of gestation: a severe HG group and a control group. The HG severity was scored using the Pregnancy-Unique Quantification of Emesis (and nausea) (PUQE).The serum levels of the maternal Ca, parathyroid hormone (PTH), Na, K, blood urea nitrogen(BUN), creatinine, vitamin D(25OHD3), and the maternal urine NTx levels were compared between the groups.ResultsIn total, 40 volunteers were enrolled in this study: 20 healthy pregnant volunteers and 20 with severe HG. There were no statistically significant differences between the maternal characteristics. The first trimester weight loss of ≥5 kg was significantly higher in the severe HG group (p < 0.001), while the control group had a significantly higher sunlight exposure ratio than the severe HG group (p = 0.021). The urine NTx levels were significantly higher in the severe HG group (39.22 ± 11.68NTx/Cre) than in the control group(32.89 ± 8.33NTx/Cre) (p = 0.028).The serum Ca, PTH, Na, K, BUN, and creatinine levels were similar between the groups (p = 0.738, p = 0.886, p = 0.841, p = 0.957, p = 0.892, and p = 0.824, respectively). In the severe HG group, the serum 25OHD3 levels were significantly lower than in the control group (p < 0.001).ConclusionsThe data from this study indicated that severe HG is associated with increased urine NTx levels. However, large-scale studies are required to understand the clinical significance of this finding, as well as the long-term consequences of elevated urine NTx levels and the underlying mechanisms.Trial registrationNCT02862496 Date of registration: 21/07/2016.

Efficacy of 4-year denosumab treatment alone or in combination with teriparatide in Japanese postmenopausal osteoporotic women

Purpose: This extended randomized prospective study aimed to compare the 4-year clinical outcomes of denosumab treatment alone or in combination with teriparatide in treatment-naïve postmenopausal Japanese patients with osteoporosis.Methods: Between July 2013 and December 2016, 30 eligible women from our previous study were enrolled. After newly adding 17 randomly assigned patients, 47 patients were classified into the denosumab alone group (denosumab group, n = 22) or denosumab plus teriparatide group (combination group, n = 25). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptide of type I collagen (NTX), and bone mineral density (BMD) of the lumbar 1–4 vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at regular time points up to 48 months of treatment to determine percentage changes.Results: BAP was significantly decreased from baseline in both groups from 24 to 48 months, with significant differences at all time points between the groups. TRACP-5b and urinary NTX were comparably decreased at every time point in both groups versus pretreatment levels. L-BMD was significantly more increased by combination therapy over denosumab alone at 24 and 30 months (21.1% increase vs. 14.2% increase at 48 months). There were no significant differences in H-BMD between the groups, although levels tended to be higher in the combination group throughout the study period (9.7% increase vs. 6.8% increase at 48 months).Conclusion: Long-term denosumab and teriparatide combination therapy represents an effective treatment option for primary osteoporosis patients with low L-BMD.

Prednisolone Effects on Urine Cross-Linked N-Telopeptides of Type I Collagen (Ntx) Diurnal Rhythms in Children.

Recently, methods for mimicking endogenous cortisol rhythms hereby potentially reducing the risk of systemic adverse effects of exogenous corticosteroids have been patented. Methods for sensitive detection of adverse effects on bone turnover of various doses, administration routes and regimens of exogenous corticosteroids have been patented. Urine cross-linked Ntelopeptides of Type I collagen (Ntx) have been established as a sensitive bone resorption marker and urine levels of Ntx have been found to exhibit a distinct diurnal rhythm. To assess whether the timing of administration of prednisolone affects the diurnal rhythm of Ntx in urine. Four girls and four boys aged 10.6 to 15.8 (mean 13.2) years with normal weight and height and pubertal stages I-IV were studied in an open randomized 2-periods cross-over trial, with a 1-day run in, and two 4-day periods of 5mg prednisolone in the morning and in the evening, respectively, separated by a 3-week washout period. At run in and on the last day of each treatment period, the first sample of urine was collected from 24.00 to 08.00h in the morning of the day of investigation. Thereafter, urine was collected in 4~hour intervals until 24.00 and in another 08.00h interval from 24.00 to 08.00h. Compared to run in and morning prednisolone treatment urine Ntx levels were suppressed from 24.00 to 8.00h during treatment with prednisolone in the evening (P < 0.01 for both comparisons) and no statistically significant circadian rhythm was observed. During morning prednisolone treatment Ntx trough and peak levels occurred from 16.00 to 20.00 and 24.00 to 08.00h, respectively, and the Ntx levels were significantly reduced from 12.00 to 20.00h as compared to run in (P < 0.005) and prednisolone treatment in the evening (P < 0.01). Depending on the time of administration, prednisolone interferes with diurnal rhythms in urine Ntx.

Friday, September 28, 2018 10:30 AM–12:00 PM abstracts: complications of cervical spine surgery: 162. Urinary N-telopeptide can predict pseudarthrosis after anterior cervical decompression and fusion (ACDF): a prospective study

BACKGROUND CONTEXT Anterior cervical decompression and fusion (ACDF) is one of the most successful and widely performed spine surgeries. Although high rates of fusion have been reported, there is a risk for pseudarthrosis. Urinary cross-linked n-telopeptide of type I collagen (uNTx), is an important marker of bone turnover and may prove useful as a predictor of fusion in pts undergoing ACDF. PURPOSE The purpose of present study was to examine the association of preop uNTx level and successful fusion after ACDF. STUDY DESIGN/SETTING Prospective cohort study. PATIENT SAMPLE Adult patients who underwent ACDF with allograft and plating technique. OUTCOME MEASURES Fusion status was assessed using radiographic criteria published by Song et al. METHODS Patients undergoing primary ACDF with allograft and plating technique from 2015 to 2017 by a single surgeon were consecutively enrolled and preop uNTx was measured. Revision cases, improperly timed uNTx collection, pts with a Cr>1.2 were excluded. Demographics, operative, laboratory and fusion data was assessed at 6 months, 1 year and 2 years. NDI and VAS outcome scores were compared between fusion and nonfusion groups. Regression analysis was performed to assess the association of preop uNTx and successful fusion. RESULTS Of the 97 patients enrolled, 67 met inclusion criteria and were studied. 41%, 33%, 18% and 8% underwent one, two, three and four level ACDFs, respectively. Fusion rates were 37.3% at 6 months (n=67), 70.9% at 1 year (n=55) and 95.3% at 2 years (n=43). The preop uNTx was higher in the fusion group at 6mo (31 vs. 22, p CONCLUSIONS Urinary NTx was higher in patients with successful ACDF fusion compared to patients with radiographic pseudarthrosis at 6 months and 1 year. A linear relationship between uNTx levels and Fusion was observed. Surgeons should consider measuring uNTx prior to cervical fusion procedures to identify patients at risk for pseudarthrosis.

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

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

Phase II trial of SM 88 in non-metastatic biochemical recurrent prostate cancer.

175 Background: Despite toxicity and no clear survival benefit, non-metastatic recurrent prostate cancer (nmPC) is typically treated with androgen deprivation therapy (ADT). SM88 is a relatively non-toxic novel combination therapy (amino acid analogue, CYP3a4 inducer, mTOR inhibitor and catalyst) based on the Warburg effect, with activity in a variety of cancers including prostate (JCO 2017 35, e16567). Phase I and II results demonstrated stable or rising testosterone levels while achieving a reduction of CTCs (circulating tumor cells) and no radiographic progression events (Annal Oncol 2017, 28(5):274-5). We now report results for toxicities typically seen with ADT. Methods: Prospective ongoing Phase Ib/II of SM88 (230mg po bid) in recurrent nmPC with rising PSA (PCWG3 definition), detectable CTCs, and no radiographically identified metastases at baseline. Results: Since Sept 2016, there have been 17 consented (of 34 planned) with 10 evaluable (completed &gt; 1 cycle) (median 7, range 1-13). Mean age was 71.2 (53-84); all had prior ADT after curative intent RT (50%) or surgery (50%); with no patient currently on ADT. Mean testosterone level was 307.6 ng/dL before SM88 and 349.2 after (p = 0.07, one-tail T test), rising in (5/10) or remained stable except for one patient who entered the trial castrate ( &lt; 2.5). Overall 70% had some grade 1-2 adverse event (AE) but no drug related serious AE. EORTC-QLQ-C30 relating to mental function domain (Q20-28) and QLQ-PR25 intimacy domains (Q44-50) remained stable, including 9 (90%) reporting no or resolved hot flashes; 7 (70%) reporting an improved or stable “interest in sex”; and 6 (60%) having “excellent” “overall health” and “QOL”. Weight and osteoporosis (measured by Urinary NTX) did not worsen; mean EKG QTc (422 ms); mean arterial pressure (95.1 mmHg); glucose (115.2 mg/dl) and hematocrit (41.5%) were not affected. Conclusions: Toxicities typically associated with ADT were not seen with SM88, a novel non-hormonal anti-neoplastic. Despite the limited follow-up, these data suggest that ADT may be avoided or delayed without progression in selected patients with nmPC. A phase III RCT of SM88 vs patient choice of hormonal or active surveillance is planned for confirmation of these results. Clinical trial information: NCT02796898.

Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial.

Tocotrienols (TT) have been shown to benefit bone health in ovariectomized animals, a model of postmenopausal women. The purpose of this study was to evaluate the effect of 12-week TT supplementation on bone markers (serum bone-specific alkaline phosphatase (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine calcium, and an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine (8-OHdG)) in postmenopausal women with osteopenia. Eighty-nine postmenopausal osteopenic women (59.7 ± 6.8year, BMI 28.7 ± 5.7kg/m2) were randomly assigned to three groups: (1) placebo (430mg olive oil/day), (2) low TT (430mg TT/day, 70% purity), and (3) high TT (860mg TT/day, 70% purity). TT, an extract from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT. Overnight fasting blood and urine samples were collected at baseline, 6, and 12weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study. Relative to the placebo group, there were marginal decreases in serum BALP level in the TT-supplemented groups over the 12-week study period. Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to TT supplementation were observed. TT supplementation did not affect serum OPG concentrations or urine calcium levels throughout the study period. There were no significant differences in NTX level, BALP/NTX ratio, sRANKL level, and sRANKL/OPG ratio between low TT and high TT groups. Twelve-week annatto-extracted TT supplementation decreased bone resorption and improved bone turnover rate via suppressing bone remodeling regulators in postmenopausal women with osteopenia. Such osteoprotective TT's effects may be, in part, mediated by an inhibition of oxidative stress. ClinicalTrials.gov identifier: NCT02058420. Tocotrienols and bone health of postmenopausal women.

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.

111P - Changes in urinary NTX in early phase of denosumab therapy might be a predictive indicator in breast cancer patients with bone metastases

111P - Changes in urinary NTX in early phase of denosumab therapy might be a predictive indicator in breast cancer patients with bone metastases

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

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