Serum Carboxy-terminal Telopeptide Of Type Research Articles

Abstract 12381: Elevated Serum Carboxy-Terminal Telopeptide of Type I Collagen is Associated With Clinical Outcomes in Patients With Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention

Background: Despite high risk of developing cardiovascular events, it was reported to be difficult to predict clinical outcomes in patients with stable angina pectoris (AP). Serum carboxy-terminal telopeptide of type I collagen (I-CTP), a marker of collagen degradation, was reportedly associated with clinical outcomes in patients with acute coronary syndrome. However, clinical usefulness of I-CTP has not yet been elucidated in patients with stable AP. The aim of this study was to examine whether I-CTP can predict clinical outcomes in patients with stable AP. Methods and Results: Serum I-CTP levels were measured in consecutive 360 patients with stable AP undergoing percutaneous coronary intervention. All patients were divided into three groups according to serum I-CTP tertiles: low I-CTP group (≤4.4 ng/ml, n=120), middle I-CTP group (4.5-6.2 ng/ml, n=118), and high I-CTP group (≥6.3 ng/ml, n=122). The high I-CTP group was older and showed higher levels of brain natriuretic peptide (BNP) and lower levels of estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) compared with other groups. During the median follow up period of 1,347 days, there were 68 cardiovascular events including all-cause deaths. Kaplan-Meier analysis showed that the high I-CTP group had the greatest risk for cardiovascular events among 3 groups. Univariate Cox proportional hazard regression analysis showed that age, multivessel disease, BNP, eGFR, LVEF, and I-CTP were significantly associated with cardiovascular events. Multivariate Cox proportional hazard analysis demonstrated that I-CTP was an independent predictor for cardiac events after adjusting for confounding risk factors. Conclusion: I-CTP could be the feasible marker for predicting cardiovascular events in patients with stable AP.

Potential of a rumen bolus containing 1,25-dihydroxyvitamin D3 glycosides for the prevention of hypocalcaemia in primiparous and multiparous dairy cows

Periparturient hypocalcaemia is a widespread metabolic disorder in dairy cows. Clinical and subclinical cases occur primarily in multiparous (Multi) cows, but subclinical cases have also been reported in primiparous (Primi) cows. A preventive strategy was investigated by administering the physiologically active vitamin D3 metabolite, 1,25-dihydroxyvitamin D3 (1,25-dihydroxycholecalciferol, 1,25(OH)2D3) as a rumen bolus. The bolus contained tablets of 1,25(OH)2D3 glycoside extract from Solanum glaucophyllum (SGE), releasing SGE over several days. The aim was to study the effect of a bolus containing 0 (C) or 500 µg (SGE) of 1,25(OH)2D3 on 1,25(OH)2D3 and mineral status in periparturient cows up to three weeks into lactation and on colostrum, milk and calves’ blood mineral contents. The bolus was administered three to four days prior to expected calving to Primi and Multi cows fed a herbage-based diet (dietary cation-anion difference of +522 mEq/kg DM). One C or SGE bolus was applied to 12 Primi and 12 Multi cows. Blood was regularly sampled (and selected a posteriori for antepartum samples) in regard to the actual calving day (d0), immediately prior to bolus application and at day −2, 0.5, 1, 1.5, 2, 4, 8, 11, 15, 18 and 22. Additional samples included urine (at bolus application, d0.5 and d2), colostrum, milk samples (weekly) and calves’ blood (d2). Blood serum 1,25(OH)2D3 increased between d0.5 and d2 in Primi-SGE, but remained unchanged in Primi-C, as did parathyroid hormone (PTH) and Ca in all Primi. Urinary Ca of Primi-SGE was increased on d2, indicating regulation of Ca excess. Three Multi-C cows with confirmed clinical hypocalcaemia needed treatment and thus were excluded from the dataset and replaced. Blood serum 1,25(OH)2D3 and PTH increased while Ca dropped by 40% between d0.5 and d2 in Multi-C, whereas 1,25(OH)2D3, Ca and PTH remained unchanged in Multi-SGE. Blood serum carboxyterminal telopeptide of type I collagen was higher in Primi than in Multi and increased with time, except in Primi-C. Mineral contents in colostrum, milk and blood serum of calves were not influenced to a relevant degree. In conclusion, Primi-C did not, in contrast to Multi-C, develop subclinical hypocalcaemia (<2.0 mmol Ca/l). Prevention of hypocalcaemia with one SGE bolus applied three to four days prior to expected calving was successful in maintaining blood Ca within normal range in Multi over the critical first two days and up to the first three weeks of lactation, without any observed detrimental effects on cows or calves.

Референтные уровни карбокситерминального телопептида коллагена I типа в сыворотке крови у жителей Украины разного возраста и пола

Целью исследования является определение референтного уровня карбокситерминального телопептида коллагена I типа (β-CTX) в сыворотке крови у практически здоровых мужчин и женщин разного возраста, проживающих на территории Украины. Материалы и методы. В исследование были включены 4754 лица в возрасте 20–89 лет (4123 женщины (средний возраст — 59,6 ± 13,6 года) и 631 мужчина (средний возраст — 49,5 ± 16,3 года)). Всех участников распределили по возрасту на 7 групп по десятилетиям (от 20 до 89 лет), и три возрастные группы — 40–49, 50–59 и 60–69 лет — дополнительно разделили на подгруппы по пятилетиям. Также распределение пациентов проводили по геронтологической классификации возраста на 4 группы: молодой возраст — 20–44 года, средний — 45–59 лет, пожилой — 60–74 года и старческий возраст — 75–89 лет. Концентрацию β-CTX определяли в сыворотке крови методом электрохемилюминесцентного иммуноанализа ECLIA на анализаторе Сobas e 411. Результаты. Определено достоверное влияние возраста на вариабельность β-CTX в сыворотке крови: достоверное повышение уровня β-CTX с возрастом у женщин (p &lt; 0,00001) и снижение у мужчин (p &lt; 0,00001). Достоверно более низкий уровень β-CTX обнаружили у женщин в возрасте 20–29 (p &lt; 0,00001) и 30–39 лет (p &lt; 0,00001) по сравнению с мужчинами данного возраста. Однако у женщин 65–69 лет (p = 0,001) выявили достоверно более высокий уровень β-CTX в сыворотке крови по сравнению с мужчинами этой же возрастной группы. Выводы. Обнаружили связь уровня β-CTX в сыворотке крови с возрастом: у мужчин он достоверно снижается с возрастом, у женщин — достоверно повышается. У молодых мужчин в возрасте 20–44 года и женщин в возрасте 65–69 лет концентрация β-CTX была достоверно выше по сравнению с лицами противоположного пола этого же возраста. Полученные нами результаты в отношении уровня β-CTX у практически здоровых лиц разного возраста, проживающих на территории нашей страны, могут быть использованы как референтные показатели для населения Украины.

Elevated serum carboxy-terminal telopeptide of type I collagen predicts clinical outcome in patients with acute coronary syndrome who underwent percutaneous coronary intervention

Abstract Introduction Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is a collagen degradation product of type I collagen in the extracellular matrix of the heart, blood vessels, and bone. The serum levels of I-CTP were reportedly a predictive marker for cardiac remodeling after acute myocardial infarction. However, it remains unclear whether I-CTP can predict poor clinical outcome in patient with acute coronary syndrome (ACS). Purpose The aim of this study was to investigate the association between serum levels of I-CTP and clinical outcome in patients with ACS. Methods Serum levels of I-CTP were measured in 200 patients with ACS who underwent percutaneous coronary intervention (PCI). All patients were prospectively followed during the median follow-up period of 1312 days with the end point of major adverse cardiovascular events (MACE). We divided the patients into tertiles according to serum I-CTP level: low I-CTP group (≤4.4 ng/ml, n=72), middle I-CTP group (4.4–6.4 ng/ml, n=65), and high I-CTP group (≥6.5 ng/ml, n=63). Results There were 44 MACE, including 24 all-cause death and 9 rehospitalization due to heart failure. I-CTP was significantly higher in patients with MACE than those without (4.90 [interquartile range (IQR): 3.80–6.38] ng/ml vs. 6.65 [IQR: 5.00–10.08] ng/ml, p&amp;lt;0.001). Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP had the greatest risk of MACE. In a univariate analysis, age, Albumin, estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (LDL-C), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP) and I-CTP were significant predictors of MACE. A multivariate Cox proportional hazard analysis showed that the high I-CTP group had a higher risk for MACE (Hazard ratio [HR] 2.6, p=0.049) compared with the low I-CTP group after adjusting for confounding factors. Conclusions I-CTP was significantly associated with MACE, suggesting that I-CTP could be a reliable marker for clinical outcome in patients with ACS who underwent PCI. Figure 1 Funding Acknowledgement Type of funding source: None

Reveromycin A Inhibits Bone Loss in Ovariectomized Mice

Background and objectives: Reveromycin A inhibits bone metastasis of lung cancer cells in natural killer cell-depleted immunodeficient mice with increasing apoptosis of osteoclasts. This knowledge suggests that reveromycin A is a potent inhibitor for osteoclasts in vivo. To determine the activity of bone loss in acute estrogen deficiency, we studied ovariectomized mice treated with reveromycin A. Materials and Methods: Eight-week-old female C57BL/6 mice were either ovariectomized or sham-operated. Reveromycin A was continuously administered for the first 2 weeks (Group RA) or the last 2 weeks (Group RP) using a subcutaneous mini osmotic pump. Mice were sacrificed 4 weeks after surgery. Inhibition was detected by images as well as serum carboxyterminal telopeptide of type I collagen (CTX). Results: BMD reduction in the RA group was significantly inhibited and was comparable with that in the sham group. In contrast, the RP group failed to inhibit BMD reduction. The plasma CTX level at the 28th day of the experiment was significantly increased in the RP and OVX groups compared with that in the sham group, while the increase was inhibited in the RA group. Morphometric analysis revealed that absorption of trabecular bone was strongly inhibited in the RA group. Conclusion: The inhibitory effects of reveromycin A administered immediately after ovariectomy was the most effective at the early phase of bone loss than at the later stage. A new reagent that inhibits bone loss in acute estrogen deficiency might be a new tool to experimentally study osteoporosis and may have clinical implications.

Effects of Curcumin on Bone Loss and Biochemical Markers of Bone Turnover in Patients with Spinal Cord Injury.

Osteoporosis is one of the most common problems of patients with spinal cord injuries (SCIs). The current study aimed to evaluate the antiosteoporotic effects of curcumin on densitometry parameters and biomarkers of bone turnovers among patients with SCI. The current controlled clinical trial was conducted among 100 patients with SCI referred to an outpatient clinic of rehabilitation in Ilam City, Iran, in 2013-2015. The intervention group received 110/mg/kg/day curcumin for 6 months and the control group received placebo. Bone mineral density (BMD) was measured in all patients. The level of procollagen type I N-terminal propeptide, serum carboxy-terminal telopeptide of type I collagen, osteocalcin, and bone-specific alkaline phosphates were compared before and after study. BMD indicators of lumbar, femoral neck, and total hip in the control group significantly decreased compared with the beginning of study. However, in the curcumin group, a significant increase was observed in BMD indicators of lumbar, femoral neck, and hip at the end of study compared with the beginning. There was also a significant difference between interventional and control groups for the mean BMD of femoral neck and hip at the end of study (0.718 ± 0.002 g/cm2 vs. 0.712 ± 0.003 g/cm2 and 0.742 ± 0.031 g/cm2 vs. 0.692 ± 0.016 g/cm2, respectively). Curcumin, via modulation of densitometry indices and bone resorption markers, showed inhibitory effects on the process of osteoporosis. Treatment with curcumin was significantly associated with a decrease in the osteoporosis progression and bone turnover markers of patients with SCI after 6 months.

Vildagliptin has the same safety profile as a sulfonylurea on bone metabolism and bone mineral density in post-menopausal women with type 2 diabetes: a randomized controlled trial

BackgroundSeveral antidiabetic therapies affect bone metabolism. Sulfonylureas have the lowest impact on bone among oral antidiabetics. The objective of this study is to compare the effects of vildagliptin and gliclazide modified release (MR) on bone turnover markers (BTMs) and bone mineral density (BMD) in postmenopausal women with uncontrolled type 2 diabetes (T2D).MethodsForty-two postmenopausal women with uncontrolled T2D were randomly allocated into vildagliptin or gliclazide MR (control) groups. The primary endpoint was the change in the BTMs in months 6 and 12 compared with the baseline. The secondary endpoint was the variation in the BMD, which was assessed via dual-energy X-ray absorptiometry at the lumbar spine, femoral neck and total hip at baseline and month 12.ResultsAfter a 12-month treatment, the BTM serum carboxy-terminal telopeptide of type 1 collagen increased 0.001 ± 0.153 ng/mL in the vildagliptin group versus 0.008 ± 0.060 ng/mL in the gliclazide MR group (p = 0.858). The serum osteocalcin, serum amino-terminal propeptide of procollagen type I and urinary amino-terminal telopeptide of type 1 collagen remained stable in both groups, and there was no statistically significant difference between the effect of vildagliptin and gliclazide MR on these variables. The lumbar spine BMD did not change in the vildagliptin or gliclazide MR groups after a 12-month treatment (0.000 ± 0.025 g/cm2 versus −0.008 ± 0.036, respectively, p = 0.434). Furthermore, there was a similar lack of change in the femoral neck and total hip BMD values in both treatments.ConclusionsBone turnover markers and BMD remained unchanged after a 12-month treatment in both groups, which suggests that vildagliptin has the same safety profile as gliclazide MR on bone metabolism.Trial Registration ClinicalTrials.gov number NCT01679899

Biochemical markers of bone turnover in benign paroxysmal positional vertigo.

ObjectiveSeveral studies have suggested a possible relationship between recurrent benign paroxysmal positional vertigo (BPPV) and altered calcium homeostasis in the endolymph of the inner ear. The present study aimed to evaluate the association between Ca2+ and vitamin D status and BPPV occurrence as well as the status of bone biochemical markers in osteoporotic patients who were diagnosed with idiopathic BPPV.MethodsThe study included total 132 patients who were referred to our clinic between August 2008 and October 2013. Based on the bone mineral density (BMD) results, the subjects were divided into three groups: normal BMD (n = 34), osteopenia (n = 40) and osteoporosis (n = 58). The biochemical markers of bone turnover including serum Carboxy-terminal telopeptide of type I collagen (s-CTX), osteocalcin, alkaline phosphatase (ALP) and urinary free deoxypyridinoline (u-DPD), were analyzed, along with the serum Ca2+ and vitamin D levels.ResultsThe mean serum calcium, phosphate and creatinine clearance levels were within the standard laboratory reference range. The incidence of vitamin D deficiency was 11.8% (4/34) in the normal BMD group, 15% (6/40) in the osteopenia group and 43.1% (25/58) in the osteoporosis group. There was a positive correlation between the 25(OH)D and BMD results in the patients with BPPV. Among the bone turnover markers, the osteocalcin and u-DPD levels were significantly elevated in the osteoporotic patients with BPPV. Multiple logistic regression analyses showed that osteoporosis and vitamin D deficiency were associated with BPPV.ConclusionOur findings suggest that the prevalence of BPPV in osteoporotic patients is associated with vitamin D deficiency and high bone turnover rates at systemic level, which could disturb local Ca2+ homeostasis in the inner ear.

Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is predictive of clinical outcome in peripheral artery disease patients following endovascular therapy.

Peripheral artery disease (PAD) is a risk factor for the development of heart failure and mortality. The serum levels of carboxy-terminal telopeptide of type I collagen (I-CTP), a marker for collagen degradation derived from the extracellular matrix of vascular and myocardial tissue, is reportedly a useful marker for cardiac events in patients with heart disease. However, it remains unclear whether I-CTP can predict poor clinical outcome in patients with PAD. Serum I-CTP was measured in 246 consecutive PAD patients who underwent endovascular therapy. Patients were prospectively followed during a median follow-up period of 887days with the end points of major adverse cardiovascular events (MACE). I-CTP was significantly higher in patients with critical limb ischemia than those without. A multivariate Cox proportional hazard analysis revealed that I-CTP was an independent predictor of MACE after adjusting for confounding factors. Patients were stratified into three groups based on I-CTP level tertile, and those with third tertile had higher levels of brain natriuretic peptide levels and high-sensitivity C-reactive protein compared to the other two groups. Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP also had the greatest risk of MACE. The net reclassification index significantly improved with the addition of I-CTP to basic predictors. I-CTP is a reliable marker and indicator for MACE in patients with PAD.

Serum carboxy-terminal telopeptide of type I collagen levels are associated with carotid atherosclerosis in patients with cardiovascular risk factors.

Carboxy-terminal telopeptide of type I collagen (ICTP) is generated through matrix metalloproteinase (MMP)-dependent type I collagen digestion, and has been widely utilized as a biomarker for bone turnover. The fact that atherosclerotic lesions are rich in both type I collagen and MMP-producing macrophages led to the hypothesis that serum ICTP concentrations may serve as a non-invasive clinical biomarker for atherosclerosis. Therefore, the association of serum ICTP concentrations with the maximum intima-media thickness (IMT) of carotid arteries, a surrogate index of systemic atherosclerosis, or brachial-ankle pulse wave velocity (baPWV) in patients with atherosclerotic risk factors was evaluated. A total of 52 male and 65 female (mean age: 62.8 yrs) patients without renal failure, malignancies or bone diseases known to affect serum ICTP concentrations were recruited. Patients with max IMTs ≥1.1 mm showed significantly higher serum ICTP concentrations compared with patients with max IMTs <1.1 mm (3.33 ± 0.97 vs 2.82 ± 0.65 ng/mL, p<0.05). Serum ICTP concentration was also positively correlated with max IMT (p<0.001) or baPWV values (p<0.05). Multivariate analyses also revealed that serum ICTP concentrations were correlated with max IMT (p<0.001; 95% CI 0.200 to 0.454). These results suggest that serum ICTP concentrations can be used as a non-invasive biomarker for systemic atherosclerosis.

Circulating semaphorin-4D and plexin-B1 levels in postmenopausal women with low bone mass: the 3-month effect of zoledronic acid, denosumab or teriparatide treatment

Objective: The evaluation of circulating semaphorin-4D (sema4D) and plexin-B1 in postmenopausal women with low bone mass and the effect of antiresorptive or osteoanabolic treatment.Methods: Serum samples were obtained from postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion (n = 30), denosumab injection (n = 30) or teriparatide initiation (n = 28) and from controls matched for age, age at menopause and body mass index (n = 30) at the same time points.Main outcome measures: Circulating sema4D and plexin-B1.Results: Circulating sema4D increased following denosumab (p = 0.026), whereas decreased following teriparatide (p = 0.013). Sema4D/plexin-B1 ratio increased following denosumab (p = 0.004). At baseline, sema4D and plexin-B1 levels were higher in patients pre-treated with bisphosphonates compared to naïve ones (p < 0.001 and p = 0.001, respectively). In bivariate correlations sema4D was inversely correlated with serum carboxyterminal telopeptide of type 1 collagen (rs -0.282, p = 0.002), intact parathyroid hormone (rs -0.388, p < 0.001) and 25(OH)D (rs -0.316, p < 0.001), whereas there was a trend towards correlation with lumbar spine bone mineral density (rs -0.191, p = 0.053).Conclusions: Sema4D levels are independently associated with previous bisphosphonate treatment, intact parathyroid hormone and 25(OH)D levels. Denosumab and teriparatide seem to exert an opposite effect on circulating sema4D levels. Further studies are needed to evaluate whether sema4D mediates the coupling effect that occurs following both antiresorptive and osteoanabolic treatment.

Strontium-89 for prostate cancer with bone metastases: the potential of cancer control and improvement of overall survival

Strontium-89 (Sr-89) has been considered to have a tumoricidal effect with minimal adverse events. However, few reports have investigated these effects in detail. In this study, we examined the tumoricidal and pain-relief effects of Sr-89 on prostate cancer with bone metastasis as well as survival. A retrospective study was performed involving 31 prostate cancer patients with bone metastasis treated with Sr-89. Using PSA as an evaluation criterion of cancer control, patients were divided into PSA responder and non-responder groups, and the survival rates of these groups were compared. In addition, using the total amount of painkillers administered as an evaluation criterion of pain relief, patients were divided into pain responder and non-responder groups, and the survival rates of these groups were also compared. As secondary investigation items, age, PSA (ng/ml), pain site, extent of the disease, the presence or absence of castration-resistant prostatic cancer (CRPC), the presence or absence of a past medical history of treatment with docetaxel in CRPC cases, Gleason Score, hemoglobin (g/dl), platelet (Plt) (/μl), serum carboxyterminal telopeptide of type I collagen (ng/ml), and bone-alkaline phosphatase (BAP) (U/l) were investigated. Longer survival was expected for the PSA responder group than for the PSA non-responder group, and whether the spine was the pain site and the presence or absence of CRPC were useful as predictors of this. Plt was suggested to be a useful indicator. Furthermore, the survival time was significantly longer in the pain responder group than in the pain non-responder group, and whether the pain site was present in the spine was considered to be a predictor; however, no significant difference was noted in any of the items assumed to be biomarkers. Sr-89 has the potential to control PSA and prolong survival. A large-scale prospective study of the therapeutic effect of Sr-89 is expected.

Serum carboxy-terminal telopeptide of type I collagen (ICTP) as a surrogate marker for vulnerable plaques in atherosclerotic patients: A pilot study

Evaluation of atherosclerotic plaques depends on invasive intravascular ultrasonography (IVUS). Carboxy-terminal telopeptide of type I collagen (ICTP) is produced by matrix metalloproteinase (MMP)-dependent digestion of type I collagen. Because vulnerable plaques are rich in type I collagen and MMPs from macrophages, we examined the association between serum ICTP and coronary plaques in patients with coronary disease. We recruited 46 men and 17 women without renal failure or bone diseases affecting serum ICTP, who underwent coronary IVUS. Serum ICTP levels were higher in patients with coronary plaques containing more than 10% necrotic core area than in patients with less than 10% necrotic core area. A positive correlation was found between serum ICTP and necrotic core area. Only serum ICTP was positively correlated with necrotic core area by multivariate analysis (p < 0.05). These results suggest that serum ICTP can be used as a non-invasive marker of vulnerable plaques in atherosclerotic patients.

Effect of methylprednisolone pulse therapy with and without alendronate on biochemical markers of bone turnover in patients with Graves’ ophthalmopathy

Immunosuppression with glucocorticoids is the method of choice in the treatment of active Graves' ophthalmopathy (GO). However, glucocorticoid therapy may have side effects, among others, it affects bone metabolism. The aim of the study was to compare the effect of methylprednisolone pulse therapy (MPPT) with and without alendronate on bone turnover markers in patients with GO with normal and reduced bone mineral density (BMD). The study included 53 patients with GO and 20 sex- and age‑matched healthy controls. Twenty patients with normal BMD (17 women, 3 men, aged 45 ±1.0 years) received only MPPT (8 g intravenously during 4 weeks). The remaining patients, with reduced BMD, were randomly assigned either to MPPT without alendronate (10 women, 2 men, aged 47 ±1.0 years) or MPPT with alendronate (18 women, 3 men, aged 47 ±1.0 years). BMD of the lumbar spine and femoral neck was assessed using dual energy X‑ray absorptiometry (DEXA) before treatment. The markers of bone formation (serum osteocalcin, carboxyterminal propeptide of type I collagen [PICP], alkaline phospatase) and the markers of bone resorption (serum carboxyterminal telopeptide of type I collagen [ICTP], cross‑linked C‑terminal telopeptide of type I collagen [CTX], serum calcium [Ca] and potassium [P], as well as urinary excretion of deoxypyridinoline, Ca, and P) were determined before and after treatment. MPPT caused a decrease in bone formation markers and an increase in some bone resorption markers. MPPT with alendronate decreased bone formation and bone resorption markers. A negative effect of MPPT on bone turnover is observed both in patients with GO with normal and with reduced BMD. Simultaneous use of MPPT and alendronate in patients with GO and reduced BMD suppresses bone resorption caused by methylprednisolone.

Levels of fetuin‐A relate to the levels of bone turnover biomarkers in male and female patients with type 2 diabetes

To evaluate the relationship of plasma fetuin-A levels with markers of bone turnover in male and female type 2 diabetic subjects. Fetuin-A, which is a serum protein produced by the liver and promotes bone mineralization, is an independent risk factor for type 2 diabetes, whilst type 2 diabetes is associated with an increased incidence of osteoporosis or fractures. It is not known how fetuin-A levels relate to parameters of bone metabolism in type 2 diabetes. Eighty patients with type 2 diabetes [40 men and 40 women matched for age, body mass index (BMI) and time since diagnosis of diabetes] were studied. Fetuin-A together with metabolic parameters and levels of serum carboxy-terminal telopeptide of type 1 collagen (C-telopeptide), osteocalcin, procollagen type 1 amino-terminal propeptide (P1NP), bone alkaline phosphatase (ALP) and sex hormones was determined in all participants. Fetuin-A levels did not differ significantly between male and female diabetic subjects. In a model adjusted for age, BMI, fatty liver index (FLI), time since diagnosis of diabetes, HbA(1c) , antidiabetic and lipid-lowering drug therapies, smoking, total serum protein, creatinine, gamma glutamyl-transferase, parathyroid hormone, C-reactive protein, glomerular filtration rate, and presence of micro-, cardio-, and peripheral vascular diabetic complications, fetuin-A showed a significant positive association with levels of bone ALP (r = 0·71, P = 0·006) in men. In women, fetuin-A was significantly negatively associated with C-telopeptide (r = -0·60, P = 0·03) levels. Results suggest an independent association of fetuin-A levels with markers of bone turnover in male and female patients with type 2 diabetes. More studies are needed to determine whether fetuin-A could serve as a new marker for fracture risk or osteoporosis in type 2 diabetes and to explore its potential sexually dimorphic effects.

Bone metabolism and the muscle–bone relationship in children, adolescents and young adults with phenylketonuria

The aim of the study was to assess body composition in subjects with phenylketonuria (PKU). Forty-five patients aged 13.8 ± 5.2 years were evaluated. Among them, 15 patients had not reached sexual maturity, showing normal serum values of phenylalanine (Phe) (subgroup 1), and 30 subjects were sexually mature (Tanner 5 stage), showing either normal serum Phe (18 cases; subgroup 2a) or increased serum Phe (12 cases; subgroup 2b). DXA-assessed spine and total body (TB) measurements [bone mineral density (BMD), bone mineral content (BMC), lean body mass (LBM) and the calculated ratios BMC/LBM] as well as laboratory parameters (serum carboxyterminal telopeptide of type I collagen, bone alkaline phosphatase, osteocalcin, parathormone, calcitonin, total and ionized calcium) were analyzed. Statistically significant differences were revealed between subgroup 1 versus 2a for TB BMC/LBM ratio SD scores and between subgroup 2a versus 2b for TB BMD, spine BMD, TB BMC/LBM ratio and spine BMC/LBM ratio SD scores. Stepwise multiple regression analysis revealed that serum Phe negatively affected bone status. The skeletal status in children with PKU is impaired by the disease. Applying body composition parameters instead of BMD alone may reflect the level of impairment in a new, different way.

Bone Metabolism in Fetuses of Pregnant Women Exposed to Single and Multiple Courses of Corticosteroids

To estimate the effect of single and recurrent doses of antenatal corticosteroids on fetal bone metabolism. This was a secondary analysis of a cohort of pregnant women from a previously reported randomized, placebo-controlled, multicenter trial of women at risk for preterm delivery who received weekly courses of betamethasone (active) or placebo after an initial course of corticosteroids. Umbilical cord serum levels of carboxy-terminal carboxy-terminal propeptide of type I procollagen and cross-linked carboxy-terminal telopeptide of type I procollagen were measured to assess the rate of fetal bone formation and resorption, respectively. Analysis was stratified according to number of repeat antenatal study courses of betamethasone or placebo (one to three compared with at least four courses, not including the initial course). Of the 251 umbilical cord serum samples, the median serum carboxy-terminal telopeptide of type I procollagen levels, but not carboxy-terminal propeptide of type I procollagen levels, was significantly lower with repeat betamethasone exposure (55.0 compared with 57.9 micrograms/L, P=.01). In the fetuses exposed to at least four repeat study courses, there was a significant decrease in median carboxy-terminal telopeptide of type-I procollagen levels between repeat betamethasone exposure and placebo (53.4 compared with 58.6 micrograms/L, respectively, P=.04), but there was no difference between groups in the fetuses exposed to 1-3 repeat study courses (57.4 compared with 56.7 micrograms/L, respectively, P=.29). Levels of umbilical cord serum markers of bone resorption but not formation are reduced in fetuses exposed to repeat courses of antenatal betamethasone. Up to four courses of antenatal betamethasone do not seem to affect fetal bone metabolism. II.

Assessment of uterus, bone, serum lipids, and hormones in postmenopausal breast cancer patients treated with TAS-108, a novel steroidal antiestrogen: Results of a randomized phase II study

1120 Background: TAS-108, a novel steroidal antiestrogen, has demonstrated a favorable safety profile, including lower agonistic activity on uterus than tamoxifen and supportive effect on bone in preclinical studies. The potential tissue-specific effect of TAS-108 was investigated in postmenopausal breast cancer patients included in a randomized phase II study. (The clinical efficacy and safety results were presented at the 31st San Antonio Breast Cancer Symposium). Methods: Postmenopausal women aged 20–80 years with hormone receptor-positive metastatic breast cancer were eligible for this study and treated with oral TAS-108 (40, 80, or 120 mg/day) once a day. Endometrial thickness (ET) was measured by ultrasonography. The change in Bone Mineral Density (BMD) at lumber spine was assessed by dual energy X-ray absorptiometry. Hormone levels, bone metabolism markers, and serum lipid parameters were also measured at regular intervals. Wilcoxon signed-rank test was used to assess the significance of changes or percentage changes from baseline. Results: Ninety one patients with a median age of 62 years (range 44–80) were included in the analysis population. TAS-108 did not cause significant endometrial thickening (median baseline ET 3.3 mm, last point ET 3.6 mm; n = 36). In particular, after at least 1 year of treatment in 13 cases, no clinically significant increase in ET was found. No change was observed in median BMD (+0.74%; n = 20). Serum carboxy-terminal telopeptide of type I collagen (I CTP) levels remained unchanged although the decrease in osteocalcin levels was significant (p = 0.019; n = 49) in patients without bone metastasis. Median triglyceride levels significantly decreased from 104.0 to 85.0 mg/dl (p = 0.000) after 4 weeks of treatment, while there were no changes in other lipid parameters. An increase in sex hormone-binding globulin and testosterone levels were observed. Conclusions: TAS-108 may have no harmful effects within these parameters and could be used safely. However, further study in a greater number of cases is needed to identify the effect of the long-term use of TAS-108 on the uterus and bone. [Table: see text]

The efficacy of alendronate in wheelchair-bound patients: a 1-year prospective study

The aim of the study was to establish the efficacy of 1-year alendronate treatment in 10 wheelchair-bound participants. In the study were included participants with z-score lower than -2.0 in one of three skeletal sites. Bone status was assessed using dual-energy X-ray absorptiometry at calcaneus and forearm and using quantitative ultrasound at hand phalanges at baseline and after a year. Laboratory variables included serum carboxyterminal telopeptide of type I collagen (ICTP) and bone alkaline phosphatase. Mean values of bone measurements did not differ between baseline and follow-up, the mean value of ICTP nonsignificantly increased and bone alkaline phosphatase significantly dropped (P<0.01). No patient treated revealed the increase in three bone densitometric variables and only one showed a decrease in ICTP exceeding 40% of baseline value. Concluding, in wheelchair-bound participants short-term alendronate therapy does not reduce bone resorption and does not improve the skeletal status.

Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality

To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality. A prospective cohort study. A total of 1280 older men and women living in residential care facilities. We measured baseline serum 25-hydroxyvitamin D (25OHD), serum intact PTH, serum amino-terminal propeptide of type I collagen (PINP) and serum carboxy-terminal telopeptide of type I collagen (CTX-I). Deaths and fractures were recorded prospectively. Hypovitaminosis D (25OHD < 39 nmol/l) and absence of secondary hyperparathyroidism (PTH > 7.0 pmol/l) in the presence of hypovitaminosis D were common in this sample with a prevalence of 77.5% and 53.3%, respectively. In the presence of hypovitaminosis D, residents showing a hyperparathyroid response (n = 406) had significantly higher serum bone turnover markers than individuals with serum PTH levels < or = 7.0 pmol/l (termed 'low vitamin D, normal PTH', n = 463). After adjusting for risk factors, mortality was significantly higher in the secondary hyperparathyroidism group than in the 'low vitamin D, normal PTH' group [hazard ratio (HR) = 1.35, 95% confidence interval (CI) 1.12-1.64; P = 0.002]. All residents with serum PTH levels < or = 7.0 pmol/l (n = 603) were similar with regard to both bone turnover and mortality, independent of their actual vitamin D status. Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D-replete elderly subjects.