Patients with cirrhosis have elevated bone turnover but normal hepatic production of osteoprotegerin

2021 ◽  
Author(s):  
Niklas Rye Jørgensen ◽  
Sarah Seberg Diemar ◽  
Gitte Lund Christensen ◽  
Nina Kimer ◽  
Karen Vagner Danielsen ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Metabolism ◽  
Type I Collagen ◽  
Alcoholic Cirrhosis ◽  
University Hospital ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Bone Metabolism Markers ◽  
Cirrhotic Patients ◽  
Control Study

Abstract Context Severe osteodystrophy is common in patients with liver dysfunction. Markers of bone metabolism may help in early diagnosis of osteodystrophy and in understanding underlying pathophysiological mechanisms. Objective To elucidate changes in bone metabolism associated with cirrhosis and to determine the route of elimination for the markers. Design Case-control study. Setting Public university hospital. Patients Fifty-nine patients with cirrhosis (47 alcoholic and 12 non-alcoholic cirrhosis), 20 controls. Interventions Participants underwent catheterization of the femoral artery, and the hepatic, kidney and femoral veins with collection of blood from all four sites. Main outcome measures Regional arterio-venous differences in concentrations of bone metabolism markers were determined: procollagen of type I collagen propeptide (PINP), C-terminal cross-linking telopeptide of type I collagen (CTX), osteocalcin (OC), tartrate-resistant acid phosphatase isoform 5b (TRAcP5b), osteoprotegerin (OPG), and sclerostin and correlated with degree of disease (Child-Pugh Classification). Results PINP concentration was higher (median: 87.9 µg/L) in patients with cirrhosis than in controls (52.6 µg/L)(p=0.001), while hepatic extraction was lower 4.3% vs. 14.5% (p<0.001). Both CTX and TRAcP5b were higher in cirrhotic patients (340 ng/L and 3.20 U/L) than in controls (215 ng/L and 1.60 U/L)(p<0.001 and p<0.0001). Hepatic sclerostin extraction was lower in cirrhotics (14.6%) than in controls (28.7%)(p<0.0001). In both groups OPG showed a hepatic release rate (production) of 6%. Conclusions Patients with cirrhosis have increased bone resorption, but unaltered bone formation. Sclerostin is eliminated through the liver while OPG is produced in the liver. Bone markers may prove useful in evaluating bone turnover in cirrhosis patients.

scholarly journals Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism

Gut ◽  
1999 ◽  
Vol 44 (3) ◽  
pp. 417-423 ◽  
Author(s):  
S Møller ◽  
M Hansen ◽  
J Hillingsø ◽  
J-E B Jensen ◽  
J H Henriksen
Keyword(s):  
Bone Mass ◽  
Bone Metabolism ◽  
Liver Dysfunction ◽  
Type I Collagen ◽  
Alcoholic Cirrhosis ◽  
Type I ◽  
Mild Degree ◽  
Liver And Kidney ◽  
Cirrhotic Patients ◽  
Carboxy Terminal

BACKGROUNDThe carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy.AIMSTo assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis.METHODSIn 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured.RESULTSCirculating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism.CONCLUSIONSICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.

scholarly journals Diurnal Rhythms of Bone Turnover Markers in Three Ethnic Groups

2016 ◽  
Vol 101 (8) ◽  
pp. 3222-3230 ◽  
Author(s):  
Jean Redmond ◽  
Anthony J. Fulford ◽  
Landing Jarjou ◽  
Bo Zhou ◽  
Ann Prentice ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Metabolism ◽  
Ethnic Groups ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Diurnal Rhythms ◽  
Type I ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Turnover Markers

Context: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role. Objective: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH. Participants: Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country). Interventions: Observational study with sample collection every 4 hours for 24 hours. Main Outcomes: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH. Results: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group. Conclusions: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss.

Prospective observational study for the impact of short-term periodic intravenous steroid premedication for gastrointestinal cancer chemotherapy on bone metabolism.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 523-523
Author(s):  
Atsushi Ishiguro ◽  
Michio Nakamura ◽  
Tetsuhito Muranaka ◽  
Satoshi Yuki ◽  
Taichi Murai ◽  
...  
Keyword(s):  
Observational Study ◽  
Bone Turnover ◽  
Bone Metabolism ◽  
Gastrointestinal Cancer ◽  
Prospective Observational Study ◽  
Type I Collagen ◽  
Reduction Rate ◽  
Type I ◽  
Significant Difference ◽  
The Impact

523 Background: Although intravenous glucocorticoid (GC) premedication (GCP) before chemotherapy (CTx) are frequently used to prevent nausea and vomiting for continuing comfortable CTx, the side effects of intermittent GCs on bone health have not yet been reported. So we designed a multicenter, prospective, observational study to evaluate the impact of periodic GCP on bone metabolism in gastrointestinal cancer (GIC) patients (pts). Methods: The eligibility criteria were as the follows: (i) histologically proven GIC. ; (ii) The duration of periodical GCP is weekly, biweekly, and triweekly. More over 4 weeks GC free intervals is not permissible. ; (iii) age over 20. The primary endpoint was to investigate the variations of bone mineral densities (BMD) at lumbar spine measured by dual energy x-ray absorptiometry (DEXA) and bone turnover biomarkers, cross-linked N-telopeptide of type I collagen (NTX) and bone alkaline phosphatase (BAP), between baseline (BL) and 16 weeks after starting CTx (16w). Results: From June 2013 to April 2015, 98 pts were enrolled. Two pts were not proven as GIC histologically. One patient (pt) was not measured on baseline DEXA. One pt was taken bisphosphonates already on BL point. Four pts were not administered CTx or GCP, and 16 pts were not measured BMD on 16w due to several reasons such as pts refusal, discontinuation of CTx, death and so on (74 pts were full analysis set). In 55 pts (74.3 % of FAS), the levels of BMD at 16w were decreased compared with BL and the average amount of BMD reduction rate was 5.83 % (-38.8 % to 31.1 %). Although no significant difference was found in the level of NTX between BL and 16w (p = 0.118), there was the significant increase of BAP level statistically (p = 0.006). There were also significant correlations between percent change in BMD and NTX, BMD and BAP, NTX and BAP (p = 0.037, 0.029, and 0.003, respectively). Conclusions: We found that periodic GCP in GIC pts caused the reduction of BMD and some influences for bone turnover. These results indicate that GCP might generate more serious osteoporosis of GIC pts during CTx. Further studies are necessary to illustrate the need to prevent GC induced osteoporosis in using GCP. Clinical trial information: 000011054.

FC 076DIAGNOSTIC ACCURACY OF BONE TURNOVER MARKERS IN RENAL OSTEODYSTROPHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Hanne Skou Jørgensen ◽  
Geert Behets ◽  
Etienne Cavalier ◽  
Patrick D'Haese ◽  
Pieter Evenepoel
Keyword(s):  
Bone Turnover ◽  
Kidney Transplant ◽  
Renal Osteodystrophy ◽  
Type I Collagen ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Predictive Values ◽  
Bone Biopsies

Abstract Background and Aims A transiliac bone biopsy is the gold standard for diagnosing renal osteodystrophy, but is not recommended as part of routine clinical workup due to its invasive nature. Suitable non-invasive alternatives have yet to be established. The aim of this study was to investigate the diagnostic accuracy novel biochemical markers of bone remodeling compared to that of biointact parathyroid hormone (PTH) for bone turnover as evaluated by histomorphometry. Method Protocolled bone biopsies were performed in end-stage kidney disease patients (ESKD, n = 80) and kidney transplant recipients (n = 119). Full-length (1-84) PTH, bone-specific alkaline phosphatase (BsAP), intact N-terminal propeptide of type I collagen (P1NP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured. Diagnostic performance was evaluated by area under the receiver operator characteristics curve (AUC). Optimal diagnostic cutoffs were established in an exploration cohort (n=100), and subsequently validated in a separate subset of patients (n=99). Results Mean age was 55±13 years, two-thirds were men (67%), and 23% had diabetes mellitus. Post-transplant eGFR was 49 [IQR 39, 59] ml/min/1.73m². Bone turnover was low in 47 (24%), normal in 119 (60%), and high in 33 (17%) patients. All biomarkers differed significantly across categories of bone turnover (p < 0.001). The AUC of biointact PTH for high turnover was 0.82 (0.73, 0.91), which was not significantly different from AUC values for BsAP, Intact P1NP, and TRAP5b (0.87, 0.90, and 0.86, respectively). AUC of biointact PTH for low turnover was 0.71 (0.63, 0.78), which was significantly lower than the values for BsAP, Intact P1NP, and TRAP5b (0.79, 0.83, and 0.79, respectively; p < 0.05, all). Calculated optimal diagnostic cutoffs in the exploration cohort are shown in Table 1. Applying these cutoffs in the validation cohort revealed high negative predictive values for both high (92 - 96%) and low (82 - 90%) bone turnover. Positive predictive values were consistently low. Conclusion The diagnostic accuracies of BsAP, Intact P1NP and TRAP5b are sufficient to rule out both high and low bone turnover in CKD. Biointact PTH shows inferior performance, particularly in kidney transplant recipients.

scholarly journals Low calcium intake is associated with increased bone resorption in postmenopausal Japanese women: Yokogoshi Study

2009 ◽  
Vol 12 (12) ◽  
pp. 2366-2370 ◽  
Author(s):  
Kazutoshi Nakamura ◽  
Toshiko Saito ◽  
Akihiro Yoshihara ◽  
Miki Ishikawa ◽  
Yasuo Tsuchiya ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Turnover ◽  
Bone Metabolism ◽  
Type I Collagen ◽  
Community Setting ◽  
Serum Markers ◽  
Japanese Women ◽  
Type I ◽  
Cross Sectional ◽  
Markers Of Bone Turnover

AbstractObjectiveLow Ca intake is common among Japanese women, but its effect on bone metabolism has not been fully elucidated. The aim of the present study was to determine the relationship between Ca intake and serum markers of bone turnover in postmenopausal Japanese women.DesignA cross-sectional study.SettingA community setting.SubjectsSubjects were 595 home-dwelling postmenopausal Japanese women. Ca intake was assessed by a validated FFQ. Serum type I collagen cross-linked N-telopeptides (NTX) and osteocalcin were measured as markers of bone turnover. The relationships between demographic characteristics, lifestyles, serum Ca, vitamin D and intact serum parathyroid hormone and bone turnover were also assessed.ResultsThe average age of the subjects was 64·5 (sd 5·8) years and the mean Ca intake was 527 (sd 160) mg/d. Ca intake was significantly associated with serum NTX (P = 0·0104), but not with serum osteocalcin. Mean serum NTX concentration in the lowest quartile of Ca intake (<417 mg/d) was significantly higher than in the fourth, referent quartile. Among these Japanese postmenopausal women, very low Ca intake (less than ∼400 mg/d) was associated with increased bone resorption but not bone formation.ConclusionsIncreased bone resorption may be one mechanism by which this Ca-depleted population normalizes bone metabolism and prevents osteoporosis.

Effect of zoledronic acid and biochemical relapse in treatment-naive patients with bone-metastatic prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 136-136
Author(s):  
Hideyasu Matsuyama ◽  
Masahiro Nozawa ◽  
Takeshi Inagaki ◽  
Kazuhiro Nagao ◽  
Isao Hara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metabolism ◽  
Metastatic Prostate Cancer ◽  
Type I Collagen ◽  
Type I ◽  
Biochemical Relapse ◽  
Bone Metabolism Markers ◽  
Treatment Naïve ◽  
Baseline Psa

136 Background: Recent reports suggest that zoledronic acid have anti-proliferative activity, and that bone metabolism markers predict patient outcome in prostate cancer. Aims of this study are if bone metabolism markers may predict patient outcome who are treated with zoledronic acid concomitant with androgen deprivation therapy (ADT), and if zoledronic acid has oncological benefit in patients with metastatic prostate cancer. Methods: A multi-institutional prospective phase II study was conducted for 54 treatment-naïve patients with bone-metastatic prostate cancer who were treated with zoledronic acid concomitant with ADT (ADT-Z group). Median age, baseline PSA of the patients were 72, and 249ng/ml, respectively. Patients were treated with zoledronic acid (4 mg iv every 4 weeks) in combination with bicalutamide (80mg po) and goserelin acetate (10.8mg sc every 3 months), and followed with a median follow-up of 24.6 months. Serum bone metabolism markers, including bone-specific alkaline phosphatase (BAP) and cross-linked C-terminal telopeptides of type I collagen (I-CTP) and urine levels of cross-linked N-terminal telopeptides of type I collagen (NTx), were measured before treatment followed by every 3 months thereafter, and were compared with biochemical relapse (BCR). BCR of those patients was compared with that of 180 patients who were treated with ADT alone (ADT group) as historical control. Results: Baseline NTx (>100), baseline PSA (>225), EOD (>2) were significantly linked with BCR. Baseline NTx (>100) was an independent predictor for BCR in multivariate analysis (p=0.02). Time to BCR was significantly longer in ADT-Z group than that in ADT group (p<0.0001, median TTP: not reached in ADT-Z vs. 15.4 months in ADT). Conclusions: Zoledronic acid may improve patient prognosis, and baseline NTx may be a useful predictor for BCR in treatment-naïve metastatic prostate cancer patients with zoledronic acid combined with ADT.

Markers of bone metabolism during short-term administration of thyroxine in healthy volunteers

1994 ◽  
Vol 131 (2) ◽  
pp. 145-149 ◽  
Author(s):  
Ernst U Frevert ◽  
Anja Biester ◽  
Manfred J Müller ◽  
Heinrich Schmidt-Gayk ◽  
Alexander von zur Mühlen ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Turnover ◽  
Healthy Volunteers ◽  
Bone Metabolism ◽  
Type I Collagen ◽  
Type I ◽  
Short Term ◽  
Term Administration ◽  
Serum Parameter

Frevert EU, Biester A, Müller MJ, Schmidt-Gayk H, von zur Mühlen A, Brabant G. Markers of bone metabolism during short-term administration of thyroxine in healthy volunteers. Eur J Endocrinol 1994;131:145–9. ISSN 0804–4643. We investigated the influence of L-thyroxine (L-T4) treatment over 3 weeks on biochemical markers of bone turnover in 12 healthy young men (age 25.6 ± 1.4 years, BMI: 22.6 ± 2.5 kg/m2). Serum parameters indicating bone formation [bone Gla protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and bone-specific alkaline phosphatase (BAP)] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and the urinary excretion of pyridinoline (Pyr) and deoxypyridinoline (D-Pyr)] were measured before and after three weeks of treatment with 300 μg L-T4/d. T3 and T4 significantly increased and TSH decreased to almost undetectable levels even when measured with a third generation TSH assay. Markers of bone formation showed variable responses with a small but significant increase in BGP but not in PICP or BAP. In contrast, all parameters of bone resorption increased significantly with a good correlation between D-Pyr excretion and the serum parameter ICTP (r = 0.78, p < 0.0001). These changes in bone-turnover markers were not necessarily paralleled by comparable increments of other markers of tissue thyrotoxicosis (SHBG, pulse rate, VO2), suggesting a variability in tissue sensitivity. These rapid responding parameters, especially in the easily obtainable serum parameter ICTP, might be valuable tools in the evaluation of several states of thyroxine excess. G Brabant, Dept. Klinische Endokrinologie, Medizinische Hochschule Hannover, D-30 623 Hannover, Germany

scholarly journals Effects of different vibration frequencies on muscle strength, bone turnover and walking endurance in chronic stroke

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhenhui Yang ◽  
Tiev Miller ◽  
Zou Xiang ◽  
Marco Y. C. Pang
Keyword(s):  
Muscle Strength ◽  
Bone Turnover ◽  
Intervention Program ◽  
Type I Collagen ◽  
Chronic Stroke ◽  
Medium Effect ◽  
Whole Body ◽  
Type I ◽  
Leg Muscle ◽  
Walking Endurance

AbstractThis randomized controlled trial aimed to evaluate the effects of different whole body vibration (WBV) frequencies on concentric and eccentric leg muscle strength, bone turnover and walking endurance after stroke. The study involved eighty-four individuals with chronic stroke (mean age = 59.7 years, SD = 6.5) with mild to moderate motor impairment (Fugl-Meyer Assessment lower limb motor score: mean = 24.0, SD = 3.5) randomly assigned to either a 20 Hz or 30 Hz WBV intervention program. Both programs involved 3 training sessions per week for 8 weeks. Isokinetic knee concentric and eccentric extension strength, serum level of cross-linked N-telopeptides of type I collagen (NTx), and walking endurance (6-min walk test; 6MWT) were assessed at baseline and post-intervention. An intention-to-treat analysis revealed a significant time effect for all muscle strength outcomes and NTx, but not for 6MWT. The time-by-group interaction was only significant for the paretic eccentric knee extensor work, with a medium effect size (0.44; 95% CI: 0.01, 0.87). Both WBV protocols were effective in improving leg muscle strength and reducing bone resorption. Comparatively greater improvement in paretic eccentric leg strength was observed for the 30 Hz protocol.

scholarly journals Serum levels of bone formation and resorption markers in relation to vitamin D status in professional gymnastics and physically active men during upper and lower body high-intensity exercise

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Jan Mieszkowski ◽  
Andrzej Kochanowicz ◽  
Elżbieta Piskorska ◽  
Bartłomiej Niespodziński ◽  
Joanna Siódmiak ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Formation ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Serum Levels ◽  
Type I ◽  
Vitamin D Metabolites ◽  
Physically Active ◽  
Turnover Markers

Abstract Purpose/introduction To compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels. Methods Sixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption. Results UBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects. Conclusion Vitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.

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