Interactions of Anemia, FGF-23, and Bone in Healthy Adults—Results From the Study of Health in Pomerania (SHIP)

2020 ◽  
Vol 106 (1) ◽  
pp. e288-e299
Author(s):  
Anke Hannemann ◽  
Matthias Nauck ◽  
Henry Völzke ◽  
Heike Weidner ◽  
Uwe Platzbecker ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Quality ◽  
Type I Collagen ◽  
Fibroblast Growth Factor 23 ◽  
Type I ◽  
Close Link ◽  
Amino Terminal ◽  
Age Related ◽  
Carboxy Terminal ◽  
Fgf 23

Abstract Context Osteoporosis and anemia are among the most common diseases in the aging population with an increasing prevalence worldwide. Objective As the bone-derived hormone fibroblast growth factor 23 (FGF-23) was recently reported to regulate erythropoiesis, we examined age-related associations between hemoglobin levels and bone quality, bone turnover, and FGF-23 concentrations. Design We used data from more than 5000 adult subjects who participated in the population-based cohorts of the Study of Health in Pomerania (SHIP and SHIP-Trend). Bone quality was assessed by quantitative ultrasound at the heel, bone turnover by measurement of carboxy-terminal telopeptide of type I collagen (CTX), and intact amino-terminal propeptide of type I procollagen (P1NP) serum concentrations, respectively. Anemia was defined as hemoglobin <13 g/dL in men and <12 g/dL in women. Carboxy-terminal FGF-23 levels were measured in plasma in a subset of 852 subjects. Results Anemic subjects had poorer bone quality, higher fracture risk, and lower serum levels of P1NP than nonanemic individuals. Linear regression models revealed positive associations between hemoglobin and bone quality in subjects aged 40 or above and inverse associations with CTX in subjects aged 60 or above. Hemoglobin and FGF-23 concentrations were inversely associated, while FGF-23 was not related to bone quality or turnover. Conclusion Our data corroborate a close link between FGF-23 and anemia, which is related to poor bone quality in elderly people. We observed no direct association of FGF-23 with bone parameters. Further studies are needed clarifying the role of FGF-23 on bone and red blood cell production.

Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen: a new serum marker of bone collagen degradation

1993 ◽  
Vol 39 (4) ◽  
pp. 635-640 ◽  
Author(s):  
J Risteli ◽  
I Elomaa ◽  
S Niemi ◽  
A Novamo ◽  
L Risteli
Keyword(s):  
Type I Collagen ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Bone Collagen ◽  
Collagen Molecule ◽  
Type I ◽  
Serum Samples ◽  
Amino Terminal ◽  
Wide Range ◽  
Carboxy Terminal

Abstract We developed a radioimmunoassay (RIA) for the carboxy-terminal telopeptides of type I collagen (ICTP), cross-linked with the helical domain of another type I collagen molecule, after isolation from human femoral bone. The cross-linked peptide was liberated by digesting insoluble, denatured bone collagen either with bacterial collagenase or with trypsin, and purified by two successive reversed-phase separations on HPLC, with monitoring of pyridinoline-specific fluorescence. The purity of the peptide was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its origin in the type I collagen fibers was determined by amino-terminal amino acid sequencing. Polyclonal antibodies and a separation reagent containing second antibody and polyethylene glycol are used in the RIA. An immunologically identical, somewhat larger antigen is present in human serum; its concentration increases in multiple myeloma and in rheumatoid arthritis. The ICTP antigen seems to be cleared from the circulation by the kidneys, because glomerular filtration rates that are two-thirds of normal or less are associated with increased circulating ICTP concentrations. The CVs of the method are between 3% and 8% for a wide range of concentrations. The analysis of 40 serum samples can be completed in 4 h.

Effects of everolimus (EVE) on disease progression in bone and bone markers (BMs) in patients (pts) with bone metastases (mets).

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Lowell L. Hart ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Bone Lesion ◽  
Phase Iii ◽  
Type I ◽  
Double Blind ◽  
Mtor Inhibition ◽  
Similar Frequency ◽  
Once Daily ◽  
Amino Terminal

102 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to nonsteroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J et al. NEJM2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effects of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers (BMs) were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a preexisting bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (p < 0.0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively), and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade 1-2 and occurred with similar frequency in EVE (2.9%)- and PBO (3.8%)-treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.

scholarly journals Effects of palliative radiotherapy and bisphosphonate usage on bone turnover marker levels in cancer patients with osteolytic bone metastases

2021 ◽  
Author(s):  
Fatih Göksel ◽  
Müge Akmansu ◽  
Ertuğrul Şentürk ◽  
Fatih Demircioğlu
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Turnover ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Repeated Measures ◽  
Type I Collagen ◽  
Bone Turnover Marker ◽  
Type I ◽  
Amino Terminal ◽  
Significant Difference

Objectives: In this study, we aimed to investigate the bone turnover marker levels according to bisphosphonate usage and radiotherapy (RT) in cancer patients with metastases in osteolytic pattern. Patients and methods: A total of 52 patients (13 males, 39 females; median age: 52 years; range, 37 to 78 years) treated with RT for osteolytic bone metastases between April 2005 and April 2006 were retrospectively analyzed. Bone-specific alkaline phosphatase (BAP), amino-terminal cross-linked telopeptide of type I collagen (NTX-I), amino-terminal propeptide of type I procollagen (PINP), osteocalcin (OC), deoxypyridinoline (DPD), pyridinoline (PYD), alkaline phosphatase (ALP), creatinine, calcium (Ca), phosphate (P), magnesium (Mg), and 24-h urine Ca levels were measured in blood and urine before the initiation of RT, six weeks and six months after RT. Results: A decrease in BAP, PINP, and creatinine levels was observed after RT (Week 6 p=0.006, Month 6 p=0.008). Sixteen patients who already used bisphosphonate before RT were excluded from statistical calculation. The remaining 36 patients who were treated with bisphosphonate after the first blood test were evaluated separately. In this group of patients, BAP, PINP, NTX, creatinine, and Ca levels significantly increased at six weeks after RT. The PINP and creatinine values significantly decreased at six months after RT. The variation between two different RT arms was assessed with repeated measures variance analysis. There was a statistically significant difference for NTX, OC, and creatinine levels between the first and second measurements. Conclusion: Radiotherapy is an effective method in the treatment of osteolytic bone metastases. Bone turnover markers can provide an objective evaluation on RT response and parallel to imaging modalities criteria for evaluation. Bisphosphonates may alter the levels of these indicators. However, in this study, there were no statistically significant differences between the levels of markers for two different RT schedules.

scholarly journals Associations of Circulating Osteoglycin With Bone Parameters and Metabolic Markers in Patients With Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Jakob Kau Starup-Linde ◽  
Rikke Viggers ◽  
Bente Langdahl ◽  
Soeren Gregersen ◽  
Simon Lykkeboe ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Microvascular Complications ◽  
Whole Body ◽  
Type I ◽  
Amino Terminal ◽  
Patients With Diabetes ◽  
Turnover Markers

ObjectiveCirculating osteoglycin may facilitate the crosstalk between bone and pancreas to empower adaptation of bone mass to whole body energy balance. We aimed to examine whether osteoglycin is associated with bone and metabolic parameters and if osteoglycin levels differ between patients with type 1 and 2 diabetes (T1D and T2D).Design and methodsA cross-sectional study of 190 patients with diabetes mellitus and stable hemoglobin A1c (HbA1c) (97 T1D and 93 T2D) was conducted. S-osteoglycin was analyzed by ELISA. Unpaired t-tests were performed to test differences between patients with T1D and T2D and linear regression analyses were performed to investigate associations between osteoglycin, glycemic markers, bone turnover markers and characteristics.ResultsS-osteoglycin did not differ between patients with T1D and T2D (p=0.10). No associations were present between osteoglycin and age, gender, microvascular complications, HbA1c, or plasma glucose in T1D or T2D patients (p&gt;0.05 for all). S-osteoglycin was not associated with levels of bone turnover markers (C-terminal cross-linked telopeptide of type-I collagen (CTX), P-procollagen type 1 amino terminal propeptide (P1NP), P-osteocalcin (OC), P-sclerostin, S-osteoprotegerin (OPG) or S-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL)) in neither T1D or T2D patients (p&gt;0.05 for all).ConclusionOsteoglycin levels were similar in T1D and T2D patients. Osteoglycin did not correlate with glucose, HbA1c or any other biochemical marker of bone turnover. Thus, we did not find evidence supporting the existence of an osteoglycin-bone-pancreas axis.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01870557.

Effects of everolimus (EVE) on disease progression in bone and bone markers (BM) in patients (pts) with bone metastases (mets).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Michael Gnant ◽  
José Baselga ◽  
Hope S. Rugo ◽  
Shinzaburo Noguchi ◽  
Kathleen I. Pritchard ◽  
...  
Keyword(s):  
Bone Turnover ◽  
Type I Collagen ◽  
Bone Lesion ◽  
Phase Iii ◽  
Type I ◽  
Double Blind ◽  
Mtor Inhibition ◽  
Similar Frequency ◽  
Once Daily ◽  
Amino Terminal

512 Background: BOLERO-2, a multinational, double-blind, placebo-controlled, phase III study in postmenopausal women with estrogen-receptor–positive breast cancer (BC) refractory to non-steroidal aromatase inhibitors (NSAIs), showed significant clinical benefits with the addition of EVE to exemestane (EXE) (Baselga J, et al. NEJM. 2011 Epub). As bone resorption is an important factor in BC mets, it is interesting to study bone-related effects of EVE. In preclinical studies, mTOR inhibition was associated with decreased osteoclast survival and activity. Exploratory analyses in BOLERO-2 evaluated the effect of EVE vs placebo (PBO) on BM levels and BC progression in bone in pts with bone mets at baseline. Methods: Eligible pts were treated with EXE (25 mg once daily) and randomized (2:1) to EVE (10 mg once daily) or PBO. Bone turnover markers were exploratory endpoints analyzed at 6 and 12 wks after treatment initiation, and included bone-specific alkaline phosphatase, amino-terminal propeptide of type I collagen, and C-terminal cross-linking telopeptide of type I collagen. Progressive disease in bone (PDB) was defined as worsening of a pre-existing bone lesion or a new bone lesion. Results: Baseline disease characteristics, including bone mets at baseline (n = 370, 76% EVE vs n = 184, 77% PBO), were well balanced between arms (N = 724), and baseline bisphosphonate use was not (44% EVE vs 55% PBO). At 12.5 mo median follow-up, progression-free survival (primary endpoint), overall response rate, and clinical benefit rate (P < .0001, all) were significantly higher with EVE (n = 485) vs PBO (n = 239). BM levels at 6 and 12 wks increased vs baseline with PBO, but decreased with EVE. The cumulative incidence rate of BC PBD was lower for EVE vs PBO at day 60 (3.03% vs 6.16%, respectively) and this trend was sustained beyond 6 months. Updated results will be presented. All bone-related adverse events reported were grade1/2 and occurred with similar frequency in EVE- (2.9%) and PBO- (3.8%) treated patients. Conclusions: Exploratory analyses from BOLERO-2 suggest that adding EVE has beneficial effects on bone turnover and BC progression in bone in pts receiving EXE therapy for NSAI-refractory BC.

scholarly journals Bone turnover markers to assess jawbone quality prior to dental implant treatment: a case-control study

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Keisuke Yasuda ◽  
Shinsuke Okada ◽  
Yohei Okazaki ◽  
Kyou Hiasa ◽  
Kazuhiro Tsuga ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Turnover ◽  
Bone Quality ◽  
Cancellous Bone ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Type I ◽  
Turnover Markers ◽  
The Relationship

Abstract Background Bone quality is as important as bone mineral density in terms of bone strength. Bone turnover markers (BTMs) are clinical indicators of bone quality. In implant dentistry, bone quality is considered equivalent to bone density on radiographic assessments. The purpose of this study was to determine whether the BTM values are reflected in jawbone condition by evaluating the relationship at baseline and during follow-up in patients with prosthodontic implants. Computed tomography (CT) scans were obtained and BTM (osteocalcin, bone-specific alkaline phosphatase, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen, and crosslinked N-telopeptide of type I collagen) levels in blood samples were measured in partially edentulous eighteen patients before implant surgery. During the follow-up observation after implant surgery, marginal bone loss (MBL) was measured on dental radiography. We investigated the relationship between the presence of BTM abnormalities and radiographic bone density. Results More women than men had abnormal BTM values. Bone turnover was accelerated in the group of women with abnormal BTM values. The density of cancellous bone at the implant placement site was significantly lower in the patients with abnormally high BTM values than in their counterparts with BTM values in the normal range. Conclusions Female patients who undergo implant treatments may have reduced bone quality; evaluations of bone strength will require assessments of both BTMs and the density of cancellous bone.

scholarly journals The Antioxidant EnzymeGPX1Gene Polymorphisms Are Associated with Low BMD and Increased Bone Turnover Markers

2010 ◽  
Vol 29 (2) ◽  
pp. 71-80 ◽  
Author(s):  
Simona Jurkovic Mlakar ◽  
Josko Osredkar ◽  
Janez Prezelj ◽  
Janja Marc
Keyword(s):  
Oxidative Stress ◽  
Bone Turnover ◽  
Bone Turnover Markers ◽  
Type I Collagen ◽  
Elderly Women ◽  
Type I ◽  
Mineral Density ◽  
General Linear Model Analysis ◽  
Age Related ◽  
Turnover Markers

Recently, oxidative stress has been suggested as participating in the development of osteoporosis. Glutathione peroxidase 1 (GPX1) is one of antioxidant enzymes responsible for the defence of cells against oxidative damage and thus for protection against age related diseases such as osteoporosis.The aim of present study was to associate genetic variances of GPX1 enzyme with bone mineral density (BMD) and biochemical bone turnover markers and to show the influence of antioxidative defence system in genetics of osteoporosis.We evaluated 682 Slovenian subjects: 571 elderly women and 111 elderly men. All subjects were genotyped for the presence ofGPX1gene polymorphisms Pro198Leu and polyAla region. BMD and biochemical markers were also measured. General linear model analysis, adjusted to height, and (one-way) analysis of variance were used to assess differences between the genotype.and haplotype subgroups, respectively.The significant or borderline significant associations were found between the polyAla or the Pro198Leu polymorphisms and total hip BMD (0.018; 0.023, respectively), femoral neck BMD (0.117; 0.026, respectively) and lumbar spine BMD (0.032; 0.086, respectively), and with biochemical bone turnover markers such as plasma osteocalcin (0.027; 0.025, respectively) and serum C-terminal telopeptide of type I collagen concentrations (0.114; 0.012, respectively) in whole group. Haplotype analysis revealed that the 6-T haplotype is associated significantly with low BMD values (p> 0.025) at all measured locations of the skeleton, and with high plasma osteocalcin concentrations (p= 0.008).This study shows for the first time that the polymorphisms polyAla and Pro198Leu of theGPX1gene, individually and in combination, are associated with BMD and therefore may be useful as genetic markers for bone disease. Moreover, it implies the important contribution of the oxidative stress to pathogenesis of osteoporosis.

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