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

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.

2019 ◽  
Vol 10 (Vol.10, No.3) ◽  
pp. 243-251
Author(s):  
Alina Deniza CIUBEAN ◽  
Laszlo IRSAY ◽  
Rodica Ana UNGUR ◽  
Viorela Mihaela CIORTEA ◽  
Ileana Monica BORDA ◽  
...  

Introduction: Osteoporosis has a strong genetic contribution, and several genes have been shown to influence bone mineral density. Variants in the human genome are considered important causes of differences in drug responses observed in clinical practice. In terms of bone mineral density, about 26–53% of patients do not respond to amino-bisphosphonate therapies, of which alendronate is the most widely used. Material and method: The current study is prospective, observational, analytical, longitudinal and cohort type. It included 25 postmenopausal women treated with alendronate for 1 year. Bone mineral density at lumbar spine and proximal femur was measured and bone turnover markers (C-terminal telopeptide of type I collagen and procollagen 1N-terminal propeptide) were evaluated at 0 and 12 months of treatment. Six single nucleotide polymorphisms in osteoporosis-candidate genes were genotyped (FDPS rs2297480, LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438, GGPS1 rs10925503 and RANKL rs2277439). Treatment response was evaluated by percentage changes in bone mineral density and bone turnover markers. Results: The heterozygous CT of FDPS rs2297480 showed lower increases in BMD values in the lumbar spine region and the homozygous CC of the GGPS1 rs10925503 showed lower increases in terms of BMD at the total hip region. No association was found for LRP5 rs3736228, SOST rs1234612, VKORC1 rs9934438 and RANKL rs2277439. Conclusions: Romanian postmenopausal women with osteoporosis carrying the CT genotype of FDPS rs2297480 or the CC genotype of GGPS1 rs10925503 could have an unsatisfactory response to alendronate treatment. Key words: osteoporosis; genetic polymorphism; alendronate; bone mineral density; bone turnover markers,


2019 ◽  
Vol 43 (5) ◽  
pp. 508-518 ◽  
Author(s):  
Rehne Lessmann Hansen ◽  
Bente Lomholt Langdahl ◽  
Peter Holmberg Jørgensen ◽  
Klaus Kjær Petersen ◽  
Kjeld Søballe ◽  
...  

Background: The osseointegrated implant system is a treatment option for people with transfemoral amputation, but implant removal is not uncommon. The association between bone mineral density changes or bone turnover markers and the need for implant removal has not previously been investigated. Objectives: The aim was to evaluate changes in bone mineral density and bone turnover markers in people with transfemoral amputations treated with osseointegrated implants. Study design: This is a prospective cohort study. Methods: Nineteen patients were followed up for 30 months or until implant removal. Bone mineral density was measured in the lumbar spine, proximal femur and seven periprosthetic regions. 25-hydroxyvitamin (D2 + D3), parathyroid hormone, N-terminal propeptide of type-I procollagen, C-telopeptide of type-I collagen, bone-specific alkaline phosphatase and osteocalcin were measured in blood samples. Results: Four fixtures and three abutments were removed. Patients with removed implants had a decreased bone mineral density in the seven periprosthetic regions between 27% (95% confidence interval = 6; 43) and 38% (95% confidence interval = 19; 52) at 30-month follow-up compared to baseline ( p < 0.02), whereas bone mineral density around non-removed implants normalized to baseline values ( p > 0.08). C-telopeptide of type-I collagen was significantly different between the groups at 18- and 24-month follow-up ( p < 0.05). None of the measured variables were significant predictors of implant removal ( p > 0.07). Conclusion: Implant removal was associated with loss of periprosthetic bone mineral density and increase in C-telopeptide of type-I collagen in the years following osseointegrated surgery. Clinical relevance This study offers new insight into changes in bone mineral density and bone turnover markers that precipitate aseptic or septic osseointegrated implant removal. Results of this study could contribute to clinical guidelines for monitoring rehabilitation progress and implant removal through dual-energy X-ray absorptiometry or surrogate markers like C-telopeptide of type-I collagen.


Author(s):  
Jan Mieszkowski ◽  
Andrzej Kochanowicz ◽  
Elżbieta Piskorska ◽  
Bartłomiej Niespodziński ◽  
Joanna Siódmiak ◽  
...  

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.


2016 ◽  
Vol 101 (8) ◽  
pp. 3222-3230 ◽  
Author(s):  
Jean Redmond ◽  
Anthony J. Fulford ◽  
Landing Jarjou ◽  
Bo Zhou ◽  
Ann Prentice ◽  
...  

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 &lt; .05). The DRs were significant for all variables and groups (P &lt; .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 &lt; .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.


Cartilage ◽  
2017 ◽  
Vol 9 (3) ◽  
pp. 255-262 ◽  
Author(s):  
Jadwiga Ambroszkiewicz ◽  
Joanna Gajewska ◽  
Grazyna Rowicka ◽  
Witold Klemarczyk ◽  
Magdalena Chelchowska

Objective There is scant research examining the prevalence of thinness in early childhood, despite its potential negative consequences for health and development across the life course. The objective of this study was to assess bone status through measurement of bone mineral density and biochemical bone turnover markers, with special attention paid to carboxylated (c-OC) as well as undercarboxylated (uc-OC) forms of osteocalcin, in the groups of thin and normal-weight children. Design The study included 80 healthy prepubertal children (median age 7.0 years), who were divided (according to Cole’s international cutoffs) into 2 subgroups: thin children ( n = 40, body mass index [BMI] = 13.5 kg/m2) and normal-weight children ( n = 40, BMI = 16.1 kg/m2). Bone mineral density (BMD) and bone mineral content (BMC) were assessed by dual-energy x-ray absorptiometry method. Serum concentrations of C-terminal telopeptide of collagen type I (CTX), total osteocalcin (OC), and c-OC, and uc-OC forms of osteocalcin were determined using enzyme-linked immunosorbent assays. Results In thin children, we observed higher levels of bone resorption marker CTX compared with normal-weight peers. Total osteocalcin concentrations were comparable in both groups of children; however, in thin children we observed higher median values of uc-OC (34.40 vs. 29.30 ng/mL, P < 0.05) and similar c-OC levels (25.65 vs. 28.80 ng/mL). The ratio of c-OC to uc-OC was significantly lower ( P < 0.05) in thin than in normal-weight children. Total BMD and BMC were significantly decreased ( P < 0.0001) in thin children compared with normal-weight peers (0.724 ± 0.092 vs. 0.815 ± 0.060 g/cm2 and 602.7 ± 159.2 vs. 818.2 ± 220.1 g, respectively). Conclusion Increased concentrations of CTX and uc-OC might lead to disturbances in bone turnover and a decrease in bone mineral density in thin children.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jakob Kau Starup-Linde ◽  
Rikke Viggers ◽  
Bente Langdahl ◽  
Soeren Gregersen ◽  
Simon Lykkeboe ◽  
...  

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.


2006 ◽  
Vol 154 (5) ◽  
pp. 745-751 ◽  
Author(s):  
Andrea Dovio ◽  
Laura Perazzolo ◽  
Laura Saba ◽  
Angela Termine ◽  
Marco Capobianco ◽  
...  

Objective: Glucocorticoids (GCs) at pharmacological doses stimulate bone resorption. Mechanisms of this action are unclear. The osteoclastogenic cytokine interleukin (IL)-6 acts through an oligomeric receptor consisting of two subunits, gp80 (or IL-6 receptor α, IL-6Rα) and gp130; both exist in membrane and soluble forms. Soluble IL-6Rα (sIL-6Rα) enhances, while sgp130 inhibits IL-6 signalling. In vitro, GCs enhance many effects of IL-6 by up-regulation of IL-6Rα. The aim of the present study was to assess acute changes of IL-6 system in the peripheral blood of patients given high-dose GCs. Subjects and methods: Serum levels of IL-6, sIL-6Rα, sgp130 and bone turnover markers were assessed before and each day during treatment in 24 multiple sclerosis (MS) patients undergoing high-dose (prednisolone, 15 mg/kg per day), short-term (3 to 5 days) intravenous GC therapy for relapse at the Regional Multiple Sclerosis Centre. Results: An immediate and marked fall of osteocalcin and an early increase of C-terminal telopeptide of type I collagen were already noticed at day 2 (P < 0.001 and P < 0.02, respectively); both became more apparent in the subsequent days. IL-6 was always below or near the detection limit of our ELISA. sgp130 showed a slight increase. sIL-6Rα significantly increased, peaking at day 4 (P < 0.01). However, inter-individual variability of response was noticed. Four patients showed a slight decrease, while no change was observed in one patient and an increase was noticed in the remaining nineteen (maximum change ranging from +10% to +67% with respect to baseline). In these patients, a significant increase of sIL-6Rα/sgp130 ratio was apparent. No correlation was found between bone turnover markers and any measured component of the IL-6 system. Conclusions: sIL-6Rα and sIL-6Rα/sgp130 ratio are precociously increased in the peripheral blood of the vast majority of patients given high-dose, intravenous GCs. The increase of systemically available sIL-6Rα conceivably results in the enhancement of IL-6-dependent osteoclastogenesis. The role of such a mechanism in the bone loss observed in inflammatory and immune-mediated diseases (where abundancy of IL-6 in the bone microenvironment is expected) requires further investigation.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Wei-Wei Hu ◽  
Zeng Zhang ◽  
Jin-Wei He ◽  
Wen-Zhen Fu ◽  
Chun Wang ◽  
...  

The reference ranges of bone turnover markers (BTMs) were important during the treatment of osteoporosis, and the associations with bone mineral density (BMD) were controversial. The aim of this study was to establish the reference ranges of N-terminal procollagen of type l collagen (P1NP), osteocalcin (OC), and beta C-terminal cross-linked telopeptides of type I collagen (β-CTX) in Shanghai area and to investigate the relationships between BTMs and BMD in postmenopausal women. 2,799 subjects recruited in Shanghai City were measured BTMs to establish the reference ranges. Additional 520 healthy postmenopausal women were also measured BTMs, these women measured BMD in addition. BTMs were measured using the Roche electrochemiluminescence system. We used the age range of 35 to 45-year-olds to calculate reference intervals. The reference range of OC was 4.91 to 13.90 ng/mL for women and 5.58 to 16.57 ng/mL for men, P1NP was 13.72 to 32.90 ng/mL for women and 16.89 to 42.43 ng/mL for men, andβ-CTX was 0.112 to 0.210 ng/mL for women and 0.100 to 0.378 ng/mL for men. BTMs significantly negatively correlated with lumbar spine and femoral and total hip in postmenopausal women ( = −0.157~−0.217,P< 0.001). We established the normal reference ranges of P1NP, OC, andβ-CTX in the Shanghai area. This study also found that BTMs correlated with BMD and suggested that BTMs were the key determining factors of early BMD decreases.


Sign in / Sign up

Export Citation Format

Share Document