scholarly journals In Men With Obesity, T2DM Is Associated With Poor Trabecular Microarchitecture and Bone Strength, and Low Bone Turnover

Author(s):  
Francesca Vigevano ◽  
Giulia Gregori ◽  
Georgia Colleluori ◽  
Rui Chen ◽  
Vimlin Autemrongsawat ◽  
...  

Abstract Introduction Obesity and type 2 Diabetes (T2D) are both associated with greater bone mineral density (BMD) but increased risk of fractures. The effect of the combination of both conditions on bone metabolism, microarchitecture and strength in the obese population remains unknown. Methods Data from 112 obese men were collected. Bone turnover and biochemical markers were measured by enzyme-linked immunosorbent assay (ELISA), body composition and BMD at all sites were assessed by dual energy X-ray absorptiometry (DXA), whereas bone microarchitecture and strength (stiffness and failure load) were measured by high-resolution peripheral computed tomography (HR-pQCT). Data were compared among metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) with and without T2D and between obese without and with T2D. Results Compared to MHO and MUHO without T2D, MUHO with T2D had significantly lower levels of osteocalcin ((7.49±3.0 and 6.03±2.47, vs 4.24±2.72 ng/ml, respectively, p=0.003) and C-terminal telopeptide of type I collagen (CTx) (0.28±0.10 and 0.29±0.13 vs. 0.21±0.15 ng/ml, respectively, p=0.02). Dividing our subjects simply into those with and without T2D showed that obese men with T2D had significantly lower levels of osteocalcin (p=0.003) and CTx (p=0.005), greater trabecular separation at the tibia and radius (p=0.03 and p=0.04, respectively) and lower tibial failure load and stiffness (both p=0.04), relative to obese men without T2D. Conclusion In men, the combination of obesity and T2D is associated with reduced bone turnover, poorer trabecular bone microarchitecture and bone strength compared to those who are obese but without T2D suggesting worse bone disease.

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 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Sain S. Safarova

Aim. The study aims to develop a practical model for screening bone turnover state in patients with diabetes and evaluate its clinical usefulness to identify diabetic osteopathy. Materials. The study was conducted in 2015–2017 in the Endocrinology Department of the Therapeutic Clinic of AM University. A total of 235 patients were assessed in the study (98 with T1DM and 137 with T2DM). 89 nondiabetic subjects served as controls. Bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)] and serum markers of bone remodeling [aminoterminal propeptide of procollagen type I (P1NP) and c-terminal telopeptide of type I collagen (CTX)], parathyrin, and 25(OH)D were measured in all 235 patients. Results. Our results show that patients with T2DM have lower b-CTx values and relatively higher levels of P1NP, reflecting less pronounced changes in bone metabolism compared to patients with T1DM, regardless of age or duration of the disease. Osteoporosis was detected in 50% of patients with T1DM, compared to 13% of patients with T2DM. Conclusion. In some cases, bone remodeling markers are useful for improving the assessment of the state of bone tissue in early stages of diabetes, while alterations in bone microarchitecture may not always be captured by bone mineral density measurements.


2003 ◽  
Vol 88 (11) ◽  
pp. 5361-5365 ◽  
Author(s):  
K. E. Naylor ◽  
A. Rogers ◽  
R. B. Fraser ◽  
V. Hall ◽  
R. Eastell ◽  
...  

Abstract Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits bone resorption by binding to receptor activator of nuclear factor κB ligand. Murine studies suggest that OPG is elevated in pregnancy, but its role in human pregnancy is unknown. We evaluated the relationship among OPG, bone turnover, and bone density in a longitudinal study of planned human pregnancy and lactation (n = 17; age, 20–36 yr). Samples were collected before conception; at 16, 26, and 36 wk gestation; and at 2 and 12 wk postpartum. Indexes of bone resorption included serum β C-terminal and urinary N-terminal (uNTX) telopeptides of type I collagen. OPG increased by 110 ± 16% (mean ± sem) at 36 wk (P < 0.001), followed by a rapid postpartum decline in both lactating and nonlactating women. Bone resorption was elevated at 36 wk (serum β C-terminal telopeptides by 76 ± 17%; urinary N-terminal telopeptides by 219 ± 41%; P < 0.001). The tissue source of OPG in pregnancy is unknown. Human breast milk contains large amounts of OPG (162 ± 58 ng/ml in milk vs. 0.42 ± 0.03 ng/ml in nonpregnant serum). However, the rapid postpartum decline in serum OPG and the low serum OPG in neonates suggest a placental source. There was no correlation between change in OPG and bone turnover or bone mineral density (P > 0.05), and the physiological importance of elevated OPG in human pregnancy remains uncertain.


2020 ◽  
Vol 14 (3) ◽  
pp. 97-106
Author(s):  
Sadra Samavarchi Tehrani ◽  
Maryam Moallem ◽  
Reyhane Ebrahimi ◽  
Seyed Reza Hosseini ◽  
Hajighorban Nooreddini ◽  
...  

AbstractBackgroundIn the aging individuals, osteoporosis is a major health problem. Due to the various limitations of dual X-ray absorptiometry (DEXA) for diagnosis osteoporosis, serum-based biochemical markers have been suggested for the discrimination between the patients and healthy subjects.ObjectiveTo investigate the serum levels of bone turnover markers in elderly osteoporosis patients.MethodsThe serum samples from elderly subjects (osteoporosis (n = 28), osteopenia (n = 28), and healthy ones (n = 28) were collected from Amirkola Health and Ageing Project study. Furthermore, serum levels of bone formation and bone resorption markers as well as estrogen and progesterone were measured by enzyme-linked immunosorbent assay. Kruskal–Wallis test and receiver operating characteristic curve analysis were used for statistical analysis using SPSS.ResultsLevels of bone alkaline phosphatase (B-ALP) and procollagen type I N-terminal propeptide (PINP) differed between groups (P = 0.003 and 0.009, respectively). Furthermore, PINP and B-ALP levels had the best area under the curve, sensitivity, and specificity for the discrimination between patients with osteoporosis and healthy individuals.ConclusionIn conditions in which we are not able to assess the bone mineral density by DEXA, analysis of the B-ALP and PINP levels may be a helpful tool.


2019 ◽  
Vol 104 (8) ◽  
pp. 3585-3594 ◽  
Author(s):  
Suet Ching Chen ◽  
Sheila Shepherd ◽  
Martin McMillan ◽  
Jane McNeilly ◽  
John Foster ◽  
...  

Abstract Context Type 1 diabetes (T1D) is associated with an increased fracture risk at all ages. Objective To understand the determinants of bone health and fractures in children with T1D. Design Case-control study of children with T1D on bone-turnover markers, dual-energy X-ray absorptiometry, and 3 Tesla-MRI of the proximal tibia to assess bone microarchitecture and vertebral marrow adiposity compared with age- and sex-matched healthy children. Results Thirty-two children with T1D at a median (range) age of 13.7 years (10.4, 16.7) and 26 controls, aged 13.8 years (10.2, 17.8), were recruited. In children with T1D, serum bone-specific alkaline phosphatase (BAP) SD score (SDS), C-terminal telopeptide of type I collagen SDS, and total body (TB) and lumbar spine bone mineral density (BMD) SDS were lower (all P < 0.05). Children with T1D also had lower trabecular volume [0.55 (0.47, 0.63) vs 0.59 (0.47, 0.63); P = 0.024], lower trabecular number [1.67 (1.56, 1.93) vs 1.82 (1.56, 1.99); P = 0.004], and higher trabecular separation [0.27 (0.21, 0.32) vs 0.24 (0.20, 0.33); P = 0.001] than controls. Marrow adiposity was similar in both groups (P = 0.25). Bone formation, as assessed by BAP, was lower in children with poorer glycemic control (P = 0.009) and who were acidotic at initial presentation (P = 0.017) but higher in children on continuous subcutaneous insulin infusion (P = 0.025). Fractures were more likely to be encountered in children with T1D compared with controls (31% vs 19%; P< 0.001). Compared with those without fractures, the T1D children with a fracture history had poorer glycemic control (P = 0.007) and lower TB BMD (P < 0.001) but no differences in bone microarchitecture. Conclusion Children with T1D display a low bone-turnover state with reduced bone mineralization and poorer bone microarchitecture.


2017 ◽  
Vol 29 (4) ◽  
pp. 513-519 ◽  
Author(s):  
Ammar Nebigh ◽  
Mohamed Elfethi Abed ◽  
Rihab Borji ◽  
Sonia Sahli ◽  
Slaheddine Sellami ◽  
...  

The aim of this study was to examine the relationship between bone mass and bone turnover markers with lean mass (LM) in pubescent soccer players. Two groups participated in this study, which included 65 elite young soccer players who trained for 6–8 hours per week and 60 controls. Bone mineral density; bone mineral content in the whole body, lower limbs, lumbar spine, and femoral neck; biochemical markers of osteocalcin; bone-specific alkaline phosphatase; C-telopeptide type I collagen; and total LM were assessed. Young soccer players showed higher bone mineral density and bone mineral content in the whole body and weight-bearing sites (P < .001). Indeed, the total LM correlated with whole-body bone mineral density and bone mineral content (P < .001). There were significant differences within the bone formation markers and osteocalcin (formation)/C-telopeptide type I collagen (resorption) ratio between young soccer players compared with the control group, but no significant difference in C-telopeptide type I collagen was observed between the 2 groups. This study showed a significant positive correlation among bone-specific alkaline phosphatase, osteocalcin, and total LM (r = .29; r = .31; P < .05) only for the young soccer players. Findings of this study highlight the importance of soccer practice for bone mineral parameters and bone turnover markers during the puberty stage.


2018 ◽  
Vol 315 (6) ◽  
pp. E1133-E1142 ◽  
Author(s):  
Samantha R. Weaver ◽  
Hannah P. Fricke ◽  
Cynthia Xie ◽  
Robert J. Aiello ◽  
Julia F. Charles ◽  
...  

Long-term effects of breastfeeding on maternal bone are not fully understood. Excessive maternal bone loss stimulated by serotonin signaling during lactation may increase bone fragility later in life. We hypothesized that inhibiting nonneuronal serotonin activity by feeding a small-molecule inhibitor of the rate-limiting enzyme in serotonin synthesis [tryptophan hydroxylase 1 (TPH1)] would preserve maternal bone postweaning without affecting neonatal bone. Chow supplemented with the small-molecule TPH1 inhibitor LP778902 (~100 mg/kg) or control chow was fed to C57BL/6 dams throughout pregnancy and lactation, and blood was collected on days 1 and 21 of lactation. Dams returned to a common diet postweaning and were aged to 3 or 9 mo postweaning. Pups were euthanized at weaning. The effect of TPH1 inhibition on dam and pup femoral bone was determined by micro-computed tomography. Peripartum dietary supplementation with LP778902 decreased maternal serum serotonin concentrations ( P = 0.0007) and reduced bone turnover, indicated by serum NH2-terminal propeptide of type I collagen ( P = 0.01) and COOH-terminal collagen cross-links ( P = 0.02) concentrations, on day 21 of lactation. Repressed bone turnover from TPH1 inhibition was not associated with structural changes in maternal femur at 3 or 9 mo postweaning. By contrast, neonates exposed to peripartum LP778902 demonstrated differences in trabecular and cortical femoral bone compared with pups from control dams, with fewer ( P = 0.02) and thinner ( P = 0.001) trabeculae as well as increased trabecular spacing ( P = 0.04). Additionally, cortical porosity was increased ( P = 0.007) and cortical tissue mineral density was decreased ( P = 0.005) in pups of LP778902-treated dams. Small-molecule TPH1 inhibitors should be carefully considered in pregnant and lactating women, given potential risks to neonatal bone development.


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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mikkel Bo Brent ◽  
Jesper Skovhus Thomsen ◽  
Annemarie Brüel

AbstractGlucocorticoids (GCs), such as prednisolone, are widely used to treat inflammatory diseases. Continuously long-term or high dose treatment with GCs is one of the most common causes of secondary osteoporosis and is associated with sarcopenia and increased risk of debilitating osteoporotic fragility fractures. Abaloparatide (ABL) is a potent parathyroid hormone-related peptide analog, which can increase bone mineral density (aBMD), improve trabecular microarchitecture, and increase bone strength. The present study aimed to investigate whether GC excess blunts the osteoanabolic effect of ABL. Sixty 12–13-week-old female RjOrl:SWISS mice were allocated to the following groups: Baseline, Control, ABL, GC, and GC + ABL. ABL was administered as subcutaneous injections (100 μg/kg), while GC was delivered by subcutaneous implantation of a 60-days slow-release prednisolone-pellet (10 mg). The study lasted four weeks. GC induced a substantial reduction in muscle mass, trabecular mineral apposition rate (MAR) and bone formation rate (BFR/BS), and endocortical MAR compared with Control, but did not alter the trabecular microarchitecture or bone strength. In mice not receiving GC, ABL increased aBMD, bone mineral content (BMC), cortical and trabecular microarchitecture, mineralizing surface (MS/BS), MAR, BFR/BS, and bone strength compared with Control. However, when administered concomitantly with GC, the osteoanabolic effect of ABL on BMC, cortical morphology, and cortical bone strength was blunted. In conclusion, at cortical bone sites, the osteoanabolic effect of ABL is generally blunted by short-term GC excess.


2022 ◽  
Vol 78 (01) ◽  
pp. 6607-2022
Author(s):  
XINRU MA ◽  
CHANGHONG GAO ◽  
MINGMAO YANG ◽  
BINGBING ZHANG ◽  
CHUANG XU ◽  
...  

This study aimed to present the characteristics of and to predict subclinical hypocalcemia in dairy cows during the transition period using blood analytes. We examined fluctuations in plasma calcium (Ca), phosphorus (P), bone metabolic markers carboxy-terminal telopeptide of type I collagen (CTX), fibroblast growth factor (FGF23), 1,25(OH)2D3, parathyroid hormone, and other blood biochemical analytes from prepartum week 2 to postpartum day 14 in 116 multiparous high-producing Holstein cows from a free-stall barn dairy farm. With a plasma concentration of Ca <2.0 mmol/L as a criterion for the diagnosis of subclinical hypocalcemia, 64 cows were classified as normocalcemic, and 52 cows as subclinically hypocalcemic. Among the 52 hypocalcemic cows, 50 were detected on postpartum days 1 or 3, and 2 on postpartum day. The subclinically hypocalcemic cows were in a state of low bone turnover in the prepartum period, with low plasma concentrations of Ca and CTX. The subclinically hypocalcemic cows showed signs of a P regulation disorder in the prepartum period. This was marked by high plasma concentrations of P and low concentrations of 1,25(OH)2D3 and FGF23, which is also considered to be the cause of the low bone turnover. The results of a multiple logistic regression model showed that prepartum plasma concentrations of FGF23, CTX, and Ca were ideal predictors of postpartum subclinical hypocalcemia in dairy cows, using the model equation 38.8-0.052*FGF23-0.492*CTX-10.645*Ca, with a score of > 0 considered as an indication of increased risk of subclinical hypocalcemia after calving. The scoring rule had an accuracy of 79.3%, sensitivity of 76.9%, and specificity of 81.3%. The plasma concentrations of FGF23, CTX, and Ca were ideal predictors of postpartum subclinical hypocalcemia in dairy cows.


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