Recapitulation of the Genetic Association of PLXNA2 with Bone Density and Osteoporosis via In Vitro Experiments Using a Korean Female Cohort

2020 ◽  
Vol 10 (6) ◽  
pp. 1418-1422
Author(s):  
Sangwook Park ◽  
Ji-Eun Oh ◽  
Hyun-Seok Jin
Keyword(s):  
Bone Density ◽  
Genetic Association ◽  
Elderly Women ◽  
Osteoporosis Treatment ◽  
The Elderly ◽  
Bone Morphogenetic Protein 2 ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Female Cohort

Osteoporosis is a bone disorder in which the imbalance of osteoclasts and osteoblasts leads to bone-destructive diseases especially among elderly women. Several factors, including genetic and environmental factors, contribute to the pathogenesis of these diseases. Bone mineral density (BMD) is a robust factor that influences osteoporosis; the development of osteoporosis in the elderly is estimated based on the BMD. Our previous microarray assay using murine preosteoblast cells revealed that Plexin A2 is associated with the differentiation and mineralization of bone-forming osteoblasts via bone morphogenetic protein 2 signaling. For our in vitro replication study using a Korean female cohort, we analyzed the genetic variation of PLEXIN A2 (PLXNA2) and its paralog genes (PLXNA1, A3, and A4) based on 125 single nucleotide polymorphisms (SNPs) associated with bone density and osteoporosis. In this study, the PLXNA2 gene was confirmed as a robust candidate gene associated with osteoporosis in Korean women. We have demonstrated that the SNPs rs4844649 (p = 9.3×10−3) and rs3748737 (p = 2.7×10−3) of PLXNA2 were the most significantly associated with bone density and osteoporosis, respectively. Consequently, this study demonstrates that the PLXNA2 gene is implicated in bone metabolism, further supporting the genetic association between polymorphisms in PLXNA2 and osteoporosis. Our current findings also suggest that polymorphisms in PLXNA2 may serve as feasible clinical targets for osteoporosis treatment in the future.

scholarly journals The Bromodomain Inhibitor N-Methyl pyrrolidone Prevents Osteoporosis and BMP-Triggered Sclerostin Expression in Osteocytes

2018 ◽  
Vol 19 (11) ◽  
pp. 3332 ◽  
Author(s):  
Barbara Siegenthaler ◽  
Chafik Ghayor ◽  
Bebeka Gjoksi-Cosandey ◽  
Nisarat Ruangsawasdi ◽  
Franz Weber
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Osteoporosis Treatment ◽  
Estrogen Deficiency ◽  
Bone Morphogenetic Protein 2 ◽  
Protein Levels ◽  
Osteoporosis Management ◽  
Promising Target

(1) Background: In an adult skeleton, bone is constantly renewed in a cycle of bone resorption, followed by bone formation. This coupling process, called bone remodeling, adjusts the quality and quantity of bone to the local needs. It is generally accepted that osteoporosis develops when bone resorption surpasses bone formation. Osteoclasts and osteoblasts, bone resorbing and bone forming cells respectively, are the major target in osteoporosis treatment. Inside bone and forming a complex network, the third and most abundant cells, the osteocytes, have long remained a mystery. Osteocytes are responsible for mechano-sensation and -transduction. Increased expression of the osteocyte-derived bone inhibitor sclerostin has been linked to estrogen deficiency-induced osteoporosis and is therefore a promising target for osteoporosis management. (2) Methods: Recently we showed in vitro and in vivo that NMP (N-Methyl-2-pyrrolidone) is a bioactive drug enhancing the BMP-2 (Bone Morphogenetic Protein 2) induced effect on bone formation while blocking bone resorption. Here we tested the effect of NMP on the expression of osteocyte-derived sclerostin. (3) Results: We found that NMP significantly decreased sclerostin mRNA and protein levels. In an animal model of osteoporosis, NMP prevented the estrogen deficiency-induced increased expression of sclerostin. (4) Conclusions: These results support the potential of NMP as a novel therapeutic compound for osteoporosis management, since it preserves bone by a direct interference with osteoblasts and osteoclasts and an indirect one via a decrease in sclerostin expression by osteocytes.

scholarly journals Postural control among elderly women with and without osteoporosis: is there a difference?

2010 ◽  
Vol 128 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Thomaz Nogueira Burke ◽  
Fabio Jorge Renovato França ◽  
Sarah Rúbia Ferreira de Meneses ◽  
Viviam Inhasz Cardoso ◽  
Rosa Maria Rodrigues Pereira ◽  
...  
Keyword(s):  
Postural Control ◽  
Elderly Women ◽  
Center Of Pressure ◽  
The Elderly ◽  
Cross Sectional Study ◽  
Clinical Test ◽  
Mineral Density ◽  
Maximum Displacement ◽  
Cross Sectional ◽  
School Of Medicine

CONTEXT AND OBJECTIVE: Little is known about postural control among elderly individuals with osteoporosis and its relationship with falls. It has been suggested that elderly women with kyphosis and osteoporosis are at greater risk of falling. The aim of this study was to evaluate posture and postural control among elderly women with and without osteoporosis. DESIGN AND SETTING: Cross-sectional study conducted at the Physical Therapy and Electromyography Laboratory, School of Medicine, Universidade de São Paulo (USP). METHODS: Sixty-six elderly women were selected from the bone metabolism disorders clinic, Division of Rheumatology, USP, and were divided into two groups: osteoporosis and controls, according to their bone mineral density (BMD). Postural control was assessed using the Limits of Stability (LOS) test and the Modified Clinical Test of Sensory Interaction and Balance (CTSIBm) and posture, using photometry. RESULTS: The elderly women with osteoporosis swayed at higher velocity on a stable surface with opened eyes (0.30 versus 0.20 degrees/second; P = 0.038). In both groups, the center of pressure (COP) was at 30% in the LOS, but with different placements: 156° in the osteoporosis group and 178° in the controls (P = 0.045). Osteoporosis patients fell more than controls did (1.0 versus 0.0; P = 0.036). CONCLUSIONS: The postural control in elderly women with osteoporosis differed from that of the controls, with higher sway velocity and maximum displacement of COP. Despite postural abnormalities such as hyperkyphosis and forward head, the COP position was posteriorized.

CRHR1 Polymorphisms Predict Bone Density in Survivors of Acute Lymphoblastic Leukemia

2008 ◽  
Vol 26 (18) ◽  
pp. 3031-3037 ◽  
Author(s):  
Terreia S. Jones ◽  
Sue C. Kaste ◽  
Wei Liu ◽  
Cheng Cheng ◽  
Wenjian Yang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Bone Density ◽  
Bone Mineral ◽  
Lymphoblastic Leukemia ◽  
Quantitative Computed Tomography ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Specific Manner ◽  
Osteoporosis Risk Factors ◽  
Z Scores

Purpose Corticosteroids are a critical component of therapy for acute lymphoblastic leukemia (ALL) but are associated with late effects, such as osteoporosis. Risk factors remain poorly defined. Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits. Patients and Methods The mean bone mineral density z scores of 309 long-term survivors of ALL were determined by quantitative computed tomography of the trabecular lumbar spine. We analyzed whether CRHR1 genotypes, adjusted for sex, ALL treatment regimen, and weight, could predict bone density. Results We found that three single nucleotide polymorphisms (SNPs), all in linkage disequilibrium, were associated with bone density in a sex-specific manner. Bone density was lower in males (P = .001), in nonblack patients (P < .08), in those who were not overweight (P < .001), and in those who received intensive antimetabolites and glucocorticoids (P < .001). After adjustment for these features, the G allele at the rs1876828 SNP was associated with lower z scores (P = .02) in males but tended to have the opposite association in females (P = .09). Conclusion CRHR1 polymorphisms may impact the risk of bone density deficits in patients treated with corticosteroids and antimetabolites in a sex-specific manner.

scholarly journals The Correlation Between Low Body Mass Index (underweight) With Bone Strength On Eldery Women

2020 ◽  
Vol 16 (1) ◽  
pp. 14
Author(s):  
Shafira Dwi Resnasari
Keyword(s):  
Body Mass Index ◽  
Bone Density ◽  
Bone Strength ◽  
Body Mass ◽  
Elderly Women ◽  
P Value ◽  
Mineral Density ◽  
Elderly Age ◽  
Cross Sectional ◽  
Low Body Mass Index

Background : Osteoporosis is a degenerative disease that often happend at women in elderly age with low body mass index. Standard examination for osteoporosis is bone density examination also known as Bone Mineral Density (BMD). This tool can interpret the patient’s bone strengthObjective : This research aims to identify the correlation between low body mass index (underweight) with bone strength on elderly women.Method : This is an observational analytic research which used cross sectional design. The sample consist of 65 respondents. The data were analyzed by using Chi-square test.Result : The result shows a large group of respondents aged 60-65 years old with a percentage of 18.5% suffers from osteopenia and a percentage of 47.7% suffers from osteoporosis. Furthermore, a percentage of 13.8% in underweight respondents suffers from osteopenia and a percentage of 47.7 % suffers from osteoporosis.Conclusion : This research proves that there is a correlation between low body mass index with bone strength on elderly women with P-value amounting to 0.022 (P < 0.05) for variable relationships between elderly age with bone strength and P-value of 0.002 (P < 0.05) for variable relationships between low body mass index with bone strength.Keyword : Osteoporosis, Body Mass Index, Bone Density

scholarly journals Triglyceride Can Predict the Discordance between QCT and DXA Screening for BMD in Old Female Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Dongjiang Xu ◽  
Ke di Wang ◽  
Jianhong Yang
Keyword(s):  
Elderly Women ◽  
Quantitative Computed Tomography ◽  
The Elderly ◽  
Dual Energy ◽  
Screening Tests ◽  
Screening Methods ◽  
Mineral Density ◽  
X Ray ◽  
Female Patients ◽  
The Relationship

Summary. Bone mineral density (BMD) data and biochemical indexes of the elderly women in the cadre department were analyzed retrospectively to find out the relationship between the biochemical indexes and the different screening results between dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Purpose. This study is aimed at exploring which indicator can predict the discordance between DXA and QCT. Methods. 192 female patients who took BMD screening tests by QCT and DXA were recruited, and the biomarkers were analyzed to study the relationship between the biomarkers and the discordance of two BMD screening methods. Results. There are 42, 78, and 72 female patients in the normal, osteopenia, and osteoporosis groups defined by DXA and 6, 54, and 132 female patients in the corresponding group defined by QCT. DXA was less sensitive than QCT. Cholesterol (CHO) and triglyceride (TG) were all negatively correlated with the discordance between these two methods. When TG > 0.89  mmol/L, the QCT result would be the same as the DXA’s; otherwise, there should be discordance between QCT and DXA. Conclusions. Triglyceride can be used to predict the discordance between QCT and DXA, and clinicians can evaluate patients’ DXA results based on patient triglyceride or cholesterol results as a supplement to QCT results.

Biomechanical comparison of single- and dual-lead pedicle screws in cadaveric spine

2008 ◽  
Vol 8 (1) ◽  
pp. 52-57 ◽  
Author(s):  
Arun T. Jacob ◽  
Aditya V. Ingalhalikar ◽  
John H. Morgan ◽  
Scott Channon ◽  
Tae-Hong Lim ◽  
...  
Keyword(s):  
Spinal Instrumentation ◽  
Pedicle Screws ◽  
The Elderly ◽  
Mineral Density ◽  
Pullout Force ◽  
Additional Surgery ◽  
Significant Difference ◽  
Dual Lead ◽  
Biomechanical Comparison

Object The pedicle screw (PS) is the cornerstone of spinal instrumentation, and its failure often entails additional surgery. Screw pullout is one of the most common reasons for screw failure, particularly in the elderly population. In this study the authors undertook a biomechanical comparison of the maximum pullout force (MPF) required for single- and dual-lead PSs in cadaver vertebrae. Methods Radiographs of 40 cadaveric vertebrae (T11–L5) were obtained, and bone mineral density (BMD) was measured in the lateral plane using dual–x-ray absorptiometry with a bone densitometer. One screw of each design was implanted for side-by-side comparison. Vertebrae were potted and mounted on an MTS test frame for accurate measurement of MPF. A total of 80 PSs were tested, 40 each of single- and dual-lead design types. Results The average MPF for dual-lead screws (533.89 ± 285.7 N) was comparable to that of single-lead screws (524.90 ± 311.6 N) (p = 0.3733). The BMD had a significant correlation with MPF for both dual-lead (r = 0.56413, p < 0.0001) and single-lead screws (r = 0.56327, p < 0.0001). Conclusions Barring the effect of BMD, this in vitro biomechanical test showed no significant difference in MPF between single- and dual-lead PSs. Dual-lead PSs can be used to achieve a faster insertion time, without compromising pullout force.

scholarly journals Osteoporosis Medication and Reduced Mortality Risk in Elderly Women and Men

2011 ◽  
Vol 96 (4) ◽  
pp. 1006-1014 ◽  
Author(s):  
Jacqueline R. Center ◽  
Dana Bliuc ◽  
Nguyen D. Nguyen ◽  
Tuan V. Nguyen ◽  
John A. Eisman
Keyword(s):  
Mortality Risk ◽  
Elderly Women ◽  
Osteoporotic Fractures ◽  
Premature Mortality ◽  
Osteoporosis Treatment ◽  
Mortality Rates ◽  
Quadriceps Strength ◽  
Community Dwelling ◽  
Mineral Density ◽  
Osteoporosis Therapy

Abstract Context: Osteoporotic fractures are associated with premature mortality. Antiresorptive treatment reduces refracture but mortality reduction is unclear. Objective: The objective of the study was to examine the effect of osteoporosis treatment [bisphosphonates (BP), hormone therapy (HT), and calcium ± vitamin D only (CaD)] on mortality risk. Design: This was a prospective cohort study (April 1989 to May 2007). Setting: The study was conducted with community-dwelling elderly (aged 60+ yr) subjects in Dubbo, a semiurban city, Australia. Subjects: Subjects included 1223 and 819 women and men in the Dubbo Osteoporosis Epidemiology Study. Main Outcome Measure: Mortality according to treatment group was recorded. Results: There were 325 (BP, n = 106; HT, n = 77; CaD, n = 142) women and 37 men (BP, n = 15; CaD, n = 22) on treatment. In women, mortality rates were lower with BP 0.8/100 person-years (0.4, 1.4) and HT 1.2/100 person-years (0.7, 2.1) but not CaD 3.2/100 person-years (2.5, 4.1) vs. no treatment 3.5/100 person-years (3.1, 3.8). Accounting for age, fracture occurrence, comorbidities, quadriceps strength, and bone mineral density, mortality risk remained lower for women on BP [hazard ratio (HR) 0.3 (0.2, 0.6)] but not HT [HR 0.8 (0.4, 1.8)]. For 429 women with fractures, mortality risk was still reduced in the BP group [adjusted HR 0.3 (0.2, 0.7)], not accounted for by a reduction in subsequent fractures. In men, lower mortality rates were observed with BP but not CaD [BP 1.0/100 person-years (0.3, 3.9) and CaD 3.1/100 person-years (1.5, 6.6) vs. no treatment 4.3/100 person-years (3.9, 4.8)]. After adjustment, mortality was similar, although not significant [HR 0.5 (0.1, 2.0)]. Conclusions: Osteoporosis therapy appears to reduce mortality risk in women and possibly men.

Factor VII activating protease

2011 ◽  
Vol 31 (03) ◽  
pp. 174-178 ◽  
Author(s):  
M. Etscheid ◽  
S. M. Kanse
Keyword(s):  
The Elderly ◽  
Factor Vii ◽  
Nucleotide Polymorphisms ◽  
Protease Activated Receptors ◽  
Single Nucleotide ◽  
Fibrinolytic Enzymes ◽  
Inflammatory Processes ◽  
Acid Exchange

SummaryFactor VII activating protease (FSAP) is a circulating serine protease with high homology to fibrinolytic enzymes. A role in the regulation of coagulation and fibrinolysis is suspected based on in vitro studies demonstrating activation of FVII or pro-urokinase plasminogen activator (uPA). However, considering the paucity of any studies in animal models or any correlative studies in humans the role of FSAP in haemostasis remains unclear. In relation to vascular remodeling processes or inflammation it has been convincingly shown that FSAP interacts with growth factors as well as protease activated receptors (PAR). Against this sparse background there are a plethora of studies which have investigated the linkage of single nucleotide polymorphisms (SNP) in the FSAP gene (HABP2) to various diseases. The G534E SNP of FSAP is associated with a low proteolytic activity due to an amino acid exchange in the protease domain. This and other SNPs have been linked to carotid stenosis, stroke as well as thrombosis in the elderly and plaque calcification. These SNP analyses indicate an important role for FSAP in the regulation of the haemostasis system as well as fibroproliferative inflammatory processes.

Sign in / Sign up

Export Citation Format

Share Document