Browsing by Subject "bone mineral density"
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Item Evaluation of the Effects of Green Tea Extracts on Bone Homeostasis in the Ts65Dn Down Syndrome Mouse Model(Office of the Vice Chancellor for Research, 2013-04-05) Abeysekera, Irushi S.; Thomas, Jared R.; Blazek, Joshua D.; Roper, Randall J.Down Syndrome (DS) is a genetic disorder that affects ~1 in 700 live births, caused by trisomy of human chromosome 21 (Hsa21), and results in cognitive impairment, craniofacial abnormalities, low muscle tone, and skeletal deficiencies. To study these phenotypes, we utilized the Ts65Dn mouse model, which contains three copies of approximately half the orthologous found on Hsa21 and exhibits similar phenotypes as found in humans with DS. Individuals with DS and Ts65Dn mice have deficits in bone mineral density (BMD), architecture, and bone strength. Over-expression of DYRK1A, a serine-threonine kinase encoded on Hsa21, has been linked to deficiencies in DS bone homeostasis. Epigallocatechin-3- gallate (EGCG), an aromatic polyphenol found in high concentrations in green tea, is a known inhibitor of Dyrk1a activity. Normalization of Dyrk1a activity by EGCG may have the potential to regulate bone homeostasis and increase BMD and bone strength in individuals with DS. In this study, we hypothesized that EGCG obtained from different sources would have differential effects in correcting bone deficits associated with DS. To test our hypothesis, we performed Liquid chromatography–mass spectrometry (LC-MS) on EGCG and related compounds from different sources. The LC-MS analysis determined the amount of EGCG and the degradation in our stock solution. Next, we treated three-weekold Ts65Dn and control male mice with EGCG for three weeks. At six weeks of age, mice were sacrificed. DXA and micro CT analysis were performed on the femurs and skulls of the mice to assess trabecular and cortical bone structure and BMD. Our results indicate the ability of EGCG to ameliorate skeletal deficiencies and compared pure EGCG with EGCG purchased from commercial vendors in correcting skeletal deficits associated with DS.Item Executive summary of the 2017 KDIGO Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters(Elsevier, 2017-07) Ketteler, Markus; Block, Geoffrey A.; Evenepoel, Pieter; Fukagawa, Masafumi; Herzog, Charles A.; McCann, Linda; Moe, Sharon M.; Shroff, Rukshana; Tonelli, Marcello A.; Toussaint, Nigel D.; Vervloet, Marc G.; Leonard, Mary B.; Medicine, School of MedicineThe KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD–mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.Item Interferon Gamma, but not Calcitriol Improves the Osteopetrotic Phenotypes in ADO2 Mice(Wiley, 2015-11) Alam, Imranul; Gray, Amie K.; Acton, Dena; Gerard-O'Riley, Rita L.; Reilly, Austin M.; Econs, Michael J.; Department of Medicine, IU School of MedicineADO2 is a heritable osteosclerotic disorder that usually results from heterozygous missense dominant negative mutations in the chloride channel 7 gene (CLCN7). ADO2 is characterized by a wide range of features and severity, including multiple fractures, impaired vision due to secondary bony overgrowth and/or the lack of the optical canal enlargement with growth, and osteonecrosis/osteomyelitis. The disease is presently incurable, although anecdotal evidence suggests that calcitriol and interferon gamma-1b (IFN-G) may have some beneficial effects. To identify the role of these drugs for the treatment of ADO2, we utilized a knock-in (G213R mutation in Clcn7) ADO2 mouse model that resembles the human disease. Six-week-old ADO2 heterozygous mice were administered vehicle (PBS) or calcitriol or IFN-G 5 times per week for 8 weeks. We determined bone phenotypes using DXA and μCT, and analyzed serum biochemistry and bone resorption markers. ADO2 mice treated with all doses of IFN-G significantly (p<0.05) attenuated the increase of whole body aBMD and distal femur BV/TV gain in both male and female compared to the vehicle group. In contrast, mice treated with low and medium doses of calcitriol showed a trend of higher aBMD and BV/TV whereas high dose calcitriol significantly (p<0.05) increased bone mass compared to the vehicle group. The calcium and phosphorus levels did not differ between vehicle and IFN-G or calcitriol treated mice; however, we detected significantly (p<0.05) elevated levels of CTX/TRAP5b ratio in IFN-G treated mice. Our findings indicate that while IFN-G at all doses substantially improved the osteopetrotic phenotypes in ADO2 heterozygous mice, calcitriol treatment at any dose did not improve the phenotype and at high dose further increased bone mass. Thus, use of high dose calcitriol therapy in ADO2 patients merits serious reconsideration. Importantly, our data support the prospect of a clinical trial of IFN-G in ADO2 patients.Item Selective inactivation of Stat3 in osteoclasts affect bone mass differently in female and male mice(Office of the Vice Chancellor for Research, 2013-04-05) Himes, Evan; Zhou, Hongkang; Li, JiliangSignal Transducer and Activator of Transcription 3 (Stat3) is activated by the binding of various cytokines to their receptors, such as IL-6. Previous studies have revealed that conditional knockouts of Stat3 in osteoblasts and osteocytes cause a decrease in bone mineral density and strength. To study the role of Stat3 in osteoclasts, osteoclast- specific knockout mice were created using cre-lox recombination. Bone mineral density (BMD) and bone mineral content (BMC) were calculated for femurs and the fourth lumbar vertebra (L4) of 8 weeks old mice. Analysis revealed a decrease in BMD of femurs of osteoclast-selective Stat3 knockout (KOOc-Stat3) mice compared to their littermate control (p<0.05). There was also a decrease in BMC of the femurs of KOOc-Stat3 mice compared to the littermate controls (p<0.05). Analysis of μCT data from trabecular bone in the distal femur showed significant decreases in trabecular number and bone volume/tissue volume in both male and female KOOc-Stat3 mice. Trabecular separation was increased in male and female KOOc-Stat3 mice. Bone histomorphometry at the distal femur revealed a significant decrease in bone formation rate in males and females KOOc-Stat3 mice compared to the littermate controls. Osteoclast number identified by tartrate resistant acid phosphatase (TRAP) stain in female KOOc-Stat3 mice was significantly deficient from their control. These data suggest that inactivation of Stat3 in osteoclasts influences bone metabolism through both osteoblasts and osteoclasts. Knockout of Stat3 in either cell type leads to decreases in bone strength, making Stat3 a good drug target for treatment of diseases such as osteoporosis.Item Serum 25-hydroxyvitamin D and bone mineral density among children and adolescents in a Northwest Chinese city(Elsevier, 2018-11) Li, Jing; Ding, Wenqing; Cao, Juan; Sun, Lijiao; Liu, Shanghong; Zhang, Jianjun; Zhao, Haiping; Epidemiology, School of Public HealthAlthough vitamin D is essential for bone health, little is known about prevalence of vitamin D deficiency and low bone mineral density (BMD) among children, especially those in developing countries. It also remains unclear whether serum 25-hydroxyvitamin D [25(OH)D] is associated with BMD among children. We investigated these questions among children and adolescents in Yinchuan (latitude: 38° N), Ningxia, an economically underdeveloped province in Northwest China. A total of 1582 children (756 boys and 826 girls), aged 6–18 years, were recruited from schools using the stratified random sampling method in fall 2015. Serum 25(OH)D concentrations were measured by enzyme-linked immunosorbent assay, and BMD was quantified by dual-energy X-ray absorptiometry. Vitamin D deficiency (defined as serum 25(OH)D ≤ 37.5 nmol/L) was present in 35.5% of study subjects. There were no clear patterns of differences in serum 25(OH)D concentrations across the four age groups compared (6–9 years, 10–13 years, 14–16 years, and 17–18 years). The prevalence of low total body less head (TBLH) BMD (defined as a Z-score of ≤ −2.0 standard deviations away from the mean BMD values of the Chinese pediatric reference population) among children examined was 1.8% and was not significantly different among the four age groups considered. Linear regression analysis revealed that age, weight, and height were significantly and positively associated with TBLH BMD and that the strongest determinant of TBLH BMD was age in boys and weight in girls. There were no significant correlations between serum 25(OH)D concentrations and BMD obtained for total body and at various skeletal sites (r ranged from −0.005 to 0.014) regardless of whether children evaluated were sufficient, insufficient, or deficient in vitamin D. In conclusion, more than one-third of children and adolescents in a Northwest Chinese city were deficient in vitamin D but only <2% of them developed low BMD.