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ABSTRACT: We sought to investigate the relationship between newly identified genetic variants and vitamin D levels and fracture risk in healthy African American (black) children. This case-control study included children of both sexes, ages 5 to 9 years, with and without forearm fractures. Serum 25-hydroxy vitamin D levels, bone mineral density, body mass index, and calcium/vitamin D intake were measured in 130 individuals (n = 60 cases and n = 70 controls). The 5 variants tested were located in the GC gene (rs2282679), in the NADSYN1 gene (rs12785878 and rs3829251), and in the promoter region of the CYP2R1 gene (rs2060793 and rs104741657). Associations between single nucleotide polymorphisms (SNPs) and vitamin D levels were tested using an analysis of covariance. Associations between SNPs and fracture status were tested using logistic regression. The GC gene variant was associated with vitamin D levels (P = 0.038). None of the SNPs were associated with fracture status in young blacks. These results suggest that the variants tested, which are associated with circulating vitamin D levels in whites, are not associated with fracture status in healthy black children. Additional research is required to discover the genetics of fracture risk in blacks.
Journal of Investigative Medicine 05/2012; 60(6):902-6. · 1.96 Impact Factor
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ABSTRACT: BACKGROUND: Recent epidemiologic and clinical data suggest men and racial and ethnic minorities may receive lower-quality care for osteoporosis and fragility fractures than female and nonminority patients. The causes of such differences and optimal strategies for their reduction are unknown. QUESTIONS/PURPOSES: A panel was convened at the May 2010 American Academy of Orthopaedic Surgeons/Orthopaedic Research Society/Association of Bone and Joint Surgeons Musculoskeletal Healthcare Disparities Research Symposium to (1) assess current understanding of sex/gender and racial/ethnic disparities in the care of osteoporosis and after fragility fractures, (2) define goals for improving the equity and quality of care, and (3) identify strategies for achieving these goals. WHERE ARE WE NOW?: Participants identified shortcomings in the quality of care for osteoporosis and fragility fractures among male and minority populations and affirmed a need for novel strategies to improve the quality and equity of care. WHERE DO WE NEED TO GO?: Participants agreed opportunities exist for health professionals to contribute to improved osteoporosis management and secondary fracture prevention. They agreed on a need to define standards of care and management for osteoporosis and fragility fractures and develop strategies to involve physicians and other health professionals in improving care. HOW DO WE GET THERE?: The group proposed strategies to improve the quality and equity of osteoporosis and care after fragility fractures. These included increased patient and physician education, with identification of "champions" for osteoporosis care within and outside of the healthcare workforce; creation of incentives for hospitals and physicians to improve care; and research comparing the effectiveness of approaches to osteoporosis screening and fracture management.
Clinical Orthopaedics and Related Research 03/2011; 469(7):1936-40. · 2.53 Impact Factor
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ABSTRACT: Defining bone quality remains elusive. From a patient perspective bone quality can best be defined as an individual's likelihood of sustaining a fracture. Fracture risk indicators and performance measures can help clinicians better understand individual fracture risk. Educational resources such as the Web can help clinicians and patients better understand fracture risk, communicate effectively, and make decisions concerning diagnosis and treatment.
We examined four questions: What tools can be used to identify individuals at high risk for fracture? What clinical performance measures are available? What strategies can help ensure that patients at risk for fracture are identified? What are some authoritative Web sites for educating providers and patients about bone quality?
Using Google, PUBMED, and trademark names, we reviewed the literature using the terms "bone quality" and "osteoporosis education." Web site legitimacy was evaluated using specific criteria. Educational Web sites were limited to English-language sites sponsored by nonprofit organizations
The Fracture Risk Assessment Tool® (FRAX®) and the Fracture Risk Calculator (FRC) are reliable means of assessing fracture risk. Performance measures relating to bone health were developed by the AMA convened Physician Consortium for Performance Improvement® and are included in the Physician Quality Reporting Initiative. In addition, quality measures have been developed by the Joint Commission. Strategies for identifying individuals at risk include designating responsibility for case finding and intervention, evaluating secondary causes of osteoporosis, educating patients and providers, performing cost-effectiveness evaluation, and using information technology. An abundance of authoritative educational Web sites exists for providers and patients.
Effective clinical indicators, performance measures, and educational tools to better understand and identify fracture risk are now available. The next challenge is to encourage broader use of these resources so that individuals at high risk for fracture will not just be identified but will also adhere to therapy.
Clinical Orthopaedics and Related Research 03/2011; 469(8):2248-59. · 2.53 Impact Factor
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Brennan T Harmon,
E Funda Orkunoglu-Suer,
Kasra Adham,
Justin S Larkin,
Heather Gordish-Dressman,
Priscilla M Clarkson,
Paul D Thompson,
Theodore J Angelopoulos,
Paul M Gordon,
Niall M Moyna,
Linda S Pescatello,
Paul S Visich,
Robert F Zoeller,
Monica J Hubal, Laura L Tosi,
Eric P Hoffman,
Joseph M Devaney
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ABSTRACT: Baseline muscle size and muscle adaptation to exercise are traits with high variability across individuals. Recent research has implicated several chemokines and their receptors in the pathogenesis of many conditions that are influenced by inflammatory processes, including muscle damage and repair. One specific chemokine, chemokine (C-C motif) ligand 2 (CCL2), is expressed by macrophages and muscle satellite cells, increases expression dramatically following muscle damage, and increases expression further with repeated bouts of exercise, suggesting that CCL2 plays a key role in muscle adaptation. The present study hypothesizes that genetic variations in CCL2 and its receptor (CCR2) may help explain muscle trait variability. College-aged subjects [n = 874, Functional Single-Nucleotide Polymorphisms Associated With Muscle Size and Strength (FAMUSS) cohort] underwent a 12-wk supervised strength-training program for the upper arm muscles. Muscle size (via MR imaging) and elbow flexion strength (1 repetition maximum and isometric) measurements were taken before and after training. The study participants were then genotyped for 11 genetic variants in CCL2 and five variants in CCR2. Variants in the CCL2 and CCR2 genes show strong associations with several pretraining muscle strength traits, indicating that inflammatory genes in skeletal muscle contribute to the polygenic system that determines muscle phenotypes. These associations extend across both sexes, and several of these genetic variants have been shown to influence gene regulation.
Journal of Applied Physiology 12/2010; 109(6):1779-85. · 3.75 Impact Factor
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Joseph M Devaney,
Heather Gordish-Dressman,
Brennan T Harmon,
Margaret K Bradbury,
Stephanie A Devaney,
Tamara B Harris,
Paul D Thompson,
Priscilla M Clarkson,
Thomas B Price,
Theodore J Angelopoulos, [......],
Bo Hyoung Kim, Laura L Tosi,
Melissa Garcia,
Rongling Li,
Joseph M Zmuda,
Matthew J Delmonico,
Robert S Lindsay,
Barbara V Howard,
William E Kraus,
Eric P Hoffman
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ABSTRACT: Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin,insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that makeup metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE)(n = 175; age 40–65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles eles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. Inolder African-American and European American subjects(Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p\0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations.
Human Genetics 11/2010; 129(2):129-39. · 5.07 Impact Factor
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Joseph M Devaney, Laura L Tosi,
David T Fritz,
Heather A Gordish-Dressman,
Shan Jiang,
Funda E Orkunoglu-Suer,
Andrew H Gordon,
Brennan T Harmon,
Paul D Thompson,
Priscilla M Clarkson,
Theodore J Angelopoulos,
Paul M Gordon,
Niall M Moyna,
Linda S Pescatello,
Paul S Visich,
Robert F Zoeller,
Cinzia Brandoli,
Eric P Hoffman,
Melissa B Rogers
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ABSTRACT: A classic morphogen, bone morphogenetic protein 2 (BMP2) regulates the differentiation of pluripotent mesenchymal cells. High BMP2 levels promote osteogenesis or chondrogenesis and low levels promote adipogenesis. BMP2 inhibits myogenesis. Thus, BMP2 synthesis is tightly controlled. Several hundred nucleotides within the 3' untranslated regions of BMP2 genes are conserved from mammals to fishes indicating that the region is under stringent selective pressure. Our analyses indicate that this region controls BMP2 synthesis by post-transcriptional mechanisms. A common A to C single nucleotide polymorphism (SNP) in the BMP2 gene (rs15705, +A1123C) disrupts a putative post-transcriptional regulatory motif within the human ultra-conserved sequence. In vitro studies indicate that RNAs bearing the A or C alleles have different protein binding characteristics in extracts from mesenchymal cells. Reporter genes with the C allele of the ultra-conserved sequence were differentially expressed in mesenchymal cells. Finally, we analyzed MRI data from the upper arm of 517 healthy individuals aged 18-41 years. Individuals with the C/C genotype were associated with lower baseline subcutaneous fat volumes (P = 0.0030) and an increased gain in skeletal muscle volume (P = 0.0060) following resistance training in a cohort of young males. The rs15705 SNP explained 2-4% of inter-individual variability in the measured parameters. The rs15705 variant is one of the first genetic markers that may be exploited to facilitate early diagnosis, treatment, and/or prevention of diseases associated with poor fitness. Furthermore, understanding the mechanisms by which regulatory polymorphisms influence BMP2 synthesis will reveal novel pharmaceutical targets for these disabling conditions.
Journal of Cellular Biochemistry 07/2009; 107(6):1073-82. · 2.87 Impact Factor
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ABSTRACT: This article summarizes the results of a comprehensive review of the literature on the use of negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.(R) Therapy (KCI, San Antonio, TX) in pediatric patients. A review of the literature revealed 20 articles that discussed the use of NPWT/ROCF in exclusively pediatric patients. Nine articles were retrospective reviews, and 11 were case studies. This review discusses the insights from these articles. This review discusses the versatility of NPWT/ROCF for use with pediatric patients with infected wounds; full-thickness burns; open fractures; large soft tissue wounds; surgical wounds of the chest, abdomen, and spine; pilonidal disease; and pressure ulcers. NPWT/ROCF has been used in children as young as a few weeks of age, and in children with comorbidities such as congenital heart disease, immunosuppression, and spina bifida. Wound healing in children can be delayed by impaired perfusion, infection, edema, and poor nutrition. Clinical considerations for using NPWT/ROCF in children can include differences in healing due to higher granulation rates requiring more frequent dressing changes, poor nutritional status, small size, and low weight. With pediatric patients, there is no consensus on foam (white or black) selection, optimum amount of negative pressure, frequency of NPWT/ROCF dressing changes, and interposing contact layer selection. Randomized prospective studies are needed to make recommendations for safe and efficacious clinical practice. Research regarding the effects of dressing types, adjunctive treatment, and wound healing in neonates and children is needed.
Journal of orthopaedic trauma 22(10 Suppl):S167-76. · 1.78 Impact Factor
