PHYSIOLOGY OF BONE METABOLISM IN AN AGING POPULATION

Summary

Principal Investigator: Sundeep Khosla
Abstract: This is a competitive renewal application for P01 AG004875, "Physiology of Bone Metabolism in an Aging Population." Osteoporosis is an enormous public health problem, and our overall goal is to better understand the mechanisms and consequences of bone loss with aging. As in the past, the major strength of our group is to bring together diverse disciplines into synergistic interactions, and the present application includes population-based epidemiology studies, intensive studies in the Clinical Research Unit (formerly the General Clinical Research Center), animal studies using novel mouse models, and basic cellular and molecular studies. Using this integrated approach, we propose to focus on three major areas: (1) Defining the mechanisms by which estrogen (E) regulates bone metabolism;(2) With increases in bone resorption, as in the setting of E deficiency, identifying the mechanisms by which osteoclasts regulate osteoblasts;and (3) Assessing the risk factors for and consequences of fractures that increase with E deficiency and with aging. Each of the Projects are aligned with one or more of these major themes: Project 1 ("Pathophysiology of Osteoporosis") uses the human as the experimental model to address key, unresolved issues regarding E action on bone, including definitively establishing whether follicle-stimulating hormone modulates bone resorption in the setting of E deficiency and defining mechanisms for the age-related decrease in bone formation;Project 2 ("Risk Factors for Fractures Among the Elderly") provides a population perspective on risk factors for fractures ("secondary" osteoporosis) that exacerbate bone loss with E deficiency and with aging;Project 3 ("Osteoclast Regulation of Bone Formation") pursues the basic biology and functional relevance of factors made by osteoclasts that regulate bone formation;and Project 4 ("Estrogen Receptor Signaling Pathways in Bone") uses in vitro and novel mouse models to dissect E signaling pathways in bone. A single Core ("Administrative and Biostatistics Core") provides the necessary infrastructure to support these Projects. Collectively, these studies strive to provide a comprehensive assesment of the pathogenesis and clinical impact of one of the most important disorders facing our aging population.
Funding Period: 1997-07-15 - 2014-06-30
more information: NIH RePORT

Top Publications

  1. pmc Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women
    Matthew T Drake
    Division of Endocrinology and Metabolism, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 95:5056-62. 2010
  2. pmc Wnt10b activates the Wnt, notch, and NFκB pathways in U2OS osteosarcoma cells
    Ulrike I Mödder
    Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    J Cell Biochem 112:1392-402. 2011
  3. pmc Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women
    Ulrike I Mödder
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 49:202-7. 2011
  4. pmc Osteoporosis: now and the future
    Tilman D Rachner
    Division of Endocrinology, Diabetes, and Bone Diseases, Dresden Technical University Medical Centre, Dresden, Germany
    Lancet 377:1276-87. 2011
  5. pmc Mortality in the vertebroplasty population
    R J McDonald
    Clinician Investigator Training Program, Department of Radiology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    AJNR Am J Neuroradiol 32:1818-23. 2011
  6. pmc Distinct effects of loss of classical estrogen receptor signaling versus complete deletion of estrogen receptor alpha on bone
    Farhan A Syed
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 49:208-16. 2011
  7. pmc TGF-β mediates suppression of adipogenesis by estradiol through connective tissue growth factor induction
    Ashok Kumar
    Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    Endocrinology 153:254-63. 2012
  8. pmc A DNA binding mutation in estrogen receptor-α leads to suppression of Wnt signaling via β-catenin destabilization in osteoblasts
    Ulrike I Mödder
    Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Cell Biochem 113:2248-55. 2012
  9. pmc Fracture risk in women with breast cancer: a population-based study
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 27:1196-205. 2012
  10. pmc Trends in subtrochanteric, diaphyseal, and distal femur fractures, 1984-2007
    A C Ng
    Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA
    Osteoporos Int 23:1721-6. 2012

Research Grants

  1. Alzheimer's Disease Research Center at Columbia University
    Scott A Small; Fiscal Year: 2013
  2. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
  3. Alzheimer's Disease Research Center
    Thomas J Montine; Fiscal Year: 2013
  4. New Approaches to Dementia Heterogeneity
    Bruce L Miller; Fiscal Year: 2013
  5. UCLA Alzheimer's Disease Research Center
    David B Teplow; Fiscal Year: 2013
  6. Alzheimer's Disease Research Center
    Oscar L Lopez; Fiscal Year: 2013
  7. Massachusetts Alzheimer's Disease Research Center
    Bradley T Hyman; Fiscal Year: 2013
  8. HEALTHY AGING AND SENILE DEMENTIA
    John Morris; Fiscal Year: 2013
  9. Behaviors on Surveys and in the Economy: HRS and Beyond
    Robert J Willis; Fiscal Year: 2013
  10. Impact of Amyloid on the Aging Brain
    Reisa A Sperling; Fiscal Year: 2013

Detail Information

Publications101 found, 100 shown here

  1. pmc Effects of parathyroid hormone treatment on circulating sclerostin levels in postmenopausal women
    Matthew T Drake
    Division of Endocrinology and Metabolism, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 95:5056-62. 2010
    ..Intermittent PTH treatment stimulates bone formation, but the mechanism(s) of this effect remain unclear. Sclerostin is an inhibitor of Wnt signaling, and animal studies have demonstrated that PTH suppresses sclerostin production...
  2. pmc Wnt10b activates the Wnt, notch, and NFκB pathways in U2OS osteosarcoma cells
    Ulrike I Mödder
    Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    J Cell Biochem 112:1392-402. 2011
    ..Interestingly, Wnt3a failed to induce the Notch and NFκB pathways, demonstrating Wnt-specificity. In conclusion, our data demonstrate that Wnt10b, but not Wnt3a, stimulates the NFκB and Notch pathways in U2OS osteosarcoma cells...
  3. pmc Effects of estrogen on osteoprogenitor cells and cytokines/bone-regulatory factors in postmenopausal women
    Ulrike I Mödder
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 49:202-7. 2011
    ....
  4. pmc Osteoporosis: now and the future
    Tilman D Rachner
    Division of Endocrinology, Diabetes, and Bone Diseases, Dresden Technical University Medical Centre, Dresden, Germany
    Lancet 377:1276-87. 2011
    ..This overview discusses these novel therapies and explains their underlying physiology...
  5. pmc Mortality in the vertebroplasty population
    R J McDonald
    Clinician Investigator Training Program, Department of Radiology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    AJNR Am J Neuroradiol 32:1818-23. 2011
    ....
  6. pmc Distinct effects of loss of classical estrogen receptor signaling versus complete deletion of estrogen receptor alpha on bone
    Farhan A Syed
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 49:208-16. 2011
    ..Further studies defining these pathways may lead to novel approaches to selectively modulate ER signaling for beneficial skeletal effects...
  7. pmc TGF-β mediates suppression of adipogenesis by estradiol through connective tissue growth factor induction
    Ashok Kumar
    Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    Endocrinology 153:254-63. 2012
    ..Moreover, estradiol-mediated induction of CTGF was abrogated by TGF-β inhibition. These data support that estradiol effects on adipogenesis involves TGF-β induction, which then induces CTGF to suppress adipogenesis...
  8. pmc A DNA binding mutation in estrogen receptor-α leads to suppression of Wnt signaling via β-catenin destabilization in osteoblasts
    Ulrike I Mödder
    Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Cell Biochem 113:2248-55. 2012
    ....
  9. pmc Fracture risk in women with breast cancer: a population-based study
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 27:1196-205. 2012
    ....
  10. pmc Trends in subtrochanteric, diaphyseal, and distal femur fractures, 1984-2007
    A C Ng
    Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA
    Osteoporos Int 23:1721-6. 2012
    ..The incidence of non-hip femur fractures increased between 1984 and 2007, with an increase in the rates for women after 1996...
  11. pmc Characterization of mesenchymal progenitor cells isolated from human bone marrow by negative selection
    Ulrike I Mödder
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 50:804-10. 2012
    ....
  12. pmc The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed?
    Sundeep Khosla
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 26:441-51. 2011
    ..In this perspective, we critically review these and other findings, leading us to conclude that our original model requires modification but not revision...
  13. pmc Fracture risk in men with prostate cancer: a population-based study
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 26:1808-15. 2011
    ..To the extent that advanced-stage disease and pathologic fractures account for the excess risk, the effectiveness of fracture prevention among men with prostate cancer may be limited...
  14. pmc Towards a diagnostic and therapeutic consensus in male osteoporosis
    J A Kanis
    WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Beech Hill Road, Sheffield, UK
    Osteoporos Int 22:2789-98. 2011
    ..The consensus views on osteoporosis in men are reported...
  15. pmc Circulating osteogenic cells: characterization and relationship to rates of bone loss in postmenopausal women
    Anita Undale
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 47:83-92. 2010
    ..Our study also provides "proof-of-concept" for the use of PB lin-/AP+ cells in clinical-investigative studies, and identifies several pathways that could potentially regulate rates of bone loss in postmenopausal women...
  16. pmc Induction of fracture repair by mesenchymal cells derived from human embryonic stem cells or bone marrow
    Anita Undale
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    J Orthop Res 29:1804-11. 2011
    ..Additional studies are needed to further modify hESCs to achieve optimal fracture healing by these cells...
  17. pmc The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors
    Erik R Nelson
    Pharmacology and Cancer Biology, Duke University Medical Center, P O Box 3813, Durham, North Carolina 27710, USA
    Endocrinology 152:4691-705. 2011
    ....
  18. pmc Effects of intermittent parathyroid hormone treatment on osteoprogenitor cells in postmenopausal women
    Matthew T Drake
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Bone 49:349-55. 2011
    ....
  19. pmc Emerging therapeutic opportunities for skeletal restoration
    Masanobu Kawai
    Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough, Maine, USA
    Nat Rev Drug Discov 10:141-56. 2011
    ..Such novel strategies offer promise not only for reducing age-related bone loss and the associated risk of fractures but also for restoring bone mineral density to healthy levels...
  20. pmc Association between myocardial infarction and fractures: an emerging phenomenon
    Yariv Gerber
    Department of Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Circulation 124:297-303. 2011
    ..Recent changes in the epidemiology of MI justify exploring this relationship. We evaluated whether MI constitutes a risk factor for osteoporotic fracture and examined secular trends in this association...
  21. pmc Regulation of circulating sclerostin levels by sex steroids in women and in men
    Ulrike Il Mödder
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 26:27-34. 2011
    ..Moreover, consistent with recent data indicating important effects of Wnts on osteoclastic cells, our findings suggest that in humans, changes in sclerostin production may contribute to effects of E on bone resorption...
  22. pmc Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS
    Alvin C Ng
    Division of Endocrinology, Department of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Blood 118:6529-34. 2011
    ..05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS...
  23. pmc Osteoporotic fractures and heart failure in the community
    Yariv Gerber
    Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Am J Med 124:418-25. 2011
    ..Recent findings suggest a role for heart failure in the etiology of osteoporotic fractures, yet the temporal sequence of occurrence of the 2 conditions needs clarification...
  24. pmc Effects of physiological variations in circulating insulin levels on bone turnover in humans
    Rita Basu
    Endocrine Research Unit, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 96:1450-5. 2011
    ..Undercarboxylated osteocalcin, in turn, enhances insulin sensitivity...
  25. pmc Estrogen and the skeleton
    Sundeep Khosla
    Endocrine Research Unit and Kogod Center on Aging, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Trends Endocrinol Metab 23:576-81. 2012
    ..Estrogen also modulates osteoblast/osteocyte and T-cell regulation of osteoclasts. Unraveling these pleiotropic effects of estrogen may lead to new approaches to prevent and treat osteoporosis...
  26. pmc Examination of nuclear receptor expression in osteoblasts reveals Rorβ as an important regulator of osteogenesis
    Matthew M Roforth
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 27:891-901. 2012
    ....
  27. pmc In vivo assessment of bone quality in postmenopausal women with type 2 diabetes
    Joshua N Farr
    Department of Medicine, Division of Endocrinology, Mayo Clinic College of Medicine, Rochester, MN, USA
    J Bone Miner Res 29:787-95. 2014
    ..Thus, the skeleton needs to be recognized as another important target tissue subject to diabetic complications. © 2014 American Society for Bone and Mineral Research...
  28. pmc Trends in fracture incidence: a population-based study over 20 years
    Shreyasee Amin
    Division of Rheumatology, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN, USA
    J Bone Miner Res 29:581-9. 2014
    ..More generally, these data indicate that the dramatic increases in the incidence of fractures at many skeletal sites that were observed decades ago have now stabilized...
  29. pmc Are young women and men with rheumatoid arthritis at risk for fragility fractures? A population-based study
    Shreyasee Amin
    From the Department of Medicine, Divisions of Rheumatology and Endocrinology, Diabetes, Metabolism and Nutrition and Department of Health Sciences Research, Divisions of Epidemiology and Biomedical Statistics and Informatics, College of Medicine, Mayo Clinic, Rochester, MN, USA
    J Rheumatol 40:1669-76. 2013
    ..We determined the risk for fractures in both young and older women and men following RA diagnosis...
  30. pmc A distal forearm fracture in childhood is associated with an increased risk for future fragility fractures in adult men, but not women
    Shreyasee Amin
    Division of Rheumatology, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, MN, USA
    J Bone Miner Res 28:1751-9. 2013
    ..Until then, men should be asked about a childhood distal forearm fracture and, if so, warrant further screening and counseling on measures to optimize bone health and prevent fractures. ..
  31. pmc Dissection of estrogen receptor alpha signaling pathways in osteoblasts using RNA-sequencing
    Matthew M Roforth
    Endocrine Research Unit and Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota, United States of America
    PLoS ONE 9:e95987. 2014
    ..These data provide a comprehensive list of genes and pathways targeted by these specific modes of ERα action and suggest that "mode-specific" ligands could be developed to modulate specific ERα functionality in bone. ..
  32. pmc Fracture risk following bariatric surgery: a population-based study
    K M Nakamura
    Johns Hopkins Hospital, Baltimore, MD, USA
    Osteoporos Int 25:151-8. 2014
    ..While further studies of fracture risk in this population are needed, bone health should be discussed in bariatric surgery clinics...
  33. pmc Coronary endothelial function in patients with obstructive sleep apnea
    Andrew Cassar
    aDepartment of Internal Medicine, Division of Cardiovascular Diseases bDepartment of Internal Medicine, Division of Pulmonary and Critical Care cDepartment of Health Sciences Research, Division of Biomedical Statistics and Informatics dDepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA
    Coron Artery Dis 25:16-22. 2014
    ..The current study evaluates the association between invasive coronary endothelial dysfunction and OSA in patients with nonobstructive coronary atherosclerosis...
  34. pmc Effects of estrogen on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in postmenopausal women
    Koji Fujita
    Mayo Clinic College of Medicine, Rochester, Minnesota 55905
    J Clin Endocrinol Metab 99:E81-8. 2014
    ..Studies in postmenopausal women have shown that estrogen reduces circulating sclerostin levels, but effects of estrogen on skeletal sclerostin mRNA levels are unknown...
  35. pmc Effects of age on bone mRNA levels of sclerostin and other genes relevant to bone metabolism in humans
    Matthew M Roforth
    Endocrine Research Unit and Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA Electronic address
    Bone 59:1-6. 2014
    ....
  36. pmc Pathogenesis of age-related bone loss in humans
    Sundeep Khosla
    Guggenheim 7, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
    J Gerontol A Biol Sci Med Sci 68:1226-35. 2013
    ..Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans...
  37. pmc TGF-β induces Wnt10b in osteoclasts from female mice to enhance coupling to osteoblasts
    Kuniaki Ota
    Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905
    Endocrinology 154:3745-52. 2013
    ..These results demonstrate that TGF-β1 stimulates Wnt10b production in osteoclasts, which may enhance restoration of the bone lost during the resorptive phase of bone turnover. ..
  38. pmc Transforming growth factor beta 1 induces CXCL16 and leukemia inhibitory factor expression in osteoclasts to modulate migration of osteoblast progenitors
    Kuniaki Ota
    Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905, USA
    Bone 57:68-75. 2013
    ..These results establish that TGF-β1 induces CXCL16 and LIF production in osteoclasts, which modulate recruitment of osteoblasts to restore the bone lost during the resorptive phase of bone turnover. ..
  39. pmc Update on Wnt signaling in bone cell biology and bone disease
    David G Monroe
    Department of Medicine Endocrine Research Unit, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Gene 492:1-18. 2012
    ..Emphasis is placed on the plethora of genetic studies in mouse models and genome wide association studies that reveal the requirement for and crucial roles of Wnt pathway components during skeletal development and disease...
  40. pmc Relationship of sympathetic activity to bone microstructure, turnover, and plasma osteopontin levels in women
    Joshua N Farr
    College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 97:4219-27. 2012
    ..Studies in rodents have demonstrated that sympathetic activity reduces bone formation and bone mass; these effects are mediated by the noncollagenous matrix protein, osteopontin...
  41. pmc Examination of ERα signaling pathways in bone of mutant mouse models reveals the importance of ERE-dependent signaling
    Kumar Chokalingam
    Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Endocrinology 153:5325-33. 2012
    ..These data demonstrate the importance of classical ERα signaling in regulating bone metabolism...
  42. pmc Effects of bisphosphonate treatment on circulating osteogenic endothelial progenitor cells in postmenopausal women
    Pilar Peris
    Endocrine Research Unit, Mayo Clinic, Rochester, MN, USA
    Mayo Clin Proc 88:46-55. 2013
    ..To evaluate whether bisphosphonates modulate vascular calcification by a modification in endothelial progenitor cells (EPCs) coexpressing osteoblastic surface markers and genes...
  43. pmc Cardiovascular and noncardiovascular disease associations with hip fractures
    Yariv Gerber
    Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Am J Med 126:169.e19-26. 2013
    ..To further explore the nature of this relationship, we systematically examined the association of hip fracture with all disease categories and assessed related secular trends...
  44. pmc Sphingosine 1-phosphate (S1P) receptors 1 and 2 coordinately induce mesenchymal cell migration through S1P activation of complementary kinase pathways
    Patrick Quint
    Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 288:5398-406. 2013
    ..These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways...
  45. pmc Multicenter precision of cortical and trabecular bone quality measures assessed by high-resolution peripheral quantitative computed tomography
    Andrew J Burghardt
    Musculoskeletal Quantitative Imaging Research Group, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA
    J Bone Miner Res 28:524-36. 2013
    ..The data generated from this study will contribute to the future design and validation of standardized procedures that are broadly translatable to multicenter study designs...
  46. pmc Long-term mortality following fractures at different skeletal sites: a population-based cohort study
    L J Melton
    Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
    Osteoporos Int 24:1689-96. 2013
    ..Adjusting for age, sex, and precipitating cause, the relative risk of death was increased following fractures at most skeletal sites...
  47. pmc Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization
    Kuniaki Ota
    Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN 55905, USA
    J Cell Biochem 114:1901-7. 2013
    ..Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation...
  48. pmc Isolation and characterization of human osteoblasts from needle biopsies without in vitro culture
    K Fujita
    College of Medicine, Mayo Clinic, Rochester, MN, USA
    Osteoporos Int 25:887-95. 2014
    ..We isolate and characterize osteoblasts from humans without in vitro culture. These techniques should be broadly applicable to studying the pathogenesis of osteoporosis and other bone disorders...
  49. pmc Female reproductive system and bone
    Bart L Clarke
    College of Medicine, Mayo Clinic, Rochester, MN, USA
    Arch Biochem Biophys 503:118-28. 2010
    ....
  50. ncbi Circulating cells with osteogenic potential
    Sundeep Khosla
    Endocrine Research Unit, Mayo Clinic, 200 First Street SW, 5 194 Joseph, Rochester, MN 55905, USA
    Ann N Y Acad Sci 1068:489-97. 2006
    ..The identification of these osteogenic cells in peripheral blood opens up new questions regarding the possible role of these cells in bone remodeling, in fracture repair, and possibly in vascular calcification...
  51. ncbi Role of TIEG1 in biological processes and disease states
    Malayannan Subramaniam
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Cell Biochem 102:539-48. 2007
    ..This review outlines TIEG1's molecular functions and roles in skeletal disease (osteopenia/osteoporosis), heart disease (hypertrophic cardiomyopathy), and cancer (breast and prostate)...
  52. pmc Decreasing utilization of hysterectomy: a population-based study in Olmsted County, Minnesota, 1965-2002
    Ebenezer O Babalola
    Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Am J Obstet Gynecol 196:214.e1-7. 2007
    ..The purpose of this study was to assess temporal trends for hysterectomy among Olmsted County, Minnesota women...
  53. ncbi Loss of ERE binding activity by estrogen receptor-alpha alters basal and estrogen-stimulated bone-related gene expression by osteoblastic cells
    Volha Rudnik
    Endocrine Research Unit, Rochester, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA
    J Cell Biochem 103:896-907. 2008
    ..Collectively, these findings indicate that ERE signaling plays a significant role in mediating effects of estrogen on osteoblastic differentiation markers and on IGF-I mRNA levels...
  54. pmc Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis
    Mario Gossl
    Division of Cardiology, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Am Coll Cardiol 52:1314-25. 2008
    ..This study was designed to test whether patients with coronary atherosclerosis have increases in circulating endothelial progenitor cells (EPCs) expressing an osteogenic phenotype...
  55. pmc Estrogen and bone: insights from estrogen-resistant, aromatase-deficient, and normal men
    Sundeep Khosla
    Bone 43:414-7. 2008
    ....
  56. pmc Fracture risk in type 2 diabetes: update of a population-based study
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    J Bone Miner Res 23:1334-42. 2008
    ....
  57. pmc Utilization of surgical procedures for pelvic organ prolapse: a population-based study in Olmsted County, Minnesota, 1965-2002
    Ebenezer O Babalola
    Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN, USA
    Int Urogynecol J Pelvic Floor Dysfunct 19:1243-50. 2008
    ..The most common indication for PFR was uterovaginal prolapse. Among women in the community, the rate of utilization and age distribution of pelvic organ prolapse surgery changed substantially between 1965 and 2002...
  58. pmc Use of renal function measurements for assessing fracture risk in postmenopausal women
    James T McCarthy
    Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA
    Mayo Clin Proc 83:1231-9. 2008
    ....
  59. pmc Building bone to reverse osteoporosis and repair fractures
    Sundeep Khosla
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    J Clin Invest 118:421-8. 2008
    ..As we discuss here, the tremendous explosion over the last two decades in our fundamental understanding of the mechanisms of bone remodeling has led to the prospect of mechanism-based anabolic therapies for bone disorders...
  60. pmc Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate
    Larry Pederson
    Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA
    Proc Natl Acad Sci U S A 105:20764-9. 2008
    ..In summary, our findings indicate that osteoclasts may recruit osteoprogenitors to the site of bone remodeling through SIP and BMP6 and stimulate bone formation through increased activation of Wnt/BMP pathways...
  61. ncbi Estrogen receptor alpha/beta isoforms, but not betacx, modulate unique patterns of gene expression and cell proliferation in Hs578T cells
    Frank J Secreto
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA
    J Cell Biochem 101:1125-47. 2007
    ..Hs578T ER expressing cell-lines provide a unique BC model system, permitting the comparison of ERalpha, ERbeta, and ERbetacx actions in the same cell-line...
  62. ncbi Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men
    Lynn A Sokolnicki
    Department of Physiology and Biomedical Engineering, JO 4 184W, Mayo Clinic College of Medicine, Rochester, MN 55901, USA
    Am J Physiol Endocrinol Metab 293:E1426-9. 2007
    ..05). We conclude that, within the doses employed in the present study, testosterone and estradiol did not consistently alter cutaneous vasodilator responsiveness in healthy older men...
  63. ncbi Clinical practice. Osteopenia
    Sundeep Khosla
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    N Engl J Med 356:2293-300. 2007
  64. ncbi Estrogen receptor isoform-specific regulation of the retinoblastoma-binding protein 1 (RBBP1) gene: roles of AF1 and enhancer elements
    David G Monroe
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Biol Chem 281:28596-604. 2006
    ..These results describe an E2-dependent, ER isoform-specific transcriptional activation of the RBBP1 gene, which in part, is explained by the differential activity of ER AF1 and enhancer element binding...
  65. ncbi Long-term fracture risk among women with proven endometriosis
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Fertil Steril 86:1576-83. 2006
    ..To determine whether women with pelvic endometriosis are at increased fracture risk...
  66. ncbi Incidence of primary hyperparathyroidism in Rochester, Minnesota, 1993-2001: an update on the changing epidemiology of the disease
    Robert A Wermers
    Division of Endocrinology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    J Bone Miner Res 21:171-7. 2006
    ..The lower rates previously noted persisted, whereas parathyroidectomies at our institution remained high. These data suggest an etiologic factor may be responsible for the peak incidence in the 1970s...
  67. ncbi Long-term risedronate treatment normalizes mineralization and continues to preserve trabecular architecture: sequential triple biopsy studies with micro-computed tomography
    B Borah
    Procter and Gamble Pharmaceuticals, Inc Health Care Research Center, 8700 Mason Montgomery Road, Mason, OH 45040, USA
    Bone 39:345-52. 2006
    ..Overall, risedronate provided sustained benefits on mineralization and architecture, two key determinants of bone strength, over 5 years lending support for its long-term efficacy in fracture risk reduction...
  68. ncbi Epidemiology of vertebral fractures: implications for vertebral augmentation
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA
    Acad Radiol 13:538-45. 2006
    ..Vertebral augmentation may be able to help many of these patients, although opportunities exist to optimize management strategies with respect to the other factors that influence long-term outcomes in this patient population...
  69. ncbi Fracture risk after the diagnosis of Parkinson's disease: Influence of concomitant dementia
    L Joseph Melton
    Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    Mov Disord 21:1361-7. 2006
    ..1). The increased fracture risk in patients with PD is not entirely explained by concomitant dementia, and additional study is needed to determine the relative contributions to fracture risk of falls versus bone loss in these patients...
  70. pmc Characterization of circulating osteoblast lineage cells in humans
    Guiti Z Eghbali-Fatourechi
    Endocrine Research Unit, Mayo Clinic College of Medicine, 200 First Street SW, 5 194 Joseph, Rochester, MN 55905, USA
    Bone 40:1370-7. 2007
    ..Further studies are needed to define the precise role of circulating OCN(pos) cells not only in bone remodeling but rather also potentially in the response to vascular injury...
  71. ncbi Effects of loss of classical estrogen response element signaling on bone in male mice
    Farhan A Syed
    Endocrine Research Unit, Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA
    Endocrinology 148:1902-10. 2007
    ..Collectively, these data demonstrate that classical ERalpha signaling is crucial for the development of the murine male skeleton...
  72. ncbi Effect of blockade of TNF-alpha and interleukin-1 action on bone resorption in early postmenopausal women
    Natthinee Charatcharoenwitthaya
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Bone Miner Res 22:724-9. 2007
    ..This is consistent with an important role for these immune cytokines in mediating the effect of estrogen deficiency on bone...
  73. pmc Influence of hysterectomy on long-term fracture risk
    L Joseph Melton
    Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    Fertil Steril 88:156-62. 2007
    ..To assess long-term fracture risk after hysterectomy, with or without oophorectomy...
  74. pmc Bone growth and turnover in progesterone receptor knockout mice
    David J Rickard
    Mayo Clinic, Rochester, Minnesota 55905, USA
    Endocrinology 149:2383-90. 2008
    ..However, at some skeletal sites, PR signaling attenuates the accumulation of cortical and cancellous bone mass during adolescence...
  75. pmc Estrogen-TGFbeta cross-talk in bone and other cell types: role of TIEG, Runx2, and other transcription factors
    J R Hawse
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    J Cell Biochem 103:383-92. 2008
    ..In this prospectus, we present known and potential roles of TIEG, Runx2, and other transcription factors as important mediators of signaling between these two pathways...
  76. pmc Coronary endothelial dysfunction in humans is associated with coronary retention of osteogenic endothelial progenitor cells
    Mario Gossl
    Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN, USA
    Eur Heart J 31:2909-14. 2010
    ..The current study was designed to test the hypothesis that early coronary atherosclerosis is associated with the retention of osteogenic EPC within the coronary circulation...
  77. pmc Recent advances in understanding the mechanisms of osteoclast precursor fusion
    Merry Jo Oursler
    Robert and Arlene Kogod Center on Aging, Endocrine Research Unit, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Cell Biochem 110:1058-62. 2010
    ....
  78. pmc Update in male osteoporosis
    Sundeep Khosla
    College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 95:3-10. 2010
    ..One in five men over the age of 50 yr will suffer an osteoporotic fracture during their lifetime, and men who sustain fractures have an increased mortality risk...
  79. pmc Physiology of bone loss
    Bart L Clarke
    Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, 200 1st Street Southwest, Rochester, MN 55905, USA
    Radiol Clin North Am 48:483-95. 2010
    ..Further elucidation of the relative importance of each of these factors will lead to improved preventive and therapeutic approaches for osteoporosis...
  80. pmc Retinoblastoma binding protein-1 (RBP1) is a Runx2 coactivator and promotes osteoblastic differentiation
    David G Monroe
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    BMC Musculoskelet Disord 11:104. 2010
    ..Since the function of RBP1 in osteoblastic differentiation and mineralization is unknown, we investigated the role of RBP1 in these processes...
  81. pmc Concise review: Insights from normal bone remodeling and stem cell-based therapies for bone repair
    Sundeep Khosla
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    Stem Cells 28:2124-8. 2010
    ..It is possible that they contribute directly to bone repair, but it is also likely that they express paracrine factors in the appropriate amounts and combinations that promote and sustain the healing process...
  82. pmc Effects of suppression of follicle-stimulating hormone secretion on bone resorption markers in postmenopausal women
    Matthew T Drake
    Division of Endocrinology and Metabolism, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 95:5063-8. 2010
    ..It has recently been proposed that the increase in bone resorption after the menopause may not be due principally to estrogen deficiency but rather to the concomitant increase in circulating FSH levels...
  83. pmc Updated fracture incidence rates for the US version of FRAX
    B Ettinger
    Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA, USA
    Osteoporos Int 21:25-33. 2010
    ..On the basis of updated fracture and mortality data, we recommend that the base population values used in the US version of FRAX be revised. The impact of suggested changes is likely to be a lowering of 10-year fracture probabilities...
  84. pmc Effects of estrogen and testosterone on resting energy expenditure in older men
    Sylvia Santosa
    Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota, USA
    Obesity (Silver Spring) 18:2392-4. 2010
    ....
  85. pmc The endogenous selective estrogen receptor modulator 27-hydroxycholesterol is a negative regulator of bone homeostasis
    Carolyn D DuSell
    Department of Pharmacology, Duke University Medical Center, Pharmacology and Cancer Biology, Durham, North Carolina 27710, USA
    Endocrinology 151:3675-85. 2010
    ..More studies are warranted to fully elucidate the mechanism of action of 27HC in bone and to identify ways to modulate this pathway therapeutically...
  86. pmc Effects of chronic estrogen treatment on modulating age-related bone loss in female mice
    Farhan A Syed
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    J Bone Miner Res 25:2438-46. 2010
    ..The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss...
  87. pmc Estrogen action on bone marrow osteoclast lineage cells of postmenopausal women in vivo
    J A Clowes
    Division of Rheumatology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Osteoporos Int 20:761-9. 2009
    ..This was not associated with changes in surface receptor for proresorptive cytokines...
  88. pmc Skeletal consequences of deletion of steroid receptor coactivator-2/transcription intermediary factor-2
    Ulrike I Mödder
    Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 284:18767-77. 2009
    ..Modulating SRC-2 action may, thus, represent a novel therapeutic target for osteoporosis...
  89. pmc Estrogen receptor beta isoform-specific induction of transforming growth factor beta-inducible early gene-1 in human osteoblast cells: an essential role for the activation function 1 domain
    John R Hawse
    Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Mol Endocrinol 22:1579-95. 2008
    ....
  90. pmc Osteoporosis in men
    Sundeep Khosla
    Endocrine Research Unit, Guggenheim 7, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    Endocr Rev 29:441-64. 2008
    ..Increasing awareness of osteoporosis in men among physicians and the lay public is critical for the prevention of fractures in our aging male population...
  91. ncbi Skeletal stem/osteoprogenitor cells: current concepts, alternate hypotheses, and relationship to the bone remodeling compartment
    Ulrike I Mödder
    Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    J Cell Biochem 103:393-400. 2008
    ....
  92. pmc Serum biomarker profile associated with high bone turnover and BMD in postmenopausal women
    Sudeepa Bhattacharyya
    Department of Orthopaedic Surgery, Center for Orthopaedic Research, Barton Research Institute, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    J Bone Miner Res 23:1106-17. 2008
    ..In conjunction with the identification of the individual proteins, this protein fingerprint may provide a novel approach to evaluate high bone turnover states...
  93. pmc Regulation of bone turnover by sex steroids in men
    Arunik Sanyal
    Endocrine Research Unit, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
    J Bone Miner Res 23:705-14. 2008
    ..The mechanism(s) by which sex steroids regulate bone turnover in humans are unclear, and recent studies have suggested that follicle-stimulating hormone (FSH) may play an important role in regulating bone resorption...
  94. pmc Effects of estrogen therapy on bone marrow adipocytes in postmenopausal osteoporotic women
    F A Syed
    Endocrine Research Unit and Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA
    Osteoporos Int 19:1323-30. 2008
    ..Estrogen treatment also prevented increases in mean adipocyte size over 1 year...
  95. pmc The skeletal response to estrogen is impaired in female but not in male steroid receptor coactivator (SRC)-1 knock out mice
    U I Modder
    Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    Bone 42:414-21. 2008
    ....
  96. pmc Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease
    Ann E Kearns
    Endocrine Research Unit, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
    Endocr Rev 29:155-92. 2008
    ..Clinical trials are exploring the effects of denosumab, a fully human anti-RANKL antibody, on bone loss in patients with osteoporosis, bone metastasis, myeloma, and rheumatoid arthritis...
  97. pmc New selective estrogen and androgen receptor modulators
    Bart L Clarke
    Mayo Clinic W18 A, Rochester, Minnesota 55905, USA
    Curr Opin Rheumatol 21:374-9. 2009
    ..Both types of compounds hold great promise for therapeutic use in multiple hormonal disorders involving tissue-specific effects mediated by estrogen or androgen receptors...
  98. pmc Secular trends in hip fracture incidence and recurrence
    L J Melton
    Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA
    Osteoporos Int 20:687-94. 2009
    ..The decline in hip fracture incidence is now accompanied by a further reduction in the likelihood of a recurrent hip fracture among survivors of the first fracture...
  99. pmc Update on estrogens and the skeleton
    Sundeep Khosla
    Endocrine Research Unit, Guggenheim 7, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA
    J Clin Endocrinol Metab 95:3569-77. 2010
    ..Given the diminishing clinical use of estrogen, it is logical to question whether estrogen regulation of bone remains a relevant issue at a clinical or basic research level...

Research Grants30

  1. Alzheimer's Disease Research Center at Columbia University
    Scott A Small; Fiscal Year: 2013
    ..HIPAA compliant data organization and statistical consulting services are provided under the ADRC to the research community at Columbia and external to it. ..
  2. Emory Alzheimer's Disease Center
    Allan I Levey; Fiscal Year: 2013
    ..abstract_text> ..
  3. Alzheimer's Disease Research Center
    Thomas J Montine; Fiscal Year: 2013
    ..Montine;Project 2: Therapeutic Effects of Intra-Nasal Insulin Detemir, Dr. Suzanne Craft;Project 3: Modulation of A peptide accumulation and neuron damage in vivo with adult bone marrow transplants, Dr. C. Dirk Keene. ..
  4. New Approaches to Dementia Heterogeneity
    Bruce L Miller; Fiscal Year: 2013
    ..Finally, we will create ideal data management approaches for neurodegenerative conditions that will be shared with other ADRCs, beginning with UC-Davis. ..
  5. UCLA Alzheimer's Disease Research Center
    David B Teplow; Fiscal Year: 2013
    ..Innovations in advancing research are proposed in each Core of this proposal. Each core has responded to criticisms and recommendations from the 2008 review in this renewal application. ..
  6. Alzheimer's Disease Research Center
    Oscar L Lopez; Fiscal Year: 2013
    ..Alzheimer's centers such as the one in Pittsburgh play a critical role in the nation's struggle to: 1) care for those currently afflicted;2) improve diagnosis and treatment;and 3) find a means of prevention. ..
  7. Massachusetts Alzheimer's Disease Research Center
    Bradley T Hyman; Fiscal Year: 2013
    ..Going forward, the MADRC will continue to expand its clinical and neuropathological resources, its innovative training and scientific programs directed toward AD research. ..
  8. HEALTHY AGING AND SENILE DEMENTIA
    John Morris; Fiscal Year: 2013
    ..Together, these projects and their supporting cores will focus on preclinical DAT in comparison with healthy brain aging and address the issue of detecting preclinical disease. ..
  9. Behaviors on Surveys and in the Economy: HRS and Beyond
    Robert J Willis; Fiscal Year: 2013
    ..abstract_text> ..
  10. Impact of Amyloid on the Aging Brain
    Reisa A Sperling; Fiscal Year: 2013
    ..This PPG brings together an exceptional multidisciplinary team of clinical, statistical, cognitive neuroscience, imaging, and laboratory investigators dedicated to exploring the impact of amyloid on the aging brain. ..
  11. Aging and Dementia in Adults with Down Syndrome
    Wayne P Silverman; Fiscal Year: 2013
    ..Further, some findings may have direct implications for promoting more successful aging for adults with DS. ..