DBLE BLIND RANDOM PLACEBO CONT TRIAL ALENDRONATE IN PRIM HYPERPARATH
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-29S40874 from National Center For Research Resources
Keywords: alendronate, bone density, drug screening /evaluation, human therapy evaluation, hyperparathyroidism, bone metabolism, clinical trial phase II /III /IV, osteopenia, osteoporosis, clinical research, human subject, placebo
Project start date: 1999-12-01
Project end date: 2000-11-30
Sponsored Links Excellgen http://Excellgen.com
THERAPY OF OSTEOPOROSIS IN MEN WITH PARATHYROID HORMONE
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-28S10732 from National Center For Research Resources
Abstract: This is a double-blind, placebo controlled, randomized trial designed to study the human parathyroid hormone (HPTH (1-34)) as a potential therapy for the uncommon disorder of idiopathic osteoporosis in men. HPTH (1-34) has been shown to increase bone density in women with postmenopausal osteoporosis.
Keywords: human therapy evaluation, osteoporosis, parathyroid hormone, skeletal disorder chemotherapy, clinical trial phase II /III /IV, drug screening /evaluation, clinical research, human subject, male
Project start date: 1998-12-01
Project end date: 1999-11-30
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-28S10141 from National Center For Research Resources
Abstract: The natural history of primary hyperparathyroidism is being examined, its sequelae and response to currently accepted treatments.
Keywords: endocrine disorder chemotherapy, human therapy evaluation, hyperparathyroidism, pathologic process, clinical research, human subject
Project start date: 1998-12-01
Project end date: 1999-11-30
DBLE BLIND RANDOM PLACEBO CONT TRIAL ALENDRONATE IN PRIM HYPERPARATH
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-28S10874 from National Center For Research Resources
Abstract: An investigator initiated, double-blind, randomized, placebo controlled trial to determine the effect of alendronate on bone mineral density in patients with primary hyperparathyroidism and osteopenia/porosis.
Keywords: alendronate, bone density, drug screening /evaluation, human therapy evaluation, hyperparathyroidism, bone metabolism, clinical trial phase II /III /IV, osteopenia, osteoporosis, clinical research, human subject, placebo
Project start date: 1998-12-01
Project end date: 1999-11-30
ALENDRONATE ON BONE DENSITY IN POSTMENOPAUSAL AFRICAN AMERICAN WOMEN
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-270663 from National Center For Research Resources
Abstract: A multicenter, randomized, double-blind, placebo-controlled, parallel- group study to determine the effect of oral alendronate sodium on bone mineral density in post-menopausal, osteopenic, black women of African- American descent.
Keywords: alendronate, bone density, human therapy evaluation, inhibitor /antagonist, osteopenia, physiologic bone resorption, postmenopause, skeletal disorder chemotherapy, clinical trial phase II /III /IV, drug screening /evaluation, normal ossification, oral administration, African American, clinical research, female, human subject, placebo, women s health
Project start date: 1997-12-01
Project end date: 1998-11-30
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-30S10141 from National Center For Research Resources
Keywords: endocrine disorder chemotherapy, human therapy evaluation, hyperparathyroidism, pathologic process, clinical research, human subject
Project start date: 2000-12-01
Project end date: 2001-11-30
THERAPY OF OSTEOPOROSIS IN MEN WITH PARATHYROID HORMONE
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-30S10732 from National Center For Research Resources
Keywords: human therapy evaluation, osteoporosis, parathyroid hormone, skeletal disorder chemotherapy, clinical trial phase II /III /IV, drug screening /evaluation, clinical research, human subject, male
Project start date: 2000-12-01
Project end date: 2001-11-30
DBLE BLIND RANDOM PLACEBO CONT TRIAL ALENDRONATE IN PRIM HYPERPARATH
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-30S10874 from National Center For Research Resources
Keywords: alendronate, bone density, drug screening /evaluation, human therapy evaluation, hyperparathyroidism, bone metabolism, clinical trial phase II /III /IV, osteopenia, osteoporosis, clinical research, human subject, placebo
Project start date: 2000-12-01
Project end date: 2001-11-30
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-29S40141 from National Center For Research Resources
Keywords: endocrine disorder chemotherapy, human therapy evaluation, hyperparathyroidism, pathologic process, clinical research, human subject
Project start date: 1999-12-01
Project end date: 2000-11-30
Sponsored Links Excellgen http://Excellgen.com
THERAPY OF OSTEOPOROSIS IN MEN WITH PARATHYROID HORMONE
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 3M01RR000645-29S40732 from National Center For Research Resources
Keywords: human therapy evaluation, osteoporosis, parathyroid hormone, skeletal disorder chemotherapy, clinical trial phase II /III /IV, drug screening /evaluation, clinical research, human subject, male
Project start date: 1999-12-01
Project end date: 2000-11-30
Grants awarded to John P Bilezikian
BONE PROPERTIES IN HYPOPARATHYROIDISM: EFFECTS OF PTH
John P Bilezikian, Md
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 5R01DK069350-05 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: Whereas much information is known about the properties of bone in primary hyperparathyroidism, a disorder of parathyroid hormone (PTH) excess, virtually nothing is known about the skeleton in hypoparathyroidism, a disorder in which PTH is absent. The purpose of this research project is to test the hypothesis that the skeleton in hypoparathyroidism is abnormal in its metabolic, densitometric, geometric, biomechanical and microarchitectural features. We will also test the hypothesis that the skeleton is dependent upon PTH for normal structure and function. Using non-invasive approaches as well as direct analysis of bone itself, the human hypoparathyroid skeleton will be thoroughly characterized. With each patient serving as his/her own control, we will determine how, to what extent, and in what ways the administration of PTH restores skeletal dynamics and structure to the hypoparathyroid skeleton. In this way, we will identify those structural and dynamic elements of the skeleton that are influenced by or dependent upon PTH. Methods to be utilized include dual energy X-ray absorptiometry, quantitative central and peripheral computed tomography, geometry and size quantification, histomorphometry by standard and microCT methods, finite element analysis, biochemical bone markers, quantitative back scattered electron imaging, and Fourier Transform Infrared Spectroscopy. This research project will extend our knowledge of the skeletal effects of PTH to its deficient range and thus complete our understanding of PTH action on bone gained by our many years of studying PTH overexpression in primary hyperparathyroidism. This investigation may also provide insight into the means by which PTH helps to restore the skeleton when it is used to treat osteoporosis
Keywords: Abscission; Back; Biochemical; Biomechanics; Blood Circulation; Blood Coagulation Factor IV; Bloodstream; Body Tissues; Bone; Bone and Bones; Bones and Bone Tissue; CAT Scan, X-Ray; CAT scan; CT X Ray; CT scan; Ca++ element; Calcium; Causality; Cell Function; Cell Process; Cell physiology; Cellular Function; Cellular Physiology; Cellular Process; Circulation; Coagulation Factor IV; Computed Tomography; Computerized Axial Tomography (Computerized Tomography); Computerized Tomography, X-Ray; Congenital Disorders; DXA; Dihydroxycholecalciferols; Dihydroxyvitamins D; Disease; Disease of parathyroid glands; Disorder; Disorders, Congenital; Dorsum; Dual-Energy X-Ray Absorptiometry; EMI scan; Electrons; Elements; Etiology; Excision; Excretory function; Extirpation; FTIR; FTIR spectroscopy; Factor IV; Finite Element Analyses; Finite Element Analysis; Fourier transform infrared spectroscopy; Goals; Head and Neck, Parathyroid; Human; Human, General; Hyperparathyroidism; Hypocalcemia; Hypocalcemia result; Hypoparathyroidism; Image; Intermediary Metabolism; Investigation; Knowledge; METBL; Man (Taxonomy); Man, Modern; Metabolic; Metabolic Processes; Metabolism; Method LOINC Axis 6; Methodology; Methods; Methods and Techniques; Methods, Other; Negative Beta Particle; Negatrons; Osteoporosis; PTH (1-84); PTH protein, human; Parathyroid; Parathyroid Diseases; Parathyroid Gland Disorder; Parathyroid Hormone; Parathyroid Hormone (1-84); Parathyroid Hormones; Parathyroid gland; Patients; Peripheral; Property; Property, LOINC Axis 2; R01 Mechanism; R01 Program; RPG; Removal; Research Grants; Research Project Grants; Research Projects; Research Projects, R-Series; Role; Skeleton; Spectroscopy, Fourier Transform Infrared; Structure; Subcellular Process; Surgical Removal; Techniques; Testing; Tissues; Tomodensitometry; Tomography, Xray Computed; X-Ray Absorptiometry, Dual-Energy; X-Ray Computed Tomography; bone; bone quality; catscan; computed axial tomography; computerized axial tomography; computerized tomography; disease causation; disease etiology; disease/disorder; disease/disorder etiology; disorder etiology; excretion; hPTH(1-84); hormone deficiency; human PTH protein; human subject; imaging; improved; insight; overexpression; parathormone; parathyroid disorder; parathyroid hormone, human; resection; skeletal; social role; urinary
Project start date: 2005-09-01
Project end date: 2010-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
5R01DK069350-05 (2009): $595072
5R01DK069350-04 (2008): $580494
5R01DK069350-03 (2007): $577905
5R01DK069350-02 (2006): $580734
1R01DK069350-01A1 (2005): $537808
PLANNING GRANT FOR A MULTIPURPOSE CLINICAL RESEARCH CTR
John P Bilezikian, Associate Professor Of Pharmacology
Medicinecolumbia University Health Sciences
columbia University Medical Center
new York, Ny 100323702
Grant 1P20AR046678-01 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: ZAR1
Abstract: This response to RFA AR99-002 proposes to assemble a group of biostatisticians, epidemiologists, health services researchers and an Advisory Committee comprised of significant stakeholders in the Columbia Health Sciences Community in research on skin and musculoskeletal diseases, and arthritis, under the umbrella of strong leadership and the highest institutional mandate, to engage in a process of forging the consensus and agreements necessary for the creation of a biostatistics and research design core for patient assessment and outcomes research. The approach has four prongs 1) hold two retreats to which members of the research base, their colleagues, appropriate institutional leaders, and campus infrastructure support directors are invited to enter the planning process and frame the structure of the a Multipurpose Clinical Research Center (MCRC); 2) separately meet institutional leaders and key personnel to forge the consensus and agreements that will form the foundation of a MCRC with institutional stability and the highest standards of scientific excellence; 3) prototype the proposed Methods Core by assembling signifcant methodological consulting services to work with selected investigators to generate three or four investigator-initated R01 grant applications during the planning grant funding period; and 4) utilize the assembled Methods Core personnel to raise the visibility of the project by hosting a methodology workshop on a topic in outcomes research in the NIAMS disease areas that ultimately results in a peer-reviewed methods publication
Keywords: epidemiology, experimental design, health science research potential, interdisciplinary collaboration, musculoskeletal disorder, outcomes research clinical research
Project start date: 1999-09-22
Project end date: 2002-06-30
1P20AR046678-01 (1999): $170212
John P Bilezikian, Associate Professor Of Pharmacology
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5R01DK032333-08 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ORTH
Abstract: This research project is a continued, systematic investigation of primary hyperparathyroidism. Appreciative of classical clinical landmarks of the disease, the proposal combines an historical approach with modern analytical techniques of clinical medicine. Accurate decisions about the patient with primary hyperparathyroidism are uncertain because many outstanding questions about its natural history, pathophysiology and the extent to which an asymptomatic patient may show evidence for bone disease after more detailed evaluation are all unanswered. The research project is attempting to improve our understanding in these areas with a standardized, longitudinal approach to a sufficiently large number of patients with primary hyperparathyroidism. Recent advances in the measurement of circulating calcium regulating hormones and in the quantitative evaluation of static, dynamic and densitometric properties of the skeleton are responsible for the five goals 1. greater knowledge of the natural history of primary hyperparathyroidism; 2. clearer understanding of the pathophysiologic mechanisms of the disease and their prognostic value; 3. comparison of complete evaluation with routine clinical assessment; 4. reversibility of the hyperparathyroid state; 5. predictive value of certain features regarding the development or prevention of complications. The ultimate goal of the research plan is to make the clinical approach to the patient afflicted with this disorder more secure as a result of greater overall understanding.
Keywords: bone metabolism disorder, hypercalcemia, hyperparathyroidism, bone density, calcium binding protein, cyclic AMP, diet route /schedule, dietary calcium, endocrine disorder diagnosis, gamma carboxyglutamate, hormone regulation /control mechanism, hydroxyproline, hypercalciuria, longitudinal human study, nutrition related tag, parathyroid hormone, parathyroidectomy, pathologic calcification, vitamin D, atomic absorption spectrometry, biopsy, densitometry, histopathology, human clinical subject, online computer, radioimmunoassay, urinalysis
Project start date: 1984-07-01
Project end date: 1992-06-30
Sponsored Links Excellgen http://Excellgen.com
Targeting Bone Remodeling For The Treatment Of Osteoporosis
John P Bilezikian, Associate Professor Of Pharmacology
American Society For Bone And Mineral Res 2025 M St Nw, Ste 800 Washington, Dc 20036
Grant 1R13AR055867-01 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases IRG: AMS
Abstract: This is a time of great excitement in the field of bone biology. In the past several years, we have gained great insight into how bone models and remodels, and this information has been applied to the treatment of osteoporosis and related skeletal disorders. Such knowledge has extended itself into areas that just a few years ago would have been incomprehensible. For example, the family of bone cells themselves, the osteoblast and the osteoclast, formerly thought to work in concert within the bone remodeling unit, now have been joined by the osteocyte, a cell newly recognized to play a pivotal role in signaling these cells and other systems. Products of these bone cells, also newly recognized, are identifying processes and mechanisms that extend to the very heart of molecular control mechanisms. This new knowledge has spanned a wide spectrum of disciplines that include cell and molecular biology, genetics, epidemiology, engineering, biomechanics, imaging, material sciences, immunology, and integrative organ physiology. Along with traditional areas that have housed the discipline, such as endocrinology and rheumatology, the field is now enriched with cross fertilization from these other areas, leading to new ideas and new knowledge. It is appropriate at this time, therefore, to hold a meeting in which these advances can be considered and in which experts in these various areas can gather together. The idea is to generate even more exciting ideas and therapeutic approaches to osteoporosis, which is a major cause of disability in our aging population. We believe it is important at this time to bring together clinical, basic and translational investigators to discuss these new advances with a view that will have therapeutic relevance. The proposed meeting will serve as an important step towards translating new knowledge into new therapeutic concepts. In addition, this meeting will identify key questions for future research. The American Society for Bone and Mineral Research is the premier society for the study and advancement of basic and clinical research in disorders relating to the skeleton. The considerations described above make it very clear that this is the time for senior thought leaders, mid-career investigators and young investigators to gather together in concert with NIH Institutes staff. Information derived from the exchanges at such a meeting will serve to provide the NIH with novel ideas about programs worthy of support in future years and lead to a vibrant exchange of ideas and a definition of vital pathways for future advances in research and treatment.
Project start date: 2007-09-17
Project end date: 2008-02-28
1R13AR055867-01 (2007): $27000
THERAPY OF OSTEOPOROSIS IN MEN WITH PARATHYROID HORMONE
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5M01RR000645-280732 from National Center For Research Resources
Abstract: This is a double-blind, placebo controlled, randomized trial designed to study the human parathyroid hormone (HPTH (1-34)) as a potential therapy for the uncommon disorder of idiopathic osteoporosis in men. HPTH (1-34) has been shown to increase bone density in women with postmenopausal osteoporosis.
Keywords: human therapy evaluation, osteoporosis, parathyroid hormone, skeletal disorder chemotherapy, clinical trial phase II /III /IV, drug screening /evaluation, clinical research, human subject, male
Project start date: 1998-12-01
Project end date: 1999-11-30
TRAINING PROGRAM IN ENDOCRINOLOGY AND METABOLISM
John P Bilezikian, Md
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Grant 3T32DK007271-31S1 from National Institute Of Diabetes And Digestive And Kidney Diseases
Abstract: The purpose of this trainingprogram in endocrinologyand metabolism is to provide an opportunity for promising post-doctoral individuals of exceptional quality to train for careers in academic endocrinologyand biomedical research. The Program has been supported by this training grant mechanism for over 45 years and presents a record among its graduates ofsuperb training and major academic achievement. The central features of the Program includeintensive research in the laboratory of the participating faculty member and didactic exposure to basic science and clinical investigation. Research areas span a wide range of endocrinological disciplines with centers of excellence in neuroendocrinology,metabolic bone diseases, diabetes, reproductive endocrinology, endocrine genetics, lipoprotein metabolism, molecular endocrinology,endocrine protein and glycoprotein chemistry, and signal transduction. The scientific methods of the faculty includeclassical endocrinological techniques of basic and clinical investigation as well as the most modern biochemicaland molecular studies of hormone action. Expertise in biochemistry,cell biology,molecularbiology,mouse genetics, and physiology are all well-represented by the faculty. Highly experienced clinical investigators provide expertise to fellows in a wide variety of subspecialties with neuroendocrinology,metabolic bone diseases, diabetes, and lipoprotein metabolism featured as particular strengths. Primary facilities are centralized in the Division of Endocrinology in the Department of Medicine. Participating laboratories outside the Division of Endocrinology extend opportunities for endocrinology trainingto laboratories in the Departments ofPhysiology and Biophysics,Geneticsand Development, Pediatrics, Microbiology, Anatomyand Cell Biology, Pharmacology, and Nutrition. Trainees are selected from a very competitive pool of applicants after a thorough review of their credentials and interviews with the directors of the Program. Fewer than 2% of applicants are selected. The majority of trainees go on to careers in investigative endocrinology.The Program focuses upon applicants who hold the MDor MD/PhD degree and have a strong interest in or prior exposure to research. RELEVANCE (See instructions)
Keywords: Endocrinology; Metabolism and Endocrinology; Training Programs
Project start date: 1977-09-30
Project end date: 2011-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
PFA/PA: PA-06-468
3T32DK007271-31S1 (2009): $60948
3T32DK007271-31S2 (2009): $31510
2T32DK007271-31 (2009): $234809
5T32DK007271-30 (2008): $345427
3T32DK007271-30S1 (2008): $31290
5T32DK007271-29 (2007): $349429
Sponsored Links Excellgen http://Excellgen.com
5T32DK007271-28 (2006): $332675
5T32DK007271-27 (2005): $321381
2T32DK007271-26 (2004): $339850
5T32DK007271-25 (2003): $267740
5T32DK007271-24 (2002): $284818
5T32DK007271-23 (2001): $243900
5T32DK007271-22 (2000): $283090
2T32DK007271-21 (1999): $278227
John P Bilezikian, Associate Professor Of Pharmacology
Columbia Univ New York Morningside Research Administration New York, Ny 100277003
Grant 5R01DK032333-03 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ORTH
Abstract: The purpose of this research project is to gain greater insight into outstanding questions regarding primary hyperparathroidism, a relatively common disorder of calcium metabolism. Despite an era of explosive growth in our knowledge of the endocrine system that helps to regulate calcium homeostatis, our appraoch to the patient with primary hyperparathyroidism is uncertain with respect to natural history, pathophysiology, objective assessment, and clinical decision making. The research project will attempt to improve our understanding in these areas with a standardized, longitudinal approach to a sufficiently large number of patients with primary hyperparathyroidism. Taking advantage of recent important advances in the measurement of circulating calcium-regulating hormones, and in the quantitative evaluation of static, dynamic, and densitometric properties of the skeleton, we plan to accomplish five specific aims 1. greater knowledge of the natural history of primary hyperparathyroidism; 2. pathophysiological subclassification of the disease and its prognostic value; 3. comparison of complete evaluation with routing clinical assessment; 4. reversibility of the hyperparathyroid state; 5. predictive value of certain features regarding the development or prevention of complications. The ultimate goal of the research plan is to increase our current understanding of primary hyperparathyroidism in order to make our clinical approach to he patient afflicted with this disorder more secure.
Keywords: DIAGNOSIS, DIAGNOSTIC TESTS, ORTHOPEDICS AND MUSCULOSKELETAL STUDY SECTION, PARATHYROID GLANDS DISORDERS, HYPERPARATHYROIDISM, CALCIUM (MINERAL) IMBALANCES, CALCIFICATION PATHOLOGIC, CALCIUM (MINERAL) IMBALANCES, HYPERCALCEMIA, CALCIUM (MINERAL) IMBALANCES, HYPERCALCIURIA, CYCLIC AMINO ACIDS, PROLINE, HYDROXYPROLINE, PARATHYROID HORMONES, SKELETAL DISORDERS, BONE METABOLISM (GENERAL), SKELETAL SYSTEM, BONE DENSITY, SKELETAL SYSTEM, BONE DEVELOPMENT, OSSIFICATION NORMAL, VITAMINS, VITAMIN D (GENERAL), parathyroidectomy, DIAGNOSTIC TESTS, BIOPSY, HUMAN, CLINICAL, PHYSICAL SEPARATION, CHROMATOGRAPHY, HIGH PRESSURE LIQUID
Project start date: 1984-07-01
Project end date: 1987-06-30
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5M01RR000645-280141 from National Center For Research Resources
Abstract: The natural history of primary hyperparathyroidism is being examined, its sequelae and response to currently accepted treatments.
Keywords: endocrine disorder chemotherapy, human therapy evaluation, hyperparathyroidism, pathologic process, clinical research, human subject
Project start date: 1998-12-01
Project end date: 1999-11-30
Sponsored Links Excellgen http://Excellgen.com
DBLE BLIND RANDOM PLACEBO CONT TRIAL ALENDRONATE IN PRIM HYPERPARATH
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 2M01RR000645-290874 from National Center For Research Resources
Abstract: Primary hyperthyroidism (PHPT) is a condition in which increased levels of parathyroid hormone lead to high blood calcium. This may result in kidney stones and bone loss,. The only available cure is surgery to remove the involved parathyroid gland(s). Currently, there is no specific medical treatment. In postmenopausal women with PHP, estrogen therapy can reduce blood calcium levels, but only by a small amount. The purpose of this study is to evaluate the effectiveness of another drug, alendronate, in lowering blood calcium concentration and improving bone density in patients with primary hyperparathyroidism. Alendronate has been studied extensively in postmenopausal women who have osteoporosis and has been shown to significantly increase bone density and reduce fracture risk. In addition, alendronate decreases blood calcium in some patients with primary hyperparathyroidism. This will be a randomized placebo controlled double blind clinical trial. Approximately 30 patients with primary hyperparathyroidism will receive either alendronate 10 mg/day or placebo. These treatment groups will continue for 12 months and then be followed by an additional 12 months period in which the group who received placebo will then receive alendronate 10 mg/day. Patients initially receiving Alendronate will continue on the same dose. We will follow patients to see if their blood calcium returns to (or toward) normal levels. We will also follow them for any improvement in bone mineral density.
Keywords: alendronate, bone density, drug screening /evaluation, human therapy evaluation, hyperparathyroidism, bone metabolism, clinical trial phase II /III /IV, osteopenia, osteoporosis, clinical research, human subject, placebo
Project start date: 1999-12-01
Project end date: 2000-11-30
John P Bilezikian, Associate Professor Of Pharmacology
Medicinecolumbia University Health Sciences
columbia University Medical Center
new York, Ny 100323702
Grant 5R01DK032333-23 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ORTH
Abstract: Primary Hyperparathyroidism is described best today as a relatively asymptomatic disease characterized by mild elevations in the serum calcium and parathyroid hormone concentrations. Over the past 18 years, this research project has helped to define the clinical, biochemical, densitometric and histomorphometric features of primary hyperparathyroidism in the modern era. As a major source of new insights, the investigation has helped to elucidate aspects of this disease that were not previously appreciated. The overall objective of this research project remains the definitive of extent, course, and reversibility of the manifestations of primary hyperparathyroidism. Other important challenges will be pursued in order to achieve a more complete understanding of primary hyperparathyroidism. The following Specific Aims will be pursued (1) to define the natural history of primary hyperparathyroidism, and the reversibility of its manifestations, over a uniquely long, systematic 23-year period of investigation. This effort will include characterization of new areas of inquiry in neuropsychological function, histomorphometric, geometrical, and cellular aspects of bone in primary hyperparathyroidism; (2) to characterize a newly recognized presentation of asymptomatic primary hyperparathyroidism without hypercalcemia; (3) to complete the characterization of the bone remodeling unit in primary hyperparathyroidism; 4) to determine fracture risk in primary hyperparathyroidium. This project will utilize state-of-the-art techniques, including bone densitometry, peripheral quantitative tomography, bone histomorphometry, quantitative backscattered electron imaging, quantitative assessment of vertebral fractures, and cognitive assessment. By the end of the renewal period, we expect to have fully characterized the long-term natural history of hyperparathyroidism, with or without surgery, as well has to have defined features of this disease that have, up to now, eluded successful investigation. The results should lead to the establishment of rational recommendations for the management of primary hyperparathyroidism
Keywords: bone metabolism disorder, disease /disorder etiology, hypercalcemia, hyperparathyroidism, longitudinal human study, parathyroid hormone, pathologic process bone density, bone metabolism, cardiovascular disorder, cognition disorder, endocrine disorder diagnosis, medical complication, outcomes research, physiologic bone resorption blood chemistry, cardiovascular imaging /visualization, clinical research, densitometry, histopathology, human subject, neuropsychological test, photon absorptiometry, statistics /biometry, tomography
Project start date: 1984-07-01
Project end date: 2008-06-30
5R01DK032333-23 (2006): $534794
5R01DK032333-22 (2005): $533468
5R01DK032333-21 (2004): $517757
5R01DK032333-20 (2003): $502508
2R01DK032333-19 (2002): $542203
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 2M01RR000645-290141 from National Center For Research Resources
Abstract: Primary hyperparathyroidism is a relatively common endocrine disease in which the parathyroid gland(s) produce excessive amounts of parathyroid hormone, leading to high blood calcium levels. Other affected organs include the skeleton and the kidneys. The aim of this study is to characterize primary hyperparathyroidism as it presents today, and to develop a rationale and guidelines for treating patients with this disease. Patients are not randomized to any treatment; rather they are followed and treated according to accepted guidelines. The approach is to follow subjects closely, using history, physical exam, biochemical, bone densitometric and bone histomorphometric techniques. Data will be analyzed by forming groups of subjects, and following relevant indices over time. After three baseline visits (over 1-3 months), patients will be seen over four months unless they undergo parathyroidectomy, in which case follow-up will be twice a year.
Keywords: endocrine disorder chemotherapy, human therapy evaluation, hyperparathyroidism, pathologic process, clinical research, human subject
Project start date: 1999-12-01
Project end date: 2000-11-30
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 5R01DK032333-12 from National Institute Of Diabetes And Digestive And Kidney Diseases IRG: ORTH
Abstract: Primary hyperparathyroidism is a different disease today than it was severa decades ago. It is now a relatively common endocrine disorder with few of the obvious features by which it used to be known. Previously held concept about primary hyperparathyroidism need careful reevaluation in light of its current profile, using newer techniques to monitor the skeleton, a major target organ for parathyroid hormone. The overall objective of this research project is to characterize modern primary hyperparathyroidism with respect to extent, course and reversibility of its manifestations. The prospective, long-term study is in the midst of obtaining information pertinent to five specific aims 1. to provide a complete of th current clinical presentation of primary hyperparathyroidism through clinical, biochemical, densitometric and histomorphometric analyses; 2. to determine the natural history and reversibility of primary hyperparathyroidism with long-term evaluation of clinical, biochemical, densitometric and histomorphometric indices; 3. to establish by histomorphometric analysis of bone, the mechanisms of cancellous bone preservation and cortical bone loss in primary hyperparathyroidism; 4. to determine the utility of non-invasive markers of bone turnover as indicator of processes in hyperparathyroid bone; 5. to establish the course and reversibility of primary hyperparathyroidism in the skeleton of postmenopausal women. Patients are evaluated as an entire study cohort and also from the viewpoint of different clinical subgroups. The project utilizes state-of-the art techniques for evaluation of the effect of parathyroid hormone on the skeleton. These techniques, including bone densitometry, histomorphometric analysis of bone, and highly promising circulating and urinary markers of bone metabolism, are combined with more conventional clinical assessments of patients. A substantial number of patients already have been enrolled, and many have been followed since 1985 With its prospective design, the research project is uniquely positioned to make systematic observations on primary hyperparathyroidism over a thirteen year period. In the renewal period, this investigation will continue to contribute insights into primary hyperparathyroidism, helping to establish guidelines so that the modern approach to patients with this disorder can b more rational and more secure.
Project start date: 1984-07-01
Project end date: 1997-06-30
5R01DK032333-12 (1995): $388008
5R01DK032333-11 (1994): $373905
Sponsored Links Excellgen http://Excellgen.com
5R01DK032333-10 (1993): $355080
2R01DK032333-09 (1992): $352816
5R01DK032333-25 (2009): $629320
2R01DK032333-24A2 (2008): $645949
THERAPY OF OSTEOPOROSIS IN MEN WITH PARATHYROID HORMONE
John P Bilezikian, Associate Professor Of Pharmacology
Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702
Grant 2M01RR000645-290732 from National Center For Research Resources
Abstract: Osteoporosis, while recognized as a major disorder of postmenopausal women, can also be seen in middle-aged men. While some of the men who present with evidence of skeletal thinning have disorders or behaviors that can explain their osteoporois, others have no apparent cause. The appropriate treatment of this small but important group of patients is unknown. One agent that potentially could be useful in these patients is biologically active parathyroid hormone (hPTH[1-34]), an agent known to stimulate bone formation. This drug has shown promise in postmenopausal women with osteoporosis, and also in a small, uncontrolled study of men with idiopathic osteoporosis. It is the aim of this study to investigate the efficacy of hPTH[1-34] in men with idiopathic osteoporosis. This is a double-blind, placebo-controlled, randomized protocol to investigate the efficacy and safety of hPTH[1-34], as a therapy for idiopathic osteoporosis in middle-aged men. After a six-month pre-treatment period, subjects will self-administer by subcutaneous injection drug or placebo for a period of 1.5 years. The study evaluates bone mass as the primary outcome variable over a period of eighteen months.
Keywords: human therapy evaluation, osteoporosis, parathyroid hormone, skeletal disorder chemotherapy, clinical trial phase II /III /IV, drug screening /evaluation, clinical research, human subject, male
Project start date: 1999-12-01
Project end date: 2000-11-30
THE EFFECT OF PRIMARY HYPERPARATHYROIDISM ON THE BONES OF POSTMENOPAUSAL WOMEN
John P Bilezikian
Helen Hayes Hospital Health Research, Inc. Menands, Ny 122042719
Grant 5P50AR039191-150005 from National Institute Of Arthritis And Musculoskeletal And Skin Diseases
Abstract: In the renewal period this Project will investigate the mechanisms of bone loss through the paradigm of primary hyperparathyroidism in estrogen deficient, postmenopausal subjects. The studies are based upon observations we have made in the previous funding period. Cancellous bone is preserved while cortical bone is at risk. Postoperatively, there is a pervasive gain in bone mass at all sites, irrespective of their composition type. In the renewal period, these central observations will be pursued further with attention to four specific areas. We will continue to monitor the course and reversibility of the hyperparathyroid process in postmenopausal women. These studies will include a longitudinal analysis utilizing serum and urinary biochemical determinations, densitometry, and histomorphometry. Second, we have identified subgroups of postmenopausal women who may be at risk for deleterious outcomes. Three groups have been identified women who present in an anomalous fashion with reduced cancellous bone content perimenopausal women whose hyperparathyroidism is potentially adversely influenced by the onset of estrogen deficiency; and women who are deficient in vitamin D. A third area of inquiry is a characterization of biochemical mediators of parathyroid hormone action as they related to other indices of disease activity, to pathophysiological consequences, and to postoperative recovery. The fourth area to be studied in Project 4 is the histomorphometric features of bone in primary hyperparathyroidism. We plan to reconstruct the dynamics of the bone remodeling unit in primary hyperparathyroidism. We plan to reconstruct the dynamics of the bone remodeling unit in primary hyperparathyroidism. We will also be assessing the histomorphometric changes that occur after patients undergo successful parathyroid surgery in an attempt to understand the counter-intuitive robust increase in bone mass that follows. Bone biopsy samples will be obtained before and one-year postoperatively. Along with detailed biochemical and densitometric studies that will be conducted over this same period, we should be uniquely poised to gain more complete understanding of the anabolic and catabolic properties of parathyroid hormone. The project melds with the overall aim of the SCOR in that it should lead to additional insight into mechanisms of bone loss in general among postmenopausal women and how these mechanisms, presumable due to estrogen deficiency, are influenced by parathyroid hormone.
Keywords: bone density, hyperparathyroidism, osteoporosis, parathyroid hormone, postmenopause, estrogen, hormone therapy, longitudinal human study, pathologic bone resorption, physiologic bone resorption, vitamin D deficiency, biopsy, blood chemistry, clinical research, densitometry, female, human subject, parathyroidectomy, urinalysis
TREATMENT OF HYPOPARATHYROIDISM WITH PARATHYROID HORMONE
John P Bilezikian, Md
Columbia University Health Sciences, Columbia University Medical Center, New York, Ny 10032-3702
Abstract: Hypoparathyroidism is a rare disorder in which parathyroid hormone (PTH) is markedly decreased or absent from the circulation. It is one of the few remaining hormone deficiency states for which replacement with the missing hormone has been heretofore unavailable. Without PTH, patients have abnormal calcium homeostasis characterized by hypocalcemia and high urinary calcium excretion. The current mainstay of therapy is calcium and vitamin D. This approach, however, has important clinical limitations. The large doses of calcium and vitamin D required are associated with risks of hypercalcemia, hypercalciuria and vitamin D toxicity. This approach also does not correct skeletal deficiencies due to lack of PTH. Because hypoparathyroidism is an orphan disease, investigators and funding agencies have all been reluctant to support the development of PTH as a therapy. Of the parathyroid hormone molecules that one might consider, the recent development of recombinant human PTH (1-84) is the most attractive because it is the native hormone, the very molecule that is missing in these individuals. Teriparatide [recombinant hPTH(1-34)] is another potential therapy but it is less attractive since it is an amino-terminal truncated form of PTH and would not provide the hypoparathyroid patient with native hormone. Although approved for osteoporosis, teriparatide has not been developed and is not approved for the treatment of hypoparathyroidism. Very little is known about the therapeutic effects of PTH (1-84) on calcium homeostasis in this population. Even less is known about the general quality of the skeleton in hypoparathyroidism and how it could be improved with PTH (1-84) therapy. This is an important concern, since in hypoparathyroidism, PTH deficiency is associated with markedly reduced bone turnover, a situation that can compromise bone strength. The major objective of this project is a therapeutic one, namely to determine whether PTH is an effective therapy for hypoparathyroidism. It builds upon data obtained from a smaller study funded, in part, by the FDA. By conducting a study that is now double-blinded and placebo controlled, the investigator expects to demonstrate clearly that PTH (1-84) treatment is a safe and effective way to overcome obstacles of management with calcium and vitamin D alone and to improve bone quality as well. With positive results from this trial with PTH (1-84), the investigator expects to be able to have the data reviewed by the FDA with the ultimate goal being approval of PTH (1-84) as a therapy for hypoparathyroidism. This sponsor-investigator expects PTH (1-84) to become the treatment of choice for this orphan disease
Relevance: Principal Investigator/Program Director (Last, First, Middle): Bilezikian, John P. This project will continue and extend our ongoing investigation into the efficacy and safety of parathyroid hormone [PTH(1-84) for hypoparathyroidism, an orphan disease. We expect that data from this study will lead to approval of PTH(1-84) as a treatment for this disease. PHS 398/2590 (Rev. 09/04, Reissued 4/2006) Page Continuation Format Page
Project start date: 2005-09-30
Project end date: 2013-07-31
Budget start date: 20-SEP-2008
Budget end date: 31-JUL-2010
PFA/PA: RFA-FD-08-001
2R01FD002525-04A1 (2008): $0
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